bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of D‐3‐phosphoglycerate dehydrogenase autoantibodies in patients with autoimmune hepatitis: Clinical significance evaluation
Authors: Xiang Daijun , Xia Qing , Chen Dexi , Feng Xia , Zhao Yan , Liu Yan , Liao Huiyu , Liu Yanmin , Li Ning , Yan Huiping 
Published: June 2011

Aim:  D‐3‐phosphoglycerate dehydrogenase (3‐PHGDH) was identified as a putative target of autoantibodies in autoimmune hepatitis (AIH). The aims of the present study were to detect anti‐3‐PHGDH in patients with AIH and other chronic liver diseases and to analyze their clinical relevance.Methods:  Human 3‐PHGDH gene was cloned and expressed in Escherichia coli and used in enzyme‐linked immunosorbent assays and Western blots. Serum from patients with AIH (n = 101), primary biliary cirrhosis (PBC, n = 122), chronic hepatitis C (CHC, n = 117), chronic hepatitis B (CHB, n = 112), and from patients with other autoimmune disease (n = 125) were investigated.Results:  The highest incidence and activity of anti‐PHGDH was observed in AIH patients. Thirty‐two of 40 untreated (80%) and 37 of 61 AIH patients treated with corticosteroid (60.7%) were positive. Antibody titers decreased significantly during corticosteroid treatment. 15.8% of PBC patients, 9.8% of CHB and 12.8% of CHC patients, were anti‐PHGDH‐positive, with less than 12% of patients positive with other autoimmune diseases via reactions with recombinant 3‐PHGDH protein.Conclusion:  Anti‐PHGDH were detected in chronic liver diseases. They occur predominantly in AIH, and corticosteroid treatment seems to decrease antibody titers. Whether the antibodies are primary or secondary phenomena and whether they are related to the etiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.
Cancer preventive effect of pegylated interferon α‐2b plus ribavirin in a real‐life clinical setting in Japan: PERFECT interim analysis
Authors: Watanabe Sumio , Enomoto Nobuyuki , Koike Kazuhiko , Izumi Namiki , Takikawa Hajime , Hashimoto Etsuko , Moriyasu Fuminori , Kumada Hiromitsu , Imawari Michio ,   PERFECT Study Group
Published: June 2011

Aim:  This study was conducted to clarify the incidence of hepatocellular carcinoma (HCC) and the factors contributing to its occurrence by following chronic hepatitis C patients who received pegylated interferon (PEG‐IFN) α‐2b plus ribavirin (RBV) combination therapy.Methods:  Patients who received PEG‐IFN α‐2b and RBV combination therapy with no history of HCC or HCC within 3 months after the start of treatment were observed for the onset of HCC at 67 centers.Results:  Sustained virological response (SVR) was observed in 999 (53.5%) of 1865 patients eligible for analysis. During the observation period (median duration: 4 years and 3 months), HCC developed in 59 patients (3.1%). A significant difference was observed in the 5‐year cumulative incidence of HCC between SVR and non‐SVR patients (1.1% vs. 7.1%). Factors contributing to HCC selected in multivariate analysis were therapeutic efficacy, sex, age, alanine aminotransferase (ALT) level at 24 weeks after the end of treatment, and platelet count. Non‐SVR patients with ALT improvement after the end of treatment had a significantly lower 5‐year cumulative incidence of HCC than those without (3.4% vs. 11.0%). HCC developed in 10 patients who achieved SVR, and multivariate analysis indicated that ALT level at 24 weeks after the end of treatment was the only significant factor contributing to HCC.Conclusion:  Several known risk factors for HCC contributed to HCC in patients who received PEG‐IFN α‐2b and RBV combination therapy, and ALT abnormality after the end of treatment contributes to the onset of HCC in both non‐SVR and SVR patients.
Screening for caries in targeted schools in the Blue Mountains and Hawkesbury districts, New South Wales, Australia: an evaluation of the School Assessment Program
Authors: Chong Gabriel Tse Feng , Evans Robin Wendell , Dennison Peter John 
Published: June 2011

