bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation study of the Victorian Birth Defects Register
Authors: Riley M , Phyland S , Halliday J 
Published: September 2004

Objective:  To determine whether there has been an improvement in ascertainment of birth defects cases (‘case validity’) by the Victorian Birth Defects Register (BDR) since an earlier study (conducted in 1993), to ascertain the accuracy of registered data (‘item validity’) and to investigate another possible source of notification.Methods:  The medical records were reviewed of 500 children born after 1 January 1993 who were consecutively admitted after 1 January 1999 to two paediatric teaching hospitals in Victoria. In addition, records of 200 children referred to a clinical genetics service were reviewed for children born after 1 January 1993 and who were seen in two periods: 2 months after 1 January 2001 and 2 months after 1 January 2002. The records from the hospitals and clinical genetics service were reviewed separately to determine whether children recorded as having a birth defect had previously been notified to the BDR.Results:  Twenty percent of the hospital records related to a child with a birth defect, as did 70% of the clinical genetics service records. Overall case validity for birth defect cases from the hospitals was 88%. There was 100% ascertainment for three of five categories. Sixty per cent of birth defects cases from the clinical genetics service had been notified to the BDR. When all diagnoses in matched cases were considered, item validity was 54%, however, if only primary diagnoses were included then 92% of cases had the same diagnosis.Conclusions:  Overall case validity from the two paediatric teaching hospitals has significantly improved since our previous study. The addition of an extra data source from a clinical genetics service would identify new cases, particularly genetic disorders and developmental delay, as well as adding new diagnoses to existing ones.This study has highlighted the need to improve item validity, perhaps through routine education for all coders and notifiers on the inclusion and exclusion of specific associated conditions when notifying major birth defects.
Striae treated by a novel combination treatment – sand abrasion and a patent mixture containing 15% trichloracetic acid followed by 6–24 hrs of a patent cream under plastic occlusion
Authors: Adatto M A , Deprez P 
Published: September 2004

SummaryBackground  Striae are a common cosmetic problem, especially for women. Little has been published about chemical peel treatment of striae.Objective  To recount 5 years experience of striae treated by a novel combination treatment – sand abrasion and a patent mixture containing 15% trichloracetic acid followed by 6–24 h of a patent cream under plastic occlusion.Materials and methods  Sixty‐nine females of various phototypes, aged 14–63 years, were treated at various anatomical sites: abdomen (43), lateral thighs (11), breasts (4), back (3), waist (3) and others (5). Striae of all types: fresh, old, mild and severe, were treated. Average follow up was 18 months.Results  After 1–8 treatments (median 4.2), appearance of the striae improved by 70%. Results were best in fresher and more superficial striae.Conclusions  A novel combination treatment is reported which safely, predictably and effectively improved striae in all skin types.
Protective Immunity to Vaccinia Virus Induced by Vaccination with Multiple Recombinant Outer Membrane Proteins of Intracellular and Extracellular Virions
Authors: Fogg Christiana , Lustig Shlomo , Whitbeck J. Charles , Eisenberg Roselyn J. , Cohen Gary H. , Moss Bernard 
Published: September 2004

ABSTRACT
Infectious intracellular and extracellular forms of vaccinia virus have different outer membrane proteins, presenting multiple targets to the immune system. We investigated the immunogenicity of soluble forms of L1, an outer membrane protein of the intracellular mature virus, and of A33 and B5, outer membrane proteins of the extracellular enveloped virus. The recombinant proteins, in 10-μg amounts mixed with a Ribi- or saponin-type adjuvant, were administered subcutaneously to mice. Antibody titers to each protein rose sharply after the first and second boosts, reaching levels that surpassed those induced by percutaneous immunization with live vaccinia virus. Immunoglobulin G1 (IgG1) antibody predominated after the protein immunizations, indicative of a T-helper cell type 2 response, whereas live vaccinia virus induced mainly IgG2a, indicative of a T-helper cell type 1 response. Mice immunized with any one of the recombinant proteins survived an intranasal challenge with 5 times the 50% lethal dose of the pathogenic WR strain of vaccinia virus. Measurements of weight loss indicated that the A33 immunization most effectively prevented disease. The superiority of protein combinations was demonstrated when the challenge virus dose was increased 20-fold. The best protection was obtained with a vaccine made by combining recombinant proteins of the outer membranes of intracellular and extracellular virus. Indeed, mice immunized with A33 plus B5 plus L1 or with A33 plus L1 were better protected than mice immunized with live vaccinia virus. Three immunizations with the three-protein combination were necessary and sufficient for complete protection. These studies suggest the feasibility of a multiprotein smallpox vaccine.
Short Interfering RNA-Mediated Inhibition of Herpes Simplex Virus Type 1 Gene Expression and Function during Infection of Human Keratinocytes
Authors: Bhuyan Prakash K. , Karikò Katalin , Capodici John , Lubinski John , Hook Lauren M. , Friedman Harvey M. , Weissman Drew 
Published: September 2004

