bluuebunny/crossref_metadata_2025 huggingface dataset:
Wavelet‐based simulation of spectrum‐compatible aftershock accelerograms
Authors: Das S. , Gupta V. K.
Published: April 2008

In damage‐based seismic design it is desirable to account for the ability of aftershocks to cause further damage to an already damaged structure due to the main shock. Availability of recorded or simulated aftershock accelerograms is a critical component in the non‐linear time‐history analyses required for this purpose, and simulation of realistic accelerograms is therefore going to be the need of the profession for a long time to come. This paper attempts wavelet‐based simulation of aftershock accelerograms for two scenarios. In the first scenario, recorded main shock and aftershock accelerograms are available along with the pseudo‐spectral acceleration (PSA) spectrum of the anticipated main shock motion, and an accelerogram has been simulated for the anticipated aftershock motion such that it incorporates temporal features of the recorded aftershock accelerogram. In the second scenario, a recorded main shock accelerogram is available along with the PSA spectrum of the anticipated main shock motion and PSA spectrum and strong motion duration of the anticipated aftershock motion. Here, the accelerogram for the anticipated aftershock motion has been simulated assuming that temporal features of the main shock accelerogram are replicated in the aftershock accelerograms at the same site. The proposed algorithms have been illustrated with the help of the main shock and aftershock accelerograms recorded for the 1999 Chi–Chi earthquake. It has been shown that the proposed algorithm for the second scenario leads to useful results even when the main shock and aftershock accelerograms do not share the same temporal features, as long as strong motion duration of the anticipated aftershock motion is properly estimated. Copyright © 2008 John Wiley & Sons, Ltd.
Estimating random variables from random sparse observations
Authors: Andrea Montanari
Published: April 2008

Let X1, … , Xn, be a collection of iid discrete random variables, and Y1, … , Ym, a set of noisy observations of such variables. Assume each observation Ya, to be a random function of a random subset of the Xi,s, and consider the conditional distribution of Xi, given the observations, namely µi,(xi,) ≡ ${\cal P}${Xi, = xi,|Y} (a posteriori probability).

We establish a general decoupling principle among the Xi,s, as well as a relation between the distribution of µi, and the fixed points of the associated density evolution operator. These results hold asymptotically in the large system limit, provided the average number of variables an observation depends on is bounded. We discuss the relevance of our result to a number of applications, ranging from sparse graph codes and multi‐user detection, to group testing. Copyright © 2008 John Wiley & Sons, Ltd.
Quantifying the contribution of genetic variants for survival phenotypes
Authors: Müller Martina , Döring Angela , Küchenhoff Helmut , Lamina Claudia , Malzahn Dörthe , Bickeböller Heike , Vollmert Caren , Klopp Norman , Meisinger Christa , Heinrich Joachim , Kronenberg Florian , Erich Wichmann H. , Heid Iris M.
Published: April 2008

Particularly in studies based on population representative samples, it is of major interest what impact a genetic variant has on the phenotype of interest, which cannot be answered by mere association estimates alone. One possible measure for quantifying the phenotype's variance explained by the genetic variant isR2. However, for survival outcomes, no clear definition ofR2is available in the presence of censored observations. We selected three criteria proposed for this purpose in the literature and compared their performance for single nucleotide polymorphism (SNP) data through simulation studies and for mortality data with candidate SNPs in the general population‐based KORA cohort. The evaluated criteria were based on: (1) the difference of deviance residuals, (2) the variation of individual survival curves, and (3) the variation of Schoenfeld residuals. Our simulation studies included various censoring and genetic scenarios. The simulation studies revealed that the deviance residuals' criterion had a high dependence on the censoring percentage, was generally not limited to the range [0; 1] and therefore lacked interpretation as a percentage of explained variation. The second criterion (variation of survival curves) hardly reached values above 60%. Our requirements were best fulfilled by the criterion based on Schoenfeld residuals. Our mortality data analysis also supported the findings in simulation studies. With the criterion based on Schoenfeld residuals, we recommend a powerful and flexible tool for genetic epidemiological studies to refine genetic association studies by judging the contribution of genetic variants to survival phenotype.Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
An item‐level analysis of the Center for Epidemiologic Studies Depression Scale (CES‐D) by race and ethnicity in patients with coronary artery disease
Authors: Boutin‐Foster Carla
Published: April 2008

Introduction

The Center for Epidemiologic Studies Depression Scale (CES‐D) is a measure of depressive symptoms that is commonly used in clinical studies. Studies employing this measure often describe variations in aggregate scores. However, few studies have examined variations in response to specific items by race and ethnicity.

Method

This was a cross‐sectional analysis among adults who were ages 50 and older and who were hospitalized for the management of coronary artery disease. Differential item functioning analysis was used to determine whether there were racial and ethnic variations in response to the items on the CES‐D.

Results

Of the 571 participants, 76% were Caucasian, 12% were African‐American, and 8% were Latino‐American. After adjusting for age, gender, and education, four items exhibited differential item functioning. The odds of Latinos endorsing the item ‘I was bothered by things that usually don't bother me’ was 2.5 (95% CL 1.2–5.9); 2.7 (95% CL 1.4–5.1) for the item ‘My sleep was restless’; 2.0 (95% CL 1.0–5.0) for the item ‘I felt that I was just as good as other people’; and 2.3 (95% CL 1.3–4.5) for the item ‘I enjoyed life’. The last two items were scored in reverse therefore; higher scores reflect more depressive symptoms. African‐Americans were 3.0 times more likely to endorse the item ‘people were unfriendly’ (95% CL 1.4–6.5).

