bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing Multiple-Choice Tests From Impeding Educational Advancement After Acquired Brain Injury
Authors: Schutz Larry E. , Rivers Kenyatta O. , Schutz Judith A. , Proctor Adele 
Published: December 2007

Purpose
The purpose of this article is to present management strategies that can be used to breach barriers created for students with acquired brain injuries by testing the students in the multiple-choice format.

Method
This article presents a case study of a high school student with severe hydrocephalus and difficulties with state-mandated reading comprehension tests who was denied exceptional student education services because her grades were “so good.”

Result
Although an honor student who received academic awards, she was never taught how to pass the state reading test and was denied her diploma at graduation.

Implications
The cognitive obstacles posed by the multiple-choice format can be specified and treated. In-service training can help school staff and officials to recognize and serve these children promptly so that academic disability can be prevented.
Fitness of
Streptococcus pneumoniae
Fluoroquinolone-Resistant Strains with Topoisomerase IV Recombinant Genes
Authors: Balsalobre Luz , de la Campa Adela G. 
Published: December 2007

ABSTRACT

The low prevalence of ciprofloxacin-resistant (Cp
r
)
Streptococcus pneumoniae
isolates carrying recombinant topoisomerase IV genes could be attributed to a fitness cost imposed by the horizontal transfer, which often implies the acquisition of larger-than-normal
parE
-
parC
intergenic regions. A study of the transcription of these genes and of the fitness cost for 24 isogenic Cp
r
strains was performed. Six first-level transformants were obtained either with PCR products containing the
parC
quinolone resistance-determining regions (QRDRs) of
S. pneumoniae
Cp
r
mutants with point mutations or with a PCR product that includes
parE
-QRDR-
ant
-
parC
-QRDR from a Cp
r
Streptococcus mitis
isolate. The latter yielded two strains, T6 and T11, carrying
parC
-QRDR and
parE
-QRDR-
ant
-
parC
-QRDR, respectively. These first-level transformants were used as recipients in further transformations with the
gyrA
-QRDR PCR products to obtain 18 second-level transformants. In addition, strain Tr7 (which contains the GyrA E85K change) was used. Reverse transcription-PCR experiments showed that
parE
and
parC
were cotranscribed in R6, T6, and T11; and a single promoter located upstream of
parE
was identified in R6 by primer extension. The fitness of the transformants was estimated by pairwise competition with R6 in both one-cycle and two-cycle experiments. In the one-cycle experiments, most strains carrying the GyrA E85K change showed a fitness cost; the exception was recombinant T14. In the two-cycle experiments, a fitness cost was observed in most first-level transformants carrying the ParC changes S79F, S79Y, and D83Y and the GyrA E85K change; the exceptions were recombinants T6 and T11. The results suggest that there is no impediment due to a fitness cost for the spread of recombinant Cp
r
S. pneumoniae
isolates, since some recombinants (T6, T11, and T14) exhibited an ability to compensate for the cost.
Treatment of Experimental Anthrax with Recombinant Capsule Depolymerase
Authors: Scorpio Angelo , Tobery Steven A. , Ribot Wilson J. , Friedlander Arthur M. 
Published: December 2007

