bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective evaluation of normal mean platelet volume in discriminating hyperdestructive thrombocytopenia from hypoproductive thrombocytopenia
Authors: NUMBENJAPON T. , MAHAPO N. , PORNVIPAVEE R. , SRISWASDI C. , MONGKONSRITRAGOON W. , LEELASIRI A. , PRAYOONWIWAT W. 
Published: August 2007

SummaryBone marrow (BM) examination is the gold standard test in discriminating between hyperdestructive thrombocytopenia and hypoproductive thrombocytopenia. However, this procedure is invasive. Mean platelet volume (MPV) is simple and may be used as an alternative diagnostic test in distinguishing these two types of thrombocytopenia. All thrombocytopenic patients (platelet count: <150.0 × 109/l), except those with congestive splenomegaly, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulopathy, were enrolled into the study prospectively. The mean MPV of normal Thais (7.9 fl) was tested as a cutoff value. Any thrombocytopenic patient with MPV of >7.9 fl would be presumptively diagnosed as hyperdestructive thrombocytopenia, whereas one with MPV of ≤7.9 fl would be presumptively diagnosed as hypoproductive thrombocytopenia. One hundred two patients were completely evaluated. When compared with the BM examination, the MPV of >7.9 fl could predict hyperdestructive thrombocytopenia with a sensitivity of 82.3% (95% CI: 70.5–90.8), a specificity of 92.5% (95% CI: 79.6–98.4), a positive predictive value of 94.4% (95% CI: 84.6–98.8), a negative predictive value of 77.1% (95% CI: 62.7–88.0), and a likelihood ratio of 11.0. In conclusion, the mean MPV of normal Thais may be used as a cutoff value in distinguishing these two types of thrombocytopenia.
The JAK2V617F tyrosine kinase mutation identifies clinically latent myeloproliferative disorders in patients presenting with hepatic or portal vein thrombosis
Authors: GOULDING C. , UTTENTHAL B. , FORONI L. , DUKE V. , TRAORE A. , KOTTARIDIS P. , HOFFBRAND A. V. , PATCH D. , MCNAMARA C. 
Published: August 2007

SummaryClinically latent myeloproliferative disorders (MPDs) are important causes of what would otherwise be considered idiopathic hepatic (HVT) or portal vein thrombosis (PVT). They may be difficult to diagnose initially because the peripheral blood count may be normal at the time of thrombosis. A strong association between an activating mutation of the gene encoding one of the Janus kinase family of tyrosine kinases (JAK2V617F) and the Philadelphia chromosome‐negative MPDs has been identified. We have studied 19 patients with unexplained HVT or PVT and tested for JAK2V617F. Fourteen (74%) of the 19 patients were heterozygous for JAK2V617F but did not meet diagnostic criteria for a MPD at the time of presentation with thrombosis. Prolonged follow‐up established the presence of an overt MPD in 13 of the 14 patients after a median duration of 38 months. We recommend testing for JAK2V617F in all patients with unexplained HVT or PVT, to identify latent MPDs and prevent potential complications.
The role of radixin in altered localization of canalicular conjugate export pump Mrp2 in cholestatic rat liver
Authors: Kojima Hideyuki , Sakurai Shinya , Yoshiji Hitoshi , Uemura Masahito , Yoshikawa Masahide , Fukui Hiroshi 
Published: August 2007