Conclusions

In this study, differences in somatic, positive affective and interpersonal symptoms were associated with the higher prevalence of depressive symptoms observed among racial and ethnic minorities when compared to Caucasians. Copyright © 2008 John Wiley & Sons, Ltd.
Basic evidence of molecular targeted therapy for oral cancer and salivary gland cancer
Authors: Hamakawa Hiroyuki , Nakashiro Koh‐ichi , Sumida Tomoki , Shintani Satoru , Myers Jeffrey N. , Takes Robert P. , Rinaldo Alessandra , Ferlito Alfio
Published: April 2008

Background

Recently, attention has been focused on molecular targeted cancer therapy in various tumors. Although there is no single consistent molecular target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer (SGC), there are a number of promising candidate proteins. The aim of this review is to introduce the basic evidences to support the molecular targeting for OSCC and SGC.

Methods

We focused on the 4 molecules, epidermal growth factor receptor (EGFR), cyclooxygenase‐2 (COX‐2), peroxisome proliferator‐activated receptor γ (PPARγ), and progesterone receptor, that are, respectively, associated with the proliferation and the differentiation of OSCC and SGC.

Results

Gefitinib (“Iressa,” ZD1839), a small molecule EGFR tyrosine kinase inhibitor, can inhibit the proliferation of OSCC cell lines in a dose‐ and time‐dependent manner and lead to cell cycle arrest with accumulation of cells in the G1 phase, and a decrease of cells in S phase. The agent suppressed tumor metastasis in the animal model. Furthermore, a cooperative antiproliferative effect was obtained when cancer cells were treated with radiation followed by gefitinib. While radiation alone did not significantly affect p38 mitogen‐activated protein kinase and MAP kinase kinase (MEK)1/2 autophosphorylation, the combination of gefitinib and radiation completely inhibited the downstream signaling of EGFR. Gefitinib enhanced tumor radioresponsiveness by multiple mechanisms, including the growth inhibition and effects on DNA repair after exposure to radiation. Next, the level of COX‐2 expression correlated inversely with increased tumor radiation sensitivity. Treatment with celecoxib, a COX‐2 selective inhibitor, enhanced the radioresponsiveness of HSC‐2 cells, which constitutively expressed COX‐2. Another promising molecular target is the PPARγ, which is a member of the nuclear receptor superfamily of ligand‐activated transcription factors. Recent studies have demonstrated that PPARγ ligands induce cellular differentiation and inhibit cell growth in carcinomas of various types. These data suggest that synthetic PPARγ ligands may be useful for molecular targeting of oral cancer. Finally, the possibility of using molecular targeted therapy directed at hormone receptors in the treatment of advanced SGCs was described.

Conclusion

The basic data strongly suggested the possibility of tumor suppression by targeting these molecules. Studies of different targeted agents alone or with more conventional treatment modalities are needed to fully determine what role the targeted therapy will play in the management of patients with OSCC and SGC. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Defective hepatitis B virus DNA is not associated with disease status but is reduced by polymerase mutations associated with drug resistance
Authors: Preiss Scott , Littlejohn Margaret , Angus Peter , Thompson Alex , Desmond Paul , Lewin Sharon R. , Sasadeusz Joe , Matthews Gail , Dore Gregory J. , Shaw Tim , Sozzi Vitini , Yuen Lilly , Lau George , Ayres Anna , Thio Chloe , Avihingsanon Anchalee , Ruxrungtham Kiat , Locarnini Stephen , Revill Peter A.
Published: April 2008

Defective hepatitis B virus DNA (dDNA) is reverse-transcribed from spliced hepatitis B virus (HBV) pregenomic messenger RNA (pgRNA) and has been identified in patients with chronic HBV (CH-B). The major 2.2-kb spliced pgRNA encodes a novel HBV gene product, the hepatitis B splice protein (HBSP) via a deletion and frame shift within the polymerase. Although spliced RNA and HBSP expression have been associated with increased HBV DNA levels and liver fibrosis, the role of dDNA in HBV-associated disease is largely undefined. Our aims were to (1) compare the relative proportions of dDNA (% dDNA) in a range of HBV-infected serum samples, including patients with human immunodeficiency virus (HIV)/HBV coinfection and HBV-monoinfected persons with differing severities of liver disease, and (2) determine the effect of mutations associated with drug resistance on defective DNA production. Defective DNA was detected in 90% of persons with CH-B. There was no significant difference in the relative abundance of dDNA between the monoinfected and HIV/HBV-coinfected groups. We also found no association between the % dDNA and alanine aminotransferase, hepatitis B e antigen status, HBV DNA levels, fibrosis levels, compensated or decompensated liver cirrhosis, genotype, or drug treatment. However, the % dDNA was significantly lower in individuals infected with lamivudine-resistant (LMV-R) HBV compared with wild-type HBV (

P

< 0.0001), indicating that antiviral drug resistance alters the balance between defective and genomic length DNA in circulation. Experiments

in vitro

using HBV encoding LMV-R mutations confirmed these results.

