bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in the incidence of nonmelanoma skin cancer in Denmark 1978–2007: Rapid incidence increase among young Danish women
Authors: Birch‐Johansen Fatima , Jensen Allan , Mortensen Lone , Olesen Anne Braae , Kjær Susanne K.
Published: April 2010

Nonmelanoma skin cancer (NMSC) is the most common cancer among Caucasian populations worldwide, and incidence rates are increasing. However, NMSC data are not routinely collected by cancer registries, but Denmark has extensive registration of NMSC in two nationwide population‐based registries. We assessed incidence trends of NMSC in Denmark from 1978 to 2007. Data for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were obtained from the Danish Cancer Registry and the Danish Registry of Pathology. For both genders, age‐specific incidence rates and overall incidence rates, age‐adjusted according to the World standard population were calculated based on combined data from the two registries. For both genders, a high increase in both BCC and SCC incidence was observed over time. Between 1978 and 2007, the age‐adjusted BCC incidence increased from 27.1 to 96.6 cases per 100,000 person‐years for women and from 34.2 to 91.2 cases for men. The SCC incidence increased from 4.6 to 12.0 cases per 100,000 person‐years for women and from 9.7 to 19.1 cases for men. For both BCC and SCC, women experienced a higher average annual percentage incidence change than men. Furthermore, the average annual percentage change in BCC incidence among persons below 40 years was significantly higher compared to older persons, especially for women. These trends may lead to an alarming NMSC incidence increase over time as population ages and will have major implications for future healthcare services. Our findings underline the need for improved preventive strategies to hamper the increasing NMSC incidence.
Expression of oncogenic K‐ras and loss of Smad4 cooperate to induce the expression of EGFR and to promote invasion of immortalized human pancreas ductal cells
Authors: Zhao Shujie , Wang Yubao , Cao Lin , Ouellette Michel M. , Freeman James W.
Published: April 2010

Activating mutation of K‐ras and inactivation of DPC4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). A separate common event in PDAC progression is increased expression of phosphotyrosine kinase receptors (PTKRs). In our study, we examined whether activating mutations of K‐ras and loss of Smad4 play a role in causing the aberrant expression of PTKRs. Immortalized human pancreas ductal cells (HPNE) were genetically modified by expressing oncogenic K‐ras and/or by shRNA knockdown of Smad4. EGFR and erbB2 protein levels but not Ron or IGF‐1R were substantially upregulated in HPNE cells that express K‐ras(GD12). The increased expression of EGFR in HPNE cells that expressed K‐ras(GD12) was mediated by both stabilizing EGFR protein and by increasing EGFR transcription. TGF‐β signaling partially suppressed K‐ras(GD12) induced EGFR transcription in Smad4 intact HPNE cells; whereas knockdown of Smad4 in cells expressing K‐ras(GD12) further enhanced expression of EGFR and erbB2. The upregulation of EGFR and erbB2 was associated with an increase of invasion, which was blocked by a kinase inhibitor of EGFR. Our study indicates for the first time, that oncogenic ras and loss of Smad signaling cooperate to upregulate EGFR and erbB2, which plays a role in promoting invasion.
Reproductive factors and exogenous hormone use and risk of adult glioma in women in the NIH‐AARP Diet and Health Study
Authors: Kabat Geoffrey C. , Park Yikyung , Hollenbeck Albert R. , Schatzkin Arthur , Rohan Thomas E.
Published: April 2010

Experimental evidence suggests that estrogen and other steroid hormones may protect against glioma. Although epidemiologic studies provide only weak support for a role of exogenous or endogenous hormones in gliogenesis, few cohort studies have addressed this question. The authors, therefore, examined the association between menstrual and reproductive factors, exogenous hormone use, and glioma risk among 225,355 women aged 50–71 years who completed the baseline questionnaire in the NIH‐AARP Diet and Health Study. During 7.5 years of follow‐up, 174 cases of incident, primary glioma were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for exposures, taking potential confounders into account. Older age at menarche was positively associated with risk: HR 1.67 (95% CI: 1.03, 2.69). Other reproductive factors, including age at first live birth, parity, age at menopause, type of menopause (natural vs. medical) and exogenous hormone use showed no association with glioma risk. The results were similar when the analysis was restricted to cases with glioblastoma (N = 130). The present study provides only limited support for the hypothesis that menstrual/reproductive factors or exogenous hormone use play a role in gliogenesis.
Enhancement of NK cell antitumor responses using an oncolytic parvovirus
Authors: Bhat Rauf , Dempe Sebastian , Dinsart Christiane , Rommelaere Jean
Published: April 2010

Natural killer (NK) cells play a vital role in the rejection of tumors. Pancreatic ductal adenocarcinoma (PDAC), however, remains a poor prognosis malignancy, due to its resistance to radio‐ and chemotherapy, and low immunogenicity. We demonstrate here that IL‐2‐activated human NK cells are able to kill PDAC cells. Currently, novel strategies are being pursued to combat PDAC. In this regard, oncolytic viruses, in addition to killing tumor cells, may also have the potential to augment antitumor immune responses. We found that, besides having an intrinsic oncolytic activity, parvovirus H‐1PV is able to enhance NK cell‐mediated killing of PDAC cells. Our results show that H‐1PV infection of Panc‐1 cells increases NK cell capacity to release IFN‐γ, TNF‐α and MIP‐1α/β. Multiple activating receptors are involved in the NK cell‐mediated killing of Panc‐1 cells. Indeed, blocking of the natural cytotoxicity receptors—NKp30, 44 and 46 in combination, and NKG2D and DNAM1 alone inhibit the killing of Panc‐1 cells. Interestingly, H‐1PV infection of Panc‐1 cells overcomes the part of inhibitory effects suggesting that parvovirus may induce additional NK cell ligands on Panc‐1 cells. The enhanced sensitivity of H‐1PV‐infected PDAC cells to NK cell‐dependent killing could be traced back to the upregulation of the DNAM‐1 ligand, CD155 and to the downregulation of MHC class I expression. Our data suggests that NK cells display antitumor potential against PDAC and that H‐1PV‐based oncolytic immunotherapy could further boost NK cell‐mediated immune responses and help to develop a combinatorial therapeutic approach against PDAC.
STAT3 is essential for the maintenance of neurosphere‐initiating tumor cells in patients with glioblastomas: A potential for targeted therapy?
Authors: Villalva Claire , Martin‐Lannerée Severine , Cortes Ulrich , Dkhissi Fatima , Wager Michel , Le Corf Amélie , Tourani Jean‐Marc , Dusanter‐Fourt Isabelle , Turhan Ali G. , Karayan‐Tapon Lucie
Published: April 2010

