bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simian Immunodeficiency Virus Engrafted with Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Epitopes: Replication, Neutralization, and Survey of HIV-1-Positive Plasma
Authors: Yuste Eloisa , Sanford Hannah B. , Carmody Jill , Bixby Jacqueline , Little Susan , Zwick Michael B. , Greenough Tom , Burton Dennis R. , Richman Douglas D. , Desrosiers Ronald C. , Johnson Welkin E. 
Published: February 2006

ABSTRACTTo date, only a small number of anti-human immunodeficiency virus type 1 (HIV-1) monoclonal antibodies (MAbs) with relatively broad neutralizing activity have been isolated from infected individuals. Adequate techniques for defining how frequently antibodies of these specificities arise in HIV-infected people have been lacking, although it is generally assumed that such antibodies are rare. In order to create an epitope-specific neutralization assay, we introduced well-characterized HIV-1 epitopes into the heterologous context of simian immunodeficiency virus (SIV). Specifically, epitope recognition sequences for the 2F5, 4E10, and 447-52D anti-HIV-1 neutralizing monoclonal antibodies were introduced into the corresponding regions of SIVmac239 by site-directed mutagenesis. Variants with 2F5 or 4E10 recognition sequences in gp41 retained replication competence and were used for neutralization assays. The parental SIVmac239 and the neutralization-sensitive SIVmac316 were not neutralized by the 2F5 and 4E10 MAbs, nor were they neutralized significantly by any of the 96 HIV-1-positive human plasma samples that were tested. The SIV239-2F5 and SIV239-4E10 variants were specifically neutralized by the 2F5 and 4E10 MAbs, respectively, at concentrations within the range of what has been reported previously for HIV-1 primary isolates (J. M. Binley et al., J. Virol.78:13232-13252, 2004). The SIV239-2F5 and SIV239-4E10 epitope-engrafted variants were used as biological screens for the presence of neutralizing activity of these specificities. None of the 92 HIV-1-positive human plasma samples that were tested exhibited significant neutralization of SIV239-2F5. One plasma sample exhibited >90% neutralization of SIV239-4E10, but this activity was not competed by a 4E10 target peptide and was not present in concentrated immunoglobulin G (IgG) or IgA fractions. We thus confirm by direct analysis that neutralizing activities of the 2F5 and 4E10 specificities are either rare among HIV-1-positive individuals or, if present, represent only a very small fraction of the total neutralizing activity in any given plasma sample. We further conclude that the structures of gp41 from SIVmac239 and HIV-1 are sufficiently similar such that epitopes engrafted into SIVmac239 can be readily recognized by the cognate anti-HIV-1 monoclonal antibodies.
Interaction of the Adenovirus Type 5 E4 Orf3 Protein with Promyelocytic Leukemia Protein Isoform II Is Required for ND10 Disruption
Authors: Hoppe Anne , Beech Stephanie J. , Dimmock John , Leppard Keith N. 
Published: February 2006

ABSTRACT
Nuclear domain 10 (ND10s), or promyelocytic leukemia protein (PML) nuclear bodies, are spherical nuclear structures that require PML proteins for their formation. Many viruses target these structures during infection. The E4 Orf3 protein of adenovirus 5 (Ad5) rearranges ND10s, causing PML to colocalize with Orf3 in nuclear tracks or fibers. There are six different PML isoforms (I to VI) present at ND10s, all sharing a common N terminus but with structural differences at their C termini. In this study, PML II was the only one of these six isoforms that was found to interact directly and specifically with Ad5 E4 Orf3 in vitro and in vivo; these results define a new Orf3 activity. Three of a series of 18 mutant Orf3 proteins were unable to interact with PML II; these were also unable to cause ND10 rearrangement. Moreover, in PML-null cells that contained neoformed ND10s comprising a single PML isoform, only ND10s formed of PML II were rearranged by Orf3. These data show that the interaction between Orf3 and PML II is necessary for ND10 rearrangement to occur. Finally, Orf3 was shown to self-associate in vitro. This activity was absent in mutant Orf3 proteins that were unable to form tracks and to bind PML II. Thus, Orf3 oligomerization may mediate the formation of nuclear tracks in vivo and may also be important for PML II binding.
Inhibition of Interferon Signaling by the Kaposi's Sarcoma-Associated Herpesvirus Full-Length Viral Interferon Regulatory Factor 2 Protein
Authors: Fuld Suzanne , Cunningham Charles , Klucher Kevin , Davison Andrew J. , Blackbourn David J. 
Published: February 2006