ABSTRACT

Bacillus anthracis
produces an antiphagocytic gamma-linked poly-
d
-glutamic acid capsule that is required for virulence. Capsule depolymerase (CapD) is a membrane-associated poly-γ-glutamate-specific depolymerase encoded on the
B. anthracis
capsule plasmid, pX02, that is reported to contribute to virulence by anchoring the capsule to the peptidoglycan and partially degrading high-molecular-weight capsule from the bacterial surface. We previously demonstrated that treatment with CapD effectively removes the capsule from anthrax bacilli, rendering them susceptible to phagocytic killing in vitro. Here we report that CapD promoted in vivo phagocytic killing of
B. anthracis
bacilli by mouse peritoneal neutrophils and that parenteral administration of CapD protected mice in two models of anthrax infection. CapD conferred significant protection compared with controls when coinjected with encapsulated bacilli from fully virulent
B. anthracis
Ames or the nontoxigenic encapsulated strain ΔAmes and when injected 10 min after infection with encapsulated bacilli from
B. anthracis
Ames. Protection was also observed when CapD was administered 30 h after infection with
B. anthracis
ΔAmes spores, while significant protection could not be demonstrated following challenge with
B. anthracis
Ames spores. These data support the proposed role of capsule in
B. anthracis
virulence and suggest that strategies to target anthrax bacilli for neutrophil killing may lead to novel postexposure therapies.
Fluoroquinolone-Resistant Mutants ofBurkholderia cepacia
Authors: Pope C. F. , Gillespie S. H. , Pratten J. R. , McHugh T. D. 
Published: December 2007

ABSTRACTFluoroquinolone-resistantBurkholderia cepaciamutants were selected on ciprofloxacin. The rate of mutation ingyrAwas estimated to be 9.6 × 10−11mutations per division. Mutations ingyrAconferred 12- to 64-fold increases in MIC, and an additionalparCmutation conferred a large increase in MIC (>256-fold). Growth rate, biofilm formation, and survival in water and during drying were not impaired in strains containing singlegyrAmutations. Double mutants were impaired only in growth rate (0.85, relative to the susceptible parent).
Tipranavir (TPV) Genotypic Inhibitory Quotient Predicts Virological Response at 48 Weeks to TPV-Based Salvage Regimens
Authors: de Requena Daniel Gonzalez , Bonora Stefano , Calcagno Andrea , D'Avolio Antonio , Siccardi Marco , Fontana Silvia , Milia Maria Grazia , Sciandra Mauro , Garazzino Silvia , Di Garbo Antonio , Baietto Lorena , Trentini Laura , Di Perri Giovanni 
Published: December 2007

ABSTRACTThe virological response (VR) to a tipranavir-ritonavir (TPV-RTV)-based regimen had been shown to be associated with a number of mutations in the protease gene, the use of enfuvirtide (T20), and the TPV phenotypic inhibitory quotient (IQ). The role of the TPV genotypic IQ (gIQ) has not yet been fully investigated. The aim of our study was to evaluate the relationship between the TPV gIQ and the VR at 48 weeks to TPV-based salvage regimens. Patients placed on regimens containing two nucleoside reverse transcriptase inhibitors plus TPV-RTV 500/200 mg twice a day with or without T20 were prospectively studied. Regular follow-up was performed over the study period. VR, considered a viral load (VL) decrease of ≥1 log unit and/or the achievement of <50 copies/ml with no VL rebound of >0.5 log unit compared to the maximal VL decrease at week 48, was assessed. Thirty-eight patients who had received multiple drugs were included. At week 48 the VL decrease was −1.48 (interquartile range [IQR], −2.88 to −0.48), 15 patients (39.5%) had VLs of <50 copies/ml, and the CD4+cell count increase was 37 cells/mm3(IQR, −30 to +175). Twenty subjects (52.6%) achieved VRs. The TPV gIQ and optimized background score (OBS) were independently associated with higher VL decreases. The TPV gIQ and OBS were also independent predictors of a VR at week 48. TPV gIQ and OBS cutoff values of 14,500 and 2, respectively, were associated with a higher rate of VR. The TPV gIQ was shown to be able to predict the VR at 48 weeks to TPV-containing salvage regimens better than the TPV trough concentration or TPV-associated mutations alone. A possible TPV gIQ cutoff value of 14,500 for reaching a VR at week 48 was suggested. Further studies are needed in order to evaluate the calculation of TPV gIQ as a new tool for the optimization of TPV-based salvage therapy.
Highly Variable Penicillin Resistance Determinants PBP 2x, PBP 2b, and PBP 1a in Isolates of Two
Streptococcus pneumoniae
Clonal Groups, Poland
23F
-16 and Poland
6B
-20
Authors: Izdebski Radosław , Rutschmann Jens , Fiett Janusz , Sadowy Ewa , Gniadkowski Marek , Hryniewicz Waleria , Hakenbeck Regine 
Published: December 2007