Glioblastoma (GBM), the highest‐grade form of gliomas, is the most frequent and the most aggressive. Recently, a subpopulation of cells with stem cells characteristics, commonly named “tumor‐initiating stem cells” (TISCs) or “cancer stem cells” (CSCs) were identified in GBM. These cells were shown to be highly resistant to chemotherapeutic drugs and to ionizing radiations. Consequently, the knowledge of the signals that regulate the functions and survival of TISCs is crucial. In our work, we describe a neurosphere‐initiating cell (NS‐IC) assay to quantify TISC/CSCs from patients with GBM and show that these cells are tumorigenic in vivo. We demonstrate that the intracellular signal transducer and activator of transcription STAT3 is constitutively activated by phosphorylation preferentially on serine 727 in these cells. Moreover, we demonstrate that the selective inhibition of STAT3 by the chemical compound Stattic or by siRNA STAT3 abrogates TISC/CSC proliferation and NS‐IC suggesting that self‐renewal of GBM “stem‐like” cells depends on the presence of STAT3 for their maintenance. Finally, we show that inhibition of STAT3 by Stattic sensitizes TISC/CSCs to the inhibitory action of Temozolomide with a strong synergistic effect of both drugs. Overall, these results suggest that strategies focused on STAT3 inhibition are efficient at the level of “stem‐like” cells and could be of interest for therapeutic purposes in patients with malignant GBM.
Comparative hepatotoxicity of deoxynivalenol in rat, mouse and human liver cells in culture
Authors: Sahu Saura C. , O'Donnell Michael W. , Wiesenfeld Paddy L.
Published: April 2010

The present study was undertaken to assess,in vitro, the hepatotoxic potential of the food‐borne mycotoxin, deoxynivalenol (DON), using rat (Clone9 and MH1C1), mouse (NBL CL2) and human (WRL68 and HepG2) liver cells in culture. The cells were treated with DON for 24 h at 37 °C in 5% CO2at concentrations of 0–25 µg ml−1. Following the treatment period, the cells were assayed for biochemical markers of hepatotoxicity that included three independent cytotoxicity assays, oxidative stress and mitochondrial dysfunction. Concentration‐dependent cytotoxicity of DON was observed in each of the five different liver cells derived from three different species (rat, mouse and human) over the entire concentration range studied, beginning at 0.1 µg ml−1. At these concentrations DON did not induce a biologically significant increase in oxidative stress in these liver cells, and showed a significant decrease in the mitochondrial function only in the rat liver MH1C1 cells compared with the control. The results of thisin vitrostudy suggest that DON is a potential hepatotoxin for the rat, mouse and human liver cells in the concentration range tested in this study. The liver cells used in this study showed distinct endpoint‐sensitivity to DON related to the species. Published in 2010 by John Wiley and Sons, Ltd.
Phosphate and calcium are required for TGFβ‐mediated stimulation of ANK expression and function during chondrogenesis
Authors: Oca Paulina , Zaka Raihana , Dion Arnold S. , Freeman Theresa A. , Williams Charlene J.
Published: April 2010

The expression of ANK, a key player in biomineralization, is stimulated by treatment with TGFβ. The purpose of this study was to determine whether TGFβ stimulation of ANK expression during chondrogenesis was dependent upon the influx of calcium and phosphate into cells. Treatment of ATDC5 cells with TGFβ increased ANK expression during all phases of chondrogenic differentiation, particularly at day 14 (proliferation) and day 32 (mineralizing hypertrophy) of culture. Phosphate uptake studies in the presence and absence of phosphonoformic acid (PFA), a competitive inhibitor of the type III Na+/Pi channels Pit‐1 and Pit‐2, indicated that the stimulation of ANK expression by TGFβ required the influx of phosphate, specifically by the Pit‐1 transporter, at all phases of differentiation. At hypertrophy, when alkaline phosphatase is highly expressed, inhibition of its activity with levamisole also abrogated the stimulatory effect of TGFβ on ANK expression, further illustrating that Pi availability and uptake by the cells is necessary for stimulation of ANK expression in response to TGFβ. Since previous studies of endochondral ossification in the growth plate have shown that L‐type calcium channels are essential for chondrogenesis, we investigated their role in the TGFβ‐stimulated ANK response in ATDC5 cells. Treatment with nifedipine to inhibit calcium influx via the L‐type channel Cav1.2 (α1C) inhibited the TGFβ stimulated increase in ANK expression at all phases of chondrogenesis. Our findings indicate that TGFβ stimulation of ANK expression is dependent upon the influx of phosphate and calcium into ATDC5 cells at all stages of differentiation. J. Cell. Physiol. 224: 540–548, 2010. © 2010 Wiley‐Liss, Inc.
Contrast‐enhanced ultrasound features of primary splenic lymphoma
Authors: Sutherland Tom , Temple Faye , Hennessy Oliver , Lee Wai‐Kit
Published: April 2010