Aim:  Cholestasis has been associated with the endocytic retrieval of multidrug resistance protein 2 (Mrp2), but its mechanism is still unclear. Recent studies have indicated that radixin, a cross‐linker between the actin filaments and membrane proteins, may be activated by phosphorylation and may be required for the canalicular localization of Mrp2.Methods:  We investigated the role of radixin in the altered localization of Mrp2 in rat models of intrahepatic (ethinyl estradiol treatment) and extrahepatic (bile duct ligation) cholestasis using immunofluorescence microscopy. The changes in localization and expression were analyzed using Scion Image for Windows.Results:  In both models, Mrp2 was localized outside as well as inside the ZO‐1 staining, indicating partial dislocation from the canalicular membrane. In contrast to the steep elevation of the immunostaining intensity curves for Mrp2 in the controls, the corresponding curves in both models were broadened and flattened, confirming endocytic retrieval into the hepatocytes. Mrp2 and radixin were colocalized at the canalicular domain in the controls, whereas in both cholestatic rats they were dissociated at some canaliculi, indicating the disturbed colocalization of Mrp2 and radixin in cholestasis. The fluorescence of phosphorylated radixin, an active form of radixin, markedly decreased in both cholestatic models, which was supported by the reduced peak fluorescence intensities.Conclusion:  The disturbed colocalization of Mrp2 and radixin may contribute to the endocytic retrieval of Mrp2 in cholestasis due to the failure to anchor Mrp2 in the canalicular membrane, in which the phosphorylated radixin may play a major role.
Pulmonary versus Systemic Delivery of Antibiotics: Comparison of Vancomycin Dispositions in the Isolated Rat Lung
Authors: de Jesús Valle María José , López Francisco González , Hurlé Alfonso Domínguez-Gil , Navarro Amparo Sánchez 
Published: August 2007

ABSTRACT
Vancomycin dispositions in the respiratory system were compared after systemic and inhalatory administration under two respiratory conditions using the isolated-lung model. Inhalatory delivery led to much higher drug levels in pulmonary tissue and fluids. The respiratory pattern affects vancomycin disposition in the pulmonary system regardless of the administration route.
Genetic Analysis of the Dihydrofolate Reductase-Thymidylate Synthase Gene from Geographically Diverse Isolates of
Plasmodium malariae
Authors: Tanomsing Naowarat , Imwong Mallika , Pukrittayakamee Sasithon , Chotivanich Kesinee , Looareesuwan Sornchai , Mayxay Mayfong , Dolecek Christiane , Hien Tran Tinh , do Rosario Virgilio E. , Arez Ana Paula , Michon Pascal , Snounou Georges , White Nicholas J. , Day Nicholas P. J. 
Published: August 2007

ABSTRACT

Plasmodium malariae
, the parasite responsible for quartan malaria, is transmitted in most areas of malaria endemicity and is associated with significant morbidity. The sequence of the gene coding for the enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) was obtained from field isolates of
P. malariae
and from the closely related simian parasite
Plasmodium brasilianum
. The two sequences were nearly 100% homologous, adding weight to the notion that they represent genetically distinct lines of the same species. A survey of polymorphisms of the
dhfr
sequences in 35 isolates of
P. malariae
collected from five countries in Asia and Africa revealed a low number of nonsynonymous mutations in five codons. In five of the isolates collected from southeast Asia, a nonsynonymous mutation was found at one of the three positions known to be associated with antifolate resistance in other
Plasmodium
species. Five isolates with the wild-type DHFR could be assayed for drug susceptibility in vitro and were found to be sensitive to pyrimethamine (mean 50% inhibitory concentration, 2.24 ng/ml [95% confidence interval, 0.4 to 3.1]).
Antiproliferative Effect of Dihydroxyacetone on
Trypanosoma brucei
Bloodstream Forms: Cell Cycle Progression, Subcellular Alterations, and Cell Death
Authors: Uzcátegui Néstor L. , Carmona-Gutiérrez Didac , Denninger Viola , Schoenfeld Caroline , Lang Florian , Figarella Katherine , Duszenko Michael 
Published: August 2007