Conclusion:

Our results identified no association between dDNA and parameters associated with disease status and suggested that the relative abundance of dDNA is largely dependent on the integrity of the HBV polymerase and is unrelated to the severity of liver disease. (Hepatology 2008.)
Identification of CYP2D6 null variants among long‐stay, chronic psychiatric inpatients: Is it strictly necessary?
Authors: Fernández‐Santander Ana , Santiago Catalina , Díez‐Durán Sarai , González María , de Castro Emilia , Guijarro Jorge , Bandrés Fernando , Lucia Alejandro , Gómez‐Gallego Félix
Published: April 2008

We identified the null variants *3,*4,*5,*6,*7 and *8 of the CYP2D6 gene [encoding for cytochrome P450 (debrisoquine hydroxylase)] in a group of 84 chronic‐stay psychiatric inpatients with severe schizophrenia or related disorders and receiving treatment with one or more CYP2D6 substrates for years. We also studied a group of 100 healthy controls of similar ethnic origin (Spanish Caucasians). Three patients were poor metabolizers (PMs) for antipsychotic drugs according to their CYP2D6 genotype (i.e. homozygous for the *4 allele) but they exhibited no adverse drug reaction over the years despite chronic treatment with CYP2D6 substrates. We suggest that CYP2D6 genetic screening is more useful in other type of psychiatric patients, particularly in younger ones starting treatment protocols. Copyright © 2008 John Wiley & Sons, Ltd.
Groundwater flow modelling of Kwa Ibo River watershed, southeastern Nigeria
Authors: Igboekwe M. U. , Gurunadha Rao V. V. S. , Okwueze E. E.
Published: April 2008

Groundwater flow modelling of the Kwa Ibo River watershed in Abia State of Nigeria is presented in this paper with the aim of assessing the degree of interaction between the Kwa Ibo River and the groundwater regime of the thick sandy aquifer. The local geology of the area comprises the Quaternary to recent Benin Formation. Potential aquifer zones that were delineated earlier using geoelectrical resistivity soundings and borehole data for the area formed the basis for groundwater flow modelling. The watershed has been modelled with a grid of 65 rows by 43 columns and with two layers. Lateral inflow from the north has been simulated with constant heads at the Government College, Umuahia, and outflow at Usaka Elegu in the south. The Kwa Ibo River traverses the middle of the watershed from north to south. The river‐stage data at Umudike, Amawom, Ntalakwu and Usaka Elegu have been used for assigning surface water levels and riverbed elevations in the model. Permeability distribution was found to vary from 3 to 14·5 m day−1. Natural recharge due to rainfall formed the main input to the aquifer system, and abstraction from wells was the main output. A steady‐state groundwater flow simulation was carried out and calibrated against the May 1980 water levels using 26 observation wells. The model computations have converged after 123 iterations. Under the transient‐state calibration, the highest rainfall (and hence groundwater recharge) over the 10‐year study period was recorded in 1996, whereas the lowest was recorded in 1991. The computed groundwater balance of 55 274 m3 day−1 was comparable to that estimated from field investigations. Results from the modelling show that abstraction is much less than groundwater recharge. Hence there is the possibility for additional groundwater exploitation in the watershed through drilling of boreholes. Copyright © 2008 John Wiley & Sons, Ltd.
Groundwater exchange with two small alpine lakes in the Canadian Rockies
Authors: Roy James W. , Hayashi Masaki
Published: April 2008

Recent studies have shown that groundwater can play an important role in the water balances of alpine lakes. However, a number of uncertainties remain, including (i) whether substantial groundwater exchange is common or rare, (ii) what types of interactions may occur, and (iii) what are the important factors affecting groundwater exchange. This understanding is important for predictions of hydrology, water chemistry and ecology patterns and interactions in the headwaters of mountain watersheds. These questions were addressed for the Lake O'Hara watershed in the Canadian Rockies, using lake water balances applied to two alpine lakes. The results were compared to those of a previously published water balance for the larger Lake O'Hara. Groundwater was a major component of the water balance in both lakes, but the type of groundwater interactions differed despite the lakes being similar in size and located only 500 m apart. The water balance for Opabin Lake was dominated by the groundwater components, with alternating periods of substantial groundwater inflow and outflow. Meanwhile, groundwater inflows were much greater than outflows for Hungabee Lake, with net groundwater fluxes of similar magnitude as the incoming streams. The study results suggest that both groundwater inflow and outflow occurred through a moraine field for Opabin Lake, while groundwater inflow occurred from a talus slope to Hungabee Lake. Thus, the presence of coarse overburden deposits in contact with alpine lakes is a potentially important factor affecting groundwater exchange, which in turn affects the hydrology and ecology of mountain watersheds. Copyright © 2008 John Wiley & Sons, Ltd and Her Majesty the Queen in right of Canada.
Effects of prescribed burnings on soil hydrological parameters
Authors: Vadilonga T. , Úbeda X. , Germann P. F. , Lorca M.
Published: April 2008

Prescribed burning is a forest management tool to reduce forest fire hazards. It is largely applied in the USA and is gaining importance worldwide, particularly in Europe. However, its effects on soils still have to be better understood. This study analyses the effects of two types of prescribed burnings (i.e. low and high burn severities of up to 200 °C and at or above 400 °C) on soil hydrophobicity, infiltration, and water storage capacity of top soils. Prescribed burnings were performed on four different plots in southern and western Catalonia, Spain. Soil samples were collected before and after burning to assess water repellency with the water drop penetration time (WDPT). Three rainfall simulations before burning and three after burning were executed on areas of 1 m2, and soil water contents at four to five depths were measured every 4 min during and after rainfall simulations using time domain reflectometry equipment (TDR). Following burning at both severities, water storage capacity of the top soil decreased between 1·7 and 5·4%vol on all four plots. No significant changes in volume flux density and velocity of the wetting fronts were discernible. Water drop penetration times increased moderately at the soil surface of the plots that were exposed to the high burn severity, and decreased slightly when burn severity was low. On two of the four plots the presence of partially moist organic litter prevented the underlying soil from excessive heating. Changes in hydrophobicity and water storage capacity of the top soil did not affect infiltration. Copyright © 2008 John Wiley & Sons, Ltd.
Toughness decrease of PLA‐PHBHHx blend films upon surface‐confined photopolymerization
Authors: Rasal Rahul M. , Hirt Douglas E.
Published: April 2008

