bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient demographic data for phase 2/3 clinical trials of a novel calcineurin inhibitor, lx 211, for the treatment of non‐infectious uveitis
Authors: BODAGHI B 
Published: September 2008

Abstract Purpose LX211 is the oral formulation of a novel calcineurin inhibitor (CNi) possessing four‐fold greater potency, an altered metabolic and pharmakokinetic profile, and potentially improved safety compared to the prototypical CNi, cyclosporine A. Methods Three global, prospective, double‐masked, parallel‐group, dose‐ranging, placebo‐controlled, randomized multicenter studies comprise the LUMINATE Program, which is currently in progress. Study LX211‐01‐UV evaluates 210 patients with active predominantly posterior manifestations. Study LX211‐03‐UV evaluates 100 patients with active predominantly anterior manifestations. Study LX211‐02‐UV evaluates 220 patients whose disease is controlled and will evaluate the role of LX211 in sparing systemic corticosteroid. Results The studies are ongoing. Pooled masked data from the studies to date indicate that in Study LX211‐01 (N=81) the distribution of patient anatomic diagnoses is : panuveitis (48.1%), intermediate uveitis (29.6%), anterior + intermediate uveitis (8.6%) and posterior uveitis (13.6%). The mean age is 42 years with a F/M of 2. Study LX211‐02 (N=101) has a similar distribution of anatomic diagnosis. The mean age of subject ins LX211‐02 is 43.4 years with a F/M of 2. Study LX211‐03 was similar to Studies LX211‐01 and LX211‐02 with respect to the proportion of female (68.6%) to male (31.4%) subjects. Conclusion The LUMINATE Program are the first randomized placebo‐controlled trials for a corticosteroid‐sparing immunomodulatory agent in various anatomic forms of sight‐threatening non‐infectious uveitis.
Commercial interest
Changes on optic nerve with sarcoidosis patients
Authors: RADUNOVIC M , VUKSANOVIC A 
Published: September 2008

Abstract Purpose Sarcoidosis is a rare autoimmune disorder. Since in 20% of the cases optical manifestations represent the first sign of a systemic disease and that 75% of sarcoidosis patients are under the age of 40, we considered it appropriate to perceive the manifestations of sarcoidosis on the optic nerve and to notice the consequences for the vision. Methods The examination was being carried out on 32 patients who had come for an ophthalmological check‐up in the Eye Clinic of the Clinical Centre of Montenegro for the first time, and who had been made sarcoidosis diagnosis. With the patients showing the obvious signs of neurosarcoidosis with the spreading over the optic nerve, additional diagnostic examinations were being carried out: FA, ICG, NMR, EEG, VEP, lumbar punction, as well as endocrinological examinations. The patients were being monitored during the following year, with monthly control check‐ups. Results Optical manifestations within the framework of the basic disease were found with 17 patients, whilst optical symptomatology was the first sign of the disease with 4 patients. The changes on the optic nerve were noticed in various forms and they appeared either as the initial manifestation of sarcoidosis or at any time during the duration of the disease. Conclusion The changes found on the optic nerve within the framework of sarcoidosis were numerous and variable. PNO edema, papillitis, granuloma PNO, retrobulbar neuritis, are only part of clinical manifestations which appear upon the optic nerve being affected by sarcoidosis.
Chlamydophila felisCF0218 Is a Novel TMH Family Protein with Potential as a Diagnostic Antigen for Diagnosis ofC. felisInfection
Authors: Ohya Kenji , Takahara Yu , Kuroda Etsuko , Koyasu Saori , Hagiwara Shigeyuki , Sakamoto Maki , Hisaka Mitsuaki , Morizane Kazuko , Ishiguro Shinryou , Yamaguchi Tsuyoshi , Fukushi Hideto 
Published: September 2008

