bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of memory T cells during treatment with interferon‐alpha in patients with chronic hepatitis B
Authors: Sun Bin , Wang Yanjun , Meng Qinghua , Liu Daojie , Dong Peiling , Ding Huiguo , Wu Hao 
Published: July 2010

Aim:  To investigate the association of memory T cell subsets with viral response during treatment with interferon‐alpha (IFN‐α).Methods:  To address this issue, the dynamics of memory T cell subsets was monitored in 57 patients with chronic hepatitis B (CHB) during treatment with pegylated IFN‐α through testing the phenotypes of memory T cells with flowcytometry.Results:  There were clear differences in the phenotypes of these cells during therapy. Memory T cells converted from the major subsets to the minor in the process of treatment with IFN‐α. Patients who presented a response showed significantly higher percentages of CD8+ TEM at 0 and 24 weeks (both P < 0.05), and lower frequency of CD8+ TCM than non‐responders at 0 and 24 weeks (both P < 0.05). Moreover, the average dosage of IFN‐α applied to patients with viral response to treatment was 1.43 ± 0.18 µg/kg, significantly higher than 1.31 ± 0.25 µg/kg in nonresponders (P < 0.01).Conclusions:  The quantity and quality of memory T cell subsets fluctuates during treatment with IFN‐α. High frequency of TEM subsets may be associated with response to treatment with IFN‐α. A better knowledge of mechanisms underlying the response to therapy may be important for development of new immunotherapeutic strategies to increase CD8 T‐cell effectiveness in CHB infection.
Current status of ectopic varices in Japan: Results of a survey by the Japan Society for Portal Hypertension
Authors: Watanabe Norihito , Toyonaga Atsushi , Kojima Seiichiro , Takashimizu Shinji , Oho Kazuhiko , Kokubu Shigehiro , Nakamura Kenji , Hasumi Akitake , Murashima Naoya , Tajiri Takashi 
Published: July 2010

Aim:  The Clinical Research Committee of the Japan Society for Portal Hypertension has conducted a nationwide questionnaire survey to clarify the current status of ectopic varices in Japan.Methods:  A total of 173 cases of ectopic varices were collected.Results:  Duodenal varices were found in 57 cases, and most of them were located in the descending to transverse parts. There were 11 cases of small intestinal varices and 6 cases of colonic varices, whereas 77 patients had rectal varices, accounting for the greatest proportion (44.5%). Other sites of varices were the biliary tract, anastomotic sites, the stoma, and the diaphragm. Liver cirrhosis was the most frequent diseases (80.3%) underlying ectopic varices. It was noted that patients with rectal varices frequently had a history of esophageal varices (94.8%) and received endoscopic treatment (87.0%). The treatments for ectopic varices were as an emergency in 46.5%, elective in 35.4% and prophylactic in 18.2%. In emergency cases, endoscopic therapy was most frequent (67.4%), followed by interventional radiology (IVR; 15.2%), and endoscopy‐IVR combination (6.5%). Elective treatment was performed by endoscopy in 34.3%, IVR in 28.6%, combined endoscopy‐IVR in 5.7%, and surgical operation in 25.7%. The prophylactic treatment was endoscopic in 50.0%, IVR in 33.3%, combined treatments in 11.1%, and prophylactic surgery in none. The change of ectopic varices after treatment was disappearance in 54.9%, remnant in 35.4% and recurrence in 9.7%. The rate of disappearance was significantly lower in rectal varices (40.8%) than in duodenal varices (73.4%). The patient outcome did not differ among the various sites of the lesion.Conslusions:  Current status of ectopic varices in Japan has been clarified by a nationwide questionnaire survey. The authors expect that the pathophysiology of ectopic varices will be further elucidated, and that improved diagnostic modalities and treatment methods are established in the future.
Evaluation of Diagnostic Applications of Monoclonal Antibodies against Avian Influenza H7 Viruses
Authors: Yang Ming , Clavijo Alfonso , Graham Jill , Pasick John , Neufeld James , Berhane Yohannes 
Published: July 2010

