bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Human Mammary Epithelial Cells Endocytose HIV-1 and Facilitate Viral Infection of CD4
+
T Lymphocytes
Authors: Dorosko Stephanie M. , Connor Ruth I. 
Published: August 2010

ABSTRACT

The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4
+
cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4
+
cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4
+
target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription and integration and productive viral infection. MEC were also tested for the ability to transfer HIV to CD4
+
target cells and to activate resting CD4
+
T cells. Our results demonstrate that MEC express HIV-1 receptor proteins CD4, CCR5, CXCR4, and galactosyl ceramide (GalCer). While no evidence for direct infection of MEC was found, HIV-1 virions were observed in MEC endosomal compartments. Coculture of HIV-exposed MEC resulted in productive infection of activated CD4
+
T cells. In addition, MEC secretions increased HIV-1 replication and proliferation of infected target cells. Overall, our results indicate that MEC are capable of endosomal uptake of HIV-1 and can facilitate virus infection and replication in CD4
+
target cells. These findings suggest that MEC may serve as a viral reservoir for HIV-1 and may enhance infection of CD4
+
T lymphocytes
in vivo
.
The ESEV PDZ-Binding Motif of the Avian Influenza A Virus NS1 Protein Protects Infected Cells from Apoptosis by Directly Targeting Scribble
Authors: Liu Hongbing , Golebiewski Lisa , Dow Eugene C. , Krug Robert M. , Javier Ronald T. , Rice Andrew P. 
Published: August 2010

ABSTRACT

The NS1 protein from influenza A viruses contains a four-amino-acid sequence at its carboxyl terminus that is termed the PDZ-binding motif (PBM). The NS1 PBM is predicted to bind to cellular PDZ proteins and functions as a virulence determinant in infected mice. ESEV is the consensus PBM sequence of avian influenza viruses, while RSKV is the consensus sequence of human viruses. Currently circulating highly pathogenic H5N1 influenza viruses encode an NS1 protein with the ESEV PBM. We identified cellular targets of the avian ESEV PBM and identified molecular mechanisms involved in its function. Using glutathione
S
-transferase (GST) pull-down assays, we found that the ESEV PBM enables NS1 to associate with the PDZ proteins Scribble, Dlg1, MAGI-1, MAGI-2, and MAGI-3. Because Scribble possesses a proapoptotic activity, we investigated the interaction between NS1 and Scribble. The association between NS1 and Scribble is direct and requires the ESEV PBM and two Scribble PDZ domains. We constructed recombinant H3N2 viruses that encode an H6N6 avian virus NS1 protein with either an ESEV or mutant ESEA PBM, allowing an analysis of the ESEV PBM in infections in mammalian cells. The ESEV PBM enhanced viral replication up to 4-fold. In infected cells, NS1 with the ESEV PBM relocalized Scribble into cytoplasmic puncta concentrated in perinuclear regions and also protected cells from apoptosis. In addition, the latter effect was eliminated by small interfering RNA (siRNA)-mediated Scribble depletion. This study shows that one function of the avian ESEV PBM is to reduce apoptosis during infection through disruption of Scribble's proapoptotic function.
Resistance to Rabies Virus Infection Conferred by the PMLIV Isoform
Authors: Blondel Danielle , Kheddache Sabrina , Lahaye Xavier , Dianoux Laurent , Chelbi-Alix Mounira K. 
Published: August 2010