We report a case of primary splenic lymphoma incidentally detected on abdominal ultrasound as a well‐defined homogenous hypoechoic splenic mass. Further characterization with contrast‐enhanced ultrasound showed the mass to enhance homogenously during the arterial phase to a degree similar to that of the normal splenic parenchyma followed by rapid washout becoming hypoenhanced on delayed phase. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010
Ultrasound demonstration of Struthers' ligament
Authors: Camerlinck Michael , Vanhoenacker Filip M. , Kiekens Gunther
Published: April 2010

The supracondylar process is a bony spur at the anteromedial surface of the distal humerus. It is associated with the Struthers' ligament, running from its apex to the medial epicondyle. Symptoms may occur due to fracture and entrapment of nerves (most frequently the median nerve) and/or blood vessels underneath the structures. We report a case in which we used MRI and high‐frequency ultrasound to investigate the supracondylar process, the Struthers' ligament, and its surrounding structures. Ultrasound is a useful alternative to MRI during the workup of potential entrapment syndromes. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:499–502, 2010
A survival case of painless chronic type A aortic dissection with a history of stroke and anticoagulant use
Authors: Tugcu Aylin , Yildirimturk Ozlem , Demiroglu I.C. Cemsid , Aytekin Saide
Published: April 2010

We report the case of a patient with completely painless chronic aortic dissection, who presented to another hospital with a left hemiparesia 3 months ago and received anticoagulation therapy with a diagnosis of ischemic stroke. Most of her symptoms had resolved when she presented to our outpatient clinic except for numbness of her left hand and dysphasia. Physical examination found a diastolic murmur at the left sternal border and a bruit over the right carotid artery. Transthoracic echocardiography and carotid sonography demonstrated aortic dissection with extension into the internal right carotid artery and severe aortic regurgitation. Surgery was performed successfully and the patient was discharged. This case emphasizes that the diagnosis of a completely painless aortic dissection with only neurologic symptoms at presentation can be extremely difficult and should always be considered as a cause of ischemic stroke to avoid catastrophic antithrombolytic or anticoagulation therapy. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:454–456, 2010
Effects of exposure to the xenoestrogen octylphenol and subsequent transfer to clean water on liver and gonad ultrastructure during early development of Zoarces viviparus embryos
Authors: Jespersen Åse , Rasmussen Tina H. , Hirche Majken , Sørensen Kristine J.K. , Korsgaard Bodil
Published: April 2010

Female eelpouts (Zoarces viviparus L.) are exposed during early pregnancy to nominal concentrations of 100 µg/L of 4‐tert‐octylphenol (OP) or 0.5 µg/L of 17β‐estradiol (E2). Effects on maternal metabolism and on liver and gonad development in embryos were examined and compared with controls (C) during exposure and after transfer to clean water (depuration). In the mother fish, significantly higher concentrations of plasma vitellogenin (vtg) and calcium were found in the two exposed groups, when compared with the C group after exposure and depuration. When compared, however, with the respective values after exposure, vtg had decreased significantly after depuration. The hepatosomatic index was normalized after depuration. In both exposed groups, the hepatocytes were rounded and not distinctly polygonal as in the controls. The amount of glycogen was considerably less while the number of mitochondria increased, and the rER significantly proliferated after exposure as well as after depuration. The gonads of nine of more than 28 embryos in the group treated with OP exhibited a number of abnormalities as compared with the normal gonad development in both sexes. Feminization of the male gonads in the exposed specimens and a number of histopathological features were observed in all the abnormal gonads, whereas reliable male features, such as formation of seminiferous tubules or spermioduct, were not observed. This study showed that 4t‐tert‐OP and 17β‐estradiol exert estrogenic effects during very early development of the embryos and that depuration had a positive effect on the motherfish and her embryos. J. Exp. Zool. 313A:399–409, 2010. © 2010 Wiley‐Liss, Inc.
Spatiotemporal changes in metallothionein gene expression during embryogenesis in the wall lizard Podarcis sicula
Authors: Simoniello Palma , Motta Chiara Maria , Scudiero Rosaria , Trinchella Francesca , Filosa Silvana
Published: April 2010

Lizard embryos are nutritionally independent from their environment. During the early phases of oogenesis, the egg prepares for development by storing reserve organelles, proteins, and RNAs sufficient to allow the zygote to transform into a juvenile. This preparation also includes the storage of metallothionein (MT) transcripts. This study investigated the localization of these transcripts by in situ hybridization throughout Podarcis sicula developmental stages. Our data show that MT expression undergoes shifts in both regional and cellular localization. MT transcripts were detected early in the central nervous system, later in tissues implicated in metabolic processes. Results are discussed highlighting differences in lizard embryonic spatial and temporal MT expression compared with piscine, amphibian, and mammalian embryos. We hypothesize that, under natural conditions, the nutritionally closed system represented by the lizard egg protects the developing embryo from an unwanted excess of metals. This mechanism would make MT expression and accumulation in detoxifying organs in developing animals unnecessary until hatching and food intake begins. Conversely, the presence of MT transcripts during brain development may ensure the correct final architecture of this organ. J. Exp. Zool. 313A:410–420, 2010. © 2010 Wiley‐Liss, Inc.
Involvement of a novel p38 mitogen‐activated protein kinase in larval metamorphosis of the polychaete Hydroides elegans (Haswell)
Authors: Wang Hao , Qian Pei‐Yuan
Published: April 2010