ABSTRACTRNA interference (RNAi) is an antiviral mechanism that is activated when double-stranded RNA is cleaved into fragments, called short interfering RNA (siRNA), that prime an inducible gene silencing enzyme complex. We applied RNAi against a herpes simplex virus type 1 (HSV-1) gene, glycoprotein E, which mediates cell-to-cell spread and immune evasion. In an in vitro model of infection, human keratinocytes were transfected with siRNA specific for glycoprotein E and then infected with wild-type HSV-1. RNAi-mediated gene silencing reproduced the small plaque phenotype of a gE-deletion mutant virus. The specificity of gene targeting was demonstrated by flow cytometry and Northern blot analyses. Exogenous siRNA can suppress HSV-1 glycoprotein E expression and function during active infection in vitro through RNAi. This work establishes RNAi as a genetic tool for the study of HSV and provides a foundation for development of RNAi as a novel antiviral therapy.
Np9 Protein of Human Endogenous Retrovirus K Interacts with Ligand of Numb Protein X
Authors: Armbruester Vivienne , Sauter Marlies , Roemer Klaus , Best Barbara , Hahn Steffen , Nty Achille , Schmid Andreas , Philipp Stephan , Mueller Anja , Mueller-Lantzsch Nikolaus 
Published: September 2004

ABSTRACT

We have recently identified Np9 as a novel nuclear protein produced by the human endogenous retrovirus K and were able to document the exclusive presence of
np9
transcript in tumors and transformed cells. With the aim of studying whether Np9 has a role in tumorigenesis, a systematic search for interacting proteins was performed. Here, we identify the RING-type E3 ubiquitin ligase LNX (ligand of Numb protein X) as an Np9-interacting partner. We furthermore show that the interaction involves N- and C-terminal domains of both proteins and can affect the subcellular localization of LNX. LNX has been reported to target the cell fate determinant and Notch antagonist Numb for proteasome-dependent degradation, thereby causing an increase in transactivational activity of Notch. We document that LNX-interacting Np9, like Numb, is unstable and degraded via the proteasome pathway and that ectopic Numb can stabilize recombinant Np9. Combined, these findings point to the possibility that Np9 affects tumorigenesis through the LNX/Numb/Notch pathway.
Integration of Clinical Data, Pathology, and cDNA Microarrays in Influenza Virus-Infected Pigtailed Macaques (Macaca nemestrina)
Authors: Baskin Carole R. , García-Sastre Adolfo , Tumpey Terrence M. , Bielefeldt-Ohmann Helle , Carter Victoria S. , Nistal-Villán Estanislao , Katze Michael G. 
Published: September 2004

ABSTRACTFor most severe viral pandemics such as influenza and AIDS, the exact contribution of individual viral genes to pathogenicity is still largely unknown. A necessary step toward that understanding is a systematic comparison of different influenza virus strains at the level of transcriptional regulation in the host as a whole and interpretation of these complex genetic changes in the context of multifactorial clinical outcomes and pathology. We conducted a study by infecting pigtailed macaques (Macaca nemestrina) with a genetically reconstructed strain of human influenza H1N1 A/Texas/36/91 virus and hypothesized not only that these animals would respond to the virus similarly to humans, but that gene expression patterns in the lungs and tracheobronchial lymph nodes would fit into a coherent and complete picture of the host-virus interactions during infection. The disease observed in infected macaques simulated uncomplicated influenza in humans. Clinical signs and an antibody response appeared with induction of interferon and B-cell activation pathways, respectively. Transcriptional activation of inflammatory cells and apoptotic pathways coincided with gross and histopathological signs of inflammation, with tissue damage and concurrent signs of repair. Additionally, cDNA microarrays offered new evidence of the importance of cytotoxic T cells and natural killer cells throughout infection. With this experiment, we confirmed the suitability of the nonhuman primate model in the quest for understanding the individual and joint contributions of viral genes to influenza virus pathogenesis by using cDNA microarray technology and a reverse genetics approach.
Low pH Is Required for Avian Sarcoma and Leukosis Virus Env-Dependent Viral Penetration into the Cytosol and Not for Viral Uncoating
Authors: Barnard Richard J. O. , Narayan Shakti , Dornadula Geethanjali , Miller Michael D. , Young John A. T. 
Published: September 2004