ABSTRACT

Various reports implicate PML and PML nuclear bodies (NBs) in an intrinsic antiviral response targeting diverse cytoplasmic replicating RNA viruses. PML conjugation to the small ubiquitin-like modifier (SUMO) is required for its localization within NBs. PML displays antiviral effects
in vivo
, as PML deficiency renders mice more susceptible to infection with the rhabdovirus vesicular stomatitis virus (VSV). Cells derived from these mice are also more sensitive to infection with rabies virus, another member of the rhabdovirus family. Alternative splicing from a single gene results in the synthesis of several PML isoforms, and these are classified into seven groups, designated PMLI to -VII. We report here that expression of PMLIV or PMLIVa, which is missing exon 5, inhibited viral mRNA and protein synthesis, leading to a reduction in viral replication. However, the expression of other nuclear isoforms (PMLI to -VI) and cytoplasmic PMLVIIb failed to impair viral production. This antiviral effect required PMLIV SUMOylation, as it was not observed with PMLIV 3KR, in which the lysines involved in SUMO conjugation were mutated. Thus, PMLIV and PMLIVa may exert this isoform-specific function through interaction with specific NB protein partners via their common C-terminal region.
Nuclear Factor NF45 Interacts with Viral Proteins of Infectious Bursal Disease Virus and Inhibits Viral Replication
Authors: Stricker Ruth L. O. , Behrens Sven-Erik , Mundt Egbert 
Published: August 2010

ABSTRACTTwo of the central issues in developing new strategies to interfere with viral infections concern the identification of cellular proteins involved in viral replication and/or antiviral measures and the dissection of the underlying molecular mechanisms. To gain initial insight into the role of host proteins in the life cycle of infectious bursal disease virus (IBDV), a double-stranded RNA virus, we examined the cellular nuclear factor 45 (NF45). NF45 was previously indicated to be involved in the replication process of other types of RNA viruses. Interestingly, by performing immunofluorescence studies, we found that in IBDV-infected cells the mainly nuclear NF45 accumulated at the sites of viral replication in the cytoplasm. NF45 was shown to specifically colocalize with the viral RNA-dependent RNA polymerase VP1, the capsid protein VP2, and the ribonucleoprotein VP3. Immunoprecipitation experiments indicated protein-protein associations between NF45 and VP1, VP2, and VP3. Expression of the individual VP3 or the combination of expression of VP1 and VP3 did not result in a cytoplasmic accumulation of NF45, which, among other data, showed that recruitment of the cellular protein in infected cells functionally correlates with the viral replication process. Since small interfering RNA(siRNA)-mediated downregulation of NF45 resulted in an approximately 5-fold increase of virus yield, our study suggests that NF45, by association with viral proteins, is part of a yet-uncharacterized cellular defense mechanism against IBDV infections.
Understanding the experiences of allergy testing: a qualitative study of people with perceived serious allergic disorders
Authors: Burton Christopher , Irshad Tasneem , Sheikh Aziz 
Published: August 2010

Abstract

Purpose
To investigate the experience of patients with perceived severe allergic disorders in obtaining allergen testing.

Design
In-depth interviews with 20 purposively sampled adults and parents of children with, or at perceived risk of, serious allergic problems. Data were analysed thematically, drawing on Frank’s classification of narratives to help interpret patient/carer accounts.

Results
Accounts fell into four main groups: (i) children with anaphylaxis occurring ‘out of the blue’ (ii) children in whom the recognition of severe allergy by professionals was perceived as delayed; (iii) adults with anaphylaxis who adapted; and (iv) adults who remained in search of an answer. Whereas children had eventually been assessed and tested in a specialist clinic, adults had difficulty in obtaining testing, and most—including those for whom current guidelines would recommend testing—had not been tested. Participants incorporated their past experience of testing into narrative accounts, which included current ways of dealing with their allergy. They saw testing as only one component of appropriate allergy management which required interpretive expertise in professionals who ordered tests. Despite the limitations in NHS allergy testing provision, there was relatively little interest among patients/carers in using complementary and alternative providers of allergy testing.