The present research investigates the effect of photoinduced grafting reaction on the bulk properties of melt processed poly(L‐lactic acid) (PLA)‐poly[(3‐hydroxybutyrate)‐co‐(3‐hydroxyhexanoate)] (PHBHHx) blend films. PLA‐PHBHHx blend films, comprising 10 wt % PHBHHx showed a remarkable toughness improvement. From dynamic mechanical analysis of melt processed PLA‐PHBHHx blend films, the blend appears to be noncompatible. Unfortunately, PLA‐PHBHHx blend films underwent rapid physical aging as characterized using differential scanning calorimetry, resulting in a significant toughness loss. Physically aged films regained the original toughness on annealing at 60°C for 30 min. Annealed PLA‐PHBHHx blend films also underwent physical aging leading to a significant toughness loss. Hydrophilic monomers like acrylic acid and acrylamide were successfully photopolymerized from the film surface using a sequential, two‐step photografting approach. The resultant films were characterized using water contact angle goniometry, ATR‐FTIR spectroscopy, and mechanical testing. PLA‐PHBHHx blend films lost their toughness significantly on surface modification and this was assigned to UV‐assisted solvent induced crystallization as characterized using wide‐angle X‐ray diffraction analyses. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Fabrication and in vitro degradation of porous fumarate‐based polymer/alumoxane nanocomposite scaffolds for bone tissue engineering
Authors: Mistry Amit S. , Cheng Stacy H. , Yeh Tiffany , Christenson Elizabeth , Jansen John A. , Mikos Antonios G.
Published: April 2008

In this work, the fabrication and in vitro degradation of porous fumarate‐based/alumoxane nanocomposites were evaluated for their potential as bone tissue engineering scaffolds. The biodegradable polymer poly (propylene fumarate)/propylene fumarate‐diacrylate (PPF/PF‐DA), a macrocomposite composed of PPF/PF‐DA and boehmite microparticles, and a nanocomposite composed of PPF/PF‐DA and surface‐modified alumoxane nanoparticles were used to fabricate porous scaffolds by photo‐crosslinking and salt‐leaching. Scaffolds then underwent 12 weeks of in vitro degradation in phosphate buffered saline at 37°C. The presence of boehmite microparticles and alumoxane nanoparticles in the polymer inhibited scaffold shrinkage during crosslinking. Furthermore, the incorporation of alumoxane nanoparticles into the polymer limited salt‐leaching, perhaps due to tighter crosslinking within the nanocomposite. Analysis of crosslinking revealed that the acrylate and overall double bond conversions in the nanocomposite were higher than in the PPF/PF‐DA polymer alone, though these differences were not significant. During 12 weeks of in vitro degradation, the nanocomposite lost 5.3% ± 2.4% of its mass but maintained its compressive mechanical properties and porous architecture. The addition of alumoxane nanoparticles into the fumarate‐based polymer did not significantly affect the degradation of the nanocomposite compared with the other materials in terms of mass loss, compressive properties, and porous structure. These results demonstrate the feasibility of fabricating degradable nanocomposite scaffolds for bone tissue engineering by photo‐crosslinking and salt‐leaching mixtures of fumarate‐based polymers, alumoxane nanoparticles, and salt microparticles. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Long‐term follow up of initial clinical cases with NF‐κB decoy oligodeoxynucleotide transfection at the site of coronary stenting
Authors: Egashira Kensuke , Suzuki Jun‐ichi , Ito Hiroshi , Aoki Motokuni , Isobe Mitsuaki , Morishita Ryuichi
Published: April 2008

Background

An essential transcription factor for inflammation, nuclear factor‐kappa B (NF‐κB), plays a pivotal role for restenosis after percutaneous coronary intervention (PCI). To evaluate the safety and effectiveness of NF‐κB decoy oligodeoxynucleotides (ODN) to prevent restenosis, we initiated an open‐label phase I/IIa clinical trial.

Methods

Seventeen patients who were suffering from angina with organic coronary stenosis were treated with NF‐κB decoy ODN after PCI using bare metal stents.

Results

Although the average coronary stenosis was 90.8 ± 7.0% before the stent implantation, the stenosis improved to 1.4 ± 5.9% after the intervention. Serum MCP‐1 levels were significantly suppressed in NF‐κB decoy ODN treated patients compared to those in non‐treated patients on day 3 after the PCI. Ticlopidine treatment was employed, since clopidogrel was not launched in Japan. Six months after the PCI and decoy ODN transfection, significant restenosis was found in only 1 of the 17 patients, and the average restenosis rate was 39.6 ± 22.3%. No in‐stent thrombosis was found and no significant systemic adverse effect occurred in any of the patients in this observation period.

Conclusions

These results suggest the clinical usefulness and safety of the NF‐κB decoy ODN transfer after PCI, although further placebo control trials are necessary. Copyright © 2008 John Wiley & Sons, Ltd.
Serologic and genetic characterization analyses of a highly pathogenic influenza virus (H5N1) isolated from an infected man in Shenzhen
Authors: Cheng Xiaowen , Wu Chunli , He Jianfan , Lv Xing , Zhang Shunxiang , Zhou Li , Wang Jingwen , Deng Riqiang , Long Qingxing , Wang Xunzhang , Cheng Jinquan
Published: April 2008