AbstractAim:  To determine if the school dental screening program in New South Wales, the School Assessment Program, achieved its aim of being the key entry point for high‐risk children to receive care.Methods:  A secondary analysis was conducted on epidemiological data gathered in 16 primary schools in New South Wales (10 for the School Assessment Program and six for the non‐School Assessment Program) in 2003. The validity of the School Assessment Program targeting criteria in identifying high‐risk schools was determined. Post‐screening treatment outcomes were evaluated from the assessment of treatment ratios.Results:  There were negligible differences in the caries experience and proportions of high‐risk children, irrespective of their School Assessment Program status. Sensitivity and specificity values were approximately 60% and 40%, respectively, using various case definitions of high risk applied to both children and schools. Deciduous dentition treatment ratios for School Assessment Program and non‐School Assessment Program children with decayed, missing, and filled teeth (dmft) ≥1 ranged from 0.48 to 0.79 and from 0.47 to 0.73, respectively. Respective permanent dentition treatment ratios for School Assessment Program and non‐School Assessment Program children with Decayed, Missing, and Filled Teeth (DMFT) ≥1 were 0.49–0.82 and 0.64–1.08.Conclusion:  The School Assessment Program failed to identify schools with high caries‐risk children or confer post‐screening caries treatment benefits.
Monte Carlo dose enhancement studies in microbeam radiation therapy
Authors: Martínez‐Rovira I. , Prezado Y. 
Published: June 2011

Purpose:A radical radiation therapy treatment for gliomas requires extremely high absorbed doses resulting in subsequent deleterious side effects in healthy tissue. Microbeam radiation therapy (MRT) is an innovative technique based on the fact that normal tissue can withstand high radiation doses in small volumes without any significant damage. The synchrotron‐generated x‐ray beam is collimated and delivered to an array of narrow micrometer‐sized planar rectangular fields. Several preclinical experiments performed at the Brookhaven National Laboratory (BNL) and at the European Synchrotron Radiation Facility (ESRF) confirmed that MRT yields a higher therapeutic index than nonsegmented beams of the same characteristics. This index can be greatly improved by loading the tumor with high atomic number (Z) contrast agents. The aim of this work is to find the high‐Z element that provides optimum dose enhancement.Methods:Monte Carlo simulations (PENELOPE/penEasy) were performed to assess the peak and valley doses as well as their ratio (PVDR) in healthy tissue and in the tumor, loaded with different contrast agents. The optimization criteria used were maximization of the ratio between the PVDR values in healthy tissue respect to the PVDR in the tumor and minimization of bone and brain valley doses.Results:Dose enhancement factors, PVDR, and valley doses were calculated for different high‐Z elements. A significant decrease of PVDR values in the tumor, accompanied by a gain in the valley doses, was found in the presence of high‐Z elements. This enables the deposited dose in the healthy tissue to be reduced. The optimum high‐Z element depends on the irradiation configuration. As a general trend, the best outcome is provided by the highest Z contrast agents considered, i.e., gold and thallium. However, lanthanides (especially Lu) and hafnium also offer a satisfactory performance.Conclusions:The remarkable therapeutic index in microbeam radiation therapy can be further improved by loading the tumor with a high‐Z element. This study reports quantitative data on several dosimetric magnitudes in order to find the optimum contrast agent. Although the final choice of the element will also depend on possible cytotoxicity, three elements were found to be worthy of mention: gold, thallium, and lutetium.
Effect of Chemotherapy on Whole-Blood Cytokine Responses to Mycobacterium tuberculosis Antigens in a Small Cohort of Patients with Pulmonary Tuberculosis
Authors: Bertholet Sylvie , Horne David J. , Laughlin Elsa M. , Savlov Margery , Tucakovic Ines , Coler Rhea N. , Narita Masahiro , Reed Steven G. 
Published: June 2011

ABSTRACT

The development of genomic and proteomic tools has enabled studies that begin to characterize the molecular targets of an effective host immune response to
Mycobacterium tuberculosis
, including understanding the specific immune responses associated with tuberculosis (TB) disease progression, disease resolution, and the development of latency. One application of such tools is the development of diagnostic reagents and assays useful as a test of cure. Such a test could be of considerable importance for the evaluation of new therapeutics. We and others have previously described immunodominant proteins of
M. tuberculosis
, including both vaccine and diagnostic candidates. In the present study, we describe the changes in immune responses to a panel of 71
M. tuberculosis
antigens in six patients during the course of therapy. The levels of six cytokines were measured in 24-h whole-blood assays with these antigens, revealing that gamma interferon (IFN-γ), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were differentially regulated in response to a subset of antigens. Therefore, measuring the production of these three cytokines in response to a panel of carefully selected
M. tuberculosis
proteins during the course of TB therapy might be a promising path toward the development of a test of cure and warrants further validation in larger cohorts of pulmonary TB patients.
N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity
Authors: Tachibana Mayumi , Wu Yimin , Iriko Hideyuki , Muratova Olga , MacDonald Nicholas J. , Sattabongkot Jetsumon , Takeo Satoru , Otsuki Hitoshi , Torii Motomi , Tsuboi Takafumi 
Published: June 2011

