bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basal and Reovirus-Induced Beta Interferon (IFN-β) and IFN-β-Stimulated Gene Expression Are Cell Type Specific in the Cardiac Protective Response
Authors: Stewart Michael J. , Smoak Kathleen , Blum Mary Ann , Sherry Barbara 
Published: February 2005

ABSTRACTViral myocarditis is an important human disease, with a wide variety of viruses implicated. Cardiac myocytes are not replenished yet are critical for host survival and thus may have a unique response to infection. Previously, we determined that the extent of reovirus induction of beta interferon (IFN-β) and IFN-β-mediated protection in primary cardiac myocyte cultures was inversely correlated with the extent of reovirus-induced cardiac damage in a mouse model. Surprisingly, and in contrast, the IFN-β response did not determine reovirus replication in skeletal muscle cells. Here we compared the IFN-β response in cardiac myocytes to that in primary cardiac fibroblast cultures, a readily replenished cardiac cell type. We compared basal and reovirus-induced expression of IFN-β, IRF-7 (an interferon-stimulated gene [ISG] that further induces IFN-β), and another ISG (561) in the two cell types by using real-time reverse transcription-PCR. Basal IFN-β, IRF-7, and 561 expression was higher in cardiac myocytes than in cardiac fibroblasts. Reovirus T3D induced greater expression of IFN-β in cardiac myocytes than in cardiac fibroblasts but equivalent expression of IRF-7 and 561 in the two cell types (though fold induction for IRF-7 and 561 was higher in fibroblasts than in myocytes because of the differences in basal expression). Interestingly, while reovirus replicated to equivalent titers in cardiac myocytes and cardiac fibroblasts, removal of IFN-β resulted in 10-fold-greater reovirus replication in the fibroblasts than in the myocytes. Together the data suggest that the IFN-β response controls reovirus replication equivalently in the two cell types. In the absence of reovirus-induced IFN-β, however, reovirus replicates to higher titers in cardiac fibroblasts than in cardiac myocytes, suggesting that the higher basal IFN-β and ISG expression in myocytes may play an important protective role.
Immune Tolerance Split between Hepatitis B Virus Precore and Core Proteins
Authors: Chen Margaret , Sällberg Matti , Hughes Janice , Jones Joyce , Guidotti Luca G. , Chisari Francis V. , Billaud Jean-Noel , Milich David R. 
Published: February 2005

ABSTRACTThe function of the hepatitis B virus (HBV) precore or HBeAg is largely unknown because it is not required for viral assembly, infection, or replication. However, the HBeAg does appear to play a role in viral persistence. It has been suggested that the HBeAg may promote HBV chronicity by functioning as an immunoregulatory protein. As a model of chronic HBeAg exposure and to examine the tolerogenic potential of the HBV precore and core (HBcAg) proteins, HBc/HBeAg-transgenic (Tg) mice crossed with T cell receptor (TCR)-Tg mice expressing receptors for the HBc/HBeAgs (i.e., TCR-antigen double-Tg pairs) were produced. This study revealed three phenotypes of HBe/HBcAg-specific T-cell tolerance: (i) profound T-cell tolerance most likely mediated by clonal deletion, (ii) T-cell clonal ignorance, and (iii) nondeletional T-cell tolerance mediated by clonal anergy and dependent on the structure, location, and concentration of the tolerogen. The secreted HBeAg is significantly more efficient than the intracellular HBcAg at eliciting T-cell tolerance. The split T-cell tolerance between the HBeAg and the HBcAg and the clonal heterogeneity of HBc/HBeAg-specific T-cell tolerance may have significant implications for natural HBV infection and especially for precore-negative chronic hepatitis.
Reduced Hepatitis B Virus (HBV)-Specific CD4+T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy
Authors: Chang J. Judy , Wightman Fiona , Bartholomeusz Angeline , Ayres Anna , Kent Stephen J. , Sasadeusz Joseph , Lewin Sharon R. 
Published: February 2005