ABSTRACT
Interferon (IFN) signal transduction involves interferon regulatory factors (IRF). Kaposi's sarcoma-associated herpesvirus (KSHV) encodes four IRF homologues: viral IRF 1 (vIRF-1) to vIRF-4. Previous functional studies revealed that the first exon of vIRF-2 inhibited alpha/beta interferon (IFN-α/β) signaling. We now show that full-length vIRF-2 protein, translated from two spliced exons, inhibited both IFN-α- and IFN-λ-driven transactivation of a reporter promoter containing the interferon stimulated response element (ISRE). Transactivation of the ISRE promoter by IRF-1 was negatively regulated by vIRF-2 protein as well. Transactivation of a full-length IFN-β reporter promoter by either IRF-3 or IRF-1, but not IRF-7, was also inhibited by vIRF-2 protein. Thus, vIRF-2 protein is an interferon induction antagonist that acts pleiotropically, presumably facilitating KSHV infection and dissemination in vivo.
Mutational Analysis of the Varicella-Zoster Virus ORF62/63 Intergenic Region
Authors: Jones Jeremy O. , Sommer Marvin , Stamatis Shaye , Arvin Ann M. 
Published: February 2006

ABSTRACT

The varicella-zoster virus (VZV) ORF62/63 intergenic region was cloned between the
Renilla
and firefly luciferase genes, which acted as reporters of ORF62 and ORF63 transcription, and recombinant viruses were generated that carried these reporter cassettes along with the intact native sequences in the repeat regions of the VZV genome. In order to investigate the potential contributions of cellular transregulatory proteins to ORF62 and ORF63 transcription, recombinant reporter viruses with mutations of consensus binding sites for six proteins within the intergenic region were also created. The reporter viruses were used to evaluate ORF62 and ORF63 transcription during VZV replication in cultured fibroblasts and in skin xenografts in SCIDhu mice in vivo. Mutations in putative binding sites for heat shock factor 1 (HSF-1), nuclear factor 1 (NF-1), and one of two cyclic AMP-responsive elements (CRE) reduced ORF62 reporter transcription in fibroblasts, while mutations in binding sites for HSF-1, NF-1, and octamer binding proteins (Oct-1) increased ORF62 reporter transcription in skin. Mutations in one CRE and the NF-1 site altered ORF63 transcription in fibroblasts, while mutation of the Oct-1 binding site increased ORF63 reporter transcription in skin. The effect of each of these mutations implies that the intact binding site sequence regulates native ORF62 and ORF63 transcription. Mutation of the only NF-κB/Rel binding site had no effect on ORF62 or ORF63 transcription in vitro or in vivo. The segment of the ORF62/63 intergenic region proximal to ORF63 was most important for ORF63 transcription, but mutagenesis also altered ORF62 transcription, indicating that this region functions as a bidirectional promoter. This first analysis of the ORF62/63 intergenic region in the context of VZV replication indicates that it is a dual promoter and that cellular transregulatory factors affect the transcription of these key VZV regulatory genes.
Relative Dominance of Gag p24-Specific Cytotoxic T Lymphocytes Is Associated with Human Immunodeficiency Virus Control
Authors: Zuñiga Rosario , Lucchetti Aldo , Galvan Patricia , Sanchez Shyla , Sanchez Carmen , Hernandez Ana , Sanchez Hugo , Frahm Nicole , Linde Caitlyn H. , Hewitt Hannah S. , Hildebrand William , Altfeld Marcus , Allen Todd M. , Walker Bruce D. , Korber Bette T. , Leitner Thomas , Sanchez Jorge , Brander Christian 
Published: February 2006

