bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Different PCR Assays for Early Detection of Acute and Relapsing Brucellosis in Humans in Comparison with Conventional Methods
Authors: Mitka Stella , Anetakis Constantine , Souliou Efimia , Diza Eudoxia , Kansouzidou Athina 
Published: February 2007

ABSTRACT
Human brucellosis is a significant public health problem in many Mediterranean countries including Greece. The conventional serological methods, as well as blood cultures, have serious limitations, especially in chronic, relapsing, and focal forms of the disease. Four different PCR assays were applied in 4,926 buffy coat, whole-blood, and serum samples received from 200 patients admitted with brucellosis to the Infectious Diseases Hospital, Thessaloniki, Greece, for the rapid diagnosis of acute infection and relapses and compared to blood culture and serological tests (i.e., Wright's seroagglutination test, Coombs' antibrucella test, and the complement fixation test). The four PCR assays had excellent sensitivity and specificity and were able to detect all of the cases of acute disease. Buffy coat and whole blood were the optimal specimens. All four PCR assays were negative in all follow-up samples from 183 patients who had completed a successful treatment and were positive in all follow-up samples from 17 patients who had relapses in the first year after therapy, including the times of the relapses. In conclusion, PCR is a very useful tool for the rapid diagnosis of acute brucellosis and a good marker for the posttreatment follow-up and the early detection of relapses.
Multicenter Evaluation of the New VITEK 2 Advanced Colorimetric Yeast Identification Card
Authors: Hata D. Jane , Hall Leslie , Fothergill Annette W. , Larone Davise H. , Wengenack Nancy L. 
Published: February 2007

ABSTRACT
The performance of the new VITEK 2 Advanced Colorimetry yeast identification (YST) card for use with the VITEK 2 system (bioMérieux, Inc., Hazelwood, MO) was compared to that of the API 20C AUX (API) system (bioMérieux SA, Marcy-l'Etoile, France) in a multicenter evaluation. A total of 12 quality control, 64 challenge, and 623 clinical yeast isolates were used in the study. Comparisons of species identification, platform reliability, and substrate reproducibility were made between YST and API, with API considered the reference standard. Quality control testing to assess system and substrate reproducibility matched expected results ≥95% of the time. The YST card correctly identified 100% of the challenge strains, which covered the species range of the manufacturer's performance claims. Using clinical isolates, the YST card correctly identified 98.5%, with 1.0% of isolates incorrectly identified and 0.5% unidentified. Among clinical isolates, the YST card generated fewer low-discrimination results (18.9%) than did API (30.0%). The time to identification with YST was 18 h, compared to 48 to 72 h with API. The colorimetric YST card used with the VITEK 2 provides a highly automated, objective yeast identification method with excellent performance and reproducibility. We found this system useful for timely and accurate identification of significant yeast species in the clinical microbiology laboratory.
Methicillin-ResistantStaphylococcus pseudintermediusin a Veterinary Teaching Hospital
Authors: Sasaki Takashi , Kikuchi Ken , Tanaka Yoshikazu , Takahashi Namiko , Kamata Shinichi , Hiramatsu Keiichi 
Published: February 2007