ABSTRACTChlamydophila felisis a causative agent of acute and chronic conjunctivitis and pneumonia in cats (feline chlamydiosis). Also,C. felisis a suspected zoonotic agent of such diseases as non-Chlamydia trachomatisconjunctivitis in humans, although this is controversial. At present, there is no serodiagnostic system that specifically detectsC. felisinfection conveniently. Current systems use antigens such as lipopolysaccharide that cross-react with all chlamydia species. In addition, it is difficult to distinguish between cats that are vaccinated with the commercial vaccine againstC. felisand cats that are infected withC. felis. Here, we describe a new candidate diagnostic antigen for diagnosis ofC. felisinfection, CF0218, that was obtained by screening a genomic expression library ofC. felisFe/C-56 withC. felis-immunized serum. CF0218 was a putative transmembrane head (TMH) family protein with bilobed hydrophobic motifs at its N terminus, and orthologues of CF0218 were not found in theChlamydophila pneumoniaeorChlamydia trachomatisgenomes. The recombinant CF0218 was not recognized by antiserum againstC. trachomatis, suggesting that CF0218 isC. felisspecific. CF0218 transcription during the course ofC. felisinfection was confirmed by reverse transcription-PCR. By indirect immunofluorescence analysis, CF0218 was colocalized with theC. felis-formed inclusion bodies in the infected cells. The antibody response against CF0218 was elevated followingC. felisinfection but not by vaccination in experimentally vaccinated and infected cats. These results suggest that CF0218, a novel TMH family protein ofC. felis, possesses potential as aC. felisinfection-specific diagnostic antigen.
Characterization of a Recombinant Newcastle Disease Virus Vaccine Strain
Authors: Cho Sun-Hee , Kwon Hyuk-Joon , Kim Tae-Eun , Kim Jae-Hong , Yoo Han-Sang , Park Man-Hoon , Park Young-Ho , Kim Sun-Joong 
Published: September 2008

ABSTRACTA recombinant La Sota strain (KBNP-C4152R2L) in which fusion (F) and hemagglutinin-neuraminidase (HN) genes were replaced with those of a contemporary genotype VIId virus, KBNP-4152, has been developed. To attenuate the virulence of the recombinant strain, the F cleavage motif was mutated from112RRQKR116to112GRQAR116, and to reduce pathogenic instability, a codon which does not allow changes to basic amino acids by single point mutation was inserted at codon 115. In addition a six-nucleotide sequence was inserted into the intergenic region between matrix protein and F genes for attenuation without breaking the “rule-of-six.” The HN protein length was increased from 571 to 577 as a marker. Serological tests revealed that the antigenicity of KBNP-C4152R2L was similar to that of KBNP-4152 but distinct from that of the La Sota strain. KBNP-C4152R2L was avirulent (intracerebral pathogenicity index, 0.0; mean death time, >168 h) and stable in pathogenicity through in vivo passages. The killed oil emulsion of and live KBNP-C4152R2L were completely protective against mortality and egg drop caused by virulent strains, and KBNP-C4152R2L was applicable to in ovo vaccination. Therefore, KBNP-C4152R2L is a promising vaccine strain and viral vector in terms of antigenicity, productivity, safety, and pathogenic stability.
Cross-Reactivity between Immunoglobulin G Antibodies of Whales and Dolphins Correlates with Evolutionary Distance
Authors: Nollens Hendrik H. , Ruiz Carolina , Walsh Michael T. , Gulland Frances M. D. , Bossart Gregory , Jensen Eric D. , McBain James F. , Wellehan James F. X. 
Published: September 2008

ABSTRACTGrowing morphological and molecular evidence indicates that the porpoises, dolphins, and whales evolved within the even-toed ungulates, formerly known as Artiodactyla. These animals are now grouped in the Cetartiodactyla. We evaluated the antigenic similarity of the immunoglobulin G (IgG) molecules of 15 cetacean species and the domestic cow. The similarity was scored using three distinct antibodies raised against bottlenose dolphin (Tursiops truncatus) IgG in a Western blot, an indirect enzyme-linked immunosorbent assay (ELISA), and a competitive ELISA format. A score was generated for the genetic distance between each species andT. truncatususing the cytochromebsequence. Each antibody displayed a distinct pattern of reactivity with the IgG antibodies of the various species. The monoclonal antibody (MAb) specific for the γ heavy chain ofT. truncatuswas reactive with all monodontids, delphinids, and phocoenids. The light-chain-specific MAb reacted with IgG of delphinoid and phocoenid species and one of the two mysticete species tested. The polyclonal antibody was broadly cross-reactive across all cetaceans and the domestic cow. Using the MAb specific for the γ heavy chain, the degree of IgG cross-reactivity ranged from less than 17% for the mysticetes to 106% for killer whaleOrcinus orca. The IgG in beaked whale and baleen whale sera was significantly less cross-reactive with bottlenose dolphin IgG than sera from other toothed whales. A strong negative correlation was demonstrated between antigenic cross-reactivity of IgG molecules and the genetic distance of their hosts. The data generated will be useful for the development of clinical serodiagnostics in diverse cetacean species.
Analysis of Mixed Sequencing Chromatograms and Its Application in Direct 16S rRNA Gene Sequencing of Polymicrobial Samples
Authors: Kommedal Øyvind , Karlsen Bjarte , Sæbø Øystein 
Published: September 2008

