bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone resorption control of tooth eruption and root morphogenesis: Involvement of the receptor activator of NF‐κB (RANK)
Authors: Castaneda Beatriz , Simon Yohann , Jacques Jaime , Hess Estelle , Choi Yong‐Wong , Blin‐Wakkach Claudine , Mueller Christopher , Berdal Ariane , Lézot Frédéric 
Published: July 2010

AbstractActivation of the receptor activator of NF‐κB (RANK) is a crucial step in osteoclastogenesis. Loss‐ and gain‐of‐function mutations in the Rank gene cause, respectively, osteopetrosis and several forms of extensive osteolysis. Tooth and alveolar bone alterations are associated with these pathologies but remain to be better characterized. The aim of the present study was to establish the tooth and alveolar bone phenotype of a transgenic mouse model of RANK over‐expression in osteoclast precursors. Early tooth eruption and accelerated tooth root elongation were observed subsequent to an increase in osteoclast numbers surrounding the tooth. The final root length appeared not to be affected by RANK over‐expression, but a significant reduction in root diameter occurred in both control and root‐morphogenesis‐defective Msx2 null mutant mice. These results indicate that root length is independent of the surrounding bone resorption activity. In contrast, root diameter is sensitive to the activity of alveolar bone osteoclasts. These data suggest that early eruption and thin root are phenotypic features that could be associated with extensive osteolytic pathologies. J. Cell. Physiol. 226: 74–85, 2010. © 2010 Wiley‐Liss, Inc.
Lentiviral airway gene transfer in lungs of mice and sheep: successes and challenges
Authors: Liu Chuanhe , Wong Edward , Miller Darren , Smith Greg , Anson Don , Parsons David 
Published: July 2010

AbstractBackgroundPersistent airway gene expression can be achieved in mouse nasal airway using a vesicular stomatitis virus glycoprotein pseudotyped lentiviral (LV) gene vector in combination with lysophosphatidylcholine (LPC) pretreatment. We have now examined the acute in vivo effects of this combination single‐dose method for airway LV gene transfer in mouse and sheep lung.MethodsMouse and sheep lungs were exposed to LPC followed 1 h later with the LV vector. Lungs were processed 7 days later using X‐gal detection to measure β‐gal gene expression and identify transduced cell types.ResultsIn mouse ciliated conducting airways, LPC pretreatment produced extensive gene transfer that extended from the tracheal dosing site into the bronchi and lower airways. Gene expression was present in both terminally differentiated surface cells and in basal cells. Without LPC pretreatment, transduction was limited to the dosing site. In sheep lung, small‐volume bronchoscopic instillation delivery produced localized and low‐level transduction near the dosing site. Gene expression was again present in surface and basal cells. Neither alterations in LPC dose parameters, nor larger vector volumes increased the level of transduction.ConclusionsThese findings are the first to confirm the applicability of LPC pretreatment in the production of extensive lentiviral gene transfer in mouse lung airways. However, improved methodologies to increase transduction efficiency are required for adult sheep lung. The results suggest that continued in vivo development of LPC‐enhanced lentiviral gene transfer is needed in the lungs of large animals to establish effective lentiviral gene transfer techniques suited to the treatment of airway disease. Copyright © 2010 John Wiley & Sons, Ltd.
Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter‐driven oncolytic adenovirus
Authors: Kubo Shuji , Kawasaki Yoshiko , Yamaoka Norie , Tagawa Masatoshi , Kasahara Noriyuki , Terada Nobuyuki , Okamura Haruki 
Published: July 2010

