bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of the Nuclear Form of Varicella-Zoster Virus Immediate-Early Protein 63 by Casein Kinase II at Serine 186
Authors: Mueller Niklaus H. , Graf Laurie L. , Orlicky David , Gilden Don , Cohrs Randall J. 
Published: September 2009

ABSTRACT
Varicella-zoster virus (VZV) open reading frame (ORF) 63 is abundantly transcribed in latently infected human ganglia and encodes a 278-amino-acid protein, IE63, with immediate-early kinetics. IE63 is expressed in the cytoplasm of neurons during VZV latency and in both the cytoplasm and the nucleus during productive infection; however, the mechanism(s) involved in IE63 nuclear import and retention has remained unclear. We constructed and identified a recombinant monoclonal antibody to detect a posttranslationally modified form of IE63. Analysis of a series of IE63 truncation and substitution mutants showed that amino acids 186 to 195 are required for antibody binding. Synthetic peptides corresponding to this region identified IE63 S186 as a target for casein kinase II phosphorylation. In addition, acidic charges supplied by E194 and E195 were required for antibody binding. Immunofluorescence analysis of VZV-infected MeWo cells using the recombinant monoclonal antibody detected IE63 exclusively in the nuclei of infected cells, indicating that casein kinase II phosphorylation of S186 occurs in the nucleus and possibly identifying an initial molecular event operative in VZV reactivation.
Multifaceted Sequence-Dependent and -Independent Roles for Reovirus FAST Protein Cytoplasmic Tails in Fusion Pore Formation and Syncytiogenesis
Authors: Barry Christopher , Duncan Roy 
Published: September 2009

ABSTRACT
Fusogenic reoviruses utilize the FAST proteins, a novel family of nonstructural viral membrane fusion proteins, to induce cell-cell fusion and syncytium formation. Unlike the paradigmatic enveloped virus fusion proteins, the FAST proteins position the majority of their mass within and internal to the membrane in which they reside, resulting in extended C-terminal cytoplasmic tails (CTs). Using tail truncations, we demonstrate that the last 8 residues of the 36-residue CT of the avian reovirus p10 FAST protein and the last 20 residues of the 68-residue CT of the reptilian reovirus p14 FAST protein enhance, but are not required for, pore expansion and syncytium formation. Further truncations indicate that the membrane-distal 12 residues of the p10 and 47 residues of the p14 CTs are essential for pore formation and that a residual tail of 21 to 24 residues that includes a conserved, membrane-proximal polybasic region present in all FAST proteins is insufficient to maintain FAST protein fusion activity. Unexpectedly, a reextension of the tail-truncated, nonfusogenic p10 and p14 constructs with scrambled versions of the deleted sequences restored pore formation and syncytiogenesis, while reextensions with heterologous sequences partially restored pore formation but failed to rescue syncytiogenesis. The membrane-distal regions of the FAST protein CTs therefore exert multiple effects on the membrane fusion reaction, serving in both sequence-dependent and sequence-independent manners as positive effectors of pore formation, pore expansion, and syncytiogenesis.
Transcriptional Analysis of the Adeno-Associated Virus Integration Site
Authors: Dutheil Nathalie , Henckaerts Els , Kohlbrenner Erik , Linden R. Michael 
Published: September 2009

ABSTRACTThe nonpathogenic human adeno-associated virus type 2 (AAV-2) has adopted a unique mechanism to site-specifically integrate its genome into the humanMBS85gene, which is embedded inAAVS1on chromosome 19. The fact that AAV has evolved to integrate into this ubiquitously transcribed region and that the chromosomal motifs required for integration are located a few nucleotides upstream of the translation initiation start codon ofMBS85suggests that the transcriptional activity ofMBS85might influence site-specific integration and thus might be involved in the evolution of this mechanism. In order to begin addressing this question, we initiated the characterization of the humanMBS85promoter region and compared its transcriptional activity to that of the AAV-2 p5 promoter. Our results clearly indicate thatAAVS1is defined by a complex transcriptional environment and that theMBS85promoter shares key regulatory elements with the viral p5 promoter. Furthermore, we provide evidence for bidirectionalMBS85promoter activity and demonstrate that the minimal motifs required for AAV site-specific integration are present in the 5′ untranslated region of the gene and play a posttranscriptional role in the regulation ofMBS85expression. These findings should provide a framework to further elucidate the complex interactions between the virus and its cellular host in this unique pathway to latency.
Hemodynamic instability during treatment of intracranial dural arteriovenous fistula and carotid cavernous fistula with Onyx: preliminary results and anesthesia considerations
Authors: Amiridze N , Darwish R 
Published: September 2009