ABSTRACT
A panel of monoclonal antibodies (MAbs) was generated from mice immunized with binary ethylenimine (BEI)-inactivated H7N1 (A/TK/ON/18-2/00) virus. Using a dot blot assay, six of seven MAbs reacted with viruses of the H7 subtype, but not with any of the other 15 hemagglutinin (HA) subtypes tested. Four of the seven MAbs reacted with 14 different H7 isolates, indicating that the MAbs binding epitopes are conserved among viruses of the H7 subtype. The binding epitopes of all seven MAbs were conformational and reacted with the HA1 fraction of the HA protein in Western blots under nonreducing conditions. Applications of these MAbs in the development of rapid tests for H7 subtype viruses were evaluated. The MAbs demonstrated reactivity with AI virus H7 antigen in immunofluorescence and immunohistochemistry assays. Monoclonal antibody 3 showed a very strong immunostaining in the formalin-fixed and paraffin-embedded tissue from the H7N3 virus-infected chicken. A double-antibody sandwich (DAS) enzyme-linked immunosorbent assay (ELISA) was developed using two of the MAbs. The DAS ELISA specifically detected all H7 strains tested in this study. A competitive ELISA (cELISA) for the detection of H7-specific antibodies was evaluated using one MAb and BEI-inactivated H7N1 virus as the antigen. All infected birds showed positive antibody responses at 7 days postinfection. The sensitivity of this cELISA was comparable with that of an influenza A nucleoprotein-based cELISA. This panel of MAbs is valuable in the development of various immunoassays.
Toxoplasma gondiiCyclophilin 18 Regulates the Proliferation and Migration of Murine Macrophages and Spleen Cells
Authors: Ibrahim Hany M. , Xuan Xuenan , Nishikawa Yoshifumi 
Published: July 2010

ABSTRACTToxoplasma gondiiis an intracellular parasite that shows a unique capacity to infect a variety of cell types in warm-blooded animals. It can invade and survive well inside immune cells, such as macrophages, that disseminate the parasite around the body because of their migratory properties. The aim of the present study was to evaluate the role ofT. gondiicyclophilin 18 (TgCyp18) in the proliferation and migration of macrophages and spleen cells (mainly T lymphocytes) in order to understand the effects of TgCyp18 on the dynamics of the infection. A high dose of TgCyp18 enhanced the proliferation of macrophages and spleen cells in a cysteine-cysteine chemokine receptor 5 (CCR5)-independent way. In contrast, TgCyp18 controlled the migration of macrophages and spleen cells in dose- and CCR5-dependent manners. Our data suggest that TgCyp18 recruits cells and enhances the growth of host cells at the site of infection for maintenance of the interaction between the parasite and host.
Ex VivoKinetics of Early and Long-Term Multifunctional Human Leukocyte Antigen E-Specific CD8+Cells in Volunteers Immunized with the Ty21a Typhoid Vaccine
Authors: Salerno-Goncalves Rosângela , Wahid Rezwanul , Sztein Marcelo B. 
Published: July 2010

ABSTRACTT cells are likely to play an important role in the host defense againstSalmonella entericaserovar Typhi, the causative agent of typhoid fever. We have shown that HLA-E can function as a restriction element forS. Typhi-specific CD8+T cells. Because of the potential importance of HLA-E-restricted CD8+responses in resistance toSalmonellainfection, we characterized these responses and investigated their kinetics of appearance and persistence in volunteers immunized orally with the licensed attenuated Ty21a strain typhoid vaccine. Cells were obtained from volunteers before and at days 2, 4, 7, 10, 14, 28, 42, 56, 120, 180, 360, and 720 after immunization. Anex vivomulticolor staining panel including antibodies to CD107a and -b, interleukin-2, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) was used to functionally assess memory T-cell subsets by flow cytometry. Increases in cytokine-secreting CD8+cells were observed in the T effector/memory (TEM) and CD45RA+TEM(TEMRA) subsets as early as 4 days after immunization and persisted, particularly in the TEMRAsubset, up to 2 years after immunization. The majority of HLA-E-restricted CD8+cells 28 to 56 days after immunization coexpressed CD107, IFN-γ, and TNF-α, showing characteristic features of multifunctional T cells. In summary, the multifunctionality and longevity of the HLA-E-restricted CD8 responses observed in this study highlight their significance in adaptive immunity toS. Typhi. Finally, this is the first demonstration, in either animals or humans, of the presence of long-term multifunctional HLA-E-restricted CD8+cells after immunization.
Mannheimia
Species Associated with Ovine Mastitis
Authors: Omaleki Lida , Barber Stuart R. , Allen Joanne L. , Browning Glenn F. 
Published: July 2010