ABSTRACT
Conflicting data on the role of total virus- and protein-specific cytotoxic-T-lymphocyte (CTL) responses in the control of human immunodeficiency virus (HIV) disease progression exist. We present data generated from a Peruvian cohort of untreated, clade B-infected subjects, demonstrating that the proportion of Gag-specific, and in particular p24-reactive, CTL responses among the total virus-specific CTL activity is associated with individuals' CD4 counts and viral loads. Analyses in a second cohort in the United States confirm these findings and point towards a dominant role of Gag-specific immunity in effective control of HIV infection, providing important guidance for HIV vaccine development.
Treatment of plantar fasciitis by LowDye taping and iontophoresis: short term results of a double blinded, randomised, placebo controlled clinical trial of dexamethasone and acetic acid
Authors: Osborne H R , Allison G T 
Published: February 2006

Objectives:To determine if, in the short term, acetic acid and dexamethasone iontophoresis combined with LowDye (low-Dye) taping are effective in treating the symptoms of plantar fasciitis.Methods:A double blinded, randomised, placebo controlled trial of 31 patients with medial calcaneal origin plantar fasciitis recruited from three sports medicine clinics. All subjects received six treatments of iontophoresis to the site of maximum tenderness on the plantar aspect of the foot over a period of two weeks, continuous LowDye taping during this time, and instructions on stretching exercises for the gastrocnemius/soleus. They received 0.4% dexamethasone, placebo (0.9% NaCl), or 5% acetic acid. Stiffness and pain were recorded at the initial session, the end of six treatments, and the follow up at four weeks.Results:Data for 42 feet from 31 subjects were used in the study. After the treatment phase, all groups showed significant improvements in morning pain, average pain, and morning stiffness. However for morning pain, the acetic acid/taping group showed a significantly greater improvement than the dexamethasone/taping intervention. At the follow up, the treatment effect of acetic acid/taping and dexamethasone/taping remained significant for symptoms of pain. In contrast, only acetic acid maintained treatment effect for stiffness symptoms compared with placebo (p  =  0.031) and dexamethasone.Conclusions:Six treatments of acetic acid iontophoresis combined with taping gave greater relief from stiffness symptoms than, and equivalent relief from pain symptoms to, treatment with dexamethasone/taping. For the best clinical results at four weeks, taping combined with acetic acid is the preferred treatment option compared with taping combined with dexamethasone or saline iontophoresis.
Shoulder strength profile in elite junior tennis players: horizontal adduction and abduction isokinetic evaluation
Authors: Silva R T , Gracitelli G C , Saccol M F , de Souza Laurino C Frota , Silva A C , Braga-Silva J L 
Published: February 2006

Objective:To establish normative data for muscle performance during isokinetic horizontal abduction and adduction of the shoulder in elite junior tennis players.Methods:Thirty six tennis players were evaluated (23 male, 13 female; mean age 14 years (range 12–18)). An isokinetic dynamometer was used to test the shoulder horizontal abductors and adductors at 60 and 180°/s. Absolute and relative peak torque (PT and PT/BW), total work (TW), endurance ratio (ER), and the ratio of the peak torque between horizontal abductors and adductors (HAB/HAD ratio) were recorded. Data were compared for the dominant and non-dominant shoulders, horizontal abductor and adductor muscles, and between players grouped according to age.Results:The dominant shoulder was significantly (p<0.05) stronger than the non-dominant shoulder in all variables except ER and HAB/HAD ratio. The abductors were significantly (p<0.05) weaker than the adductors in all subjects. The type of backhand (one handed or two handed) did not influence the strength of the shoulder horizontal abductors on the dominant side. The number of years of tennis practice had an effect on muscle strength as evaluated by absolute data (PT and TW) but not relative measurements (PT/BW and TW/BW).Conclusion:The findings confirm that horizontal abduction and adduction are stronger in the dominant shoulder of junior tennis players. The clinical relevance of these findings is not established, and more studies are needed to compare tennis players with athletes from other sports and non-athletes.
Evolution of the treatment options of ulnar collateral ligament injuries of the elbow
Authors: Langer P , Fadale P , Hulstyn M 
Published: February 2006