Background and aim9 patients with 10 arteriovenous fistulas were treated with Onyx at our institution over a period of 19 months: 4 direct and indirect carotid–cavernous fistulas (CCFs) and 6 dural arteriovenous fistula (DAVFs). Complete occlusion was achieved with no recurrences or permanent complications in our small series. We report hemodynamic instability, including severe bradycardia and asystole, during embolization of DAVF and CCF with Onyx in several patients. These changes were reversible with interruption of Onyx injection and administration of atropine. No recurrence of symptoms after atropine administration was noted as Onyx embolization continued during the same session or during postprocedural 24 h monitoring. No adverse clinical consequences were noted.ResultsBradycardia was observed in 4 cases, with a brief asystole in 2 of these patients during transarterial and transvenous Onyx delivery at cavernous sinus and orbital levels. Based on our observation, hemodynamic instability was demonstrated during Onyx injection into the vessels that were in close proximity to the trigeminal nerve or its branches, especially in low-flow/low-volume compartment and may represent a direct effect of dimethyl sulfoxide/Onyx on the trigeminal nerve, resulting in vagal response from trigeminocardiac reflex.ConclusionProposed measures to prevent this complication include pretreatment with atropine or prophylactic placement of transvenous pacemakers in patients with underlying heart block and patients with contraindications to atropine use.
DynaCT evaluation of in-stent restenosis following Wingspan stenting of intracranial stenosis
Authors: Moskowitz S I , Kelly M E , Haynes J , Fiorella D 
Published: September 2009

Objective and importanceTo describe the use of DynaCT angiographic imaging for the evaluation of Wingspan in-stent restenosis (ISR).MethodsTwo patients were treated with Wingspan stenting and percutaneous transluminal angioplasty (Patient 1 had treatment of a severe stenosis of the right middle cerebral artery and patient 2 had severe stenosis of the left intracranial internal carotid artery. Both patients developed ISR and were evaluated with high resolution DynaCT angiographic imaging.ResultsDynaCT demonstrated circumferential soft tissue density material distributed within the stent as the cause of the stenosis visualized with conventional angiography.ConclusionsThese findings support the hypothesis that ISR is caused by neointimal proliferation, rather than vascular re-coil with stent collapse.
Reconstruction of the right anterior circulation with the Pipeline embolization device to achieve treatment of a progressively symptomatic, large carotid aneurysm
Authors: Fiorella D , Albuquerque F , Gonzalez F , McDougall C G , Nelson P K 
Published: September 2009

IntroductionWe present the use of the Pipeline embolization device (PED) to achieve reconstruction of the right anterior circulation in a patient with a dolichoectatic internal carotid artery (ICA) and middle cerebral artery (MCA) and an associated symptomatic, large, carotid-ophthalmic segment aneurysm.Clinical presentationA 36-year-old man presented with progressive right eye vision loss followed by sudden severe headache. Subsequent neuroimaging revealed a large right carotid-ophthalmic segment aneurysm and diffuse ectasia of the supraclinoid ICA and proximal MCA. A coil embolization of the aneurysm was performed without stent support. Over the next year, the patient experienced increasing headache and progressive bitemporal vision loss. Serial MRI showed progressive coil compaction and recanalization of the aneurysm.TreatmentThe right anterior circulation was reconstructed with a total of six PEDs that extended from the distal M1 segment of the MCA proximally into the distal cavernous segment of the ICA. Follow-up angiography at 1 and 4 months demonstrated progressive complete occlusion of the aneurysm and a reorganization of blood flow to the anterior cerebral and anterior choroidal arteries. MRI and radiographic imaging provided evidence of progressive contraction of the intra-aneurysmal thrombus. The patient's headaches resolved and serial visual field examinations have demonstrated gradual improvement after treatment.ConclusionExtensive cerebrovascular reconstructions that are not possible using commercially available endovascular devices can be achieved with Pipeline. The safety, efficacy and long term implications of such reconstructions are currently being defined.
An Immersed Boundary Method for the Weather Research and Forecasting Model
Authors: Lundquist Katherine A. , Chow Fotini Katopodes , Lundquist Julie K. 
Published: September 2009