Highly pathogenic avian influenza (HPAI) H5N1 virus caused a wave of outbreaks in China during 2005–2006, resulting in a total of 20 cases of human infection in 14 provinces of China. On June16, 2006, a case of H5N1 human infection was confirmed in Shenzhen. The virus isolated from the patient, A/Guangdong/2/06, was characterized genetically and the relationship between the tracheal virus load and the antibody titer of the infected man was analyzed. Serological analysis confirmed that the patient's neutralizating antibodies had been generated 2 weeks after the onset of symptoms. The patient's serum antibodies could efficiently neutralize A/Guandong/2/06 infectivity in vitro. Phylogenetic analysis showed that the H5N1 virus of Shenzhen belonged to subclade 2.3.4, which contained viruses that were mainly responsible for the outbreaks in domestic poultry and in the cases of human infection in southern China. Homology and molecular characterization analysis revealed that all the segments of Shenzhen H5N1 virus still belonged to avian segments. Several specific amino acid residue mutations were detected. J. Med. Virol. 80:1058–1064, 2008. © 2008 Wiley‐Liss, Inc.
DNA microarray technology for simultaneous detection and species identification of seven human herpes viruses
Authors: Zheng Zhi‐Bei , Wu Yi‐Dong , Yu Xi‐Lin , Shang Shi‐Qiang
Published: April 2008

The aim of the study was to develop a multiplex PCR‐based DNA microarray technology for simultaneous detection and species identification of seven human herpes viruses, namely herpes simplex virus type 1, type 2 (HSV‐1, HSV‐2), varicella‐zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 6 (HHV‐6A, HHV‐6B), and to apply this technology to accurate diagnosis of herpesvirus‐associated diseases. Primers and oligonucleotide probes were designed and synthesized based on the highly conserved regions of the DNA polymerase gene in human herpes viruses. DNA microarrays were made by printing the oligonucleotide probes onto special glass slides. After amplification and labeling with CY5, the PCR products were hybridized with the DNA microarrays and species identified. Sixty‐one cerebrospinal fluid (CSF) and 132 blood specimens were analyzed by this technique, and the results were compared with those of TaqMan PCR. Several specimens were sequenced further after cloning. The PCR products of the seven human herpes viruses ranged from 224 to 252 bp, and could be species identified with DNA microarrays. The detection limits were 101 copies/µl for each virus. And the test showed no cross‐reaction to DNA extracted from S. aureus, E. coli, hepatitis B virus, Cryptococcus neoformans, Candida albicans and human genome. Among 132 blood and 61 CSF specimens, 55 were tested positive for human herpes virus DNA. Compared with the results of TaqMan PCR, the sensitivity and specificity of the DNA microarray technology was 96.2% and 99.3%, respectively. This multiplex PCR‐based DNA microarray technology, which is rapid, specific and sensitive, serves as an effective technique for simultaneous detection and species identification of seven human herpes viruses. J. Med. Virol. 80:1042–1050, 2008. © 2008 Wiley‐Liss, Inc.
Genetic characterization of hantaviruses isolated from Guizhou, China: Evidence for spillover and reassortment in nature
Authors: Zou Yang , Hu Jing , Wang Zhao‐Xiao , Wang Ding‐Ming , Yu Chun , Zhou Jing‐Zhu , Fu Zhen F. , Zhang Yong‐Zhen
Published: April 2008

To gain more insights into the epidemiology of hantaviruses in the Guizhou province, China, rodents were captured in Guizhou during the period from 2001 to 2003. In addition, serum sample was collected from one patient. Virus isolation was attempted from human serum and rodent samples. Four hantaviruses were isolated successfully in cell culture from one human, two A. agrarius, and one R. norvegicus. The nucleotide sequences for the entire S and M and partial L segment were determined from these four isolates as well as six viruses isolated in 1980s. Phylogenetic analysis revealed that the S segment from all isolates belong to the Hantaan virus (HTNV) clade, regardless of the sources from which they were derived. According to the S sequences, these viruses could be divided into three distinct phylogroups, showing geographical clustering. Analysis of the entire M and the partial L segment sequences demonstrated that 8 out of the 10 isolates belong to the HTNV clade. However, two isolates (CGRn8316 and CGRn9415) isolated from R. norvegicus belong to the Seoul virus (SEOV) clade. In addition, these two isolates were distinct from other known members of SEOV clade. Together, the data suggest that at least three groups of HTNV are co‐circulating and one new variant of SEOV may be present in Guizhou. Our results also suggest that HTNV from A. agrarius spilled over to R. norvegicus and natural reassortment between HTNV and SEOV occurred during or after the spillover. J. Med. Virol. 80:1033–1041, 2008. © 2008 Wiley‐Liss, Inc.
Occurrence rate and genotype distribution of the JC virus (JCV) in a sample from the Polish population
Authors: Kmieciak Dariusz , Dębicki Szymon , Trzeciak Wiesław H.
Published: April 2008

The JC virus (JCV) is a common human virus persisting in renal tissue. In immunocompromised individuals it may reactivate and cause progressive multifocal leukoencephalopathy (PML). JCV has also been implicated in cancerogenesis, leading to various brain tumors and cancers of gastrointestinal tract. In this study the JCV excretion in urine of 113 healthy Polish donors was analyzed. A 215‐bp region of the viral gene coding for a major capsid protein VP1 was PCR‐amplified and detected in 52 individuals (46.0%). The occurrence rate increased with age and was highest in the group of over 60‐year‐old donors (63.6%). Sequence analysis of the VP1 gene fragment revealed the following distribution of JCV genotypes in the investigated group: 1A, 31 (59.6%); 1B, 13 (25.0%); 2A, 2 (3.8%); and 2C, 6 samples (11.5%). The frequency and distribution of the JCV genotypes in the Polish population resembles that in other European countries, with the most abundant genotype 1 (84.6%). However, while in those countries the second most frequent genotype was usually 4, in the investigated group genotype 4 was not detected. J. Med. Virol. 80:1079–1083, 2008. © 2008 Wiley‐Liss, Inc.
Non‐structural protein NSP2 induces heterotypic antibody responses during primary rotavirus infection and reinfection in children
Authors: Kirkwood Carl D. , Boniface Karen , Richardson Simone , Taraporewala Zenobia F. , Patton John T. , Bishop Ruth F.
Published: April 2008