ABSTRACT

Mannheimia glucosida
,
M. haemolytica
, and
M. ruminalis
were isolated from cases of acute mastitis in ewes.
M. glucosida
was found to be a common cause of clinical mastitis in sheep. Selected phenotypic tests in addition to genotyping were needed to definitively identify
Mannheimia
species causing ovine mastitis.
Peptide Ligands Selected with CD4-Induced Epitopes on Native Dualtropic HIV-1 Envelope Proteins Mimic Extracellular Coreceptor Domains and Bind to HIV-1 gp120 Independently of Coreceptor Usage
Authors: Dervillez Xavier , Klaukien Volker , Dürr Ralf , Koch Joachim , Kreutz Alexandra , Haarmann Thomas , Stoll Michaela , Lee Donghan , Carlomagno Teresa , Schnierle Barbara , Möbius Kalle , Königs Christoph , Griesinger Christian , Dietrich Ursula 
Published: July 2010

ABSTRACT
During HIV-1 entry, binding of the viral envelope glycoprotein gp120 to the cellular CD4 receptor triggers conformational changes resulting in exposure of new epitopes, the highly conserved CD4-induced (CD4i) epitopes that are essential for subsequent binding to chemokine receptor CCR5 or CXCR4. Due to their functional conservation, CD4i epitopes represent attractive viral targets for HIV-1 entry inhibition. The aim of the present study was to select peptide ligands for CD4i epitopes on native dualtropic (R5X4) HIV-1 envelope (Env) glycoproteins by phage display. Using CD4-activated retroviral particles carrying Env from the R5X4 HIV-1 89.6 strain as the target, we performed screenings of random peptide phage libraries under stringent selection conditions. Selected peptides showed partial identity with amino acids in the extracellular domains of CCR5/CXCR4, including motifs rich in tyrosines and aspartates at the N terminus known to be important for gp120 binding. A synthetic peptide derivative (XD3) corresponding to the most frequently selected phages was optimized for Env binding on peptide arrays. Interestingly, the optimized peptide could bind specifically to gp120 derived from HIV-1 strains with different coreceptor usage, competed with binding of CD4i-specific monoclonal antibody (MAb) 17b, and interfered with entry of both a CCR5 (R5)-tropic and a CXCR4 (X4)-tropic Env pseudotyped virus. This peptide ligand therefore points at unique properties of CD4i epitopes shared by gp120 with different coreceptor usage and could thus serve to provide new insight into the conserved structural details essential for coreceptor binding for further drug development.
Differential Localization and Function of PB1-F2 Derived from Different Strains of Influenza A Virus
Authors: Chen Chi-Jene , Chen Guang-Wu , Wang Ching-Ho , Huang Chih-Heng , Wang Yeau-Ching , Shih Shin-Ru 
Published: July 2010

ABSTRACT
PB1-F2 is a viral protein that is encoded by the PB1 gene of influenza A virus by alternative translation. It varies in length and sequence context among different strains. The present study examines the functions of PB1-F2 proteins derived from various human and avian viruses. While H1N1 PB1-F2 was found to target mitochondria and enhance apoptosis, H5N1 PB1-F2, surprisingly, did not localize specifically to mitochondria and displayed no ability to enhance apoptosis. Introducing Leu into positions 69 (Q69L) and 75 (H75L) in the C terminus of H5N1 PB1-F2 drove 40.7% of the protein to localize to mitochondria compared with the level of mitochondrial localization of wild-type H5N1 PB1-F2, suggesting that a Leu-rich sequence in the C terminus is important for targeting of mitochondria. However, H5N1 PB1-F2 contributes to viral RNP activity, which is responsible for viral RNA replication. Lastly, although the swine-origin influenza virus (S-OIV) contained a truncated form of PB1-F2 (12 amino acids [aa]), potential mutation in the future may enable it to contain a full-length product. Therefore, the functions of this putative S-OIV PB1-F2 (87 aa) were also investigated. Although this PB1-F2 from the mutated S-OIV shares only 54% amino acid sequence identity with that of seasonal H1N1 virus, it also increased viral RNP activity. The plaque size and growth curve of the viruses with and without S-OIV PB1-F2 differed greatly. The PB1-F2 protein has various lengths, amino acid sequences, cellular localizations, and functions in different strains, which result in strain-specific pathogenicity. Such genetic and functional diversities make it flexible and adaptable in maintaining the optimal replication efficiency and virulence for various strains of influenza A virus.
Local Conformational Stability of HIV-1 gp120 in Unliganded and CD4-Bound States as Defined by Amide Hydrogen/Deuterium Exchange
Authors: Kong Leopold , Huang Chih-chin , Coales Stephen J. , Molnar Kathleen S. , Skinner Jeff , Hamuro Yoshitomo , Kwong Peter D. 
Published: July 2010