AbstractBackgroundMalignant mesothelioma is a highly aggressive tumor with poor prognosis. We hypothesized that the tumor‐specific midkine (Mdk) promoter could confer transcriptional targeting to oncolytic adenoviruses for effective treatment of malignant mesothelioma.MethodsWe analysed Mdk expression by quantitative reverse transcription‐polymerase chain reaction in six human mesothelioma cell lines, and tested Mdk promoter activity by luciferase reporter assay. On the basis of these data, we constructed a replication‐selective oncolytic adenovirus designated AdMdk‐E1‐iresTK. This virus contains a Mdk promoter‐driven adenoviral E1 gene and herpes simplex virus‐thymidine kinase (TK) suicide gene and cytomagalovirus promoter‐driven enhanced green fluorescent protein marker gene. Selectivity of viral replication and cytolysis were characterized in normal versus mesothelioma cells in vitro, and intratumoral spread and antitumor efficacy were investigated in vivo.ResultsMdk promoter activity was restricted in normal cells, but highly activated in mesothelioma cell lines. AdMdk‐E1‐iresTK was seen to efficiently replicate, produce viral progeny and spread in multiple mesothelioma cell lines. Lytic spread of AdMdk‐E1‐iresTK mediated the efficient killing of these mesothelioma cells, and its in vitro cytocidal effect was significantly enhanced by treatment with the prodrug, ganciclovir. Intratumoral injection of AdMdk‐E1‐iresTK caused complete regression of MESO4 and MSTO human mesothelioma xenografts in athymic mice. In vivo fluorescence imaging demonstrated intratumoral spread of AdMdk‐E1‐iresTK‐derived signals, which vanished after tumor eradication.ConclusionsThese data indicate that transcriptional targeting of viral replication by the Mdk promoter represents a promising general strategy for oncolytic virotherapy of cancers with up‐regulated Mdk expression, including malignant mesothelioma. Copyright © 2010 John Wiley & Sons, Ltd.
High frequency of lamivudine resistance mutations in Brazilian patients co‐infected with HIV and hepatitis B
Authors: Mendes‐Correa M.C. , Pinho J.R.R. , Locarnini S. , Yuen L. , Sitnik R. , Santana R.A.F. , Gomes‐Gouvêa M.S. , Leite O.M. , Martins L.G. , Silva M.H. , Gianini R.J. , Uip D.E. 
Published: July 2010

AbstractThis study analyzed the genotype distribution and frequency of lamivudine (LAM) and tenofovir (TDF) resistance mutations in a group of patients co‐infected with HIV and hepatitis B virus (HBV). A cross‐sectional study of 847 patients with HIV was conducted. Patients provided blood samples for HBsAg detection. The load of HBV was determined using an “in‐house” real‐time polymerase chain reaction. HBV genotypes/subgenotypes, antiviral resistance, basal core promoter (BCP), and precore mutations were detected by DNA sequencing. Twenty‐eight patients with co‐infection were identified. The distribution of HBV genotypes among these patients was A (n = 9; 50%), D (n = 4; 22.2%), G (n = 3; 16.7%), and F (n = 2; 11.1%). Eighteen patients were treated with LAM and six patients were treated with LAM plus TDF. The length of exposure to LAM and TDF varied from 4 to 216 months. LAM resistance substitutions (rtL180M + rtM204V) were detected in 10 (50%) of the 20 patients with viremia. This pattern and an accompanying rtV173L mutation was found in four patients. Three patients with the triple polymerase substitution pattern (rtV173L + rtL180M + rtM204V) had associated changes in the envelope gene (sE164D + sI195M). Mutations in the BCP region (A1762T, G1764A) and in the precore region (G1896A, G1899A) were also found. No putative TDF resistance substitution was detected. The data suggest that prolonged LAM use is associated with the emergence of particular changes in the HBV genome, including substitutions that may elicit a vaccine escape phenotype. No putative TDF resistance change was detected after prolonged use of TDF. J. Med. Virol. 82:1481–1488, 2010. © 2010 Wiley‐Liss, Inc.
Occult hepatitis B in the genotype H‐infected Nahuas and Huichol native Mexican population
Authors: Roman Sonia , Tanaka Yasuhito , Khan Anis , Kurbanov Fuat , Kato Hideaki , Mizokami Masashi , Panduro Arturo 
Published: July 2010