Hydroides elegans is a common marine fouling organism in most tropical and subtropical waters. The life cycle of H. elegans includes a planktonic larval stage in which swimming larvae normally take 5 days to attain competency to settle. Larval metamorphosis marks the beginning of its benthic life; however, the endogenous molecular mechanisms that regulate metamorphosis remain largely unknown. In this study, a PCR‐based suppressive subtractive hybridization (SSH) library was constructed to screen the genes expressed in competent larvae but not in precompetent larvae. Among the transcripts isolated from the library, 21 significantly matched sequences in the GenBank. Many of these isolated transcripts have putative roles in the reactive oxygen species (ROS) signal transduction pathway or in response to ROS stress. A putative novel p38 mitogen‐activated protein kinase (MAPK), which was also isolated with SSH screen, was then cloned and characterized. The MAPK inhibitors assay showed that both p38 MAPK inhibitors SB202190 and SB203580 effectively inhibited the biofilm‐induced metamorphosis of H. elegans. A cell stressors assay showed that H2O2 effectively induced larval metamorphosis of H. elegans, but the inductivity of H2O2 was also inhibited by both SB inhibitors. The catalase assay showed that the catalase could effetely inhibit H. elegans larvae from responding to inductive biofilm. These results showed that the p38 MAPK‐dependent pathway plays critical role in controlling larval metamorphosis of the marine polychaete H. elegans, and the reactive oxygen radicals produced by biofilm could be the cue inducing larval metamorphosis. J. Exp. Zool. (Mol. Dev. Evol.) 314B:390–402, 2010. © 2010 Wiley‐Liss, Inc.
Developmental plasticity links local adaptation and evolutionary diversification in foraging morphology
Authors: Young Rebecca L. , Badyaev Alexander V.
Published: April 2010

Developmental plasticity is thought to reconcile the constraining role of natural selection in maintaining local adaptation with evolutionary diversification under novel conditions, but empirical documentations are rare. In vertebrates, growth and development of bones is partially guided by contractions of attached musculature and such muscle activity changes progressively through embryonic development from sporadic motility to direct functional effects. In species with short generation times, delayed skull maturation extends the guiding effects of muscle activity on formation of foraging morphology into adulthood, providing an opportunity to directly examine the links between plasticity of bone development, ecological adaptations, and evolutionary diversification in foraging morphology. In this case, the morphological consequences of inputs due to local functional requirements should be evident in adaptive divergence across taxa. Here we provide evidence that epigenetic regulation of bone growth in Soricid shrews may enable both development of local adaptations and evolutionary divergence in mandibular morphology. We contrast the effects of muscle stimulation on early‐ vs. late‐maturing components of, foraging apparatus to show that the morphology of late‐maturing components is more affected by functional requirements than are early‐ossifying traits. Further, the divergence in foraging morphology across shrew species occurs along the directions delineated by inductive effects of muscle loading and bite force on bone formation in late‐maturing but not early‐maturing mandible components within species. These results support the hypothesis that developmental plasticity can link maintenance of local adaptations with evolutionary diversification in morphology.J. Exp. Zool. (Mol. Dev. Evol.) 314B:434–444, 2010. © 2010 Wiley‐Liss, Inc.
Collaborating with patients and their families
Authors: Johnson Bev , Ford Dan , Abraham Marie
Published: April 2010

Patient‐ and family‐centered care is a healthcare approach that emphasizes collaboration among patients, families, and healthcare providers. The key concepts of patient‐ and family‐centered care can be applied in any healthcare setting to enhance patient safety, reduce the risk of medical errors, improve risk management processes, and create an organizational culture supportive of risk managers and open, honest communication.
Implementation of a patient‐friendly medication schedule to improve patient safety within a healthcare system
Authors: Fredericks Jodi E. , Bunting Jr. Robert F.
Published: April 2010

Preventable adverse drug events have a direct impact on the well‐being of patients. The creation and implementation of a patient‐friendly daily medication schedule improved the way care is delivered at Memorial Healthcare System. The staff collaborated with patients and families and empowered them with the knowledge and tools needed to make their healthcare safer. Patient and family participation, a critical component of patient‐ and family‐centered care, is a vital part of making healthcare safer. This tool enhances communication with patients and family members and enables patients to better understand the medications they receive while hospitalized. An additional welcomed byproduct is the prevention of potential medication errors.
Apoptosis markers related to pathogenesis of pediatric chronic hepatitis C virus infection: M30 mirrors the severity of steatosis
Authors: Valva Pamela , De Matteo Elena , Galoppo María C. , Gismondi María I. , Preciado María V.
Published: April 2010

Apoptosis involvement in liver damage related to hepatitis C virus (HCV) chronic infection has been suggested. Although liver biopsy represents the gold standard for evaluating disease severity, non‐invasive tests are a growing medical need. The aim of this study was to detect apoptosis markers in liver and serum from pediatric HCV‐infected patients and to assess its utility to predict liver damage progression. Twenty‐three patients were included. Liver biopsies were used for histological analysis as well as for immunodetection of a viral protein (NS3) and apoptosis markers (activated caspase‐3 [casp‐3a], caspase‐generated CK‐18 fragment [M30] and TUNEL). M30 was quantified in paired serum and biopsy samples. NS3 correlated both with casp‐3a (r = 0.83, P < 0.0001) and TUNEL (r = 0.61, P < 0.0017). Casp‐3a and TUNEL also displayed a correlation (r = 0.56, P = 0.005). Both NS3 and casp‐3a were associated with fibrosis stage (P = 0.03). Serum M30 [median: 122.15 UL‐1 (86.68–794.58)] was higher in patients than in controls [median: 81.44 UL‐1 (41.17–129.30)], (P < 0.0001). M30 showed a correlation with steatosis, and indeed it was linked to severe grade (P = 0.004). In children, HCV would be involved in liver damage through apoptosis induction. The apoptosis markers detected reflect liver injury. Serum M30 might be useful as a marker to detect the extent of liver steatosis. J. Med. Virol. 82:949–957, 2010. © 2010 Wiley‐Liss, Inc.
Hantaviruses in small mammals and humans in the coastal region of Zhejiang Province, China
Authors: Zhang Yong‐Zhen , Lin Xian‐Dan , Shi Nan‐Feng , Wang Wen , Liao Xiao‐Wei , Guo Wen‐Ping , Fan Fei‐Neng , Huang Xiu‐Min , Li Ming‐Hui , Li Mei‐Fu , Chen Yi , Chen Xiao‐Ping , Wang Shao‐Bin , Fu Zhen F. , Plyusnin Alexander
Published: April 2010