ABSTRACTWe surveyed methicillin-resistant coagulase-positive staphylococcus (MRCPS) strains from 57 (26 inpatient and 31 outpatient) dogs and 20 veterinary staff in a veterinary teaching hospital. From the staff, three MRCPS strains were isolated, and two were methicillin-resistantStaphylococcus aureus(MRSA). In contrast, 18 MRCPS strains were detected in both inpatient (12 of 26 [46.2%]) and outpatient (6 of 31 [19.4%]) dogs. Among them, only one strain was MRSA. Using direct sequencing ofsodAandhsp60genes, the 18 MRCPS strains other than MRSA from a staff and 17 dogs, were finally identified asStaphylococcus pseudintermedius, a novel species ofStaphylococcusfrom a cat. All of the methicillin-resistantS. pseudintermedius(MRSP) strains were multidrug resistant to erythromycin, clindamycin, trimethoprim-sulfamethoxazole, and levofloxacin. Most of the MRSP strains showed high-level resistance to oxacillin (≥128 μg/ml, 15 of 18 [83.3%]), and 10 of 15 (66.7%) high-level oxacillin-resistant MRSP strains carried type III SCCmec. DNA fingerprinting of MRSP strains by pulsed-field gel electrophoresis yielded eight clusters: clone A with four subtypes, clone B with four subtypes, clone C with three subtypes, and five other different single clones. MRSP strains from the staff and some inpatient and outpatient dogs shared three major clones (clones A, B, and C), but the strains of the other five different clusters were distributed independently among inpatient or outpatient dogs. This genetic diversity suggested that the MRSP strains were not only acquired in this veterinary teaching hospital but also acquired in primary veterinary clinics in the community. To our knowledge, this is the first report of MRSP in dogs and humans in a veterinary institution.
Role of the Transmembrane Domain of Marburg Virus Surface Protein GP in Assembly of the Viral Envelope
Authors: Mittler Eva , Kolesnikova Larissa , Strecker Thomas , Garten Wolfgang , Becker Stephan 
Published: February 2007

ABSTRACT

The major protein constituents of the filoviral envelope are the matrix protein VP40 and the surface transmembrane protein GP. While VP40 is recruited to the sites of budding via the late retrograde endosomal transport route, GP is suggested to be transported via the classical secretory pathway involving the endoplasmic reticulum, Golgi apparatus, and
trans
-Golgi network until it reaches the plasma membrane where most filoviral budding takes place. Since both transport routes target the plasma membrane, it was thought that GP and VP40 join there to form the viral envelope. However, it was recently shown that, upon coexpression of both proteins, GP is partially recruited into peripheral VP40-enriched multivesicular bodies, which contained markers of the late endosome. Accumulation of GP and VP40 in this compartment was presumed to play an important role in the formation of the filoviral envelope. Using a domain-swapping approach, we were able to show that the transmembrane domain of GP was essential and sufficient for (i) partial recruitment of chimeric glycoproteins into VP40-enriched multivesicular bodies and (ii) incorporation into virus-like particles (VLPs) that were released upon expression of VP40. Only those chimeric glycoproteins which were targeted to VP40-enriched endosomal multivesicular bodies were subsequently recruited into VLPs. These data show that the transmembrane domain of GP is critical for the mixing of VP40 and GP in multivesicular bodies and incorporation of GP into the viral envelope. Results further suggest that trapping of GP in the VP40-enriched late endosomal compartment is important for the formation of the viral envelope.
Transcriptional Coactivator LEDGF/p75 Modulates Human Immunodeficiency Virus Type 1 Integrase-Mediated Concerted Integration
Authors: Pandey Krishan K. , Sinha Sapna , Grandgenett Duane P. 
Published: February 2007

ABSTRACT
Human transcriptional coactivator p75/lens epithelium-derived growth factor (LEDGF) binds human immunodeficiency virus type 1 (HIV-1) integrase (IN). We studied the effects of LEDGF on the assembly and activity of HIV-1 synaptic complexes, which, upon association with a target, mediate concerted integration of viral DNA substrates in vitro. We found that while augmenting single-ended viral DNA integration into target DNA, the host factor was able to either stimulate or abrogate concerted integration in a concentration-dependent manner. LEDGF modestly stimulated (two- to threefold) concerted integration at low molar ratios to IN (<1). The modest stimulation was independent of solution conditions and several different viral DNA substrates. In solution, concerted integration was inhibited if the molar ratios of LEDGF to IN were >1, apparently due to the disruption of IN-IN interactions essential for the formation of active synaptic complexes prior to their association with a circular target. The isolated IN binding domain of LEDGF was sufficient to stimulate and inhibit concerted integration, as observed with full-length protein, albeit at lower efficiencies. Our data show that LEDGF differentially affects IN-DNA complexes mediating single-ended viral DNA integration and synaptic complexes mediating concerted integration. Synaptic complexes associated with target, termed strand transfer complexes, are resistant to disruption by high concentrations of LEDGF. The results suggest that LEDGF may influence HIV-1 integration in vivo.
Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy
Authors: Law Mansun , Cardoso Rosa M. F. , Wilson Ian A. , Burton Dennis R. 
Published: February 2007

