bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistence of Genital Tract T Cell Responses in HIV-Infected Women on Highly Active Antiretroviral Therapy
Authors: Mkhize Nonhlanhla N. , Gumbi Pamela P. , Liebenberg Lenine J. , Ren Yuan , Smith Peter , Denny Lynette , Passmore Jo-Ann S. 
Published: August 2010

ABSTRACTInitiation of highly active antiretroviral therapy (HAART) for HIV-infected individuals is associated with control of viremia, improved CD4 counts, and declining systemic HIV-specific immune responses. While HAART effectively reduces plasma viremia, it remains unclear how effectively antiretroviral drugs reach mucosal surfaces, such as those of the genital tract. The aim of this study was to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV shedding, and HIV-specific T cell responses. Cervical cytobrush and blood specimens were obtained from 35 HIV-infected, HAART-naïve women and 27 women on HAART in order to investigate HIV Gag-specific T cell responses by intracellular gamma interferon (IFN-γ) staining. Interleukin 1β (IL-1β), IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We show that for HIV-infected women, HAART is associated with significantly improved CD4 T cell counts both in blood and at the cervix. While HAART effectively suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in blood were lost, while those at the cervix were preserved.
The Viral Latency-Associated Nuclear Antigen Augments the B-Cell Response to AntigenIn Vivo
Authors: Sin Sang-Hoon , Fakhari Farnaz D. , Dittmer Dirk P. 
Published: August 2010

ABSTRACTGammaherpesviruses, including Kaposi sarcoma-associated herpesvirus (KSHV), establish latency in B cells. We hypothesized that the KSHV latency-associated nuclear antigen (LANA/orf73) provides a selective advantage to infected B cells by driving proliferation in response to antigen. To test this, we used LANA B-cell transgenic mice. Eight days after immunization with antigen without adjuvant, LANA mice had significantly more activated germinal center (GC) B cells (CD19+PNA+CD71+) than controls. This was dependent upon B-cell receptor since LANA did not restore the GC defect of CD19 knockout mice. However, LANA was able to restore the marginal zone defect in CD19 knockout mice.
A gC1qR Prevents White Spot Syndrome Virus Replication in the Freshwater CrayfishPacifastacus leniusculus
Authors: Watthanasurorot Apiruck , Jiravanichpaisal Pikul , Söderhäll Irene , Söderhäll Kenneth 
Published: August 2010

ABSTRACTThe gC1qR/p32 protein is a multiple receptor for several proteins and pathogens. We cloned a gC1qR homologue in a crustacean,Pacifastacus leniusculus, and analyzed the expression ofP. leniusculusC1qR (PlgC1qR) in various tissues. The gC1qR/p32 transcript was significantly enhanced by white spot syndrome virus (WSSV) infection 6 h after viral infection bothin vitroin a hematopoietic tissue cell culture (Hpt) andin vivocompared to appropriate controls. Moreover,PlgC1qRsilencing in both the Hpt cell culture and live crayfish enhanced the WSSV replication. In addition, by making a recombinantPlgC1qR protein we could show that if this recombinant protein was injected in a crayfish,Pacifastacus leniusculus, followed by injection of WSSV, this significantly reduced viral replicationin vivo. Furthermore, if the recombinantPlgC1qR was incubated with Hpt cells and then WSSV was added, this also reduced viral replication. These experiments clearly demonstrate that recombinantPlgC1qR reduce WSSV replication bothin vivoandin vitro. The results from a far-Western overlay and glutathioneS-transferase pull-down assays showed thatPlgC1qRcould bind to VP15, VP26, and VP28. Altogether, these results demonstrate a role forPlgC1qR in antiviral activity against WSSV.
Inactivation and Disassembly of the Anaphase-Promoting Complex during Human Cytomegalovirus Infection Is Associated with Degradation of the APC5 and APC4 Subunits and Does Not Require UL97-Mediated Phosphorylation of Cdh1
Authors: Tran Karen , Kamil Jeremy P. , Coen Donald M. , Spector Deborah H. 
Published: August 2010