Rotaviruses are the single most important causes of severe acute diarrhoea in children worldwide. Despite success in developing vaccines, there is still a lack of knowledge about many components of the immune response, particularly those to non‐structural proteins. This study established radioimmunoprecipitation (RIP) assays using labeled G1P[8], G2P[4], and G4P[6] human rotaviruses to examine the spectrum and duration of rotavirus antibodies in sera collected sequentially for 18–36 months from 27 children after hospitalization for primary rotavirus gastroenteritis. Five children experienced rotavirus re‐infections. Primary responses detected to non‐structural protein NSP2 declined to baseline after 100–150 days. Responses were heterotypic between NSP2 of G1P[8] and G4P[8] rotaviruses. Re‐infections after 465–786 days boosted antibody levels to NSP2of both serotypes, together with the appearance of anti‐NSP2 to G2P[4], even though there was no evidence of infection with this serotype. We developed an enzyme‐immunoassay to measure sequential levels of anti‐NSP2 IgG and IgA, using recombinant (heterotypic) NSP2 derived from SA11 (G3P[2]). Anti‐NSP2 IgG and IgA were detected in sera from 23/23 (100%) and 18/24 (75%) of children after primary infection, declined to baseline after 100–150 days, were boosted after rotavirus re‐infections, and again declined to baseline 150 days later. Anti‐NSP2 IgA was also detected after primary infection, in duodenal juice from 14/16 (87%), and faecal extract from 11/19 (57%) of children. Sequential estimation of anti‐NSP2 EIA levels in sera could be a sensitive index of rotavirus infection and re‐infection. The potential of anti‐NSP2 to limit viral replication after re‐infection deserves further study. J. Med. Virol. 80:1090–1098, 2008. © 2008 Wiley‐Liss, Inc.
Changes in circulation of B and non‐B HIV strains: Spotlight on a reference centre for infectious diseases in Northern Italy
Authors: Baldanti Fausto , Paolucci Stefania , Ravasi Giovanni , Maccabruni Anna , Moriggia Alberto , Barbarini Giorgio , Maserati Renato
Published: April 2008

Stored demographic data and HIV RT and protease sequences of 877 HIV patients attending for the first time the HIV/AIDS outpatient clinics of a reference Infectious Diseases centre in Northern Italy between 1999 and 2006 were stratified by 3‐year spanning periods according to date of HIV infection. In the period 1980–1982, new infections were entirely caused by HIV‐1 subtype B strains and were all diagnosed in injection drug users, 88.9% of whom were males. Injection drug users accounted for 12.8% of new infections in 2004–2006. The frequency of heterosexually‐transmitted infections consistently increased until 2000 (from almost none to 51.5%) remaining stable afterwards. About half of heterosexual patients were females. HIV infections among homosexual men increased from 0% in 1980–1982 to 15–21% between 1998 and 2006. Overall, the frequency of non‐B subtypes HIV strains increased from 0% in 1980–1982 to 20.3% in 2004–2006 with a greater impact in heterosexuals (from 0% in 1980–1982 to 30.5% in 2004–2006). In conclusion, a picture of the changing scenario of circulating HIV types and subtypes in a reference Infectious Diseases centre in Northern Italy over the past 26 years is provided. A progressive modification in risk factors for HIV infection and a significant increase in the frequency of non‐B HIV strains were observed. J. Med. Virol. 80:947–952, 2008. © 2008 Wiley‐Liss, Inc.
Analysis of the entire nucleotide sequence of hepatitis B causing consecutive cases of fatal fulminant hepatitis in Miyagi Prefecture Japan
Authors: Nagasaki Futoshi , Ueno Yoshiyuki , Niitsuma Hirofumi , Inoue Jun , Kogure Takayuki , Fukushima Koji , Kobayashi Koju , Shimosegawa Tooru
Published: April 2008

We encountered five consecutive patients with fulminant hepatitis induced by acute hepatitis B virus (HBV) infection in 2000–2001 in Japan. They had not had previous contact each other, and were referred to us from different hospitals. Although a 69‐year‐old woman could be rescued by intensive internal treatment, the four patients died. We analyzed the partial (nt 278–646) and entire nucleotide sequences of the HBV obtained from them, and their divergences were 0–0.3% and 0–0.2%, respectively. The results suggested that they had been infected with the same HBV isolates. The isolates belonged to genotype B and subgenotype B2 on the phylogenetic tree analysis (AB302942–AB302946). As for the nucleotides sequences of them, previously reported mutations of G1896A, A1762T, and G1764A were present. Amino acid analysis revealed that previously reported Ile97Leu and Pro130Non‐Pro in the core region and Trp28Stop in the precore region were present. As for the entire nucleotide sequences among B2, AB302942 showed low divergences with AF121245 and AB073834 (1.7%), and X97850 from patients with fulminant hepatitis (3.2%). We compared the two consensus nucleotides derived from AB302942 and X97850 (fulminant hepatitis) versus AY121245 and AB073834 (non‐fulminant hepatitis), which revealed a difference in nt 1,504 located in the P and X region. Nucleotide 1,504 was C for isolates from fulminant hepatitis and G for non‐fulminant hepatitis, and it was recognized among most of the isolates belonging to B2 registered on GenBank. Further studies could disclose the mechanism of severe inflammation of liver that finally leads to fulminant hepatitis. J. Med. Virol. 80:967–973, 2008. © 2008 Wiley‐Liss, Inc.
Impaired cytokine response in myeloid dendritic cells in chronic hepatitis C virus infection regardless of enhanced expression of Toll‐like receptors and retinoic acid inducible gene‐I
Authors: Miyazaki Masanori , Kanto Tatsuya , Inoue Michiyo , Itose Ichiyo , Miyatake Hideki , Sakakibara Mitsuru , Yakushijin Takayuki , Kakita Naruyasu , Hiramatsu Naoki , Takehara Tetsuo , Kasahara Akinori , Hayashi Norio
Published: April 2008