To gain more insights into the epidemiology of hantaviruses in the coastal region of Zhejiang Province, China, the morbidity and mortality of hemorrhagic fever with renal syndrome (HFRS) were analyzed in two coastal areas: Cixi (hilly terrain) and Wenzhou (mountainous terrain). More HFRS cases have been reported in Cixi than in Wenzhou. Annual incidence rate of HFRS in Cixi had been on the level of approximately 1.5/100,000 from 1968 (when the first HFRS case was reported) to 2007, with the highest incidence rate of 8.54/100,000 in 1999. The annual incidence rate in Wenzhou has been relatively low, less than 0.5/100,000 since the first HFRS case was reported in 1981. A total of 461 rodents and 199 shrews were captured in these two areas. Hantavirus antibodies were detected in 16 of 241 (6.64%) Rattus norvegicus and 13 of 122 (10.66%) R. flavipectus. Interestingly, hantavirus antigens were identified in 6 of 196 (3.06%) Suncus murinus. Genetic analysis showed that partial M and S segment sequences recovered from rats in the two regions belong to Seoul virus (SEOV) and can be assigned into two genetic lineages. SEOV variants that belong to these two lineages of viruses are distributed widely in China and have been found outside China. As most trapped rodents were rats and SEOV was the only hantavirus detected, these results suggested that SEOV plays an important role in human hantavirus infections. They also reinforce the need for vigilance in preventing HFRS caused by hantaviruses in the coastal region. J. Med. Virol. 82:987–995, 2010. © 2010 Wiley‐Liss, Inc.
No evidence of family history as a risk factor for herpes zoster in patients with post‐herpetic neuralgia
Authors: Gatti A. , Pica F. , Boccia M.T.Y. , De Antoni F. , Sabato A.F. , Volpi A.
Published: April 2010

Little is known about reactivation of latent varicella zoster virus as herpes zoster in individuals with no underlying immunosuppression. Risk factors include age, sex, ethnicity, exogenous boosting of immunity from varicella contacts, underlying cell‐mediated immune disorders, mechanical trauma, psychological stress, and immunotoxin exposure. An association between herpes zoster and family history of zoster has been proposed. A case‐control study involving patients affected by post‐herpetic neuralgia, which usually follows more severe acute herpes zoster, was performed. The patients with post‐herpetic neuralgia were enrolled at the Pain Clinic of the Policlinico Tor Vergata in Rome, Italy, within 1 year from the onset of acute zoster. The controls matched for sex and age were chosen among healthy subjects without a history of herpes zoster presenting at the Internal Medicine Outpatient Clinic for hypertension in the same time period. All the participants in the study gave informed consent and were interviewed by medically trained and blinded investigators using a questionnaire. Similar proportions of the patients and the controls reported a family history of herpes zoster irrespective of the degree of relationship, i.e., 17.4% and 18.2%, respectively, by analyzing only the first‐degree relatives [RR 1.03 (CI 95%: 0.78–1.37)], and 28.4% and 29.6%, respectively, by analyzing the total number of relatives [RR 1.03 (CI 95%: 0.81–1.31)]. Further and larger prospective cohort studies are needed to ascertain whether a family history of herpes zoster is really an independent predictor of zoster in different geographical settings. J. Med. Virol. 82:1007–1011, 2010. © 2010 Wiley‐Liss, Inc.
DNA of mouse mammary tumor virus‐like virus is present in human tumors influenced by hormones
Authors: Johal Harpreet , Faedo Margaret , Faltas Jacqueline , Lau Amie , Mousina Railya , Cozzi Paul , deFazio Anna , Rawlinson William D.
Published: April 2010

Mouse mammary tumor virus (MMTV) is a hormonally regulated, oncogenic virus of mice. MMTV‐like virus DNA has previously been detected in human breast cancers, liver disease, and liver cancers. It is hypothesized that local hormonal effects might be of primary importance in determining MMTV‐like virus detection in human tumors. MMTV‐like virus envelope (env) DNA was determined using nested PCR in 89 ovarian, 147 prostate, 50 endometrial, 141 skin, and 51 lung cancers. Viral‐positive sequences were compared with published MMTV‐like viral sequences from human breast cancer, liver cancer and MMTV. Immunohistochemistry for estrogen receptor (ER‐α) and progesterone receptor (PgR) was performed on a subset of tumors. MMTV‐like virus env DNA was detected in ovarian cancers (14/89; 16%), prostate cancers (53/147; 36%), endometrial cancers (5/50; 10%), skin cancers (13/141; 9%) but not in lung cancers (0/51). Phylogenetic analysis of the viral‐positive sequences showed no clustering of the isolates according to tissue type. A significant association was observed between the presence of hormone receptors and detection of MMTV‐like virus in the human cancers screened (P = 0.01). A significant association between MMTV‐like virus and PgR was noted in skin cancers (P = 0.003). Therefore, unlike the mouse model, the detection of MMTV‐like env sequences in human cancers in addition to breast indicates that MMTV‐like viral expression is not breast cancer‐specific and may relate to hormone‐dependent viral expression. J. Med. Virol. 82:1044–1050, 2010. © 2010 Wiley‐Liss, Inc.
Isolated norovirus GII.7 strain within an extended GII.4 outbreak
Authors: Hoffmann Dieter , Seebach Judith , Foley Brian T. , Frösner Gert , Nadas Korinna , Protzer Ulrike , Schätzl Hermann M.
Published: April 2010