ABSTRACT

Infection of quiescent cells by human cytomegalovirus (HCMV) elicits severe cell cycle deregulation, resulting in a G
1
/S arrest, which can be partly attributed to the inactivation of the anaphase-promoting complex (APC). As we previously reported, the premature phosphorylation of its coactivator Cdh1 and/or the dissociation of the core complex can account for the inactivation. We have expanded on these results and further delineated the key components required for disabling the APC during HCMV infection. The viral protein kinase UL97 was hypothesized to phosphorylate Cdh1, and consistent with this, phosphatase assays utilizing a virus with a UL97 deletion mutation (ΔUL97 virus) indicated that Cdh1 is hypophosphorylated at early times in the infection. Mass spectrometry analysis demonstrated that UL97 can phosphorylate Cdh1
in vitro
, and the majority of the sites identified correlated with previously characterized cyclin-dependent kinase (Cdk) consensus sites. Analysis of the APC core complex during ΔUL97 virus infection showed APC dissociation occurring at the same time as during infection with wild-type virus, suggesting that the UL97-mediated phosphorylation of Cdh1 is not required for this to occur. Further investigation of the APC subunits showed a proteasome-dependent loss of the APC5 and APC4 subunits that was temporally associated with the disassembly of the APC. Immediate early viral gene expression was not sufficient for the degradation of APC4 and APC5, indicating that a viral early gene product(s), possibly in association with a
de novo
-synthesized cellular protein(s), is involved.
Simian Immunodeficiency Virus-Specific CD8+T Cells Recognize Vpr- and Rev-Derived Epitopes Early after Infection
Authors: Sacha Jonah B. , Buechler Matthew B. , Newman Laura P. , Reed Jason , Wallace Lyle T. , Loffredo John T. , Wilson Nancy A. , Watkins David I. 
Published: August 2010

ABSTRACTThe kinetics of CD8+T cell epitope presentation contribute to the antiviral efficacy of these cells yet remain poorly defined. Here, we demonstrate presentation of virion-derived Vpr peptide epitopes early after viral penetration and prior to presentation of Vif-derived epitopes, which requiredde novoVif synthesis. Two Rev epitopes exhibited differential presentation kinetics, with one Rev epitope presented within 1 h of infection. We also demonstrate that cytolytic activity mirrors the recognition kinetics of infected cells. These studies show for the first time that Vpr- and Rev-specific CD8+T cells recognize and kill simian immunodeficiency virus (SIV)-infected CD4+T cells early after SIV infection.
Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model
Authors: Kaida Sachiko , Cabral Horacio , Kumagai Michiaki , Kishimura Akihiro , Terada Yasuko , Sekino Masaki , Aoki Ichio , Nishiyama Nobuhiro , Tani Toru , Kataoka Kazunori 
Published: August 2010

Abstract
Nanoparticle therapeutics are promising platforms for cancer therapy. However, it remains a formidable challenge to assess their distribution and clinical efficacy for therapeutic applications. Here, by using multifunctional polymeric micellar nanocarriers incorporating clinically approved gadolinium (Gd)–based magnetic resonance imaging contrast agents and platinum (Pt) anticancer drugs through reversible metal chelation of Pt, simultaneous imaging and therapy of an orthotopic animal model of intractable human pancreatic tumor was successfully performed without any serious toxicity. The strong tumor contrast enhancement achieved by the micelles correlated with the 24 times increase of r1 of the Gd chelates, the highest for the formulations using clinically approved Gd chelates reported to date. From the micro-synchrotron radiation X-ray fluorescence spectrometry scanning of the lesions, we confirmed that both the Gd chelates and Pt drugs delivered by the micelles selectively colocalized in the tumor interior. Our study provides new insights for the design of theranostic micelles with high contrast enhancement and site-specific clinical potential. Cancer Res; 70(18); 7031–41. ©2010 AACR.
Characteristic brain magnetic resonance imaging abnormalities in central nervous system aquaporin-4 autoimmunity
Authors: Kim Woojun , Min Su Park  , Sang Hyun Lee  , Kim Su-Hyun , In Ja Jung  , Takahashi Toshiyuki , Misu Tatsuro , Fujihara Kazuo , Ho Jin Kim  
Published: August 2010