Ulnar collateral ligament (UCL) insufficiency is potentially a career threatening, or even a career ending, injury, particularly in overhead throwing athletes. The evolution of treating modalities provides afflicted athletes with the opportunity to avoid premature retirement. There have been several clinical and basic science research efforts which have investigated the pathophysiology of UCL disruption, the biomechanics specific to overhead throwing, and the various types of treatment modalities. UCL reconstruction is currently the most commonly performed surgical treatment option. An in depth analysis of the present treatment options, both non-operative and operative, as well as their respective results and biomechanical evaluation, is lacking in the literature to date. This article provides a comprehensive current review and comparative analysis of these modalities. Over the last 30 years there has been an evolution of the original UCL reconstruction. Yet, despite the variability in modifications, such as the docking technique, interference screw fixation, and use of suture anchors, the unifying concepts of UCL reconstruction are that decreased dissection of the flexor-pronator mass and decreased handling of the ulnar nerve leads to improved outcomes.
Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse
Authors: Graham M R , Grace F M , Boobier W , Hullin D , Kicman A , Cowan D , Davies B , Baker J S 
Published: February 2006

Objectives:The long term effects (>20 years) of anabolic-androgenic steroid (AAS) use on plasma concentrations of homocysteine (HCY), folate, testosterone, sex hormone binding globulin (SHBG), free androgen index, urea, creatinine, haematocrit (HCT), vitamin B12, and urinary testosterone/epitestosterone (T/E) ratio, were examined in a cohort of self-prescribing bodybuilders.Methods:Subjects (n = 40) were divided into four distinct groups: (1) AAS users still using AAS (SU; n = 10); (2) AAS users abstinent from AAS administration for 3 months (SA; n = 10); (3) non-drug using bodybuilding controls (BC; n = 10); and (4) sedentary male controls (SC; n = 10).Results:HCY levels were significantly higher in SU compared with BC and SC (p<0.01), and with SA (p<0.05). Fat free mass was significantly higher in both groups of AAS users (p<0.01). Daily energy intake (kJ) and daily protein intake (g/day) were significantly higher in SU and SA (p<0.05) compared with BC and SC, but were unlikely to be responsible for the observed HCY increases. HCT concentrations were significantly higher in the SU group (p<0.01). A significant linear inverse relationship was observed in the SU group between SHBG and HCY (r = −0.828, p<0.01), indicating a possible influence of the sex hormones in determining HCY levels.Conclusions:With mounting evidence linking AAS to adverse effects on some clotting factors, the significantly higher levels of HCY and HCT observed in the SU group suggest long term AAS users have increased risk of future thromboembolic events.
Liver infiltrating mononuclear cells in children with type 1 autoimmune hepatitis
Authors: De Biasio M B , Periolo N , Avagnina A , García de Dávila M T , Ciocca M , Goñi J , de Matteo E , Galoppo C , Cañero-Velasco M C , Fainboim H , Muñoz A E , Fainboim L , Cherñavsky A C 
Published: February 2006

Objective:To investigate infiltrating cells in the liver of children with type 1 autoimmune hepatitis (AH-1).Methods:liver biopsies from 24 untreated AH-1 patients (14 children, 10 adults), five patients with hepatitis C virus related chronic hepatitis (HCV), and 10 control liver specimens (CL) were processed for immunohistochemical cell characterisation.Results:Two different cell distribution patterns were detected in the liver of patients with AH-1: (1) CD4+and CD20+cells were found in the central areas of the portal tracts (portal distribution); (2) CD8+cells were observed at the periphery of the portal space (periportal distribution). Some cell subsets, like CD56, CD57, Fas-L, and Bak, showed a non-defined distribution pattern. The presence of two well defined patterns of cell distribution was not observed in HCV and CL (CD4+, CD20+, and CD8+cells were uniformly distributed in the portal space). In AH-1 and CL, the NK markers CD56 and CD57 were found scattered throughout the liver parenchyma. However, in HCV biopsies, CD56+cells were also clearly increased in both the portal and the periportal areas. Biopsies of AH-1 and HCV patients showed a uniform distribution of Fas-L and Bak in the portal and periportal areas, with Bak staining also detected in the hepatic parenchyma.Conclusions:Despite clinical and genetic differences, there was a similar distribution of liver infiltrating mononuclear cells in children and adults with AH-1. These results raise the possibility of reclassifying cryptogenic chronic hepatitis by immunohistochemical analysis of infiltrating liver cells.
Clinical rotation in pathology: description of a case based approach
Authors: Bezuidenhout J , Wasserman E , Mansvelt E , Meyer C , van Zyl G , Orth H , Els A 
Published: February 2006