ABSTRACT
A novel entry mechanism has been proposed for the avian sarcoma and leukosis virus (ASLV), whereby interaction with specific cell surface receptors activates or primes the viral envelope glycoprotein (Env), rendering it sensitive to subsequent low-pH-dependent fusion triggering in acidic intracellular organelles. However, ASLV fusion seems to proceed to a lipid mixing stage at neutral pH, leading to the suggestion that low pH might instead be required for a later stage of viral entry such as uncoating (L. J. Earp, S. E. Delos, R. C. Netter, P. Bates, and J. M. White. J. Virol. 77:3058-3066, 2003). To address this possibility, hybrid virus particles were generated with the core of human immunodeficiency virus type 1 (HIV-1), a known pH-independent virus, and with subgroups A or B ASLV Env proteins. Infection of cells by these pseudotyped virions was blocked by lysosomotropic agents, as judged by inhibition of HIV-1 DNA synthesis. Furthermore, by using HIV-1 cores that contain a Vpr-β-lactamase fusion protein (Vpr-BlaM) to monitor viral penetration into the cytosol, we demonstrated that virions bearing ASLV Env, but not HIV-1 Env, enter the cytosol in a low-pH-dependent manner. This effect was independent of the presence of the cytoplasmic tail of ASLV Env. These studies provide strong support for the model, indicating that low pH is required for ASLV Env-dependent viral penetration into the cytosol and not for viral uncoating.
Memory T-Cell-Mediated Immune Responses Specific to an Alternative Core Protein in Hepatitis C Virus Infection
Authors: Bain Christine , Parroche Peggy , Lavergne Jean Pierre , Duverger Blandine , Vieux Claude , Dubois Valérie , Komurian-Pradel Florence , Trépo Christian , Gebuhrer Lucette , Paranhos-Baccala Glaucia , Penin François , Inchauspé Geneviève 
Published: September 2004

ABSTRACTIn vitro studies have described the synthesis of an alternative reading frame form of the hepatitis C virus (HCV) core protein that was named F protein or ARFP (alternative reading frame protein) and includes a domain coded by the +1 open reading frame of the RNA core coding region. The expression of this protein in HCV-infected patients remains controversial. We have analyzed peripheral blood from 47 chronically or previously HCV-infected patients for the presence of T lymphocytes and antibodies specific to the ARFP. Anti-ARFP antibodies were detected in 41.6% of the patients infected with various HCV genotypes. Using a specific ARFP 99-amino-acid polypeptide as well as four ARFP predicted class I-restricted 9-mer peptides, we show that 20% of the patients display specific lymphocytes capable of producing gamma interferon, interleukin-10, or both cytokines. Patients harboring three different viral genotypes (1a, 1b, and 3) carried T lymphocytes reactive to genotype 1b-derived peptides. In longitudinal analysis of patients receiving therapy, both core and ARFP-specific T-cell- and B-cell-mediated responses were documented. The magnitude and kinetics of the HCV antigen-specific responses differed and were not linked with viremia or therapy outcome. These observations provide strong and new arguments in favor of the synthesis, during natural HCV infection, of an ARFP derived from the core sequence. Moreover, the present data provide the first demonstration of the presence of T-cell-mediated immune responses directed to this novel HCV antigen.
Immediate-Early Expression of the Herpes Simplex Virus Type 1 ICP27 Transcript Is Not Critical for Efficient Replication In Vitro or In Vivo
Authors: Sun Aixu , Devi-Rao G. V. , Rice M. K. , Gary L. W. , Bloom D. C. , Sandri-Goldin R. M. , Ghazal P. , Wagner E. K. 
Published: September 2004