Abstract
This paper describes an immersed boundary method that facilitates the explicit resolution of complex terrain within the Weather Research and Forecasting (WRF) model. Mesoscale models, such as WRF, are increasingly used for high-resolution simulations, particularly in complex terrain, but errors associated with terrain-following coordinates degrade the accuracy of the solution. The use of an alternative-gridding technique, known as an immersed boundary method, alleviates coordinate transformation errors and eliminates restrictions on terrain slope that currently limit mesoscale models to slowly varying terrain. Simulations are presented for canonical cases with shallow terrain slopes, and comparisons between simulations with the native terrain-following coordinates and those using the immersed boundary method show excellent agreement. Validation cases demonstrate the ability of the immersed boundary method to handle both Dirichlet and Neumann boundary conditions. Additionally, realistic surface forcing can be provided at the immersed boundary by atmospheric physics parameterizations, which are modified to include the effects of the immersed terrain. Using the immersed boundary method, the WRF model is capable of simulating highly complex terrain, as demonstrated by a simulation of flow over an urban skyline.
Effects of chronic exposure to DDT and TCDD on disease activity in murine systemic lupus erythematosus
Authors: Li J , McMurray RW 
Published: September 2009

Oestrogens contribute to the female preponderance of autoimmune diseases such as systemic lupus erythematosus (SLE). Environmental xenoestrogens superimposed upon endogenous pituitary-gonadal axis may affect the development of autoimmunity. This study examined the effects of chronic exposure to xenoestrogens – o,p’-dichlorodiphenyltrichloroethane (DDT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on disease activity in the New Zealand Black/New Zealand White F1 hybrid (B/W) mouse model of SLE. Intact female mice had repeatedly received injections of DDT, TCDD or control vehicle since 6 weeks of age. Weight change, albuminuria, mortality, relevant immunological and histological parameters were assessed. DDT exposure markedly increased the incidence of albuminuria and reduced uterine weight but had no measured effects on immunity or mortality in this study. TCDD-exposed mice had significantly lower incidence of albuminuria, serum anti-DNA antibody and total IgG levels, and mortality compared to controls. Also, TCDD group had significantly lower thymic and splenic weights, decreased percentages of CD4+CD8+ thymocytes and splenic CD4+ T cells, increased percentage of splenic B220+sIgM+ B cells and higher serum interferon gamma concentration. Taken together, DDT exposure appeared to accelerate the development of albuminuria in lupus-prone mice. TCDD was immunosuppressive to murine SLE. Xenoestrogens may have compound- and tissue-specific effects that require further elucidation in future work.
Variability and correlates of high sensitivity C-reactive protein in systemic lupus erythematosus
Authors: Nikpour M , Gladman DD , Ibañez D , Urowitz MB 
Published: September 2009

In the general population, high-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is relatively stable over time and independently predicts cardiovascular events. Systemic lupus erythematosus (SLE), a chronic inflammatory disease, is strongly associated with coronary artery disease (CAD). The objective of this study was to determine the variability and correlates of hsCRP in patients with SLE. Two cohorts from the University of Toronto Lupus Clinic, one with newly diagnosed and the other with prevalent SLE for 4 or more years, were selected. HsCRP was measured on serially collected samples, and hsCRP levels were ranked according to quartiles of cardiovascular risk. Correlates of hsCRP were determined using multivariate regression modelling with analysis of repeated measures. Among 58 patients in the inception cohort, over time, 36 (62%) moved from one hsCRP risk quartile to another. Among 414 patients in the prevalent cohort, 294 (71.0%) moved from one risk quartile to another. In both cohorts, within-patient variance comprised the majority of total variance in hsCRP levels. In multivariate regression analysis, hsCRP increased with age ( P = 0.002), postmenopausal status ( P = 0.03), smoking ( P = 0.007) and presence of infection ( P = 0.0001) and decreased with use of immunosuppressives ( P = 0.02). There is marked variability of hsCRP level over time in SLE, regardless of disease duration. This variability is due to age and SLE treatment, menopausal status, smoking and the occurrence of infection. The variability of hsCRP in SLE casts doubt over its usefulness as an independent predictor of CAD risk in this disease and potentially in other chronic inflammatory diseases.
Treatment of femoral head osteonecrosis in patients with systemic lupus erythematosus by free vascularised fibular grafting
Authors: Sun Y , Zhang CQ , Chen SB , Sheng JG , Jin DX , Zeng BF 
Published: September 2009