Conclusions
Patients perceived major shortfalls in relation to NHS allergy testing provision, focusing on both the availability of testing and expertise in interpreting the results. Any increased provision of testing needs to be matched by access to specialist interpretation of these tests.
Tumor Regression and Curability of Preclinical Neuroblastoma Models by PEGylated SN38 (EZN-2208), a Novel Topoisomerase I Inhibitor
Authors: Pastorino Fabio , Loi Monica , Sapra Puja , Becherini Pamela , Cilli Michele , Emionite Laura , Ribatti Domenico , Greenberger Lee M. , Horak Ivan D. , Ponzoni Mirco 
Published: August 2010

AbstractPurpose: Treatment of neuroblastoma is successful in less than half of patients with high-risk disease. The antitumor activity of a water soluble pegylated SN38 drug conjugate, EZN-2208, was compared with CPT-11 (a prodrug for SN38) in preclinical models of human neuroblastoma.Experimental Design: The in vitro cytotoxicity of EZN-2208 was tested by counting trypan blue dye– and Annexin V–positive cells, whereas its therapeutic efficacy was evaluated, in terms of survival, and antitumor and antiangiogenic activities, in s.c. luciferase-transfected, pseudometastatic, and orthotopic neuroblastoma animal models.Results: EZN-2208 was about 100-fold more potent than CPT-11 in vitro, by inducing apoptosis/necrosis and p53 expression and by reducing hypoxia-inducible factor (HIF)-1α/HIF-2α expression. EZN-2208 gave superior antitumor effects compared with CPT-11 in neuroblastoma xenografts. EZN-2208 treatment always resulted in lack of tumor detection at the end of trials whereas only small therapeutic effects were observed with CPT-11, as assessed by luciferase assay or tumor size, or even by staining histologic sections of tumors with antibodies recognizing neuroblastoma cells and cell proliferation. In a neuroblastoma model resistant to doxorubicin, cisplatin, vincristine, fenretinide, and topotecan, EZN-2208 induced 100% curability. It also blocked tumor relapse after topotecan-vincristine-doxorubicin combined treatment. Mechanistic experiments showed statistically significantly enhanced terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and Histone H2ax staining as well as decreased vascular endothelial growth factor, CD31, matrix metalloproteinase (MMP)-2, and MMP-9 expression in tumors removed from EZN-2208–treated mice and radiating vessels invading the tumor implanted onto the chorioallantoic membranes.Conclusions: EZN-2208 should be considered a most promising novel antineuroblastoma agent. An ongoing phase I study in pediatric patients should identify the optimal dose for a phase II study. Clin Cancer Res; 16(19); 4809–21. ©2010 AACR.
A randomized controlled trial investigating the effects of craniosacral therapy on pain and heart rate variability in fibromyalgia patients
Authors: Castro-Sánchez Adelaida María , Matarán-Peñarrocha Guillermo A , Sánchez-Labraca Nuria , Quesada-Rubio José Manuel , Granero-Molina José , Moreno-Lorenzo Carmen 
Published: August 2010

Context: Fibromyalgia is a prevalent musculoskeletal disorder associated with widespread mechanical tenderness, fatigue, non-refreshing sleep, depressed mood and pervasive dysfunction of the autonomic nervous system: tachycardia, postural intolerance, Raynaud’s phenomenon and diarrhoea. Objective: To determine the effects of craniosacral therapy on sensitive tender points and heart rate variability in patients with fibromyalgia. Design: A randomized controlled trial. Subjects: Ninety-two patients with fibromyalgia were randomly assigned to an intervention group or placebo group. Interventions: Patients received treatments for 20 weeks. The intervention group underwent a craniosacral therapy protocol and the placebo group received sham treatment with disconnected magnetotherapy equipment. Main measures: Pain intensity levels were determined by evaluating tender points, and heart rate variability was recorded by 24-hour Holter monitoring. Results: After 20 weeks of treatment, the intervention group showed significant reduction in pain at 13 of the 18 tender points ( P < 0.05). Significant differences in temporal standard deviation of RR segments, root mean square deviation of temporal standard deviation of RR segments and clinical global impression of improvement versus baseline values were observed in the intervention group but not in the placebo group. At two months and one year post therapy, the intervention group showed significant differences versus baseline in tender points at left occiput, left-side lower cervical, left epicondyle and left greater trochanter and significant differences in temporal standard deviation of RR segments, root mean square deviation of temporal standard deviation of RR segments and clinical global impression of improvement. Conclusion: Craniosacral therapy improved medium-term pain symptoms in patients with fibromyalgia.
The effect of electrical stimulation in combination with Bobath techniques in the prevention of shoulder subluxation in acute stroke patients
Authors: Fil Ayla , Armutlu Kadriye , Atay Ahmet Ozgur , Kerimoglu Ulku , Elibol Bulent 
Published: August 2010