ABSTRACTWe constructed a promoter mutation altering the immediate-early expression of the herpes simplex virus type 1 (HSV-1) ICP27 transcript and its cognate wild-type rescue viruses in order to assess the role of the ICP27 protein in the earliest stages of viral infection by global transcriptional analysis with a DNA microarray. This mutant, ICP27/VP16, replaces the whole ICP27 promoter/enhancer with the VP16 promoter. It demonstrates loss of immediate-early expression of ICP27 according to the criteria expression in the absence of de novo protein synthesis and earliest expression in the kinetic cascade. Significant differences in relative transcript abundances between the mutant and wild-type rescue viruses were limited at the earliest times measured and not evident at all by 4 h after infection. Consistent with this observation, levels of some critical proteins were reduced in the mutant as compared to rescue virus infections at the earliest times tested, but were equivalent by 8 h postinfection. Further, both single and multistep levels of virus replication were equivalent with both mutant and rescue viruses. Thus, altering the immediate-early kinetics of ICP27 leads to a suboptimal quantitative lag phase in gene expression but without consequence for replication fitness in vitro. Infections in vivo also revealed equivalent ability of mutant and rescue viruses to invade the central nervous system of mice following footpad injections. Limitations to an immediate-early role of ICP27 in the biology of HSV are discussed in light of these observations.
Protective Immunoglobulin A and G Antibodies Bind to Overlapping Intersubunit Epitopes in the Head Domain of Type 1 Reovirus Adhesin σ1
Authors: Helander Anna , Miller Cathy L. , Myers Kimberly S. , Neutra Marian R. , Nibert Max L. 
Published: September 2004

ABSTRACT
Nonfusogenic mammalian orthoreovirus (reovirus) is an enteric pathogen of mice and a useful model for studies of how an enteric virus crosses the mucosal barrier of its host and is subject to control by the mucosal immune system. We recently generated and characterized a new murine immunoglobulin A (IgA)-class monoclonal antibody (MAb), 1E1, that binds to the adhesin fiber, σ1, of reovirus type 1 Lang (T1L) and thereby neutralizes the infectivity of that strain in cell culture. 1E1 is produced in hybridoma cultures as a mixture of monomers, dimers, and higher polymers and is protective against peroral challenges with T1L either when the MAb is passively administered or when it is secreted into the intestines of mice bearing subcutaneous hybridoma tumors. In the present study, selection and analysis of mutants resistant to neutralization by 1E1 identified the region of T1L σ1 to which the MAb binds. The region bound by a previously characterized type 1 σ1-specific neutralizing IgG MAb, 5C6, was identified in the same way. Each of the 15 mutants isolated and analyzed was found to be much less sensitive to neutralization by either 1E1 or 5C6, suggesting the two MAbs bind to largely overlapping regions of σ1. The tested mutants retained the capacity to recognize specific glycoconjugate receptors on rabbit M cells and cultured epithelial cells, even though viral binding to epithelial cells was inhibited by both MAbs. S1 sequence determinations for 12 of the mutants identified σ1 mutations at four positions between residues 415 and 447, which contribute to forming the receptor-binding head domain. When aligned with the σ1 sequence of reovirus type 3 Dearing (T3D) and mapped onto the previously reported crystal structure of the T3D σ1 trimer, the four positions cluster on the side of the σ1 head, across the interface between two subunits. Three such interface-spanning epitopes are thus present per σ1 trimer and require the intact quaternary structure of the head domain for MAb binding. Identification of these intersubunit epitopes on σ1 opens the way for further studies of the mechanisms of antibody-based neutralization and protection with type 1 reoviruses.
Entry and Transcription as Key Determinants of Differences in CD4 T-Cell Permissiveness to Human Immunodeficiency Virus Type 1 Infection
Authors: Ciuffi Angela , Bleiber Gabriela , Muñoz Miguel , Martinez Raquel , Loeuillet Corinne , Rehr Manuela , Fischer Marek , Günthard Huldrych F. , Oxenius Annette , Meylan Pascal , Bonhoeffer Sebastian , Trono Didier , Telenti Amalio 
Published: September 2004