The purpose of this study was to review the radiographs of symptomatic femoral head osteonecrosis in patients with systemic lupus erythematosus (SLE) and to assess the results of treatment using free vascularised fibular grafting. We retrospectively reviewed 50 patients (80 hips) with SLE who underwent free vascularised fibular grafting for osteonecrosis of the femoral head. All patients were followed up for at least 2 or more years (average, 4.3 years). The mean Harris hip score improved from 72 to 88. At the latest follow-up, we found improved or unchanged radiographs in 12 of initially Stage II hips and in 60 of 64 Stage III or IV hips. No hips failed treatment and underwent total hip arthroplasty. The data suggest that free vascularised fibular grafting was successful in maintaining joint function and in delaying the need for joint replacement procedure.
Very long-term outcome of pure lupus membranous nephropathy treated with glucocorticoid and azathioprine
Authors: Mok CC , Ying KY , Yim CW , Ng WL , Wong WS 
Published: September 2009

The aim of this study is to report the long-term outcome of pure membranous lupus nephropathy (MLN) treated with glucocorticoid and azathioprine (AZA). A cohort of patients with SLE who had biopsy-confirmed pure MLN was treated initially with prednisone (0.8–1.0 mg/kg/day) and AZA (targeted to 2 mg/kg/day). Patients were followed for the following outcomes: remission rate at 12 months, renal flares, extra-renal flares and renal function deterioration. The cumulative risks of renal flares and renal function decline were studied by Kaplan–Meier analysis. Thirty-eight patients were studied (31 women; age 35.0 ± 9.2 years; mean SLE duration 48.5 ± 59 months; WHO Class Va 45%, Vb 55%). Twenty-two (58%) patients were nephrotic and four (11%) were hypertensive at presentation. All patients were treated with prednisolone (0.85 ± 0.24 mg/kg/day) and AZA (1.72 ± 0.43 mg/kg/day). At 12 months, 24 (67%) patients achieved complete response (CR), 8 (22%) had partial response (PR) and 4 (11%) were treatment resistant. After a follow-up of 12 ± 5.8 years, 19 episodes of renal flares (15 proteinuric and 4 nephritic) occurred in 13 (34%) patients. The cumulative risks of renal flares at 5, 10 and 15 years were 19.4, 32.0 and 36.8%, respectively. Retreatment with an augmented dosage of prednisolone, ± another immunosuppressive agent, resulted in CR and PR in 15 (79%) and 4 (21%) of these flare episodes, respectively. At last visit, three (8%) patients had doubling of serum creatinine, whereas six (16%) patients had decline of creatinine clearance by ≥30% (none developed end stage renal failure). Seven episodes of thromboembolic complications occurred in five (13%) patients and 11 episodes of infective complications (five major, six minor) were reported in seven (18%) patients. In the absence of co-existing proliferative lesions, MLN runs a relatively benign course with low risk of renal function deterioration. Treatment with high-dose prednisolone and AZA is effective, inexpensive and well-tolerated. Prolonged observation shows that one of three patients develop renal flares, which are often proteinuric and responsive to reinduction therapy.
Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR
Authors: Kimkong I , Avihingsanon Y , Hirankarn N 
Published: September 2009

HIN200 is a human IFN-inducible gene and homologous to murine IFI202 gene, which was identified as a candidate gene for SLE susceptibility in lupus mouse model. We determined these gene expressions in leukocytes from 20 SLE patients and 10 healthy controls and in renal biopsies from 29 SLE patients and 15 kidney donors using sensitive real-time reverse transcriptase–polymerase chain reaction (RT-PCR). The expressions of MNDA, IFIX, IFI16 and AIM2 genes significantly increased in leukocytes but not in kidney biopsies from SLE patients as compared to the control individuals, with P = 0.0003, P = 0.0056, P = 0.0002 and P < 0.0001, respectively. We also assessed the expression profiles of IFIX and IFI16 isoforms using semi-quantitative RT-PCR. We found up-regulation of B isoform (short product) of IFI16 in SLE patients. In addition, the expression levels were analyzed in correlation with disease activity and clinical characteristics. Interestingly, higher expression of MNDA was observed in patients who were positive for anti-dsDNA antibodies than in patients who were negative ( P = 0.0276). In conclusion, it is suggested that the HIN200 genes have a role in SLE pathogenesis. Our study also observed a possible important role of a specific short isoform of IFI16 as well as a link between MNDA and anti-dsDNA antibody production.
Class IV-G and IV-S lupus nephritis in Chinese patients: a large cohort study from a single center
Authors: Yu F , Tan Y , Wu L-H , Zhu S-N , Liu G , Zhao M-H 
Published: September 2009