Objective: To examine the efficiency of electrical stimulation in combination with Bobath techniques in the prevention of inferior and anterior shoulder subluxation in acute stroke patients. Design: A prospective randomized controlled trial. Setting: Intensive care unit and inpatient clinics of neurology in a university hospital. Subjects: Forty-eight patients with acute stroke, divided equally into control and study groups. Intervention: Subjects in both groups were treated in accordance with the Bobath concept during the early hospitalization period. In addition to Bobath techniques, electrical stimulation was also applied to the supraspinatus muscle, mid and posterior portions of the deltoid muscle of patients in the study group. Main measures: Two radiological methods were used to measure the horizontal, vertical and total asymmetry and vertical distance values of the shoulder joint. Motor functions of the arm were evaluated with the Motor Assessment Scale. Results: The hospitalization period was 12.62 ± 2.24 days for the control group and 11.66 ± 1.88 days for the study group. Shoulder subluxation occurred in 9 (37.5%) subjects in the control group, whereas it was not observed in the study group. All shoulder joint displacement values were higher in the control group than in the study group (horizontal asymmetry P = 0.0001, vertical asymmetry P = 0.0001, total asymmetry P = 0.0001, vertical range P = 0.002). Conclusion: Application of electrical stimulation combined with the Bobath approach proved to be efficient in preventing inferior and anterior shoulder subluxation in the acute stages of stroke.
Preoperative Factors Correlating with Prolonged Range of Motion Deficit after Anterior Cruciate Ligament Reconstruction
Authors: Quelard Bénédicte , Sonnery-Cottet Bertrand , Zayni Rachad , Ogassawara Roger , Prost Thierry , Chambat Pierre 
Published: August 2010

Background Impaired postoperative range of motion remains one of the most frequent complications after anterior cruciate ligament reconstruction. Purpose This study was undertaken to determine the preoperative factors associated with prolonged range of motion deficit after anterior cruciate ligament reconstruction. Study Design Cohort study; Level of evidence, 3. Methods Between January 2007 and March 2008, a consecutive series of 217 patients underwent anterior cruciate ligament reconstruction and were reviewed at 6 weeks and 3 months after surgery. In this series, all data of patients who required a further surgery for arthrolysis until December 2009 were studied. Goniometric range of motion measurement was performed the day before surgery and at 6 weeks and 3 months postoperatively. Bone contusions were analyzed on preoperative magnetic resonance imaging (MRI). All MRI scans were performed in the 6 months before surgery. Seven potential risk factors—age, sex, limited preoperative range of motion, meniscal lesions, bone contusion(s), operative delay less than 45 days, and rehabilitation—were assessed using univariate analysis. The correlations between the significant factors previously identified were analyzed further using multivariate logistic regression analysis. Results Limited preoperative range of motion (P < .001), typical bone contusions of the lateral compartment (P < .001), operative delay less than 45 days (P = .003), and female sex (P = .049) were found to be significantly correlated with delayed recovery. The limited preoperative mobility and the presence of typical contusions were strongly correlated (P < .001). In the group of patients who underwent surgery within 45 days, delayed recovery was strongly correlated with limited preoperative mobility (P = .0008) and to the presence of typical contusions (P < .001). Arthrolysis was correlated with delayed range of motion (odds ratio [OR], 8.2; 95% confidence interval [CI], 1.9-50; P =.001) and bone bruise (OR, 7.6; 95% CI, 1.7-46.1; P = .002). Conclusion Preoperative limited range of motion and typical bone bruises of the lateral femoral condyle and tibial plateau are major risk factors for a difficult rehabilitation after anterior cruciate ligament reconstruction.
Prevalence of Nonanatomical Graft Placement in a Series of Failed Anterior Cruciate Ligament Reconstructions
Authors: Marchant Bryant G. , Noyes Frank R. , Barber-Westin Sue D. , Fleckenstein Cassie 
Published: August 2010