ABSTRACT
The membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 is a target of broadly neutralizing monoclonal antibodies (MAbs) 2F5, 4E10, and Z13. Here we engrafted the MPER into the V1/2 region of HIV-1 gp120 to investigate the ability of the engineered antigens to elicit virus-neutralizing antibodies (NAbs). To promote the correct folding and presentation of the helical 4E10 epitope, we flanked the epitope with helical domains and manipulated the helix by sequential deletion of residues preceding the epitope. Binding of the recombinant proteins to MAb 4E10 increased four- to fivefold with the deletion of one or two residues, but it returned to the wild-type level when three residues were deleted, suggesting rotation of the 4E10 epitope along the helix. Immunization of mice and rabbits by electroporation-mediated DNA priming and protein boosting with these constructs elicited high levels of gp120-specific antibodies. A consistent NAb response against the neutralization-resistant, homologous JR-FL virus was detected in rabbits but not in mice. Analysis of the neutralizing activity revealed that the NAbs do not target the MPER or the V1, V2, or V3 region. Through this study, we learned the following. (i) The 4E10 epitope can be manipulated using a “rotate-the-helix” strategy that alters the helix register. However, presentation of this epitope in the immunogenic V1/2 region did not render it immunogenic in mice or rabbits. (ii) DNA vaccination with monomeric gp120-based antigens can elicit a consistent NAb response against the homologous neutralization-resistant virus by targeting epitopes outside the V1, V2, and V3 regions.
Identification of Amino Acid Residues in APOBEC3G Required for Regulation by Human Immunodeficiency Virus Type 1 Vif and Virion Encapsidation
Authors: Huthoff Hendrik , Malim Michael H. 
Published: February 2007

ABSTRACT
The human immunodeficiency virus type-1 (HIV-1) accessory protein Vif serves to neutralize the human antiviral proteins apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G [A3G]) and A3F. As such, the therapeutic blockade of Vif function represents a logical objective for rational drug design. To facilitate such endeavors, we have employed molecular genetics to define features of A3G that are required for its interaction with Vif. Using alanine-scanning mutations and multiple different substitutions at key residues, we confirm the central role played by the aspartic acid at position 128 and identify proline 129 and aspartic acid 130 as important contributory residues. The overall negative charge of this 3-amino-acid motif appears critical for recognition by Vif, as single lysine substitutions are particularly deleterious and a double alanine substitution at positions 128 and 130 is far more inhibitory than single-residue mutations at either position. Our analyses also reveal that the immediately adjacent 4 amino acids, residues 124 to 127, are important for the packaging of A3G into HIV-1 particles. Most important are tyrosine 124 and tryptophan 127, and mutations at these positions can ablate virion incorporation, as well as the capacity to inhibit virus infection. Thus, while pharmacologic agents that target the acidic motif at residues 128 to 130 have the potential to rescue A3G expression by occluding recognition by Vif, care will have to be taken not to perturb the contributions of the neighboring 124-to-127 region to packaging if such agents are to have therapeutic benefit by promoting A3G incorporation into progeny virions.
Management of patients with HBeAg-negative chronic hepatitis B
Authors: Saikia Nripen , Talukdar Rupjyoti , Mazumder Subhasish , Khanna Sudeep , Tandon Rakesh 
Published: February 2007

Abstract
Chronic hepatitis B (CHB) is one of the leading causes of morbidity and mortality worldwide. Although various drugs are available for the treatment of CHB, emergence of the hepatitis B e antigen (HBeAg)-negative mutant variant, specifically in Asia, the Middle East and southern Europe, is creating a new challenge as this variant is less responsive to available treatments. HBeAg-negative CHB rapidly progresses to cirrhosis and its related complications. This review discusses the available literature on the approved and under-trial treatment options and their respective efficacies for HBeAg-negative CHB.
Basal thumb arthritis
Authors: Dias Richard , Chandrasenan Jeevan , Rajaratnam Vaikunthan , Burke Frank D 
Published: February 2007