ABSTRACT
Investigation of clinical samples by direct 16S rRNA gene sequencing provides the possibility to detect nonviable bacteria and bacteria with special growth requirements. This approach has been particularly valuable for the diagnosis of patients who have received antibiotics prior to sample collection. In specimens containing more than one bacterium, direct sequencing gives mixed chromatograms that complicate further interpretation. We designed an algorithm able to analyze these ambiguous chromatograms and implemented it as a Web-based service. The algorithm contains both a new base-calling procedure and a new database search procedure. 16S rRNA gene sequencing was performed on polybacterial suspensions prepared in the laboratory. The computer program identified all bacteria correctly to the species level in 23 out of 23 samples containing two different bacteria. For samples containing three different bacteria, correct identification to the species level was achieved for three out of five and to the genus level for five out of five.
Sequencing of
hsp65
Gene for Identification of
Mycobacterium
Species Isolated from Environmental and Clinical Sources in Rio de Janeiro, Brazil
Authors: Senna Simone G. , Battilana Jaqueline , Costa Juliana C. , Silva Marlei G. , Duarte Rafael S. , Fonseca Leila S. , Suffys Philip N. , Bogo Mauricio R. 
Published: September 2008

ABSTRACT

This study evaluated the biodiversity of 28 clinical and 24 environmental
Mycobacterium
isolates from Rio de Janeiro, Brazil, by using
hsp65
sequences, with the aim of contributing to a better understanding of the genetic diversity and usefulness of this marker. An extensive phylogenetic analysis was performed. The nucleotide diversity was similar between clinical (0.06508) and environmental (0.06221) isolates.
Detection of Perinatal Cytomegalovirus Infection and Sensorineural Hearing Loss in Belgian Infants by Measurement of Automated Auditory Brainstem Response
Authors: Verbeeck Jannick , Van Kerschaver Erwin , Wollants Elke , Beuselinck Kurt , Stappaerts Luc , Van Ranst Marc 
Published: September 2008

ABSTRACTSince auditory disability causes serious problems in the development of speech and in the total development of a child, it is crucial to diagnose possible hearing impairment as soon as possible after birth. This study evaluates the neonatal hearing screening program in Flanders, Belgium. The auditory ability of 118,438 babies was tested using the automated auditory brainstem response. We selected 194 babies with indicative hearing impairment and 332 matched controls to investigate the association between the presence of human cytomegalovirus (HCMV) in urine samples and sensorineural hearing loss and to analyze the sensibility and specificity of a cell culture assay and a quantitative PCR detection method. Our results indicate that significantly more babies with confirmed hearing impairment were HCMV positive after birth. Further, based on the results of our study, babies with HCMV viral loads above 4.5 log copies/ml urine seem to be 1.4 times more likely to have confirmed hearing impairment. Our follow-up study suggests that the hearing impairment of children infected with HCMV after birth is less likely to improve than that of HCMV-negative infants. Our results confirm that the presence of HCMV before or shortly after birth influences the outcome of hearing impairment.
Rapid Identification of Mycobacteria from Smear-Positive Sputum Samples by Nested PCR-Restriction Fragment Length Polymorphism Analysis
Authors: Wu Tsu-Lan , Chia Ju-Hsin , Kuo An-Jing , Su Lin-Hui , Wu Ting-Shu , Lai Hsin-Chih 
Published: September 2008

ABSTRACTThe rapid identification of mycobacteria from smear-positive sputum samples is an important clinical issue. Furthermore, the availability of a cheap, technically simple, and accurate method also would benefit mycobacterial laboratories in developing countries. In the present study, we aimed to develop an assay allowing the identification of theMycobacterium tuberculosiscomplex (MTBC) and other frequently isolated nontuberculous mycobacteria (NTM) directly from smear-positive sputum samples. A nested PCR-restriction fragment length polymorphism analysis (nested-PRA) assay that focuses on the analysis of thehsp65gene was developed and evaluated for its efficiency compared to that of traditional culture methods and 16S rRNA gene sequencing identification. A total of 204 smear-positive and culture-positive sputum specimens were prospectively collected for analysis between November 2005 and May 2006. The samples were classified according to an acid-fast bacillus (AFB) staining scale as rare/1+, 2+, or 3+. The results of the nested-PRA showed that the identification rate for AFB 3+, AFB 2+, and AFB rare/1+ samples was 100, 95, and 53%, respectively, and that the overall identification rate was 89%. All positive results by the nested-PRA method agreed with the results by culture and 16S rRNA gene sequence analysis. The nested-PRA appears to have clinical applicability when used for the direct identification of mycobacterial organisms (both MTBC and NTM) that are present in smear-positive sputum samples, especially for countries in which MTBC is endemic.
Real-Time PCR Measurement of Persistence of
Bordetella pertussis
DNA in Nasopharyngeal Secretions during Antibiotic Treatment of Young Children with Pertussis
Authors: Bidet Philippe , Liguori Sandrine , De Lauzanne Agathe , Caro Valérie , Lorrot Mathie , Carol Agnès , Faye Albert , Guiso Nicole , Bingen Edouard , Bonacorsi Stéphane 
Published: September 2008