Background: Although neuromyelitis optica has been traditionally regarded as a disease without brain involvement, brain abnormalities are not uncommon in patients with neuromyelitis optica-related disorders. Methods: We aimed to characterize the brain magnetic resonance imaging (MRI) abnormalities in neuromyelitis optica spectrum disorder patients who are seropositive for anti-aquaporin-4 autoantibody (AQP4 Ab). Of 236 consecutive patients with inflammatory demyelinating central nervous system diseases, we retrospectively analyzed MRI characteristics of 78 patients who were seropositive for AQP4 Ab. Results: For an average observational period of 6.3 years, 62 patients (79%) had brain lesions on MRI. Twenty-four patients (31%) had brain MRI abnormalities at the onset of disease, and 35 (45%) had symptomatic brain involvement. Characteristic brain MRI abnormalities were classified into five categories: (1) lesions involving corticospinal tracts (e.g. posterior limb of internal capsule and cerebral peduncle (44%); (2) extensive hemispheric lesions likely due to vasogenic edema (29%); (3) periependymal lesions surrounding aqueduct and the third and fourth ventricles (22%); (4) periependymal lesions surrounding lateral ventricles (40%); and (5) medullary lesions, often contiguous with cervical lesions (31%). Fifty-four patients (69%) showed at least one kind of brain abnormality among the five characteristic MRI lesions. Ten patients showed gadolinium-enhancing lesions, which were characterized by multiple patchy enhancing patterns with blurred margins. Conclusions: In central nervous system AQP4 autoimmunity, brain MRI abnormalities were more common than is generally appreciated and were characterized by their unique localization and configuration.
Muscle fiber size increases following resistance training in multiple sclerosis
Authors: Dalgas U , Stenager E , Jakobsen J , Petersen T , Overgaard K , Ingemann-Hansen T 
Published: August 2010

Objective: To test the hypothesis that lower body progressive resistance training (PRT) leads to an increase of the muscle fiber cross-sectional area (CSA) and a shift in the proportion of fiber types in patients with multiple sclerosis (MS). Methods: The present study was a two-arm, randomized controlled trial (RCT). Thirty-eight MS patients (Expanded Disability Status Scale (EDSS) 3—5.5) were randomized to a PRT group (Exercise, n = 19) or a control group (Control, n = 19). The Exercise group performed a biweekly 12-week lower body PRT program [five exercises progressing from 15RM (Repetition Maximum) towards 8RM], whereas the Control group maintained their usual daily activity level during the trial period. Muscle biopsies from vastus lateralis were taken before (pre) and after the trial (post). Thigh volume (TV) was estimated from anthropometric measurements. Isokinetic muscle strength of the knee extensors (KE) and flexors (KF) were evaluated at slow (90°/s) and fast (180°/s) angular velocities. Results: In the Exercise group the mean CSA of all muscle fibers (7.9 ± 15.4% vs. -3.5 ± 9.0%, p = 0.03) and of type II muscle fibers (14.0 ± 19.4% vs. -2.6 ± 15.5%, p = 0.02) increased in comparison with the Control group. No changes occurred in the proportion of fiber types in the Exercise group. Neither was there any change in total TV. Isokinetic strength at KE180, KF90 and KF180 improved significantly after PRT when compared with the control group (10.2—21.3%, p ≤ 0.02). Conclusions: We conclude that progressive resistance training induces a compensatory increase of muscle fiber size in patients with the central nervous system disorder, multiple sclerosis.
Inhibition of erythropoiesis in malaria anemia: role of hemozoin and hemozoin-generated 4-hydroxynonenal
Authors: Skorokhod Oleksii A. , Caione Luisa , Marrocco Tiziana , Migliardi Giorgia , Barrera Valentina , Arese Paolo , Piacibello Wanda , Schwarzer Evelin 
Published: August 2010

Abstract
Severe malaria anemia is characterized by inhibited/altered erythropoiesis and presence of hemozoin-(HZ)-laden bone-marrow macrophages. HZ mediates peroxidation of unsaturated fatty acids and production of bioactive aldehydes such as 4-hydroxynonenal (HNE). HZ-laden human monocytes inhibited growth of cocultivated human erythroid cells and produced HNE that diffused to adjacent cells generating HNE-protein adducts. Cocultivation with HZ or treatment with low micromolar HNE inhibited growth of erythroid cells interfering with cell cycle without apoptosis. After HZ/HNE treatment, 2 critical proteins in cell-cycle regulation, p53 and p21, were increased and the retinoblastoma protein, central regulator of G1-to-S-phase transition, was con-sequently hypophosphorylated, while GATA-1, master transcription factor in erythropoiesis was reduced. The resultant decreased expression of cyclin A and D2 retarded cell-cycle progression in erythroid cells and the K562 cell line. As a second major effect, HZ and HNE inhibited protein expression of crucial receptors (R): transferrinR1, stem cell factorR, interleukin-3R, and erythropoietinR. The reduced receptor expression and the impaired cell-cycle activity decreased the production of cells expressing glycophorin-A and hemoglobin. Present data confirm the inhibitory role of HZ, identify HNE as one HZ-generated inhibitory molecule and describe molecular targets of HNE in erythroid progenitors possibly involved in erythropoiesis inhibition in malaria anemia.
How I treat patients with thrombotic thrombocytopenic purpura: 2010
Authors: George James N. 
Published: August 2010