ABSTRACTThe aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluatedEscherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of thePlasmodium falciparumNF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites toAnopheles stefensimosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity againstP. falciparum.
Immunogenicity and Safety of the Influenza A/H1N1 2009 Inactivated Split-Virus Vaccine in Young and Older Adults: MF59-Adjuvanted Vaccine versus Nonadjuvanted Vaccine
Authors: Cheong Hee Jin , Song Joon Young , Heo Jung Yeon , Noh Ji Yun , Choi Won Suk , Park Dae Won , Wie Seong-Heon , Kim Woo Joo 
Published: June 2011

ABSTRACT

Since initial reports in April 2009, the pandemic influenza A (H1N1) virus has spread globally. Influenza vaccines are the primary method for the control of influenza and its complications. We conducted a multicenter clinical trial to evaluate the immunogenicity and safety of H1N1 vaccine (Green Cross Co.) in young adults (18 to 64 years) and the elderly (≥65 years) using a two-dose regimen, with the doses administered 21 days apart. Three different regimens of hemagglutinin antigen were comparatively analyzed: 3.75 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) versus 15 μg (nonadjuvanted) in young adults and 3.75 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) in the elderly. In young adults, all three vaccine regimens met the European Agency for the Evaluation of Medicinal Products (EMA) criteria after the first dose. In the elderly, on day 21 after the first dose, the rates of seroprotection and seroconversion were significantly higher for the 7.5-μg dose of MF59 adjuvanted vaccine than for the 3.75-μg dose (58.0% versus 44.3% [
P
= 0.03] and 53.7% versus 37.2% [
P
< 0.01], respectively). After the second dose, the geometric mean titer (GMT) increment was blunted with a 15-μg dose of nonadjuvanted vaccine, whereas the GMT increased about 2-fold with MF59 adjuvanted vaccines. In conclusion, a single 7.5-μg dose of MF59 adjuvanted vaccine would have a practical advantage over a two-dose, 3.75-μg, MF59 adjuvanted vaccine priming schedule. Following a two-dose priming schedule, the increase in hemagglutinin inhibition titers was higher with MF59 adjuvanted vaccine than with nonadjuvanted vaccine.
Does Immunotherapy Protect Equines from Reinfection by the Oomycete Pythium insidiosum?
Authors: Santos Carlos E. P. , Marques Luiz C. , Zanette Régis A. , Jesus Francielli P. K. , Santurio Janio M. 
Published: June 2011

ABSTRACTA cutaneousPythium insidiosumreinfection was diagnosed in an equine in Brazil. Lesions with focal presentation appeared 2 years apart. The first infection and even immunotherapy were not likely to develop enough immune response to prevent reinfection. The use of adjuvants should be considered in the immunotherapy of pythiosis.
Immunochromatographic Test with Recombinant Em18 Antigen for the Follow-Up Study of Alveolar Echinococcosis
Authors: Sako Yasuhito , Tappe Dennis , Fukuda Kenta , Kobayashi Yukuharu , Itoh Sonoyo , Frosch Matthias , Grüner Beate , Kern Peter , Ito Akira 
Published: June 2011

ABSTRACTThe performance of a rapid and simple immunochromatographic test (ICT) with recombinant Em18 (rEm18) antigen for serological follow-up ofEchinococcus multilocularisinfection was evaluated by comparison with that of an enzyme-linked immunosorbent assay (ELISA) with rEm18, using serum samples from patients who underwent surgery and/or received antiparasitic chemotherapy. The degree of Em18-band intensity on the ICT correlated highly with the absorbance value obtained by the ELISA. The kinetics of antibody levels obtained by the ICT paralleled those of the ELISA. These data suggest that the ICT has high potential as an easy-to-handle, fast, and reliable follow-up tool to monitor the status of alveolar echinococcosis in different stages.
Diagnosis of Mediterranean Visceral Leishmaniasis by Detection of Leishmania Antibodies and Leishmania DNA in Oral Fluid Samples Collected Using an Oracol Device
Authors: Galaï Yousr , Chabchoub Najla , Ben-Abid Meriem , Ben-Abda Imène , Ben-Alaya-Bouafif Nissaf , Amri Fethi , Aoun Karim , Bouratbine Aïda 
Published: June 2011