Dendritic cells utilize various sets of Toll‐like receptors (TLR) or cytosolic sensors to detect pathogens and evoke immune responses. In patients with hepatitis C virus (HCV) infection, a higher prevalence of various infectious diseases is reported; suggesting that innate immunity against pathogens is impaired. The aim of this study was to clarify whether the TLR and retinoic acid inducible gene‐I (RIG‐I) system in myeloid dendritic cells is preserved or not in chronic HCV infection. The expression of TLRs, RIG‐I and its relatives were compared in myeloid dendritic cells between 39 patients and 52 healthy volunteers. The induction of type‐I interferon (IFN) and inflammatory cytokines was examined in response to agonists for TLR2 (palmitoyl‐3‐cysteine‐serine‐lysine‐4), TLR3/RIG‐I (polyinosine–polycytidylic acid) or TLR4 (lipopolysaccharide). The relative expressions of TLR2, TLR4, RIG‐I, and LGP2 from the patients were significantly higher than those from the volunteers, whereas TLR3 and MDA‐5 expressions did not differ. In search for factors regulating TLR/RIG‐I expression, it was shown that IFN‐α, polyinosine–polycytidylic acid and lipopolysaccharide induced TLR3, TLR4 and RIG‐I, but TNF‐α, HCV core or HCV non‐structural proteins did not. For the functional analyses, myeloid dendritic cells from the patients induced significantly less amounts of IFN‐β, TNF‐α and IL‐12p70 in response to polyinosine–polycytidylic acid or lipopolysaccharide. It is noteworthy that the expression of TRIF and TRAF6, which are essential adaptor molecules transmitting TLR3 or TLR4‐dependent signals, is reduced in the patients. Thus, innate cytokine responses in myeloid dendritic cells are impaired regardless of enhanced expressions of TLR2, TLR4, and RIG‐I in HCV infection. J. Med. Virol. 80:980–988, 2008. © 2008 Wiley‐Liss, Inc.
Predictive factors for cytomegalovirus reactivation in cytomegalovirus‐seropositive kidney‐transplant patients
Authors: Kamar Nassim , Mengelle Catherine , Esposito Laure , Guitard Joëlle , Mehrenberger Marion , Lavayssière Laurence , Ribes David , Cointault Olivier , Durand Dominique , Izopet Jacques , Rostaing Lionel
Published: April 2008

The aims of the present study were to assess the incidence of cytomegalovirus (CMV) reactivation, and to determine the predictive factors for CMV reactivation in CMV seropositive kidney‐transplant patients. One hundred ninety CMV seropositive kidney‐transplant patients were included in this study; of these, 39 patients had received CMV prophylaxis. CMV DNAemia was assessed by real‐timepolymerase chain reaction assay every 2 weeks until day 120, then every 3–4 weeks until day 180, and then every month until day 365. One hundred seven patients (56.3%) had at least one positive CMV DNAemia within the first year. The time between renal transplantation and the first positive CMV DNAemia was 59 ± 5 days. The number of positive CMV DNAemia/patient was 3.28 ± 0.22. CMV viral load at first positive CMV DNAemia was 704 (10–742,000) copies/ml. The donor CMV seropositivity, the absence of CMV prophylaxis, and the occurrence of acute rejection before CMV reactivation were independent factors associated with CMV reactivation within the first year after kidney transplantation. Hence, CMV reactivation is frequent after kidney transplantation. CMV prophylaxis in CMV seropositive kidney‐transplant patients should be offered to avoid CMV‐related side‐effects. J. Med. Virol. 80:1012–1017, 2008. © 2008 Wiley‐Liss, Inc.
Therapy with interferon‐α and ribavirin for chronic hepatitis C virus infection upregulates membrane HLA‐ABC, CD86, and CD28 on peripheral blood mononuclear cells
Authors: Cheng Pin‐Nan , Wei Ya‐Ling , Chang Ting‐Tsung , Chen Jiann‐Shiuh , Young Kung‐Chia
Published: April 2008

Multiple interferon‐stimulated genes (ISGs) involving T‐cell activation are upregulated during initial interferon‐α‐based therapy for chronic hepatitis C virus (HCV) infection. However, the long‐term impact on therapeutic outcome in patients remains unknown. In this study, the effects of anti‐HCV therapy on the surface ex‐pression of HLA‐ABC, CD86, and CD28 were longitudinally assessed. These proteins are integral membrane receptors of antigen presentation and triggering of costimulatory signals for activating CD8+ T cells. Peripheral blood mononuclear cells were collected at baseline and post‐treatment for 1 day, and 2, 4, 12, and 24 weeks, respectively. This treatment led to a time‐related elevation of membrane levels of HLA‐ABC and CD86 on B‐cells and monocytes in patients with a sustained response (n = 23), but not in those without (n = 8). Meanwhile, upregulation of CD28 on CD4+ and CD8+ T cells was comparable in both groups of sustained responders and non‐responders. Steady increases in the B cells' surface and intracellular HLA‐ABC were observed, thus, the surface‐to‐intracellular ratios did not alter over the period of treatment. Furthermore, multivariate analysis shows that increased HLA‐ABC on monocytes by week 12 correlates significantly with sustained response (P = 0.033). In conclusion, differential modulation of T‐cell activation ISGs, such as HLA‐ABC and CD86 might correlate with the outcome of interferon‐α‐based therapy in chronic hepatitis C patients. J. Med. Virol. 80:989–996, 2008. © 2008 Wiley‐Liss, Inc.
Clinical impact of human metapneumovirus genotypes and genotype‐specific seroprevalence in Yamagata, Japan
Authors: Matsuzaki Yoko , Itagaki Tsutomu , Abiko Chieko , Aoki Yoko , Suto Asuka , Mizuta Katsumi
Published: April 2008