Abstract
Basal thumb arthritis is a common condition seen in hand clinics across the United Kingdom and is often associated with other pathological conditions such as carpal tunnel syndrome and scaphotrapezial arthritis. Typically, patients complain of pain localised to the base of the thumb. This pain is often activity related, particularly after excessive use involving forceful pinch. A detailed history and examination is normally all that is needed to make the diagnosis. Provocative manoeuvres may be helpful in localising symptoms to the basal joint with degenerative changes or synovitis. Radiographs are useful for confirming the diagnosis and staging the disease in order to plan for surgery. The mainstay of initial treatment of basal thumb arthritis of any stage is activity modifications, rest, nonsteroidal anti-inflammatory drugs, exercises and splinting. A variety of surgical procedures are available to treat the condition when conservative measures have failed, in order to control symptoms and improve function. We review the current literature and discuss the clinical aspects of this condition, staging, and treatment options available, and the difficulties treating this group of patients.
Views of specialist registrars on specialty care in the community: employment prospects and the need for additional training
Authors: Azam N , Moshkovska T , Mayberry J F 
Published: February 2007

Abstract

Aim
To obtain the views of specialist registrars on specialty care in the community.

Method
Specialist registrars from five Deaneries in England completed an online questionnaire about their views on employment prospects, the role of specialty care in the community, and the need for additional training in this area.

Results
One hundred and twenty seven replies were received over a four week period. Thirty (24%) viewed their future employment prospects as consultants as poor or very worrying. Seventy seven (61%) specialist registrars considered that as consultants they will need to work directly in the community. Thirty nine of these (51%) considered the need to work close to patients directly in the community as either a “bad” or “very bad” development. However, 102 (80%) specialist registrars believed that they should receive training on the delivery of specialty care in the community and 96 (76%) wanted this in the form of a university based degree.
Inhibition of fibroblast to myofibroblast transition by halofuginone contributes to the chemotherapy-mediated antitumoral effect
Authors: Sheffer Yuval , Leon Oded , Pinthus Jehonathan H. , Nagler Arnon , Mor Yoram , Genin Olga , Iluz Maya , Kawada Norifumi , Yoshizato Katsutoshi , Pines Mark 
Published: February 2007

Abstract
Stromal myofibroblasts play an important role in tumor progression. The transition of fibroblasts to myofibroblasts is characterized by expression of smooth muscle genes and profuse synthesis of extracellular matrix proteins. We evaluated the efficacy of targeting fibroblast-to-myofibroblast transition with halofuginone on tumor progression in prostate cancer and Wilms' tumor xenografts. In both xenografts, low doses of halofuginone treatment, independent of the route of administration, resulted in a trend toward inhibition in tumor development. Moreover, halofuginone synergizes with low dose of docetaxel in prostate cancer and vincristine and dactinomycin in Wilms' tumor xenografts, resulting in significant reduction in tumor volume and weight comparable to the effect observed by high doses of the respective chemotherapies. In prostate cancer and Wilms' tumor xenografts, halofuginone, but not the respective chemotherapies, inhibited the synthesis of collagen type I, α-smooth muscle actin, transgelin, and cytoglobin, all of which are characteristics of activated myofibroblasts. Halofuginone, as the respective chemotherapies, increased the synthesis of Wilms' tumor suppressor gene product (WT-1) and prostate apoptosis response gene-4 (Par-4), resulting in apoptosis/necrosis. These results suggest that targeting the fibroblast-to-myofibroblast transition with halofuginone may synergize with low doses of chemotherapy in achieving a significant antitumoral effect, avoiding the need of high-dose chemotherapy and its toxicity without impairing treatment efficacy. [Mol Cancer Ther 2007;6(2)570–7
The thymic theme of acetylcholinesterase splice variants in myasthenia gravis
Authors: Gilboa-Geffen Adi , Lacoste Paul P. , Soreq Lilach , Cizeron-Clairac Geraldine , Le Panse Rozen , Truffault Frederique , Shaked Iftach , Soreq Hermona , Berrih-Aknin Sonia 
Published: February 2007