AbstractThrombotic thrombocytopenic purpura (TTP) is the common name for adults with microangiopathic hemolytic anemia, thrombocytopenia, with or without neurologic or renal abnormalities, and without another etiology; children without renal failure are also described as TTP. The diagnosis of TTP is an indication for plasma exchange treatment, but beginning treatment requires sufficient confidence in the diagnosis to justify the risk of plasma exchange complications. Documentation of a severe deficiency of plasma ADAMTS13 activity, defined as less than 10% of normal, is not essential for the diagnosis of TTP. Some patients without severe ADAMTS13 deficiency may benefit from plasma exchange treatment; in addition, some patients with severe ADAMTS13 deficiency may subsequently be diagnosed with another cause for their clinical features. However, severe acquired ADAMTS13 deficiency does define a subgroup of patients who appear to benefit from treatment with corticosteroids and other immunosuppressive agents in addition to plasma exchange but who have a high risk for relapse. Approximately 80% of patients survive their acute episode, a survival rate that has not changed since the introduction of plasma exchange treatment. Although recovery may appear to be complete, many patients have persistent minor cognitive abnormalities. More effective as well as safer treatment for TTP is needed.
Octamer-binding factor 6 (Oct-6/Pou3f1) is induced by interferon and contributes to dsRNA-mediated transcriptional responses
Authors: Hofmann Elisabeth , Reichart Ursula , Gausterer Christian , Guelly Christian , Meijer Dies , Müller Mathias , Strobl Birgit 
Published: August 2010

AbstractBackgroundOctamer-binding factor 6 (Oct-6, Pou3f1, SCIP, Tst-1) is a transcription factor of the Pit-Oct-Unc (POU) family. POU proteins regulate key developmental processes and have been identified from a diverse range of species. Oct-6 expression is described to be confined to the developing brain, Schwann cells, oligodendrocyte precursors, testes, and skin. Its function is primarily characterised in Schwann cells, where it is required for correctly timed transition to the myelinating state. In the present study, we report that Oct-6 is an interferon (IFN)-inducible protein and show for the first time expression in murine fibroblasts and macrophages.ResultsOct-6 was induced by type I and type II IFN, but not by interleukin-6. Induction of Oct-6 after IFNβ treatment was mainly dependent on signal transducer and activator of transcription 1 (Stat1) and partially on tyrosine kinase 2 (Tyk2). Chromatin immunopreciptitation experiments revealed binding of Stat1 to the Oct-6 promoter in a region around 500 bp upstream of the transcription start site, a region different from the downstream regulatory element involved in Schwann cell-specific Oct-6 expression. Oct-6 was also induced by dsRNA treatment and during viral infections, in both casesviaautocrine/paracrine actions of IFNα/β. Using microarray and RT-qPCR, we furthermore show that Oct-6 is involved in the regulation of transcriptional responses to dsRNA, in particular in the gene regulation of serine/threonine protein kinase 40 (Stk40) and U7 snRNA-associated Sm-like protein Lsm10 (Lsm10).ConclusionOur data show that Oct-6 expression is not as restricted as previously assumed. Induction of Oct-6 by IFNs and viruses in at least two different cell types, and involvement of Oct-6 in gene regulation after dsRNA treatment, suggest novel functions of Oct-6 in innate immune responses.
MLTreeMap - accurate Maximum Likelihood placement of environmental DNA sequences into taxonomic and functional reference phylogenies
Authors: Stark Manuel , Berger Simon A , Stamatakis Alexandros , von Mering Christian 
Published: August 2010

Abstract

Background
Shotgun sequencing of environmental DNA is an essential technique for characterizing uncultivated microbes in situ. However, the taxonomic and functional assignment of the obtained sequence fragments remains a pressing problem.