Background:The implementation of a system based, integrated curriculum at the Faculty of Health Sciences of Stellenbosch University, Western Cape, South Africa, resulted in less contact time for the pathology disciplines during theoretical modules, while a weekly rotation in pathology was introduced during clinical training in the fourth and fifth years.Objective:To describe a problem based approach for this rotation.Methods:Students are presented with a clinical “paper” case daily, integrating as many of the pathology disciplines as possible to demonstrate the interdependence of the various disciplines. They receive chemical pathology tutorials, visit the various laboratories, and receive practical training in fine needle aspiration biopsy. On the final day, the case studies are assessed and discussed.Results:Most students appreciated all activities. This rotation enhanced student interactivity and autonomy and guaranteed immediate feedback. On evaluation of the rotation it was found that the students enjoyed the rotation, learnt something new, and realised the value of group work.Conclusions:This innovation integrates pathology with clinical practice and illustrates the use of laboratory medicine in the management of common diseases seen in this country. Students appreciate learning practical skills and having to request special investigations under a pathologist’s supervision changes their approach to pathology requests. Familiarity with the pathology environment empowers the student to use pathology with greater ease. A bank of case studies that can be expanded to include all medical disciplines will facilitate the application of a problem based approach and enhance communication between the basic science disciplines and the clinical and pathology disciplines.
Accuracy of frozen section in the diagnosis of liver mass lesions
Authors: Rakha E , Ramaiah S , McGregor A 
Published: February 2006

Objective:To evaluate the diagnostic accuracy of intraoperative frozen sections diagnosis of liver lesions thought to be malignant tumours.Methods:285 frozen sections of liver from 173 patients were reviewed. The examinations were done between 1998 and 2004.Results:Final histological diagnosis was divided into positive (32%) and negative (68%) for malignancy. In four cases (2%), diagnosis was deferred to paraffin section. There was one false positive and two false negative diagnoses. Sensitivity was 96.9% and specificity was 99.1%, and the overall accuracy to determine the lesions was 95%. The cases were further analysed to ascertain the nature of diagnostic difficulties, which comprised pathological misinterpretation, sampling error, and technical imperfections. Biliary hamartoma was the most common entity that was confused with malignant tumours in frozen sections.Conclusions:The data are in accordance with those of similar studies in other sites, and confirm that the frozen section is an accurate and reliable method for intraoperative diagnosis of suspected liver lesions.
Expression of receptor activator of nuclear factor κβ ligand (RANKL) and tumour necrosis factor related, apoptosis inducing ligand (TRAIL) in breast cancer, and their relations with osteoprotegerin, oestrogen receptor, and clinicopathological variables
Authors: Cross S S , Harrison R F , Balasubramanian S P , Lippitt J M , Evans C A , Reed M W R , Holen I 
Published: February 2006

Background:Receptor activator of nuclear factor κβ ligand (RANKL) has an important role in bone remodelling, and tumour necrosis factor related, apoptosis inducing ligand (TRAIL) can induce apoptosis in cancer cells. Their functions are linked by their interactions with osteoprotegerin (OPG).Objective:To investigate the expression of RANKL and TRAIL in a large series of unselected breast cancers and to analyse the relations between these expressions and the expression of OPG, oestrogen receptor, and clinicopathological variables.Methods:395 breast cancers were sampled into tissue microarrays and immunohistochemistry undertaken for RANKL and TRAIL.Results:There was strong expression of RANKL in 14% of the cancers and strong expression of TRAIL in 30%. Expression of RANKL had a negative association with expression of oestrogen receptor (p = 0.036). Expression of TRAIL had a negative association with the Nottingham Prognostic Index (p = 0.021). There was a significant negative relation between expression of RANKL and TRAIL (p<0.005). Unsupervised cluster analysis produced a dendrogram that showed a clear division into two groups, and the expression of oestrogen receptor was significantly higher in one of those groups (p = 0.012).Conclusions:There is apparent loss of expression of RANKL in 86% of breast cancers; those tumours that retain expression tend to be oestrogen receptor negative and of a high histological grade. There is strong expression of TRAIL in 30% of breast cancers and these tend to be of better prognostic type. These results may be important in the processes of metastasis to bone and the apoptotic cell death pathway in cancer.