ABSTRACTFunctional hepatitis B virus (HBV)-specific T cells are significantly diminished in individuals chronically infected with HBV compared to individuals with self-limiting HBV infection or those on anti-HBV therapy. In individuals infected with human immunodeficiency virus type 1 (HIV-1), coinfection with HBV is associated with an increased risk of worsening liver function following antiviral therapy and of more rapid HBV disease progression. Total HBV-specific T-cell responses in subjects with diverse genetic backgrounds were characterized by using a library of 15-mer peptides overlapping by 11 amino acids and spanning all HBV proteins. The magnitude and breadth of CD4+and CD8+T-cell responses to HBV in peripheral blood were examined by flow cytometry to detect gamma interferon production following stimulation with HBV peptide pools. Chronic HBV carriers (n= 34) were studied, including individuals never treated for HBV infection (n= 7), HBV-infected individuals receiving anti-HBV therapy (n= 13), and HIV-1-HBV-coinfected individuals receiving anti-HBV therapy (n= 14). CD4+and CD8+HBV-specific T-cell responses were more frequently detected and the CD8+T-cell responses were of greater magnitude and breadth in subjects on anti-HBV treatment than in untreated chronic HBV carriers. There was a significant inverse correlation between detection of a HBV-specific T-cell response and HBV viral load. HBV-specific CD4+and CD8+T-cell responses were significantly (fivefold) reduced compared with HIV-specific responses. Although, the frequency and breadth of HBV-specific CD8+T-cell responses were comparable in the monoinfected and HIV-1-HBV-coinfected groups, HBV-specific CD4+T-cell responses were significantly reduced in HIV-1-HBV-coinfected individuals. Therefore, HIV-1 infection has a significant and specific effect on HBV-specific T-cell immunity.
Human Cytomegalovirus Tegument Protein ppUL35 Is Important for Viral Replication and Particle Formation
Authors: Schierling Karina , Buser Christopher , Mertens Thomas , Winkler Michael 
Published: February 2005

ABSTRACT
The tegument proteins ppUL35 and ppUL82 (pp71) of human cytomegalovirus (HCMV) physically interact and cooperatively activate the major immediate-early transcription. While an HCMV mutant lacking UL82 displayed a multiplicity of infection (MOI)-dependent growth, the biological significance of ppUL35 has not been addressed so far. We generated a mutant virus with a deletion of the UL35 gene. Using an MOI of 0.1, the progeny virus yield of this mutant was reduced by a factor of 1,000; however, when infected at a low MOI (0.01), the gene was essential. Characterization of the replication cycle showed that the mutant virus had two defects: when virus inoculum was standardized by the amount of viral DNA, a reduced immediate-early gene expression was observed, leading to a strongly delayed expression of lytic genes. A second defect was apparent in the virus assembly, as fewer enveloped particles and no dense bodies were present in cells infected with the mutant virus. However, the particles produced by wild-type and mutant viruses did not show significant ultrastructural differences. These results suggest an important role for ppUL35 in immediate-early gene expression and virus assembly.
Equine Herpesvirus 1 Utilizes a Novel Herpesvirus Entry Receptor
Authors: Frampton Arthur R. , Goins William F. , Cohen Justus B. , von Einem Jens , Osterrieder Nikolaus , O'Callaghan Dennis J. , Glorioso Joseph C. 
Published: February 2005

ABSTRACT
The well-described herpesvirus entry receptors HveA (TNFRSF14), HveB (nectin 2), and HveC (nectin 1) have been shown to mediate the entry of alphaherpesviruses. Our findings showed that the alphaherpesvirus equine herpesvirus 1 (EHV-1) efficiently entered and replicated in CHO-K1 cells that lack the entry receptors HveA, HveB, and HveC, demonstrating that EHV-1 utilizes a unique entry receptor. As with other alphaherpesviruses, efficient EHV-1 entry was dependent on glycoprotein D and cell surface glycosaminoglycans.
Severe Acute Respiratory Syndrome Coronavirus 3a Protein Is a Viral Structural Protein
Authors: Ito Naoto , Mossel Eric C. , Narayanan Krishna , Popov Vsevolod L. , Huang Cheng , Inoue Taisuke , Peters Clarence J. , Makino Shinji 
Published: February 2005

ABSTRACT
The present study showed the association of a severe acute respiratory syndrome coronavirus (SCoV) accessory protein, 3a, with plasma membrane and intracellular SCoV particles in infected cells. 3a protein appeared to undergo posttranslational modifications in infected cells and was incorporated into SCoV particles, establishing that 3a protein was a SCoV structural protein.
Mutational Analysis of Hepatitis C Virus Nonstructural Protein 5A: Potential Role of Differential Phosphorylation in RNA Replication and Identification of a Genetically Flexible Domain
Authors: Appel Nicole , Pietschmann Thomas , Bartenschlager Ralf 
Published: February 2005