ABSTRACT

We evaluated the effects of dihydroxyacetone (DHA) on
Trypanosoma brucei
bloodstream forms. DHA is considered an energy source for many different cell types.
T. brucei
takes up DHA readily due to the presence of aquaglyceroporins. However, the parasite is unable to use it as a carbon source because of the absence of DHA kinase (DHAK). We could not find a homolog of the relevant gene in the genomic database of
T. brucei
and have been unable to detect DHAK activity in cell lysates of the parasite, and the parasite died quickly if DHA was the sole energy source in the medium. In addition, during trypanosome cultivation, DHA induced growth inhibition with a 50% inhibitory concentration of about 1 mM, a concentration that is completely innocuous to mammals. DHA caused cell cycle arrest in the G
2
/M phase of up to 70% at a concentration of 2 mM. Also, DHA-treated parasites showed profound ultrastructural alterations, including an increase of vesicular structures within the cytosol and the presence of multivesicular bodies, myelin-like structures, and autophagy-like vacuoles, as well as a marked disorder of the characteristic mitochondrion structure. Based on the toxicity of DHA for trypanosomes compared with mammals, we consider DHA a starting point for a rational design of new trypanocidal drugs.
Phase 2 Study of Ceftaroline versus Standard Therapy in Treatment of Complicated Skin and Skin Structure Infections
Authors: Talbot George H. , Thye Dirk , Das Anita , Ge Yigong 
Published: August 2007

ABSTRACT

Ceftaroline, the bioactive metabolite of ceftaroline fosamil (previously PPI-0903, TAK-599), is a broad-spectrum cephalosporin with potent in vitro activity against multidrug-resistant gram-positive aerobic pathogens, including methicillin-resistant
Staphylococcus aureus
. A randomized, observer-blinded study to evaluate the safety and efficacy of ceftaroline versus standard therapy in treating complicated skin and skin structure infections (cSSSI) was performed. Adults with cSSSI, including at least one systemic marker of inflammation, were randomized (2:1) to receive intravenous (i.v.) ceftaroline (600 mg every 12 h) or i.v. vancomycin (1 g every 12 h) with or without adjunctive i.v. aztreonam (1 g every 8 h) for 7 to 14 days. The primary outcome measure was the clinical cure rate at a test-of-cure (TOC) visit 8 to 14 days after treatment. Secondary outcomes included the microbiological success rate (eradication or presumed eradication) at TOC and the clinical relapse rate 21 to 28 days following treatment. Of 100 subjects enrolled, 88 were clinically evaluable; the clinical cure rate was 96.7% (59/61) for ceftaroline versus 88.9% (24/27) for standard therapy. Among the microbiologically evaluable subjects (i.e., clinically evaluable and having had at least one susceptible pathogen isolated at baseline), the microbiological success rate was 95.2% (40/42) for ceftaroline versus 85.7% (18/21) for standard therapy. Relapse occurred in one subject in each group (ceftaroline, 1.8%; standard therapy, 4.3%). Ceftaroline exhibited a very favorable safety and tolerability profile, consistent with that of marketed cephalosporins. Most adverse events from ceftaroline were mild and not related to treatment. Ceftaroline holds promise as a new therapy for treatment of cSSSI and other serious polymicrobial infections.
Contributions of the Combined Effects of Topoisomerase Mutations toward Fluoroquinolone Resistance in
Escherichia coli
Authors: Morgan-Linnell Sonia K. , Zechiedrich Lynn 
Published: August 2007

ABSTRACT

In defined, isogenic strains, at least three mutations, two of which must be in
gyrA
, were required to exceed the CLSI breakpoint for fluoroquinolone resistance. Strains with double mutations in both
gyrA
and
parC
had even higher MICs of fluoroquinolones than strains with totals of three mutations.
Targeted Intranasal Mupirocin To Prevent Colonization and Infection by Community-Associated Methicillin-Resistant
Staphylococcus aureus
Strains in Soldiers: a Cluster Randomized Controlled Trial
Authors: Ellis Michael W. , Griffith Matthew E. , Dooley David P. , McLean Joseph C. , Jorgensen James H. , Patterson Jan E. , Davis Kepler A. , Hawley Joshua S. , Regules Jason A. , Rivard Robert G. , Gray Paula J. , Ceremuga Julia M. , DeJoseph Mary A. , Hospenthal Duane R. 
Published: August 2007