ABSTRACT

Penicillin-binding proteins (PBPs) in representatives of two
Streptococcus pneumoniae
clonal groups that are prevalent in Poland, Poland
23F
-16 and Poland
6B
-20, were investigated by PBP profile analysis, antibody reactivity pattern analysis, and DNA sequence analysis of the transpeptidase (TP) domain-encoding regions of the
pbp2x
,
pbp2b
, and
pbp1a
genes. The isolates differed in their MICs of β-lactam antibiotics. The majority of the 6B isolates were intermediately susceptible to penicillin (penicillin MICs, 0.12 to 0.5 μg/ml), whereas all 23F isolates were penicillin resistant (MICs, ≥2 μg/ml). The 6B isolates investigated had the same sequence type (ST), determined by multilocus sequence typing, as the Poland
6B
-20 reference strain (ST315), but in the 23F group, isolates with three distinct single-locus variants (SLVs) in the
ddl
gene (ST173, ST272, and ST1506) were included. None of the isolates showed an identical PBP profile after labeling with Bocillin FL and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and only one pair of 6B isolates and one pair of 23F isolates (ST173 and ST272) each contained an identical combination of PBP 2x, PBP 2b, and PBP 1a TP domains. Some 23F isolates contained PBP 3 with an apparently higher electrophoretic mobility, and this feature also did not correlate with their STs. The data document a highly variable pool of PBP genes as a result of multiple gene transfer and recombination events within and between different clonal groups.
Microbicidal Properties and Cytocidal Selectivity of Rhesus Macaque Theta Defensins
Authors: Tran Dat , Tran Patti , Roberts Kevin , Ösapay George , Schaal Justin , Ouellette Andre , Selsted Michael E. 
Published: December 2007

ABSTRACTRhesus macaque θ-defensins (RTDs) are unique macrocyclic antimicrobial peptides. The three RTDs (RTD 1-3), isolated from macaque leukocytes, have broad-spectrum antimicrobial activities in vitro and share certain structural features with acyclic porcine protegrins, which are microbicidal peptides of the cathelicidin family. To understand the structural features that confer the respective cytocidal properties to θ-defensins and protegrins, we determined and compared the biological properties of RTD 1-3 and protegrin 1 (PG-1) in assays for antimicrobial activity, bacterial membrane permeabilization, and toxicity to human cells. RTD 1-3 and PG-1 had similar microbicidal potencies againstEscherichia coli,Staphylococcus aureus, andCandida albicansin low-ionic-strength (10 mM) buffers at pH 7.4. The inclusion of physiologic sodium chloride partially inhibited the microbicidal activities of the RTDs, and the degree of inhibition depended on the buffer used in the assay. Similarly, the inclusion of 10% normal human serum partially antagonized the bactericidal activities of all four peptides. In contrast, the microbicidal activities of PG-1 and RTD 1-3 againstE. coliwere unaffected by physiologic concentrations of calcium chloride and magnesium chloride. Treatment ofE. coliML35 cells with RTD 1-3 or PG-1 rapidly rendered the bacteria permeable toο-nitrophenyl-β-d-galactopyranoside, and this was accompanied by the rapid entry of the RTDs. Finally, although PG-1 was toxic to human fibroblasts and caused a marked lysis of erythrocytes, the RTDs were not cytotoxic or hemolytic. Thus, compared to PG-1, RTD 1-3 possess substantially greater cytocidal selectivity against microbes. Surprisingly, the low cytotoxicity of the RTDs did not depend on the peptides’ cyclic conformation.
The Naphthyridinone GSK364735 Is a Novel, Potent Human Immunodeficiency Virus Type 1 Integrase Inhibitor and Antiretroviral
Authors: Garvey Edward P. , Johns Brian A. , Gartland Margaret J. , Foster Scott A. , Miller Wayne H. , Ferris Robert G. , Hazen Richard J. , Underwood Mark R. , Boros Eric E. , Thompson James B. , Weatherhead Jason G. , Koble Cecilia S. , Allen Scott H. , Schaller Lee T. , Sherrill Ronald G. , Yoshinaga Tomokazu , Kobayashi Masanori , Wakasa-Morimoto Chiaki , Miki Shigeru , Nakahara Koichiro , Noshi Takeshi , Sato Akihiko , Fujiwara Tamio 
Published: December 2007