ABSTRACT
Nonstructural protein 5A of the hepatitis C virus (HCV) is a highly phosphorylated molecule implicated in multiple interactions with the host cell and most likely involved in RNA replication. Two phosphorylated variants of NS5A have been described, designated according to their apparent molecular masses (in kilodaltons) as p56 and p58, which correspond to the basal and hyperphosphorylated forms, respectively. With the aim of identifying a possible role of NS5A phosphorylation for RNA replication, we performed an extensive mutation analysis of three serine clusters that are involved in phosphorylation and hyperphosphorylation of NS5A. In most cases, alanine substitutions for serine residues in the central cluster 1 that enhanced RNA replication to the highest levels led to a reduction of NS5A hyperphosphorylation. Likewise, several highly adaptive mutations in NS4B, which is also part of the replication complex, resulted in a reduction of NS5A hyperphosphorylation too, arguing that alterations of the NS5A phosphorylation pattern play an important role for RNA replication. On the other hand, a deletion encompassing all highly conserved serine residues in the C-terminal region of NS5A that are involved in basal phosphorylation did not significantly affect RNA replication but reduced formation of p56. This region was found to tolerate even large insertions with only a moderate effect on replication. Based on these results, we propose a model of the role of NS5A phosphorylation in the viral life cycle.
Chimeric Human Immunodeficiency Virus Type 1 Virions That Contain the Simian Immunodeficiency Virus
nef
Gene Are Cyclosporin A Resistant
Authors: Khan Mahfuz , Jin Lingling , Miles Lesa , Bond Vincent C. , Powell Michael D. 
Published: February 2005

ABSTRACT

We have previously shown that human immunodeficiency virus type 1 (HIV-1) virions which have their own
nef
gene deleted and are
trans
complemented to contain HIV-2 or simian immunodeficiency virus (SIV) Nef become resistant to treatment with cyclosporin A. To expand and confirm these studies, we have tested an HIV-1 isolate in which the HIV-1
nef
gene has been replaced by the
nef
gene from SIV in a multiround infectivity assay using more physiologically relevant cell types. Our results confirm that HIV-1 virions that contain SIV
nef
can replicate in a cyclophilin-independent fashion.
Can we evaluate population screening strategies in UK general practice? A pilot randomised controlled trial comparing postal and opportunistic screening for genital chlamydial infection
Authors: Senok Abiola , Wilson Phil , Reid Margaret , Scoular Anne , Craig Neil , McConnachie Alex , Fitzpatrick Bridie , MacDonald Alison 
Published: February 2005

Study objective:To assess whether opportunistic and postal screening strategies forChlamydia trachomatiscan be compared with usual care in a randomised trial in general practice.Design:Feasibility study for a randomised controlled trial.Setting:Three West of Scotland general medical practices: one rural, one urban/deprived, and one urban/affluent.Participants:600 women aged 16–30 years, 200 from each of three participating practices selected at random from a sample of West of Scotland practices that had expressed interest in the study. The women could opt out of the study. Those who did not were randomly assigned to one of three groups: postal screening, opportunistic screening, or usual care.Results:38% (85 of 221) of the approached practices expressed interest in the study. Data were collected successfully from the three participating practices. There were considerable workload implications for staff. Altogether 124 of the 600 women opted out of the study. During the four month study period,55% (81 of 146) of the control group attended their practice but none was offered screening.Some 59% (80 of 136) women in the opportunistic group attended their practice of whom 55% (44 of 80) were offered screening. Of those, 64% (28 of 44) accepted, representing 21% of the opportunistic group. Forty eight per cent (59 of 124) of the postal group returned samples.Conclusion:A randomised controlled trial comparing postal and opportunistic screening for chlamydial infection in general practice is feasible, although resource intensive. There may be problems with generalising from screening trials in which patients may opt out from the offer of screening.
Study of familial Parkinson’s disease in Russia, Uzbekistan, and Zambia
Authors: Atadzhanov M , Zumla A , Mwaba P 
Published: February 2005

Abstract

Objective
The aims of this study were (A) to determine inheritance patterns of familial Parkinson’s disease in three different geographical areas (Russia, Uzbekistan, and Zambia); (B) compare clinical characteristics of familial with sporadic Parkinson’s disease; and (C) assess whether there were ethnic differences in clinical manifestations of the disease.

Methods
Fifty two index cases of familial Parkinson’s disease in Moscow, 55 in Tashkent, and 27 in Lusaka were selected on the basis of the typical clinical features of Parkinson’s disease with a familial history. The sex ratio, transmission patterns, and segregation ratio were determined by pedigree analysis.

Results
Familial Parkinson’s disease was found in all three countries (30 families in Russia, 12 in Uzbekistan, and seven in Zambia), and appeared more common in Russia. Both autosomal dominant and autosomal recessive patterns of inheritance were seen, but autosomal dominance was more common in all countries.