Results
Existing algorithms are largely optimized for speed and coverage; in contrast, we present here a software framework that focuses on a restricted set of informative gene families, using Maximum Likelihood to assign these with the best possible accuracy. This framework ('MLTreeMap'; http://mltreemap.org/) uses raw nucleotide sequences as input, and includes hand-curated, extensible reference information.

Conclusions
We discuss how we validated our pipeline using complete genomes as well as simulated and actual environmental sequences.
Recurrent advanced colonic cancer occurring 11 years after initial endoscopic piecemeal resection: a case report
Authors: Kishino Takayoshi , Matsuda Takahisa , Sakamoto Taku , Nakajima Takeshi , Taniguchi Hirokazu , Yamamoto Seiichiro , Saito Yutaka 
Published: August 2010

Abstract

Background
The high frequency of local recurrence occurring after endoscopic piecemeal resection (EPMR) for large colorectal tumors is a serious problem. However, almost all of these cases of local recurrence can be detected within 1 year and cured by additional endoscopic resection. We report a rare case of recurrent advanced colonic cancer diagnosed 11 years after initial EPMR treatment.

Case presentation
A 65-year-old male was diagnosed with a sigmoid colon lesion following a routine health check-up. Total colonoscopy revealed a 12 mm type 0-Is lesion in the sigmoid colon, which was diagnosed as an adenoma or intramucosal cancer and treated by EPMR in 1996. The post-resection defect was closed completely using metallic endoclips to avoid delayed bleeding. In 2007, at the third follow up, colonoscopy revealed a 20 mm submucosal tumor (SMT) like recurrence at the site of the previous EPMR. The recurrent lesion was treated by laparoscopic assisted sigmoidectomy with lymph node dissection.

Conclusion
When it is difficult to evaluate the depth and margins of resected tumors following EPMR, it is important that the defect is not closed in order to avoid tumor implantation, missing residual lesions and to enable earlier detection of recurrence. It is crucial that the optimal follow-up protocol for EPMR cases is clarified, particularly how often and for how long they should be followed.
Population screening for glucose-6-phosphate dehydrogenase deficiencies in Isabel Province, Solomon Islands, using a modified enzyme assay on filter paper dried bloodspots
Authors: Kuwahata Melissa , Wijesinghe Rushika , Ho Mei-Fong , Pelecanos Anita , Bobogare Albino , Landry Losi , Bugora Hugo , Vallely Andrew , McCarthy James 
Published: August 2010

AbstractBackgroundGlucose-6-phosphate dehydrogenase deficiency poses a significant impediment to primaquine use for the elimination of liver stage infection withPlasmodium vivaxand for gametocyte clearance, because of the risk of life-threatening haemolytic anaemia that can occur in G6PD deficient patients. Although a range of methods for screening G6PD deficiency have been described, almost all require skilled personnel, expensive laboratory equipment, freshly collected blood, and are time consuming; factors that render them unsuitable for mass-screening purposes.MethodsA published WST8/1-methoxy PMS method was adapted to assay G6PD activity in a 96-well format using dried blood spots, and used it to undertake population screening within a malaria survey undertaken in Isabel Province, Solomon Islands. The assay results were compared to a biochemical test and a recently marketed rapid diagnostic test.ResultsComparative testing with biochemical and rapid diagnostic test indicated that results obtained by filter paper assay were accurate providing that blood spots were assayed within 5 days when stored at ambient temperature and 10 days when stored at 4 degrees. Screening of 8541 people from 41 villages in Isabel Province, Solomon Islands revealed the prevalence of G6PD deficiency as defined by enzyme activity < 30% of normal control was 20.3% and a prevalence of severe deficiency that would predispose to primaquine-induced hemolysis (WHO Class I-II) of 6.9%.ConclusionsThe assay enabled simple and quick semi-quantitative population screening in a malaria-endemic region. The study indicated a high prevalence of G6PD deficiency in Isabel Province and highlights the critical need to consider G6PD deficiency in the context ofP. vivaxmalaria elimination strategies in Solomon Islands, particularly in light of the potential role of primaquine mass drug administration.