ABSTRACT

We used real-time PCR to examine the persistence of
Bordetella pertussis
DNA in serial nasopharyngeal aspirates from 22 children treated for pertussis. After 5 days of treatment, PCR was positive for all 21 assessable patients. After 14 and 21 days, PCR was still positive for 83% (10/12) and 66% (4/6) of assessable patients, respectively. One patient was tested 1 month after treatment initiation, and
B. pertussis
DNA was still detectable. Quantitative analysis showed that the DNA concentration diminished during treatment in all except one case. The PCR cycle threshold at which
B. pertussis
DNA became detectable increased by a mean of 1.7 cycles per day (range, 0.86 to 3.68 cycles per day). Real-time PCR can thus be used to diagnose pertussis in young children for up to 3 weeks after treatment initiation. Its potential value for assessing the treatment outcome remains to be determined.
The Cellular Antiviral Protein Viperin Is Attenuated by Proteasome-Mediated Protein Degradation in Japanese Encephalitis Virus-Infected Cells
Authors: Chan Yi-Lin , Chang Tsung-Hsien , Liao Ching-Len , Lin Yi-Ling 
Published: September 2008

ABSTRACT
Viperin is identified as an antiviral protein induced by interferon (IFN), viral infections, and pathogen-associated molecules. In this study, we found that viperin is highly induced at the RNA level by Japanese encephalitis virus (JEV) and Sindbis virus (SIN) and that viperin protein is degraded in JEV-infected cells through a proteasome-dependent mechanism. Promoter analysis revealed that SIN induces viperin expression in an IFN-dependent manner but that JEV by itself activates the viperin promoter through IFN regulatory factor-3 and AP-1. The overexpression of viperin significantly decreased the production of SIN, but not of JEV, whereas the proteasome inhibitor MG132 sustained the protein level and antiviral effect of viperin in JEV-infected cells. Knockdown of viperin expression by RNA interference also enhanced the replication of SIN, but not that of JEV. Our results suggest that even though viperin gene expression is highly induced by JEV, it is negatively regulated at the protein level to counteract its antiviral effect. In contrast, SIN induces viperin through the action of IFN, and viperin exhibits potent antiviral activity against SIN.
Active-Site Mutations in the South African Human Immunodeficiency Virus Type 1 Subtype C Protease Have a Significant Impact on Clinical Inhibitor Binding: Kinetic and Thermodynamic Study
Authors: Mosebi Salerwe , Morris Lynn , Dirr Heini W. , Sayed Yasien 
Published: September 2008

ABSTRACT
Human immunodeficiency virus (HIV) infections in sub-Saharan Africa represent about 56% of global infections. Study of active-site mutations (the V82A single mutation and the V82F I84V double mutation) in the less-studied South African HIV type 1 subtype C (C-SA) protease indicated that neither mutation had a significant impact on the proteolytic functioning of the protease. However, the binding affinities of, and inhibition by, saquinavir, ritonavir, indinavir, and nelfinavir were weaker for each variant than for the wild-type protease, with the double mutant exhibiting the most dramatic change. Therefore, our results show that the C-SA V82F I84V double mutation decreased the binding affinities of protease inhibitors to levels significantly lower than that required for effective inhibition.
Growth Determinants for H5N1 Influenza Vaccine Seed Viruses in MDCK Cells
Authors: Murakami Shin , Horimoto Taisuke , Mai Le Quynh , Nidom Chairul A. , Chen Hualan , Muramoto Yukiko , Yamada Shinya , Iwasa Ayaka , Iwatsuki-Horimoto Kiyoko , Shimojima Masayuki , Iwata Akira , Kawaoka Yoshihiro 
Published: September 2008