Conclusions
In all three countries men have a higher risk of developing Parkinson’s disease than women and there are ethnic differences in clinical manifestations of the disease. The onset of both familial and sporadic Parkinson’s disease in Zambian patients occurs at a younger age and is associated with slow progression and a benign course, and generally responds well to levodopa treatment.
Modified electrode placement must be recorded when performing 12-lead electrocardiograms
Authors: Jowett N I , Turner A M , Cole A , Jones P A 
Published: February 2005

Abstract

Background
Local observation has suggested that placing limb leads on the torso when recording the standard 12-lead resting electrocardiogram (ECG) has become commonplace. This non-standard modification has the important advantages of ease and speed of application, and in an emergency may be applied with minimal undressing. Limb movement artefact is also reduced. It is believed that ECGs obtained with torso electrodes are interchangeable with standard ECGs and any minor electrocardiographic variations do not affect diagnostic interpretation.

Study design
The study compared 12-lead ECGs in 100 patients during routine electrocardiography, one being taken in the approved way and one taken with modified limb electrodes.

Results
It was found that the use of torso leads produced important amplitude and waveform changes associated with a more vertical and rightward shift of the QRS frontal axis, particularly in those with abnormal standard ECGs. Such changes generated important ECG abnormalities in 36% of patients with normal standard ECGs, suggesting “heart disease of electrocardiographic origin”. In those with abnormal standard ECGs, moving the limb leads to the torso made eight possible myocardial infarcts appear and five inferior infarcts disappeared. Twelve others developed clinically important T wave or QRS frontal axis changes.

Conclusions
It is vital that ECGs should be acquired in the standard way unless there are particular reasons for not doing so, and that any modification of electrode placement must be reported on the ECG itself. Marking the ECG “torso-positioned limb leads” or “non-standard” should alert the clinician to its limitations for clinical or investigative purposes, as any lead adaptation may modify the tracing and could result in misinterpretation.
Identification and functional characterization of a novel 27-bp deletion in the macroglycopeptide-coding region of the GPIBA gene resulting in platelet-type von Willebrand disease
Authors: Othman Maha , Notley Colleen , Lavender Frances Louise , White Helen , Byrne Christopher D. , Lillicrap David , O'Shaughnessy Denise Frances 
Published: February 2005

AbstractInteraction between the platelet glycoprotein Ibα (GPIbα) receptor and its adhesive ligand von Willebrand factor (VWF) has a critical role in the process of hemostasis. Platelet-type von Willebrand disease (PT-VWD) is a rare bleeding disorder that results from gain-of-function mutations in the GPIBA gene. We studied this gene from 5 members of a previously unreported family with a PT-VWD phenotype. We identified a novel in-frame deletion of 27 base pair (bp) in the macroglycopeptide region. This deletion was not found in the unaffected family members or in 50 healthy controls. The patients' platelets expressed normal quantities of GPIb/IX/V complex on their surface and the mutant (Mut) GPIbα was expressed at levels indistinguishable from the wild-type (WT) receptor on the surface of transfected Chinese hamster ovary (CHO) β/IX cells. Analysis of ristocetin-mediated 125I-VWF binding showed that the Mut receptor binds VWF in the absence of ristocetin and displays an increased sensitivity to lower concentrations of the modulator. This is the first report of a gain-of-function mutation in the GPIbα receptor outside the VWF-binding domain in patients with PT-VWD. The mutation provides a molecular basis for the PT-VWD phenotype and supports a role for the macroglycopeptide region in receptor function.
Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo
Authors: Hamasaki Makoto , Hideshima Teru , Tassone Pierfrancesco , Neri Paola , Ishitsuka Kenji , Yasui Hiroshi , Shiraishi Norihiko , Raje Noopur , Kumar Shaji , Picker Donald H. , Jacob Gary S. , Richardson Paul G. , Munshi Nikhil C. , Anderson Kenneth C. 
Published: February 2005

AbstractAzaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine; trade name, Atiprimod) is an orally bioavailable cationic amphiphilic compound that significantly inhibits production of interleukin 6 (IL-6) and inflammation in rat arthritis and autoimmune animal models. We here characterize the effect of atiprimod on human multiple myeloma (MM) cells. Azaspirane significantly inhibited growth and induced caspase-mediated apoptosis in drug-sensitive and drug-resistant MM cell lines, as well as patient MM cells. IL-6, insulin-like growth factor 1 (IGF-1), or adherence of MM cells to bone marrow stromal cells (BMSCs) did not protect against atiprimod-induced apoptosis. Both conventional (dexamethasone, doxorubicin, melphalan) and novel (arsenic trioxide) agents augment apoptosis induced by atiprimod. Azaspirane inhibits signal transducer activator of transcription 3 (STAT3) and a PI3-K (phosphatidylinositol 3-kinase) target (Akt), but not extracellular signal-regulated kinase 1 and 2 (ERK1/2), inhibits phosphorylation triggered by IL-6, and also inhibits inhibitorκBα (IκBα) and nuclear factor κB (NFκB) p65 phosphorylation triggered by tumor necrosis factor α (TNF-α). Of importance, azaspirane inhibits both IL-6 and vascular endothelial growth factor (VEGF) secretion in BMSCs triggered by MM cell binding and also inhibits angiogenesis on human umbilical vein cells (HUVECs). Finally, azaspirane demonstrates in vivo antitumor activity against human MM cell growth in severe combined immunodeficient (SCID) mice. These results, therefore, show that azaspirane both induces MM cell apoptosis and inhibits cytokine secretion in the BM milieu, providing the framework for clinical trials to improve patient outcome in MM.
Impaired base excision repair and accumulation of oxidative base lesions in CD4+ T cells of HIV-infected patients
Authors: Aukrust Pål , Luna Luisa , Ueland Thor , Johansen Rune F. , Müller Fredrik , Frøland Stig S. , Seeberg Erling C. , Bjørås Magnar 
Published: February 2005

AbstractSeveral studies have reported enhanced oxidative stress in patients with HIV infection. An important pathophysiologic consequence of increased oxidative stress is endogenous DNA damage, and the base excision repair pathway is the most important mechanism to withstand such deleterious effects. To investigate the role of base excision repair in HIV infection, we examined 7,8-dihydro-8-oxoguanine (8-oxoG) levels as a marker of oxidative DNA damage and DNA glycosylase activities in CD4+ and CD8+ T cells of HIV-infected patients and controls. These results showed that the HIV-infected patients, particularly those with advanced disease, had increased levels of 8-oxoG in CD4+ T cells and marked declines in DNA glycosylase activity for the repair of oxidative base lesions in these cells. In contrast, CD8+ T cells from HIV-infected patients, with 8-oxoG levels similar to those in healthy controls, showed enhanced capacity to repair oxidative DNA damage. Finally, highly active antiretroviral therapy induced increased glycosylase activity in CD4+ T cells and normalized 8-oxoG levels. This imbalance between the accumulation of oxidative DNA damage and the capacity to repair such lesions in CD4+ T cells may represent a previously unrecognized mechanism involved in the numerical and functional impairment of CD4+ T cells in patients with HIV infection. (Blood. 2005; 105:4730-4735)
Correlation of exhaled breath temperature with bronchial blood flow in asthma
Authors: Paredi Paolo , Kharitonov Sergei A , Barnes Peter J 
Published: February 2005

AbstractIn asthma elevated rates of exhaled breath temperature changes (Δe°T) and bronchial blood flow (Qaw) may be due to increased vascularity of the airway mucosa as a result of inflammation.We investigated the relationship of Δe°T with Qaw and airway inflammation as assessed by exhaled nitric oxide (NO). We also studied the anti-inflammatory and vasoactive effects of inhaled corticosteroid and β2-agonist.Δe°T was confirmed to be elevated (7.27 ± 0.6 Δ°C/s) in 19 asthmatic subjects (mean age ± SEM, 40 ± 6 yr; 6 male, FEV1 74 ± 6 % predicted) compared to 16 normal volunteers (4.23 ± 0.41 Δ°C/s, p < 0.01) (30 ± 2 yr) and was significantly increased after salbutamol inhalation in normal subjects (7.8 ± 0.6 Δ°C/ s, p < 0.05) but not in asthmatic patients. Qaw, measured using an acetylene dilution method was also elevated in patients with asthma compared to normal subjects (49.47 ± 2.06 and 31.56 ± 1.6 μl/ml/min p < 0.01) and correlated with exhaled NO (r = 0.57, p < 0.05) and Δe°T (r = 0.525, p < 0.05). In asthma patients, Qaw was reduced 30 minutes after the inhalation of budesonide 400 μg (21.0 ± 2.3 μl/ml/min, p < 0.05) but was not affected by salbutamol.Δe°T correlates with Qaw and exhaled NO in asthmatic patients and therefore may reflect airway inflammation, as confirmed by the rapid response to steroids.