ABSTRACT

The naphthyridinone GSK364735 potently inhibited recombinant human immunodeficiency virus type 1 (HIV-1) integrase in a strand transfer assay (mean 50% inhibitory concentration ± standard deviation, 8 ± 2 nM). As expected based on the structure of the drug, it bound competitively with another two-metal binding inhibitor (
K

d

[binding constant], 6 ± 4 nM). In a number of different cellular assays, GSK364735 inhibited HIV replication with potency at nanomolar concentrations (e.g., in peripheral blood mononuclear cells and MT-4 cells, 50% effective concentrations were 1.2 ± 0.4 and 5 ± 1 nM, respectively), with selectivity indexes of antiviral activity versus in-assay cytotoxicity of at least 2,200. When human serum was added, the antiviral potency decreased (e.g., a 35-fold decrease in the presence of 100% human serum was calculated by extrapolation from the results of the MT-4 cell assay). In cellular assays, GSK364735 blocked viral DNA integration, with a concomitant increase in two-long-terminal-repeat circles. As expected, this integrase inhibitor was equally active against wild-type viruses and mutant viruses resistant to approved drugs targeting either reverse transcriptase or protease. In contrast, some but not all viruses resistant to other integrase inhibitors were resistant to GSK364735. When virus was passaged in the presence of the inhibitor, we identified resistance mutations within the integrase active site that were the same as or similar to mutations arising in response to other two-metal binding inhibitors. Finally, either additive or synergistic effects were observed when GSK364735 was tested in combination with approved antiretrovirals (i.e., no antagonistic effects were seen). Thus, based on all the data, GSK364735 exerted potent antiviral activity through the inhibition of viral DNA integration by interacting at the two-metal binding site within the catalytic center of HIV integrase.
Urine Bactericidal Activity against
Escherichia coli
Isolates Exhibiting Different Resistance Phenotypes/Genotypes in an In Vitro Pharmacodynamic Model Simulating Urine Concentrations Obtained after Oral Administration of a 400-Milligram Single Dose of Cefditoren-Pivoxil
Authors: Sevillano David , Aguilar Lorenzo , Alou Luis , Giménez María-José , Torrico Martha , González Natalia , Cafini Fabio , Relaño María-Teresa , Coronel Pilar , Prieto José 
Published: December 2007

ABSTRACT

Activity of simulated cefditoren urinary concentrations was determined against seven
Escherichia coli
isolates. Bactericidal activity was obtained from 4 to 24 h against TEM-1 (penicillinase production/hyperproduction), TEM-34 (IRT-6), and TEM-116 (extended-spectrum beta-lactamase [ESBL]) and from 6 to 8 h against SHV/TEM-116 (ESBL) but never against SHV/TEM-1 (ESBL). Extension of bactericidal activity depended on the resistance genotype/phenotype tested.
Enhanced Production of Phospholipase C and Perfringolysin O (Alpha and Theta Toxins) in a Gatifloxacin-Resistant Strain of
Clostridium perfringens
Authors: Rafii Fatemeh , Park Miseon , Bryant Amy E. , Johnson Shemedia J. , Wagner Robert D. 
Published: December 2007