Noroviruses are a major cause of viral gastroenteritis and have been detected with increasing prevalence in recent years. Currently, two main genogroups GI and GII with an increasing number of subtypes are differentiated. Because of a high genetic variability new variants emerge constantly allowing epidemiological tracing of viruses from year to year and location to location. A 282 bp sequence at the 5′end of the capsid gene was analyzed in isolates originating from the University hospital, Technische Universität München. Phylogenetic analysis was based on 20 GII positive samples from an outbreak in March/April 2006 and 8 samples from the following winter season 2006–2008. In the initial outbreak two distinct genotypes were identified. The GII.4 strain 2006a found in the majority of outbreaks in 2006 worldwide was isolated from all but two patients. These two individuals were infected with a GII.7 strain clustering mainly with isolates from Asia. Of note, they excreted noroviral RNA for 81 and 27 days, respectively. Longitudinal analysis of an extended 1381 bp sequence revealed positive selection in the P2 domain. The variant was very similar to GII.7 strains isolated in 1990 and 1994 suggesting slow evolution with evidence of recombination according to the SimPlot analysis. Strains found in the following years 2006–2008 clustered around the isolate GII.4 2006b, characterized in the spring of 2006 and reaching a high prevalence in 2006–2007. The results provide an insight into norovirus evolution at a University hospital over 3 years and describe intraindividual evolution within a patient infected chronically. J. Med. Virol. 82:1058–1064, 2010. © 2010 Wiley‐Liss, Inc.
Characterization of common and rare human papillomaviruses in Portuguese women by the polymerase chain reaction, restriction fragment length polymorphism and sequencing
Authors: Nobre Rui Jorge , Cruz Eugénia , Real Odete , de Almeida Luís Pereira , Martins Teresa C.
Published: April 2010

The present study aimed to provide additional information on the prevalence of mucosal human papillomavirus (HPV) types in Portuguese women by using polymerase chain reaction, restriction fragment length polymorphism and sequencing. HPV was detected in 15.5% (15/97) of the control samples, 23.5% (12/51) of atypical squamous cells of undetermined significance, 52.8% (28/53) of low‐grade lesions, 82.4% (28/34) of high‐grade lesions, and 100% (44/44) of carcinomas. Overall, 28 HPV types were detected: 11 high‐risk (HPV 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, and 59), 3 probable high‐risk (HPV 53, 66, and 73), 6 low‐risk (HPV 6, 11, 44, 61, 70, and 81), and 8 unknown‐risk types (HPV 34, 62, 67, 71, 83, 84, 102, and 108). The most prevalent type was HPV 16, detected in 33.8% of women infected with HPV, followed by HPV 58 (9.2%), HPV 33 (7.0%), HPV 18 (6.3%), HPV 53 (5.6%), HPV 31 and 56 (4.9% each), HPV 6 (3.5%), and HPV 66 and 81 (2.8% each). Of 44 cervical carcinoma samples, 71% were associated with HPV 16 (60%) and HPV 18 (11.1%), followed by the high‐risk types 33 (11.1%), 35 (4.4%), 45 (4.4%), and 56 (2.2%), the probable high‐risk type 53 (4.4%) and the unknown‐risk type 67 (2.2%). This study provides information on the most common HPV types in Portuguese women and suggests that the current prophylactic HPV 16/18 vaccine may be useful for the prevention of cervical cancer in this population. J. Med. Virol. 82:1024–1032, 2010. © 2010 Wiley‐Liss, Inc.
Molecular characterization of hepatitis B virus and a 9‐year clinical profile in a patient infected with genotype I
Authors: Osiowy Carla , Kaita Kelly , Solar Kaarina , Mendoza Kenneth
Published: April 2010

An unusual hepatitis B virus (HBV) variant, assigned provisionally to genotype I, was recently reported, characterized by an anomalous genotyping pattern and putative recombination; however, the natural history of this unusual strain is unknown. This study analyzed longitudinal sera collected over a 9‐year period from a patient infected with this variant to investigate the clinical profile and intrahost viral evolution over time. The patient, who had immigrated to Canada in 1998 from Vietnam, was treated with lamivudine in 2000. Approximately 4–5 years following the withdrawal of lamivudine therapy, a genomic “shift” occurred coincident with ALT flares and increasing HBV viral load, resulting in numerous stable nucleotide substitutions within the core coding region, suggesting altered immune control that may provide a selective advantage to the virus. Analysis of quasispecies diversity over time demonstrated further this shift, with two sequence clusters associated with time points either prior to or following relapse observed, including increased diversity among quasispecies prior to relapse. In keeping with the complex nature of genotype I strains, majority population genomes had a mean genetic distance from genotype C of 7.6 ± 0.1%, although large genomic segments lacked significant homology with any HBV genotype. Further study is needed to understand the evolutionary origin and natural history of infection with this unique HBV variant. J. Med. Virol. 82:942–948, 2010. © 2010 Wiley‐Liss, Inc.
Epidemiology of hepatitis A in Finland in 1990–2007
Authors: Broman Mia , Jokinen Sari , Kuusi Markku , Lappalainen Maija , Roivainen Merja , Liitsola Kirsi , Davidkin Irja
Published: April 2010