ABSTRACT
H5N1 influenza A viruses are exacting a growing human toll, with more than 240 fatal cases to date. In the event of an influenza pandemic caused by these viruses, embryonated chicken eggs, which are the approved substrate for human inactivated-vaccine production, will likely be in short supply because chickens will be killed by these viruses or culled to limit the worldwide spread of the infection. The Madin-Darby canine kidney (MDCK) cell line is a promising alternative candidate substrate because it supports efficient growth of influenza viruses compared to other cell lines. Here, we addressed the molecular determinants for growth of an H5N1 vaccine seed virus in MDCK cells, revealing the critical responsibility of the Tyr residue at position 360 of PB2, the considerable requirement for functional balance between hemagglutinin (HA) and neuraminidase (NA), and the partial responsibility of the Glu residue at position 55 of NS1. Based on these findings, we produced a PR8/H5N1 reassortant, optimized for this cell line, that derives all of its genes for its internal proteins from the PR8(UW) strain except for the NS gene, which derives from the PR8(Cambridge) strain; its N1 NA gene, which has a long stalk and derives from an early H5N1 strain; and its HA gene, which has an avirulent-type cleavage site sequence and is derived from a circulating H5N1 virus. Our findings demonstrate the importance and feasibility of a cell culture-based approach to producing seed viruses for inactivated H5N1 vaccines that grow robustly and in a timely, cost-efficient manner as an alternative to egg-based vaccine production.
Within-Host Genetic Diversity of Endemic and Emerging Parvoviruses of Dogs and Cats
Authors: Hoelzer Karin , Shackelton Laura A. , Holmes Edward C. , Parrish Colin R. 
Published: September 2008

ABSTRACT
Viral emergence can result from the adaptation of endemic pathogens to new or altered host environments, a process that is strongly influenced by the underlying sequence diversity. To determine the extent and structure of intrahost genetic diversity in a recently emerged single-stranded DNA virus, we analyzed viral population structures during natural infections of animals with canine parvovirus (CPV) or its ancestor, feline panleukopenia virus (FPV). We compared infections that occurred shortly after CPV emerged with more recent infections and examined the population structure of CPV after experimental cross-species transmission to cats. Infections with CPV and FPV showed limited genetic diversity regardless of the analyzed host tissue or year of isolation. Coinfections with genetically distinct viral strains were detected in some cases, and rearranged genomes were seen in both FPV and CPV. The sporadic presence of some sequences with multiple mutations suggested the occurrence of either particularly error-prone viral replication or coinfection by more distantly related strains. Finally, some potentially organ-specific host effects were seen during experimental cross-species transmission, with many of the mutations located in the nonstructural protein NS2. These included residues with evidence of positive selection at the population level, which is compatible with a role of this protein in host adaptation.
Charge Cluster-to-Alanine Scanning of UL128 for Fine Tuning of the Endothelial Cell Tropism of Human Cytomegalovirus
Authors: Schuessler Andrea , Sampaio Kerstin Laib , Sinzger Christian 
Published: September 2008

ABSTRACT
The viral genes UL128, UL130, and UL131A have been identified as major determinants of endothelial cell (EC) tropism of human cytomegalovirus (HCMV), with deletion of either gene causing a null phenotype. We hypothesized that a functional scanning of these genes by minor genetic modifications would allow for the generation of mutants with an intermediate phenotype. By combining charge cluster-to-alanine (CCTA) mutagenesis with markerless mutagenesis of a bacterial artificial chromosome-cloned endotheliotropic HCMV strain, we analyzed UL128 in order to identify functional sites and hence enable targeted modulation of the EC tropism of HCMV. A total of nine mutations in eight charge clusters were tested. Three of the CCTA mutations severely reduced EC tropism, three were irrelevant, two had a weak effect on cell tropism, and one mutation in the most C-terminal cluster caused an intermediate phenotype. All of the highly effective mutations were located in a core region (amino acids 72 to 106) which appears to be particularly crucial for EC tropism. The intermediate effect of mutations in the C-terminal cluster could be modulated by varying the number of amino acids replaced with alanine. This study provides a rational approach for targeted modulation of HCMV cell tropism, which may aid in the development of HCMV strains with a desired degree of attenuation.
Role of Hypercytokinemia in NF-κB p50-Deficient Mice after H5N1 Influenza A Virus Infection
Authors: Droebner Karoline , Reiling Sarah Julia , Planz Oliver 
Published: September 2008

ABSTRACT
During H5N1 influenza virus infection, proinflammatory cytokines are markedly elevated in the lungs of infected hosts. The significance of this dysregulated cytokine response in H5N1-mediated pathogenesis remains to be determined. To investigate the influence of hypercytokinemia, or “cytokine storm,” a transgenic mouse technology was used. The classical NF-κB pathway regulates the induction of most proinflammatory cytokines. Deletion of the p50 subunit leads to a markedly reduced expression of the NF-κB-regulated cytokines and chemokines. Here we show that H5N1 influenza virus infection of this transgenic mouse model resulted in a lack of hypercytokinemia but not in altered pathogenesis.