ABSTRACT

Clostridium perfringens
-induced gas gangrene is mediated by potent extracellular toxins, especially alpha toxin (a phospholipase C [PLC]) and theta toxin (perfringolysin O [PFO], a thiol-activated cytolysin); and antibiotic-induced suppression of toxin synthesis is an important clinical goal. The production of PLC and PFO by a gatifloxacin-induced, fluoroquinolone-resistant mutant strain of
C. perfringens
, strain 10G, carrying a stable mutation in DNA gyrase was compared with that of the wild-type (WT) parent strain. Zymography (with sheep red blood cell and egg yolk overlays) and time course analysis [with hydrolysis of egg yolk lecithin and
O
-(4 nitrophenyl-phosphoryl)choline] demonstrated that strain 10G produced more PLC and PFO than the WT strain. Increased toxin production in strain 10G was not related either to differences in growth characteristics between the wild-type and the mutant strain or to nonsynonymous polymorphisms in PLC, PFO, or their known regulatory proteins. Increased PLC and PFO production by strain 10G was associated with increased cytotoxic activity for HT-29 human adenocarcinoma cells and with increased platelet-neutrophil aggregate formation. Four other gatifloxacin-induced gyrase mutants did not show increased toxin production, suggesting that gatifloxacin resistance was not always associated with increased toxin production in all strains of
C. perfringens
. This is the first report of increased toxin production in a fluoroquinolone-resistant strain of
C. perfringens
.
Assessment of Serum (1→3)-β-
d
-Glucan Concentration as a Measure of Disease Burden in a Murine Model of Invasive Pulmonary Aspergillosis
Authors: Wiederhold Nathan P. , Najvar Laura K. , Vallor Ana C. , Kirkpatrick William R. , Bocanegra Rosie , Molina Destiny , Olivo Marcos , Graybill John R. , Patterson Thomas F. 
Published: December 2007

ABSTRACT

Serum (1→3)-β-
d
-glucan concentrations were serially measured in the presence and absence of antifungal therapy in a murine model of invasive pulmonary aspergillosis. Serum (1→3)-β-
d
-glucan was detected early during the course of infection, and reductions in this biomarker were associated with improved survival in animals treated with antifungal agents.
Monoclonal Antibodies That Bind to Common Epitopes on the Dengue Virus Type 2 Nonstructural-1 and Envelope Glycoproteins Display Weak Neutralizing Activity and Differentiated Responses to Virulent Strains: Implications for Pathogenesis and Vaccines
Authors: Falconar Andrew K. I. 
Published: December 2007

ABSTRACTThe abilities of monoclonal antibodies (MAbs) that bind to defined sequential epitopes on the dengue virus (DENV) nonstructural-1 (NS1) glycoproteins to cross-react with epitopes on the DENV envelope (E) glycoproteins were investigated. In this study, some of these MAbs cross-reacted with the DENV type 2 (DENV-2) E glycoprotein and with synthetic peptides representing X-ray crystallographically confirmed surface-exposed regions on this glycoprotein. MAb 1G5.3 cross-reacted with the flavivirus-conserved 101-WGNGCGLFG-109 fusion sequence, the 273-SSGNL-277 DENV-2 hinge region sequence, and the 156-GKHGKEIKIT-165 sequence of virulent DENV-2 strains. MAb 1G5.4-A1-C3 cross-reacted with the 67-NTTTESRCPT-76 and 156-GKHGKEIKIT-165 sequences of virulent DENV-2 strains, the 338-EIMDLDNRHV-347 sequence from a highly virulent DENV-2 (M2) strain, and two epitopes on a virulent DENV-3 strain (288-KMDKLELKG-296 and 323-RVEYRGEDAP-332), which all contained target ELK/KLE-type motifs (underlined). These MAbs showed reduced cross-reactions with the corresponding sequences from weakly pathogenic strains of all four DENV serotypes and had either no (MAb 1G5.4-A1-C3) or weak (MAb 1G5.3) neutralizing activity against them. MAb 1G5.3 more strongly neutralized DENV-2 strains with higher pathogenic capacities, while MAb 1G5.4-A1-C3 showed increasing neutralizing titers against the virulent DENV-3 strain and the moderately virulent and highly virulent (M2) DENV-2 strains. These cross-reactions with the E glycoprotein accord with the observation that MAb 1G5.3 caused dramatic and lethal antibody-enhanced replication (AER) of a DENV-2 strain in vivo. Together with in vivo AER studies of these DENV strains using MAb 1G5.4-A1-C3, these results may account for the increased pathogenic capacities of such strains, which is likely to have important implications for pathogenesis and vaccines.
Reduction of Chemokine Secretion in Response to Mycobacteria in Infliximab-Treated Patients
Authors: Newton Sandra M. , Mackie Sarah L. , Martineau Adrian R. , Wilkinson Katalin A. , Kampmann Beate , Fisher Corinne , Dutta Shouma , Levin Michael , Wilkinson Robert J. , Pasvol Geoffrey 
Published: December 2007