The seroepidemiology of hepatitis A virus (HAV) for the period 1990–2007 and the molecular epidemiology for the period 1994–2007 in Finland were studied. The incidence of hepatitis A has been very low since 1990, at 0.3–3.6/100,000 inhabitants, excluding two outbreaks in 1994–1995 and 2002–2003, both of which were connected to intravenous drug use. Serum samples (3,217) collected in the period 1997–1998 were tested for hepatitis A antibodies to assess the percentage of seropositive Finns. More than 50% of Finns aged over 55 were seropositive for hepatitis A, while less than 5% of those aged under 40 were seropositive. In addition, patient samples (52,012) from the period 1990 to 2007 were assessed for antibodies against HAV. In these samples the proportion of acute HAV infections stayed at around 2% per year (excluding outbreaks), whereas the overall seropositivity for hepatitis A increased from some 30% to 45%, which was most likely due to increased vaccinations. For molecular epidemiology, samples from 1994 to 2007 were analyzed by RT‐PCR and sequencing. The results showed that most of the strains (82%) of HAV were of genotype IA but with an increasing number of genotypes IB and IIIA appearing during the last years of the study. All the cases seemed to be travel related and there was no endemic strain circulating in Finland. The low seroprevalence, especially in younger age groups, makes the population vulnerable to infection, which can be compensated for by increasing the number of vaccinations. J. Med. Virol. 82:934–941, 2010. © 2010 Wiley‐Liss, Inc.
Full genomic analysis of a porcine–bovine reassortant G4P[6] rotavirus strain R479 isolated from an infant in China
Authors: Wang Yuan‐Hong , Kobayashi Nobumichi , Nagashima Shigeo , Zhou Xuan , Ghosh Souvik , Peng Jin‐Song , Hu Quan , Zhou Dun‐Jin , Yang Zhan‐Qiu
Published: April 2010

During the 2004 surveillance of rotaviruses in Wuhan, China, a G4P[6] rotavirus strain R479 was isolated from a stool specimen collected from a 2‐year‐old child with diarrhea. The strain R479 had an uncommon subgroup specificity I + II, and analysis of the VP6 gene suggested that it was related to porcine rotaviruses. In the present study, full‐length nucleotide sequences of all the RNA segments of R479 were determined and analyzed phylogenetically to identify the origin of individual RNA segments. According to the rotavirus genotyping system based on 11 RNA segments, the genotype of R479 was expressed as G4‐P[6]‐I5‐R1‐C1‐M1‐A1‐N1‐T7‐E1‐H1. This genotype includes the porcine‐like VP6 genotype (I5) and bovine‐like NSP3 genotype (T7). Phylogenetic analysis revealed that R479 genes encoding VP1, VP2, VP3, VP6, VP7, VP8*, NSP1, NSP4, and NSP5 were more closely related to those of porcine rotaviruses than human or other animal rotaviruses. In contrast, it was remarkable that the NSP3 gene of R479 was genetically closely related to only a bovine rotavirus strain UK. The NSP2 gene of R479 was also unique and clustered with only the G5P[8] human strain IAL28 and G3P[24] simian strain TUCH. These results suggested that R479 may be a reassortant virus having the NSP3 gene from a bovine rotavirus in the genetic background of a porcine rotavirus, with an NSP2 gene related to the porcine‐human reassortant strain IAL28. To our knowledge, R479 is the first porcine–bovine reassortant rotavirus isolated from a human. J. Med. Virol. 82:1094–1102, 2010. © 2010 Wiley‐Liss, Inc.
Genetic characterization of norovirus GII.4 2006b variants from Jeju island, South Korea
Authors: Le Van Phan , Jung Yeon Chang , Kang Ki Soo , Lim Inseok , Myung Soon Chul , Kim Wonyong
Published: April 2010

Ninety‐seven fecal specimens collected from children with acute gastroenteritis between 2007 and 2008 that were found to be negative for group A rotavirus in prescreening by ELISA with VP6‐specific antibody were re‐screened for viruses by reverse transcription (RT)‐PCR. Forty (41.2%) samples were found to be positive for virus by RT‐PCR; of these, norovirus (32.5%, n = 13) and rotavirus (32.5%, n = 13) were the most common, followed by astrovirus (5.0%, n = 2) and enterovirus (2.5%, n = 1). Co‐infection was found in 11 (27.5%) samples. Phylogenetic analyses of the ORF2 nucleotide sequences of 21 norovirus strains showed that 19 (90.5%) belonged to the genogroup GII genotype 4 and two (9.5%) belonged to genogroup GI genotype 4. The GII.4 strains demonstrated high sequence homology and were closely related to new 2006b variants observed in Europe, China, Hong Kong, and Japan in 2006. This study provides new information concerning the recent global epidemic of 2006b strains. J. Med. Virol. 82:1065–1070, 2010. © 2010 Wiley‐Liss, Inc.
Association of cytokine genetic polymorphisms with the humoral immune response to recombinant vaccine against HBV in infants
Authors: Macedo Luciana Conci , Isolani Aline Paula , Visentainer Jeane Eliete Laguila , Moliterno Ricardo Alberto
Published: April 2010

The prevention of hepatitis B by vaccination is one the most efficient tools to avoid the transmission of the virus, although a considerable variability to the anti‐HBsAg antibody response has been described. Recently, polymorphisms of cytokine regulating genes have been described which seem to influence the immune response to various antigens. This article's objective was to evaluate the influence of cytokine genetic polymorphisms onto the humoral immune response to hepatitis B vaccine in infants. Vaccinated children were classified according to the level of anti‐HBsAg antibody titles. The genotyping for TNF (−308), TGFB1 (+869, +915), IL‐10 (−1082, −819, −592), IL‐6 (−174), and IFNG (+874) was accomplished by the PCR‐SSP technique. The TNF (−308) allele A presented a lower but not statistically significant frequency at 5% level in high responder patients (3.7% vs. 12.3%, P = 0.0919). The same was seen for the TNF (−308) genotype GA (7.4% vs. 24.5%, P = 0.0757). Further studies in other populations and evaluation of a greater number of individuals may contribute for a better understanding of the cytokine gene polymorphism influence in general and TNF polymorphism more specifically in the humoral immune response to the HBsAg vaccination in newborn children. J. Med. Virol. 82:929–933, 2010. © 2010 Wiley‐Liss, Inc.
Co‐circulation of multiple measles virus genotypes during an epidemic in France in 2008
Authors: Waku‐Kouomou Diane , Freymuth François , du Châtelet Isabelle Parent , Wild T. Fabian , Horvat Branka
Published: April 2010