This study is to assess the difference between IV-G and IV-S in a large cohort of Chinese patients with lupus nephritis. The detailed data of patients with subclass IV-G and IV-S were retrospectively analyzed. Serum ANCA and anti-C1q antibodies were detected. A total of 172 cases were classified as class IV, including 152 cases with IV-G and 20 cases with IV-S. In IV-S, the level of haemoglobin was significantly higher ( P = 0.024), proteinuria was milder ( P = 0.003), serum creatinine was lower ( P = 0.021), serum C3 was higher ( P = 0.045) and the ratio of positive serum anti-cardiolipin antibodies was higher ( P = 0.014). On pathological evaluation, the ratio of glomerular fibrinoid necrosis was significantly higher ( P = 0.006) and the score of endocapillary hypercellualrity, interstitial inflammation and total activity indices was significantly lower ( P < 0.001, P = 0.01, P = 0.006, respectively) in IV-S. The frequency of serum ANCA was significantly higher in IV-S than that in IV-G (20 vs 4.6%, P = 0.008). The frequencies of anti-C1q IgG1 and IgG3 subclass were significantly higher in IV-G ( P = 0.006, P = 0.011, respectively). There are significant differences in clinical and pathological manifestations between IV-S and IV-G lupus nephritis which need further investigation.
IAN5 polymorphisms are associated with systemic lupus erythematosus
Authors: Lim MK , Sheen DH , Kim SA , Won SK , Lee S-S , Chae S-C , Chung H-T , Shim SC 
Published: September 2009

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical animal model which develops autoimmune diseases with lymphopenia which results from a frame-shift mutation in the immune-associated nucleotide ( IAN) 5 gene. IAN5 is involved in the regulation of T-cell activation and survival. To examine the association of IAN5 gene with SLE, we scrutinised the single nucleotide polymorphisms (SNPs) in the IAN5 gene. We conducted a case–control study where 132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were genotyped for four SNPs in the IAN5 gene. Two SNPs (+2071C > T and +2677G > A) were associated with susceptibility to SLE ( P = 0.040 and 0.045, respectively), and −4432G > A SNP was associated with the development of leukopenia ( P = 0.028) and the requirement of steroid pulse therapy ( P = 0.040) in SLE patients. Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to SLE ( P = 0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the development of nephritis ( P = 0.017, 0.019, 0.022, respectively). In conclusion, the IAN5 polymorphisms were associated with susceptibility to SLE and the development of clinical disease manifestations in a strictly Korean population.
Inflammatory stress in primary venous and aortic endothelial cells of type 1 diabetic mice
Authors: Bucciarelli Loredana G. , Pollreisz Andreas , Kebschull Moritz , Ganda Anjali , Kalea Anastasia Z. , Hudson Barry I. , Zou Yu Shan , Lalla Evanthia , Ramasamy Ravichandran , Colombo Paolo C. , Schmidt Ann Marie , Yan Shi Fang 
Published: September 2009

Objective: The progression of diabetes is associated with profound endothelial dysfunction. We tested the hypothesis that cellular stress would be detectable in ECs retrieved from arterial and venous vessels of diabetic mice. Method: We describe a method for direct isolation of well-characterised aortic and venous ECs from mice in which cells are not subjected to propagation in culture. Results: Gene expression profiling, confirmed by real-time PCR, revealed a progressive increase in markers of injury within two main gene families, EC activation and EC apoptosis, in aortic and venous ECs recovered from diabetic versus non-diabetic mice. In short-term diabetes, Il1b mRNA transcripts were higher in aortic and venous ECs of diabetic mice versus controls. In long-term diabetes, casp-1 mRNA transcripts were higher in aortic and venous ECs of diabetic mice versus controls. Conclusion: These data suggest that diabetes imparts diffuse endothelial perturbation in the arterial and venous endothelium.