ABSTRACTThe binding reaction of the HIV-1 gp120 envelope glycoprotein to the CD4 receptor involves exceptional changes in enthalpy and entropy. Crystal structures of gp120 in unliganded and various ligand-bound states, meanwhile, reveal an inner domain able to fold into diverse conformations, a structurally invariant outer domain, and, in the CD4-bound state, a bridging sheet minidomain. These studies, however, provide only hints as to the flexibility of each state. Here we use amide hydrogen/deuterium exchange coupled to mass spectrometry to provide quantifications of local conformational stability for HIV-1 gp120 in unliganded and CD4-bound states. On average, unliganded core gp120 displayed >10,000-fold slower exchange of backbone-amide hydrogens than a theoretically unstructured protein of the same composition, with binding by CD4 reducing the rate of gp120 amide exchange a further 10-fold. For the structurally constant CD4, alterations in exchange correlated well with alterations in binding surface (Pvalue = 0.0004). For the structurally variable gp120, however, reductions in flexibility extended outside the binding surface, and regions of expected high structural diversity (inner domain/bridging sheet) displayed roughly 20-fold more rapid exchange in the unliganded state than regions of low diversity (outer domain). Thus, despite an extraordinary reduction in entropy, neither unliganded gp120 nor free CD4 was substantially unstructured, suggesting that most of the diverse conformations that make up the gp120 unliganded state are reasonably ordered. The results provide a framework for understanding how local conformational stability influences entropic change, conformational diversity, and structural rearrangements in the gp120-CD4 binding reaction.
Bub1 and CENP-F Can Contribute to Kaposi's Sarcoma-Associated Herpesvirus Genome Persistence by Targeting LANA to Kinetochores
Authors: Xiao Bingyi , Verma Subhash C. , Cai Qiliang , Kaul Rajeev , Lu Jie , Saha Abhik , Robertson Erle S. 
Published: July 2010

ABSTRACT

The latency-associated nuclear antigen (LANA) encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) is critical for segregation of viral episomes to progeny nuclei and allows for maintenance of the viral genome in newly divided daughter cells. LANA binds to KSHV terminal repeat (TR) DNA and simultaneously associates with chromatin-bound cellular proteins. This process tethers the viral episomes to host chromosomes. However, the mechanism of tethering is complex and involves multiple protein-protein interactions. Our previous proteomics studies which showed the association of LANA with centromeric protein F (CENP-F) prompted us to further study whether LANA targets centromeric proteins for persistence of KSHV episomes during cell division. Here we show that LANA colocalized with CENP-F as speckles, some of which are paired at centromeric regions of a subset of chromosomes in KSHV-infected JSC-1 cells. We also confirm that both the amino and carboxy termini of LANA can bind to CENP-F. Moreover, LANA associated with another kinetochore protein, Bub1 (budding uninhibited by benzimidazole 1), which is known to form a complex with CENP-F. Importantly, we demonstrated the dynamic association of LANA and Bub1/CENP-F and the colocalization between Bub1, LANA, and the KSHV episome tethered to the host chromosome using fluorescence
in situ
hybridization (FISH). Knockdown of Bub1 expression by lentivirus-delivered short hairpin RNA (shRNA) dramatically reduced the number of KSHV genome copies, whereas no dramatic effect was seen with CENP-F knockdown. Therefore, the interaction between LANA and the kinetochore proteins CENP-F and Bub1 is important for KSHV genome tethering and its segregation to new daughter cells, with Bub1 potentially playing a more critical role in the long-term persistence of the viral genome in the infected cell.
Functional Divergence among CD103+Dendritic Cell Subpopulations following Pulmonary Poxvirus Infection
Authors: Beauchamp Nicole M. , Busick Rhea Y. , Alexander-Miller Martha A. 
Published: July 2010