ABSTRACT

Current methods for diagnosis of visceral leishmaniasis (VL) require invasive sampling procedures such as visceral aspiration and/or blood drawing. The use of diagnostic tests using oral fluid, which is easier to collect, would be more simple and practical for VL diagnosis, especially under field conditions. Oral fluids from 37 VL patients and 40 healthy controls were collected using Oracol devices. Blood samples and oral fluid specimens from both groups were analyzed by recombinant protein K39 (rK39) enzyme-linked immunosorbent assay and quantitative real-time PCR. Detection of antibodies in the oral fluid had a sensitivity of 100% and a specificity of 97.5%. Antibody levels measured in serum and oral fluid showed a significant positive correlation (ρ = 0.655 and
P
= 0.01). Detection of
Leishmania
DNA in oral fluid had a sensitivity of 94.6% and a specificity of 90%. The median parasite load estimated in blood was 133 parasites/ml (interquartile range [IR], 10 to 1,048), whereas that in oral fluid specimens was 3 parasites/ml (IR, 0.41 to 92). However, there was no significant linear relationship between parasite loads assessed in the two biological samples (ρ = 0.31 and
P
= 0.06). VL diagnosis based on specific antibody detection and
Leishmania
DNA identification using oral fluid samples was equivalent in accuracy to that using blood and therefore is promising for clinical use.
First Three Reported Cases of Nosocomial Fungemia Caused by Candida auris
Authors: Lee Wee Gyo , Shin Jong Hee , Uh Young , Kang Min Gu , Kim Soo Hyun , Park Kyung Hwa , Jang Hee-Chang 
Published: June 2011

ABSTRACT

Candida auris
is a newly described species whose clinical significance is not clear. Here, we describe the first three cases of nosocomial fungemia caused by
C. auris
, which confirms that it is a causative agent of bloodstream infections. All three patients presented persistent fungemia for 10 to 31 days. The isolates obtained from the three patients were misidentified as
Candida haemulonii
and
Rhodotorula glutinis
by the Vitek 2 and the API 20C systems, respectively.
C. auris
was confirmed by sequence analysis of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. The MIC ranges of amphotericin B (AMB), fluconazole (FLU), itraconazole, and voriconazole were 0.5 to 1, 2 to 128, 0.125 to 2, and 0.06 to 1 μg/ml, respectively. All isolates were susceptible to caspofungin (MIC = 0.06 μg/ml) and micafungin (MIC = 0.03 μg/ml). One patient developed breakthrough fungemia while receiving FLU therapy, and two patients who received FLU therapy followed by AMB showed therapeutic failure and fatal outcomes. Our cases show that
C. auris
fungemia can be persistent, despite FLU or AMB therapy, which emphasizes the importance of accurately identifying this species.
Prototype Foamy Virus Gag Nuclear Localization: a Novel Pathway among Retroviruses
Authors: Müllers Erik , Stirnnagel Kristin , Kaulfuss Sylvia , Lindemann Dirk 
Published: June 2011