AbstractMexico is considered to be a low endemic country for HBV infection. However, a high anti‐HBc against a low hepatitis B surface antigen (HBsAg) seroprevalence is the reported characteristic of native Mexicans. HBV diagnosis and genotype distribution was examined in native populations (Nahuas and Huichol, n = 306), and compared to a non‐native population (Mestizos, n = 17). Overall, 6% of the natives were positive for HBsAg and 33% had detectable anti‐HBc. HBsAg prevalence was lower in Nahuas compared to Huichols (1.4% vs. 9.4%,P < 0.002). Occult hepatitis B was detected in 14.2% (41/289) of natives, who either tested positive (5.88%, 17/289 HBsAg‐negative) or negative for anti‐HBc marker (8%, 24/289 HBsAg‐negative). Age‐adjusted anti‐HBc seroprevalence and HBsAg quantitation revealed a sub‐optimal sensitivity of conventional immunoassays. Nahuas had HBV/H and Huichol had HBV/A as the predominant genotypes followed by genotypes D, C, B, A, and D, G and H, respectively. A less variable HBV/H was characteristic in Mestizos, compared to a much variable HBV/H identified among the Nahuas. In conclusion, these findings indicate a high HBV endemicity among native Mexican groups where occult B infection is common. The different distribution of HBV genotypes among natives suggests multiple reservoirs of HBV from which these genotypes spread into the local communities. High anti‐HBc seroprevalence against a low HBsAg prevalence rate may be due to the limited sensitivity of the immunoassays for the detection of HBsAg that are available in Mexico and/or unknown immunogenetic characteristics of native Mexicans. J. Med. Virol. 82:1527–1536, 2010. © 2010 Wiley‐Liss, Inc.
Early and reliable detection of herpes simplex virus type 1 and varicella zoster virus DNAs in oral fluid of patients with idiopathic peripheral facial nerve palsy: Decision support regarding antiviral treatment?
Authors: Lackner Andreas , Kessler Harald H. , Walch Christian , Quasthoff Stefan , Raggam Reinhard B. 
Published: July 2010

AbstractIdiopathic peripheral facial nerve palsy has been associated with the reactivation of herpes simplex virus type 1 (HSV‐1) or varicella zoster virus (VZV). In recent studies, detection rates were found to vary strongly which may be caused by the use of different oral fluid collection devices in combination with molecular assays lacking standardization. In this single‐center pilot study, liquid phase‐based and absorption‐based oral fluid collection was compared. Samples were collected with both systems from 10 patients with acute idiopathic peripheral facial nerve palsy, 10 with herpes labialis or with Ramsay Hunt syndrome, and 10 healthy controls. Commercially available IVD/CE‐labeled molecular assays based on fully automated DNA extraction and real‐time PCR were employed. With the liquid phase‐based oral fluid collection system, three patients with idiopathic peripheral facial nerve palsy tested positive for HSV‐1 DNA and another two tested positive for VZV DNA. All patients with herpes labialis tested positive for HSV‐1 DNA and all patients with Ramsay Hunt syndrome tested positive for VZV DNA. With the absorption‐based oral fluid collection system, detections rates and viral loads were found to be significantly lower when compared to those obtained with the liquid phase‐based collection system. Collection of oral fluid with a liquid phase‐based system and the use of automated and standardized molecular methods allow early and reliable detection of HSV‐1 and VZV DNAs in patients with acute idiopathic peripheral facial nerve palsy and may provide a valuable decision support regarding start of antiviral treatment at the first clinical visit. J. Med. Virol. 82:1582–1585, 2010. © 2010 Wiley‐Liss, Inc.
Association of NKG2D genetic polymorphism with susceptibility to chronic hepatitis B in a Han Chinese population
Authors: Ma Juan , Guo Xinhui , Wu Xiaopan , Li Junhong , Zhu Xilin , Li Zhuo , Li Jingyun , Pan Liping , Li Tianjie , Li Hui , Liu Ying 
Published: July 2010

AbstractNatural killer (NK) cells are important antiviral effectors of innate immunity because of their contribution to virus elimination. NK cell‐mediated immunological reaction to hepatitis B virus (HBV) infection depends on a fine balance between inhibitory and activating receptors. The aim of the study was to investigate genetic polymorphisms in NK cell receptors (NKR)—KLRD1 (CD94), KLRK1 (NKG2D), KLRC4 (NKG2F), and KLRC1 (NKG2A)—to evaluate the association of NKR genetic polymorphisms with susceptibility to chronic hepatitis B in a Han Chinese population. Twelve single nucleotide polymorphisms (SNPs), including rs2302489 in CD94; rs2255336, rs2617160, rs7980470, rs 2734565, and rs17513986 in NKG2D; rs2617170, rs17549004, and rs3825295 in NKG2F; rs2734414, rs7301582, and rs2734440 in NKG2A, were selected in the present study. SNP genotyping was undertaken in 500 Han Chinese patients (285 patients with chronic hepatitis B and 215 patients who cleared HBV spontaneously) by a polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and by the TaqMan method. Single marker association analysis was conducted and the SNP rs2617160 with a TT genotype in NKG2D was associated significantly with an increased risk of chronic hepatitis B (P = 0.044; OR = 1.49; 95% CI = 1.01–2.19). Haplotype analysis with multiple loci indicated that there was no significant association between the haplotypes of the NKR genes and susceptibility to chronic hepatitis B. The SNP rs2617160 in NKG2D associated with susceptibility to chronic hepatitis B in a Han Chinese population. J. Med. Virol. 82:1501–1507, 2010. © 2010 Wiley‐Liss, Inc.
Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg‐negative patients
Authors: Lin L.Y. , Wong V.W.S. , Zhou H.J. , Chan H.Y. , Gui H.L. , Guo S.M. , Wang H. , Huang L. , Bao S.S. , Xie Q. , Chan H.L.Y. 
Published: July 2010

AbstractHepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg‐negative chronic hepatitis B patients. Thirty‐three treatment‐naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/106 cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg‐negative chronic hepatitis B. J. Med. Virol. 82:1494–1500, 2010. © 2010 Wiley‐Liss, Inc.
Confirmation of Choclo virus as the cause of hantavirus cardiopulmonary syndrome and high serum antibody prevalence in Panama
Authors: Nelson Randin , Cañate Raul , Pascale Juan Miguel , Dragoo Jerry W. , Armien Blas , Armien Anibal G. , Koster Frederick 
Published: July 2010

AbstractChoclo virus (CHOV) was described in sigmodontine rodents, Oligoryzomys fulvescens, and humans during an outbreak of hantavirus cardiopulmonary syndrome (HCPS) in 1999–2000 in western Panama. Although HCPS is rare, hantavirus‐specific serum antibody prevalence among the general population is high suggesting that CHOV may cause many mild or asymptomatic infections. The goals of this study were to confirm the role of CHOV in HCPS and in the frequently detected serum antibody and to establish the phylogenetic relationship with other New World hantaviruses. CHOV was cultured to facilitate the sequencing of the small (S) and medium (M) segments and to perform CHOV‐specific serum neutralization antibody assays. Sequences of the S and M segments found a close relationship to other Oligoryzomys‐borne hantaviruses in the Americas, highly conserved terminal nucleotides, and no evidence for recombination events. The maximum likelihood and maximum parsimony analyses of complete M segment nucleotide sequences indicate a close relationship to Maporal and Laguna Negra viruses, found at the base of the South American clade. In a focus neutralization assay acute and convalescent sera from six Panamanian HCPS patients neutralized CHOV in dilutions from 1:200 to 1:6,400. In a sample of antibody‐positive adults without a history of HCPS, 9 of 10 sera neutralized CHOV in dilutions ranging from 1:100 to 1:6,400. Although cross‐neutralization with other sympatric hantaviruses not yet associated with human disease is possible, CHOV appears to be the causal agent for most of the mild or asymptomatic hantavirus infections, as well as HCPS, in Panama. J. Med. Virol. 82:1586–1593, 2010. © 2010 Wiley‐Liss, Inc.
Diagnosis of occult hepatitis C without the need for a liver biopsy
Authors: Castillo Inmaculada , Bartolomé Javier , Quiroga Juan Antonio , Barril Guillermina , Carreño Vicente 
Published: July 2010

AbstractThe diagnosis of occult hepatitis C virus (HCV) infection is based on the presence of HCV‐RNA in the liver. This study aimed to evaluate the use of combining non‐invasive assays to diagnose occult HCV. A total of 122 patients with occult HCV (HCV‐RNA in the liver without detectable anti‐HCV and serum HCV‐RNA) and 45 patients with cryptogenic chronic hepatitis (without HCV‐RNA in the liver and negative for anti‐HCV and serum HCV‐RNA) were included. HCV‐RNA was tested in peripheral blood mononuclear cells (PBMCs) and in 2 ml of ultracentrifuged serum. Anti‐core HCV was examined by a non‐commercial enzyme‐linked immunosorbent assay. All controls were negative for the three HCV markers studied. Among patients with occult HCV, 36% were anti‐core HCV positive, 57% had serum HCV‐RNA after ultracentrifugation, and 61% had HCV‐RNA in PBMCs. Combining the results of the assays, 91% of the patients were positive for at least one marker. Intrahepatic HCV‐RNA load was significantly higher in patients who were positive simultaneously for the three HCV markers than in patients who were negative for all markers (P = 0.006) and than in those with one or two HCV markers (P = 0.039). Replication of HCV in liver was detected more frequently in patients with three (93%, P = 0.002), two (82%, P = 0.001), and one HCV marker (73%, P = 0.011) than in those without markers (27%). In conclusion, testing for all these markers allows diagnosis of occult HCV without the need for a liver biopsy and these assays may help to elucidate the clinical significance of occult HCV infection. J. Med. Virol. 82:1554–1559, 2010. © 2010 Wiley‐Liss, Inc.
Evaluation of a new screening assay for HTLV‐1 and ‐2 antibodies for large‐scale use
Authors: Malm Kerstin , Kjerstadius Torbjörn , Andersson Sören 
Published: July 2010