AbstractCholinergic signaling and acetylcholinesterase (AChE) influence immune response and inflammation. Autoimmune myasthenia gravis (MG) is mediated by antibodies to the acetylcholine receptor and current therapy is based on anti-AChE drugs. MG is associated with thymic hyperplasia, showing signs of inflammation. The objectives of this study were to analyze the involvement of AChE variants in thymic hyperplasia. We found lower hydrolytic activities in the MG thymus compared with adult controls, accompanied by translocation of AChE-R from the cytoplasm to the membrane and increased expression of the signaling protein kinase PKC-βII. To explore possible causal association of AChE-R changes with thymic composition and function, we used an AChE-R transgenic model and showed smaller thymic medulla compared with strain-matched controls, indicating that AChE-R overexpression interferes with thymic differentiation mechanisms. Interestingly, AChE-R transgenic mice showed increased numbers of CD4+CD8+ cells that were considerably more resistant in vitro to apoptosis than normal thymocytes, suggesting possibly altered positive selection. We further analyzed microarray data of MG thymic hyperplasia compared with healthy controls and found continuous and discrete changes in AChE-annotated GO categories. Together, these findings show that modified AChE gene expression and properties are causally involved in thymic function and development.
Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils
Authors: Zhang Mai , Angata Takashi , Cho Jae Youn , Miller Marina , Broide David H. , Varki Ajit 
Published: February 2007

AbstractCD33-related Siglecs (CD33rSiglecs) are a family of sialic acid–recognizing lectins on immune cells whose biologic functions are unknown. We studied in vivo functions of Siglec-F, the CD33rSiglec expressed on mouse eosinophils, which are prominent in allergic processes. Induction of allergic lung inflammation in mice caused up-regulation of Siglec-F on blood and bone marrow eosinophils, accompanied by newly induced expression on some CD4+ cells, as well as quantitative up-regulation of endogenous Siglec-F ligands in the lung tissue and airways. Taken together with the tyrosine-based inhibitory motif in the cytosolic tail of Siglec-F, the data suggested a negative feedback loop, controlling allergic responses of eosinophils and helper T cells, via Siglec-F and Siglec-F ligands. To pursue this hypothesis, we created Siglec-F–null mice. Allergen-challenged null mice showed increased lung eosinophil infiltration, enhanced bone marrow and blood eosinophilia, delayed resolution of lung eosinophilia, and reduced peribronchial-cell apoptosis. Anti–Siglec-F antibody cross-linking also enhanced eosinophil apoptosis in vitro. These data support the proposed negative feedback role for Siglec-F, represent the first in vivo demonstration of biologic functions for any CD33rSiglec, and predict a role for human Siglec-8 (the isofunctional paralog of mouse Siglec-F) in regulating the pathogenesis of human eosinophil-mediated disorders.
Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs
Authors: Martinez Caridad , Hofmann Ted J. , Marino Roberta , Dominici Massimo , Horwitz Edwin M. 
Published: February 2007

Abstract
Mesenchymal stromal cells (MSCs) have enormous potential for the regeneration of bone, cartilage, and other tissues derived from primitive mesoderm. Despite extensive research, there is still no single marker that reliably identifies MSCs within the bone marrow. Using immunocytochemistry and flow cytometry, we demonstrate here that the neural ganglioside GD2 is expressed by MSCs either newly isolated from bone marrow or expanded in tissue culture; this finding was supported by reverse transcriptase–polymerase chain reaction (RT-PCR) analysis showing expression of the mRNA for GD2 synthase, an essential enzyme for GD2 biosynthesis. GD2 was also expressed on MSCs isolated from adipose tissue, but not on foreskin fibroblasts. Importantly, MSCs were the only cells within normal marrow that expressed this marker. Thus, GD2 appears to be the first reported single surface marker that uniquely distinguishes MSCs from other marrow elements. GD2 may prove valuable to study MSC biology and for the preparation of MSCs for clinical applications.