ABSTRACT

Gag nuclear localization has long been recognized as a hallmark of foamy virus (FV) infection. Two required motifs, a chromatin-binding site (CBS) and a nuclear localization signal (NLS), both located in glycine-arginine-rich box II (GRII), have been described. However, the underlying mechanisms of Gag nuclear translocation are largely unknown. We analyzed prototype FV (PFV) Gag nuclear localization using a novel live-cell fluorescence microscopy assay. Furthermore, we characterized the nuclear localization route of Gag mutants tagged with the simian vacuolating virus 40-NLS (SV40-NLS) and also dissected the respective contributions of the CBS and the NLS. We found that PFV Gag does not translocate to the nucleus of interphase cells by NLS-mediated nuclear import and does not possess a functional NLS. PFV Gag nuclear localization occurred only by tethering to chromatin during mitosis. This mechanism was found for endogenously expressed Gag as well as for Gag delivered by infecting viral particles. Thereby, the CBS was absolutely essential, while the NLS was dispensable. Gag CBS-dependent nuclear localization was neither essential for infectivity nor necessary for Pol encapsidation. Interestingly, Gag localization was independent of the presence of Pol, Env, and viral RNA. The addition of a heterologous SV40-NLS resulted in the nuclear import of PFV Gag in interphase cells, rescued the nuclear localization deficiency but not the infectivity defect of a PFV Gag ΔGRII mutant, and did not enhance FV's ability to infect G
1
/S-phase-arrested cells. Thus, PFV Gag nuclear localization follows a novel pathway among orthoretroviral Gag proteins.
Structural Analysis of Histo-Blood Group Antigen Binding Specificity in a Norovirus GII.4 Epidemic Variant: Implications for Epochal Evolution
Authors: Shanker Sreejesh , Choi Jae-Mun , Sankaran Banumathi , Atmar Robert L. , Estes Mary K. , Prasad B. V. Venkataram 
Published: June 2011

ABSTRACT
Susceptibility to norovirus (NoV), a major pathogen of epidemic gastroenteritis, is associated with histo-blood group antigens (HBGAs), which are also cell attachment factors for this virus. GII.4 NoV strains are predominantly associated with worldwide NoV epidemics with a periodic emergence of new variants. The sequence variations in the surface-exposed P domain of the capsid protein resulting in differential HBGA binding patterns and antigenicity are suggested to drive GII.4 epochal evolution. To understand how temporal sequence variations affect the P domain structure and contribute to epochal evolution, we determined the P domain structure of a 2004 variant with ABH and secretor Lewis HBGAs and compared it with the previously determined structure of a 1996 variant. We show that temporal sequence variations do not affect the binding of monofucosyl ABH HBGAs but that they can modulate the binding strength of difucosyl Lewis HBGAs and thus could contribute to epochal evolution by the potentiated targeting of new variants to Lewis-positive, secretor-positive individuals. The temporal variations also result in significant differences in the electrostatic landscapes, likely reflecting antigenic variations. The proximity of some of these changes to the HBGA binding sites suggests the possibility of a coordinated interplay between antigenicity and HBGA binding in epochal evolution. From the observation that the regions involved in the formation of the HBGA binding sites can be conformationally flexible, we suggest a plausible mechanism for how norovirus disassociates from salivary mucin-linked HBGA before reassociating with HBGAs linked to intestinal epithelial cells during its passage through the gastrointestinal tract.
Gene N Proximal and Distal RNA Motifs Regulate Coronavirus Nucleocapsid mRNA Transcription
Authors: Mateos-Gómez Pedro A. , Zuñiga Sonia , Palacio Lorena , Enjuanes Luis , Sola Isabel 
Published: June 2011

ABSTRACT
Coronavirus subgenomic mRNA (sgmRNA) transcription requires a discontinuous RNA synthesis mechanism driven by the transcription-regulating sequences (TRSs), located at the 3′ end of the genomic leader (TRS-L) and also preceding each gene (TRS-B). In transmissible gastroenteritis virus (TGEV), the free energy of TRS-L and cTRS-B (complement of TRS-B) duplex formation is one of the factors regulating the transcription of sgmRNAs. In addition, N gene sgmRNA transcription is controlled by a transcription-regulating motif, including a long-distance RNA-RNA interaction between complementary proximal and distal elements. The extension of complementarity between these two sequences increased N gene transcription. An active domain, a novel essential component of the transcription-regulating motif, has been identified. The active domain primary sequence was necessary for its activity. Relocation of the active domain upstream of the N gene TRS core sequence in the absence of the proximal and distal elements also enhanced sgmRNA N transcription. According to the proposed working model for N gene transcriptional activation, the long-distance RNA-RNA interaction relocates the distant active domain in close proximity with the N gene TRS, which probably increases the frequency of template switching during the synthesis of negative RNA. The transcription-regulating motif has been optimized to a minimal sequence showing a 4-fold activity increase in relation to the native RNA motif. Full-length TGEV infectious viruses were generated with the optimized transcription-regulating motif, which enhanced by 5-fold the transcription of the 3a gene and can be used in expression vectors based in coronavirus genomes.