AbstractLaboratory testing for Human T‐lymphotropic Virus type 1 and 2 (HTLV‐1 and ‐2) infections has become routine in blood transfusion, tissue transplantation and clinical diagnoses in many countries worldwide. Screening is usually based on the detection of antibodies to HTLV‐1 and/ or ‐2. The number of commercially available assays is limited, and among them, ELISA tests based on microtiter format are most commonly used. Recently, the new rHTLV‐I/II assay (Abbott Laboratories, Abbott Park, IL) was released; this assay was developed for an automatic large‐scale screening platform. This assay was evaluated using pre‐characterized serum panels and routine samples from the clinical laboratory. The sensitivity was 100% for HTLV‐1 and ‐2 (99/99 and 42/42, respectively, including one sample that was dually reactive, HTLV‐1 + 2). To test assay specificity, panels of blood donor sera, specimens from patients with autoimmune diseases and some viral infections were used. False‐reactive samples from previous HTLV diagnoses were also included. With these panels, the specificity was 99.4% (619/623). However, the four false‐reactive samples all belonged to the group of samples that were previously considered as false‐reactive for HTLV‐antibodies. All other samples were negative by the rHTLV‐I/II assay, and thus 100% specificity was obtained. The 1,412 samples tested in the clinic by this assay in routine use were all negative (100% specificity). Taken together, the overall specificity was 99.8%. The assay was sensitive, specific and appropriate for the large‐scale screening of samples for HTLV‐1/2 antibodies. J. Med. Virol. 82:1606–1611, 2010. © 2010 Wiley‐Liss, Inc.
Pharmacokinetic/ Pharmacodynamic‐Driven Drug Development
Authors: Gallo James M. 
Published: July 2010

AbstractThe drug discovery and development enterprise, traditionally an industrial juggernaut, has spanned into the academic arena that is partially motivated by the National Institutes of Health Roadmap highlighting translational science and medicine. Because drug discovery and development represents a pipeline of basic to clinical investigations, it meshes well with the “bench to the bedside” prime directive of translational medicine. The renewed interest in drug discovery and development in academia provides an opportunity to rethink the hiearchary of studies with the hope of improving the staid approaches that have been criticized for lacking innovation. One area that has received limited attention concerns the use of pharmacokinetic and pharmacodynamic studies in the drug‐development process. Using anticancer drug development as a focus, this review will address past and current deficencies in how pharmacokinetic/pharmacodynamic studies are conducted and offer new strategies that might bridge the gap between preclinical and clinical trials. Mt Sinai J Med 77:381–388, 2010. © 2010 Mount Sinai School of Medicine
Pursuit of Personalized Anticancer Therapy: Leveraging Collaboration Between Academia and the Biotech/Pharmaceutical Industry
Authors: Buck Elizabeth , Mulvihill Mark , Iwata Kenneth K. 
Published: July 2010

AbstractOver the past 2 decades, our increased understanding of tumor biology has resulted in the delivery of a new generation of molecularly targeted cancer drugs with greater efficacy and less toxicity. This understanding has also provided pharmaceutical and academic institutions with a greater appreciation for the complexities and challenges associated with discovering and developing molecularly targeted drugs. To deal with the complexities of tumor biology and the associated technologies needed to develop molecularly targeted drugs, there has been increased cooperation and collaboration between academic and pharmaceutical‐industry researchers in a broader number of aspects of the drug discovery and development continuum, including structural biology and translational research. This collaborative effort has played a role in molecularly targeted drugs such as cetuximab, trastuzumab, imatinib, and new promising drug candidates such as OSI‐906. Cooperative efforts by industry and academia have also provided important insights to optimize the use of such agents in the clinic. This review aims to emphasize the need for academic/industrial collaborations for success and efficiency through the drug discovery and development continuum, and will highlight several examples of collaborations between academic and industrial scientists that facilitated the development of molecularly targeted antitumor agents into the clinic. Mt Sinai J Med 77:358–365, 2010. © 2010 Mount Sinai School of Medicine