ABSTRACTIsolated primary human cells from different donors vary in their permissiveness—the ability of cells to be infected and sustain the replication of human immunodeficiency virus type 1 (HIV-1). We used replicating HIV-1 and single-cycle lentivirus vectors in a population approach to identify polymorphic steps during viral replication. We found that phytohemagglutinin-stimulated CD4+CD45RO+CD57−T cells from healthy blood donors (n= 128) exhibited a 5.2-log-unit range in virus production. For 20 selected donors representing the spectrum of CD4 T-cell permissiveness, we could attribute up to 42% of the total variance in virus production to entry factors and 48% to postentry steps. Efficacy at key intracellular steps of the replicative cycle (reverse transcription, integration, transcription and splicing, translation, and budding and release) varied from 0.71 to 1.45 log units among donors. However, interindividual differences in transcription efficiency alone accounted for 64 to 83% of the total variance in virus production that was attributable to postentry factors. While vesicular stomatitis virus G protein-mediated fusion was more efficacious than CCR5/CD4 entry, the latter resulted in greater transcriptional activity per proviral copy. The phenotype of provirus transcription was stable over time, indicating that it represents a genetic trait.
Construction and Characterization of a Fluorescently Labeled Infectious Human Immunodeficiency Virus Type 1 Derivative
Authors: Müller Barbara , Daecke Jessica , Fackler Oliver T. , Dittmar Matthias T. , Zentgraf Hanswalter , Kräusslich Hans-Georg 
Published: September 2004

ABSTRACT

The introduction of a label which can be detected in living cells opens new possibilities for the direct analysis of dynamic processes in virus replication, such as the transport and assembly of structural proteins. Our aim was to generate a tool for the analysis of the trafficking of the main structural protein of human immunodeficiency virus type 1 (HIV-1), Gag, as well as for the analysis of virus-host cell interactions in an authentic setting. We describe here the construction and characterization of infectious HIV derivatives carrying a label within the Gag polyprotein. Based on our initial finding that a short epitope tag could be inserted near the C terminus of the matrix domain of Gag without affecting viral replication, we constructed HIV derivatives carrying the
egfp
gene at the analogous position, resulting in the expression of a Gag-EGFP fusion protein in the authentic viral context. Particles displaying normal viral protein compositions were released from transfected cells, and Gag-EGFP was efficiently processed by the viral protease, yielding the expected products. Furthermore, particles with mature morphology were observed by thin-section electron microscopy. The modified virus was even found to be infectious, albeit with reduced relative infectivity. By preparing mixed particles containing equimolar amounts of Gag-EGFP and Gag, we were able to obtain highly fluorescently labeled virion preparations which displayed normal morphology and full wild-type infectivity, demonstrating that the process of HIV particle assembly displays a remarkable flexibility. The fluorescent virus derivative is a useful tool for investigating the interaction of HIV with live cells.
African Swine Fever Virus Inhibits Induction of the Stress-Induced Proapoptotic Transcription Factor CHOP/GADD153
Authors: Netherton Christopher L. , Parsley James C. , Wileman Thomas 
Published: September 2004

ABSTRACT
Stress signaling from mitochondria and the endoplasmic reticulum (ER) leads to the induction of the proapoptotic transcription factor CHOP/GADD153. Many viruses use the ER as a site of replication and/or envelopment, and this activity can lead to the activation of ER stress and apoptosis. African swine fever virus (ASFV) is assembled on the cytoplasmic face of the ER and ultimately enveloped by ER membrane cisternae. The virus also recruits mitochondria to sites of viral replication and induces the mitochondrial stress protein hsp60. Here we studied the effects of ASFV on the induction of CHOP/GADD153 in infected cells. Interestingly, unlike other ER-tropic viruses, ASFV did not activate CHOP and was able to inhibit the induction of CHOP/GADD153 by a number of exogenous stimuli.
T-Cell Responses to the M3 Immune Evasion Protein of Murid Gammaherpesvirus 68 Are Partially Protective and Induced with Lytic Antigen Kinetics
Authors: Obar Joshua J. , Donovan Douglas C. , Crist Sarah G. , Silvia Ondine , Stewart James P. , Usherwood Edward J. 
Published: September 2004

ABSTRACTDNA vaccination with theM3gene, encoding an immune evasion molecule expressed during both the acute lytic and persistent phases of murid gammaherpesvirus 68 infection, yielded a significantly lower titer of virus in the lung than controls. The protection seen was dependent on T cells, and we mapped an epitope recognized by CD8 T cells. The immune response to this epitope follows the same kinetics as lytic cycle antigens, despite the fact that this gene is expressed in both lytic and persistent stages of infection. This has important implications for our understanding of T-cell responses to putative latency-associated gammaherpesvirus proteins and how vaccination may improve control of these viruses.