In 2008, measles reappeared in France in a series of outbreaks. During this period, 604 measles cases were reported to a routine surveillance system and 305 (50%) of these cases were then confirmed in the laboratory. To understand better the current epidemiological situation and the circulation of different measles strains, a phylogenetic characterization of 113 (19%) of the measles cases from these outbreaks was performed. All measles cases met the WHO clinical criteria and were confirmed either by laboratory detection of measles‐specific IgM and/or by detection of the virus genome by polymerase chain reaction (PCR) and viral isolation. PCR products generated from blood, oral fluid, urine, or nasopharyngeal‐swab samples were sequenced for molecular epidemiology studies. Phylogenetic analysis showed a co‐circulation of genotypes D4 and D5 during the first measles outbreak in the city of Reims in early 2008. Over the course of the year, the A, B3.2, D8, and D9 genotypes also appeared. The data from this study show the simultaneous circulation of several measles genotypes in France and describe genotypes D8 and D9 for the first time in this country. The data also suggest that there are still many pockets of unvaccinated individuals helping to maintain the circulation of measles virus in the population. Phylogenetic studies allowed the corroboration of epidemiologic links and showed that nosocomial transmission can create significant risk for measles dissemination. Finally, the pattern of changes in viral genotypes during 2008 suggests a regular introduction of measles strains from abroad. J. Med. Virol. 82:1033–1043, 2010. © 2010 Wiley‐Liss, Inc.
Functional disorder of primary immunity responding to respiratory syncytial virus infection in offspring mice exposed to a flame retardant, decabrominated diphenyl ether, perinatally
Authors: Watanabe Wataru , Shimizu Tomomi , Sawamura Rie , Hino Akane , Konno Katsuhiko , Kurokawa Masahiko
Published: April 2010

Perinatal exposure to a representative flame retardant, decabrominated diphenyl ether (DBDE), was shown previously to increase viral titers in the lungs of respiratory syncytial virus (RSV)‐infected offspring on day 5 post‐infection, resulting in exacerbation of pneumonia. In this study, the significant increase of pulmonary viral titers was confirmed even on day 1 post‐infection and the effect on the primary immune response to RSV infection were examined to assess a mode of DBDE action on developmental immunotoxicity. On day 1 after infection, the secretion of both TNF‐α and IL‐6 decreased significantly in the bronchoalveolar lavage fluid prepared from RSV‐infected offspring exposed to DBDE perinatally, but IL‐1β increased. However, in ex vivo lipopolysaccharide stimulation test, the productivity of TNF‐α in the bronchoalveolar lavage cells, which are mainly primary immune cells responding to RSV infection, prepared from offspring mice exposed to DBDE perinatally was not lower than that in the control. The primary immune cells retained normally the ability of cytokine production after the DBDE exposure. Gene expressions of innate pattern recognition receptors (Toll‐like receptor 3 and 4, melanoma differentiation‐associated gene‐5, and retinoic acid‐inducible gene I) in lung tissues were not affected by DBDE exposure. Because the levels of TNF‐α, IL‐6, and IL‐1β are known to be elevated in the lungs of RSV‐infected mice, these irregular productions due to perinatal DBDE exposure indicate a disorder of the primary immune response to RSV infection. Thus, perinatal exposure to DBDE was suggested to cause a functional disorder of primary immunity responding to RSV infection. J. Med. Virol. 82:1075–1082, 2010. © 2010 Wiley‐Liss, Inc.
Neurovirulence and latency of drug‐resistant clinical herpes simplex viruses in animal models
Authors: Dambrosi Sarah , Martin Mélanie , Yim Kevin , Miles Brian , Canas Julio , Sergerie Yan , Boivin Guy
Published: April 2010

Herpes simplex virus (HSV) resistance to acyclovir or foscarnet results from mutations in viral thymidine kinase (TK) and/or DNA polymerase (pol) genes. Replication kinetics and virulence of TK and/or DNA pol clinical mutants were assessed using models of mouse encephalitis and cotton rat genital infection. Replication capacities in Vero cells of a DNA pol altered strain (L850I) and a TK/DNA pol mutant (C467deletion/A912V) were significantly lower than those of unrelated wild‐type (WT) strains, while a double DNA pol mutant (S724N/P920S) demonstrated replication kinetics similar to the WT. The replication of a TK‐deficient mutant (G439.5addition) was impaired (low m.o.i.) or unaltered (high m.o.i.) compared to that of a WT virus depending on the viral inoculum. Compared to a survival rate of 6% for mice infected intranasally with WT HSV‐1 or ‐2 viruses, G439.5add, C467deletion/A912V and L850I strains were associated with survival rates of 100% (P < 0.05) whereas mice infected with the S724N/P920S mutant had a survival rate of 33% (P = 0.08). Brain viral titers were higher in mice infected with WT HSV‐1 or ‐2 strains and the double DNA pol mutant. All strains except the DNA pol mutant L850I were able to establish latency in the dorsal root ganglia of cotton rats. A good correlation was generally found between replication kinetics of DNA pol mutants and their neurovirulence potential in mice whereas such correlation was not straightforward for TK mutants. J. Med. Virol. 82:1000–1006, 2010. © 2010 Wiley‐Liss, Inc.