ABSTRACTThe use of anti-tumor necrosis factor (TNF) agents as a treatment for chronic inflammatory conditions has been shown to be associated with an increased risk of developing tuberculosis. We studied the effect of the anti-TNF antibody infliximab on antimycobacterial immunity in 26 patients with rheumatoid arthritis or ankylosing spondylitis by use of an in vitro whole-blood model employing a reporter mycobacterium. Blood samples taken before and 30 min and 7 days after a 2-hour infliximab infusion were compared in terms of their abilities both to suppress luminescence ofMycobacterium bovisbacillus Calmette-Guérinluxand to secrete chemokines and cytokines 24 and 96 h after infection. No immediate effect of infliximab on mycobacterial luminescence was detected using this bioassay, irrespective of whether patients were receiving their first (n= 14) or maintenance (n= 12) doses of infliximab. Moreover, no effect on mycobacterial luminescence was detected when blood was taken 7 days after infliximab treatment (n= 7). By contrast, there was a significant reduction in the chemokines implicated in cellular trafficking, namely, interleukin-8, macrophage-inhibitory protein-1α (MIP-1α), MIP-1β (24 h and 96 h), and monocyte chemoattractant protein-1 (MCP-1) (24 h) following BCGluxstrain infection in the 30-minute post-infliximab-infusion blood samples (P< 0.05). This effect was sustained by MIP-1β and MCP-1 (24 h;P< 0.05) at 7 days after infusion. Our results suggest that the development of tuberculosis in infliximab-treated patients is not directly related to the mycobactericidal effects of TNF but may be due to inhibition of TNF-dependent chemokine gradients disrupting cellular migration necessary to maintain the integrity of the granuloma.
Borrelia burgdorferiComplement Regulator-Acquiring Surface Protein 2 (CspZ) as a Serological Marker of Human Lyme Disease
Authors: Kraiczy Peter , Seling Annekatrin , Brissette Catherine A. , Rossmann Evelyn , Hunfeld Klaus-Peter , Bykowski Tomasz , Burns Logan H. , Troese Matthew J. , Cooley Anne E. , Miller Jennifer C. , Brade Volker , Wallich Reinhard , Casjens Sherwood , Stevenson Brian 
Published: December 2007

ABSTRACTSerological diagnosis of Lyme disease may be complicated by antigenic differences between infecting organisms and those used as test references. Accordingly, it would be helpful to include antigens whose sequences are well conserved by a broad range of Lyme disease spirochetes. In the present study, line blot analyses were performed using recombinant complement regulator-acquiring surface protein 2 (BbCRASP-2) fromBorrelia burgdorferisensu stricto strain B31 and serum samples from human Lyme disease patients from throughout the United States and Germany. The results indicated that a large proportion of the patients had produced antibodies recognizing recombinant BbCRASP-2. In addition, Lyme disease spirochetes isolated from across North America and Europe were found to contain genes encoding proteins with high degrees of similarity to theB. burgdorferitype strain B31 BbCRASP-2, consistent with the high percentage of serologically positive patients. These data indicate that BbCRASP-2 may be valuable for use in a widely effective serological assay.