ABSTRACTA large number of dendritic cell (DC) subsets have now been identified based on the expression of a distinct array of surface markers as well as differences in functional capabilities. More recently, the concept of unique subsets has been extended to the lung, although the functional capabilities of these subsets are only beginning to be explored. Of particular interest are respiratory DCs that express CD103. These cells line the airway and act as sentinels for pathogens that enter the lung, migrating to the draining lymph node, where they add to the already complex array of DC subsets present at this site. Here we assessed the contributions of these individual populations to the generation of a CD8+T-cell response following respiratory infection with poxvirus. We found that CD103+DCs were the most effective antigen-presenting cells (APC) for naive CD8+T-cell activation. Surprisingly, we found no evidence that lymph node-resident or parenchymal DCs could prime virus-specific cells. The increased efficacy of CD103+DCs was associated with the increased presence of viral antigen as well as high levels of maturation markers. Within the CD103+DCs, we observed a population that expressed CD8α. Interestingly, cells bearing CD8α were less competent for T-cell activation than their CD8α−counterparts. These data show that lung-migrating CD103+DCs are the major contributors to CD8+T-cell activation following poxvirus infection. However, the functional capabilities of cells within this population differ with the expression of CD8, suggesting that CD103+cells may be divided further into distinct subsets.
Use of afterload hemodynamic stress as a practical method for assessing cardiac performance in rats with heart failure
Authors: dos Santos Leonardo , Antonio Ednei L. , Souza Ana F.M. , Tucci Paulo J.F. 
Published: July 2010

After myocardial infarction, the hemodynamics under basal conditions might appear to be unaltered, which makes it difficult to identify cardiac dysfunction by the usual approaches. Thus, we tested the response to sudden afterload stress in infarcted rats with apparently normal ejection function. Control (CT) and infarcted (MI) Wistar rats with various MI sizes were submitted to echocardiography 30 days after coronary occlusion, followed by assessment of hemodynamics under basal conditions and during a pharmacologically induced sudden pressure overload (phenylephrine 15−25 µg/kg, i.v.). Coronary occlusion resulted in cardiac remodeling proportional to MI size, although several functional parameters such as systolic pressure (SP), stroke volume (SV), and stroke work (SW) of all MI rats were similar to those of CT rats. However, the afterload stress that was produced led to a relative preservation of SV and an increase of SW in CT rats; MI rats exhibited a significant reduction in SV and SW generation, although global cardiac function was normal under basal conditions, as indicated by regular echocardiography and hemodynamics assessment. Thus, we propose the use of sudden pharmacologically induced afterload stress as a practical and efficient procedure for identifying impaired performance of the heart in anesthetized rats, providing an additional physiological variable to be evaluated in experimental therapeutic studies.
Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity
Authors: Jiang Shih Sheng , Fang Wen-Tsen , Hou Ya-Hsiue , Huang Shiu-Feng , Yen B. Linju , Chang Junn-Liang , Li Shih-Miao , Liu Hui-Ping , Liu Ying-Lan , Huang Chih-Ting , Li Yu-Wei , Jang Te-Hsuan , Chan Shih-Hsuan , Yang Su Jing , Hsiung Chao A. , Wu Cheng-Wen , Wang Lu-Hai , Chang I-Shou 
Published: July 2010

Abstract
Purpose: SOX9 is an important transcription factor required for development and has been implicated in several types of cancer. However, SOX9 has never been linked to lung cancer to date. Here, we show that SOX9 expression is upregulated in lung adenocarcinoma and show how it is associated with cancer cell growth.
Experimental Design: Data mining with five microarray data sets containing 490 clinical samples, quantitative reverse transcription-PCR validation assay in 57 independent samples, and immunohistochemistry assay with tissue microarrays containing 170 lung tissue cores were used to profile SOX9 mRNA and protein expression. Short interference RNA suppression of SOX9 in cell lines was used to scrutinize functional role(s) of SOX9 and associated molecular mechanisms.
Results: SOX9 mRNA and protein were consistently overexpressed in the majority of lung adenocarcinoma. Knockdown of SOX9 in lung adenocarcinoma cell lines resulted in marked decrease of adhesive and anchorage-independent growth in concordance with the upregulation of p21 (CDKN1A) and downregulation of CDK4. In agreement with higher SOX9 expression level in lung adenocarcinoma, the p21 mRNA level was significantly lower in tumors than that in normal tissues, whereas the opposite was true for CDK4, supporting the notion that SOX9 negatively and positively regulated p21 and CDK4, respectively. Finally, whereas SOX9-knockdown cells showed significantly attenuated tumorigenicity in mice, SOX9 transfectants consistently showed markedly stronger tumorigenicity.
Conclusions: Our data suggest that SOX9 is a new hallmark of lung adenocarcinoma, in which SOX9 might contribute to gain of tumor growth potential, possibly acting through affecting the expression of cell cycle regulators p21 and CDK4. Clin Cancer Res; 16(17); 4363–73. ©2010 AACR.