The clinical impact of human metapneumovirus (hMPV) genotypes and the relation between the hMPV genotype in circulation and genotype‐specific seroprevalence are yet to be clarified. We determined the genotypes of 93 hMPV strains that were isolated between 2004 and 2006 in Yamagata, Japan, and identified 35 genotype A2, 14 genotype B1, and 44 genotype B2 isolates. Children infected with genotype A2 hMPV were significantly older than those infected with genotype B1 hMPV. Diagnosis of laryngitis was more common in children with genotype B1 hMPV infection and wheezing was more prevalent in children with genotype B1 and B2 hMPV infection than in those with genotype A2 hMPV infection. We then examined genotype‐specific seroprevalence by neutralization assay. The higher seropositive rate for the B2 genotype among the children aged 1–2 years is likely to reflect the outbreak of B2 genotype strains in the previous year in this community. The low seropositive rate for the B1 genotype among children aged 1–2 years appears to be associated with a finding that more than 70% of children infected with the B1 genotype were less than 3 years old. In conclusion, we found that the different clinical characteristics of hMPV infection may be associated with hMPV genotype, and the predominant genotype during a season and the affecting age may be closely related to genotype‐specific immune status within a community. J. Med. Virol. 80:1084–1089, 2008. © 2008 Wiley‐Liss, Inc.
Molecular epidemiological study of HEV‐B enteroviruses involved in the increase in meningitis cases occurred in Spain during 2006
Authors: Cabrerizo María , Echevarria Juan E. , González Irene , de Miguel Teresa , Trallero Gloria
Published: April 2008

Human enteroviruses are one of the main etiological agents of aseptic meningitis and other central nervous system infections, particularly the serotypes included in the enterovirus B species. Molecular methods have proved useful to identify serotypes in clinical samples, facilitating the epidemiological study of these viruses. In the spring of 2006, there was a significant increase in meningitis cases caused by enteroviruses in Spain. In the present study, 138 enteroviruses directly detected in clinical samples of patients with aseptic meningitis (n = 116) and other neurological pathologies (n = 22) received by the National Center for Microbiology during the year, were genotyped by amplification and sequencing part of the VP1 region and phylogenetic analysis. Echovirus 30 was the most frequent serotype, followed in decreasing order by echovirus 6, 9, 13, 18, enterovirus 75, coxsackievirus A9, echovirus 11, 14, 29, 4, and coxsackievirus B4 and B5. Phylogenetic analysis with all Spanish echovirus 30 strains detected in 2006 and other reported echovirus 30 sequences, demonstrated that Spanish strains formed a new lineage, different from others previously described. In conclusion, echovirus 30 is the most commonly reported enterovirus serotype associated with aseptic meningitis in Spain. Direct molecular typing of clinical samples also allows rapid identification of the serotypes involved in an epidemic alert and phylogenetic analysis in the 3′‐VP1 region is useful to study viral epidemiology. J. Med. Virol. 80:1018–1024, 2008. © 2008 Wiley‐Liss, Inc.
Development of RNA interference (RNAi) as potential antiviral strategy against enterovirus 70
Authors: Tan Eng Lee , Marcus Kah Fai Ho , Poh Chit Laa
Published: April 2008

Enterovirus 70 (EV70) is recognized as the main causative agent of acute hemorrhagic conjunctivitis (AHC), a highly contagious viral infection of the eye. Currently, there is no available treatment for EV70 infections. In this study, we developed a potential intervention strategy using RNA interference (RNAi) against EV70 infection in an in vitro system. Two synthetic 19‐mer siRNAs, si‐3D1 and si‐3D2, were designed to target the 3Dpol region of the EV70 genome. Significant dosage dependent inhibition of EV70 in rhabdomyosarcoma cell line, as shown by reduction of viral RNA and VP1 production, was observed. Both siRNAs prevented EV70 replication in RD cells when transfected into these cells 48 hr prior to virus infection. Introduction of these siRNAs into RD cells 1–3 hr after infection with EV70 reduced production of viral RNA by approximately 60%. Thus, RNAi is a promising strategy to prevent EV70 infections and may have therapeutic potential. J. Med. Virol. 80:1025–1032, 2008. © 2008 Wiley‐Liss, Inc.
Metalworking emulsions from industrial vegetable oils
Authors: Jain Anuj , Bisht R. P. S.
Published: April 2008

In the present work, an attempt has been made to develop the indigenous formulation for metalworking lubricants by replacing mineral oils partially with non‐edible industrial oils like rapeseed and karanja oil. Metalworking formulations consist of vegetable oil, mineral oil, an emulsifier and commercial additives for better performance. Non‐edible vegetable oils such as karanja and rapeseeds are renewable, biodegradable and cheaper than synthetic fluids. The constituent vegetable oils and mineral oils were evaluated for physico‐chemical characteristics and blended as per the saponification value and viscosity requirements of the reference oils. The so formulated oils are taken as 5% oil‐in‐water emulsion and tested for lubricity, load bearing capacity, particle size distribution, wear test, weld load test and plate‐out test. Performance of all formulated oils was compared with that of the reference oils, and optimized to meet the market requirements. Copyright © 2008 John Wiley & Sons, Ltd.