Background Anterior cruciate ligament reconstruction employing transtibial tunnel techniques may result in less than ideal femoral and tibial vertical graft placement, with a residual pivot shift and instability symptoms. Hypothesis Nonanatomical graft placement is highly prevalent among knees with failed primary and revision anterior cruciate ligament grafts. Study Design Case series; Level of evidence, 4. Methods A total of 122 consecutive patients presented to the authors’ center with a failed anterior cruciate ligament reconstruction. Radiographs, magnetic resonance imaging, and operative reports were used to define graft placement. Arthroscopic confirmation of graft placement was obtained in 92 knees during subsequent revision surgery. A nonanatomical graft placement was assigned when ≥50% of the graft was outside of the native tibial and femoral insertions. All patients prospectively completed Cincinnati Knee Rating System questionnaires. Results A nonanatomical graft placement occurred in 107 of 122 (88%) knees; 61% of the grafts were entirely on the intercondylar femoral roof, and 35% extended posterior to the anterior cruciate ligament tibial attachment. A transtibial technique had been used in 83%. The mean values for the coronal and sagittal graft placement showed a significantly increased vertical orientation in comparison with a control group (P < .01). Forty-two of the 107 nonanatomical grafts had undergone 1 or more revisions without correction of the misplaced graft tunnels, and these subsequently failed. Conclusion The occurrence of nonanatomical graft placement in primary and revision knees may represent an inadequacy of transtibial tunnel drilling techniques to obtain graft placement within the native femoral and tibial footprints. In revision cases, the prior graft location requires close scrutiny so the new graft tunnels are placed at the native anterior cruciate ligament attachments. Independent drilling of tibial and femoral tunnels is recommended using either 2-incision or anteromedial portal techniques.
Clinical Results of Arthroscopic Single-Bundle Transtibial Posterior Cruciate Ligament Reconstruction
Authors: Kim Young-Mo , Lee Cassandra A. , Matava Matthew J. 
Published: August 2010

Background: Reconstruction of the posterior cruciate ligament has traditionally been performed using an arthroscopically assisted single-bundle transtibial technique. Unfortunately, clinical studies evaluating this procedure are rare. In addition, there are no pooled analyses evaluating the effectiveness of this procedure for isolated posterior cruciate ligament tears. Hypothesis: Patients who undergo arthroscopically assisted, single-bundle, transtibial posterior cruciate ligament reconstruction will exhibit subjective improvement in knee function despite persistent objective knee laxity. Study Design: Systematic review. Methods: A structured literature search was performed to identify those clinical studies assessing the results of an arthroscopically assisted single-bundle transtibial posterior cruciate ligament reconstruction for isolated posterior cruciate ligament tears. The published data meeting the inclusion criteria were systematically reviewed with an emphasis on residual posterior laxity, subjective and objective functional outcome, activity level, patient satisfaction, incidence of osteoarthritis, and postoperative complications. Results: A total of 10 studies were identified that met the inclusion criteria. Mean postoperative instrumented posterior knee laxity varied from 1.96 mm to 5.90 mm, which was considerably improved from preoperative values (range, 8.38-12.3 mm). The range of mean values of the Lysholm knee scores was 81 to 100 points. The overall International Knee Documentation Committee rating was categorized as “normal” or “nearly normal” in 75% of patients and the mean Tegner activity score varied from 4.7 to 6.3 points. Degenerative osteoarthritis was frequently noted at the time of the most recent follow-up. There were few complications reported. Conclusion: Arthroscopically assisted single-bundle transtibial posterior cruciate ligament reconstruction for isolated posterior cruciate ligament tears can improve posterior knee laxity by 1 grade, although this procedure does not reliably restore normal knee stability. Return to recreational and athletic activity was predictable, with 75% of patients exhibiting a normal or nearly normal objective outcome, although degenerative osteoarthritis was not prevented by this procedure.