ABSTRACT

Community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) is an emerging pathogen that primarily manifests as uncomplicated skin and soft tissue infections. We conducted a cluster randomized, double-blind, placebo-controlled trial to determine whether targeted intranasal mupirocin therapy in CA-MRSA-colonized soldiers could prevent infection in the treated individual and prevent new colonization and infection within their study groups. We screened 3,447 soldiers comprising 14 training classes for CA-MRSA colonization from January to December 2005. Each training class was randomized to either the mupirocin or placebo study group, and the participants identified as CA-MRSA colonized were treated with either mupirocin or placebo. All participants underwent repeat screening after 8 to 10 weeks and were monitored for 16 weeks for development of infection. Of 3,447 participants screened, 134 (3.9%) were initially colonized with CA-MRSA. Five of 65 (7.7%; 95% confidence interval [95% CI], 4.0% to 11.4%) placebo-treated participants and 7 of 66 (10.6%; 95% CI, 7.9% to 13.3%) mupirocin-treated participants developed infections; the difference in the infection rate of the placebo- and mupirocin-treated groups was −2.9% (95% CI, −7.5% to 1.7%). Of those not initially colonized with CA-MRSA, 63 of 1,459 (4.3%; 95% CI, 2.7% to 5.9%) of the placebo group and 56 of 1,607 (3.5%; 95% CI, 2.6% to 5.2%) of the mupirocin group developed infections; the difference in the infection rate of the placebo and mupirocin groups was 0.8% (95% CI, −1.0% to 2.7%). Of 3,447 participants, 3,066 (89%) were available for the second sampling and completed follow-up. New CA-MRSA colonization occurred in 24 of 1,459 (1.6%; 95% CI, 0.05% to 2.8%) of the placebo group participants and 23 of 1,607 (1.4%; 95% CI, 0.05% to 2.3%) of the mupirocin group participants; the difference in the infection rate of the placebo and mupirocin groups was 0.2% (95% CI, −1.3% to 1.7%). Despite CA-MRSA eradication in colonized participants, this study showed no decrease in infections in either the mupirocin-treated individuals or within their study group. Furthermore, CA-MRSA eradication did not prevent new colonization within the study group.
Identification ofFrancisella tularensis Himar1-Based Transposon Mutants Defective for Replication in Macrophages
Authors: Maier Tamara M. , Casey Monika S. , Becker Rachel H. , Dorsey Caleb W. , Glass Elizabeth M. , Maltsev Natalia , Zahrt Thomas C. , Frank Dara W. 
Published: August 2007

ABSTRACTFrancisella tularensis, the etiologic agent of tularemia in humans, is a potential biological threat due to its low infectious dose and multiple routes of entry.F. tularensisreplicates within several cell types, eventually causing cell death by inducing apoptosis. In this study, a modifiedHimar1transposon (HimarFT) was used to mutagenizeF. tularensisLVS. Approximately 7,000 Kmrclones were screened using J774A.1 macrophages for reduction in cytopathogenicity based on retention of the cell monolayer. A total of 441 candidates with significant host cell retention compared to the parent were identified following screening in a high-throughput format. Retesting at a defined multiplicity of infection followed by in vitro growth analyses resulted in identification of approximately 70 candidates representing 26 unique loci involved in macrophage replication and/or cytotoxicity. Mutants carrying insertions in seven hypothetical genes were screened in a mouse model of infection, and all strains tested appeared to be attenuated, which validated the initial in vitro results obtained with cultured macrophages. Complementation and reverse transcription-PCR experiments suggested that the expression of genes adjacent to theHimarFTinsertion may be affected depending on the orientation of the constitutivegroELpromoter region used to ensure transcription of the selective marker in the transposon. A hypothetical gene, FTL_0706, postulated to be important for lipopolysaccharide biosynthesis, was confirmed to be a gene involved in O-antigen expression inF. tularensisLVS and Schu S4. These and other studies demonstrate that therapeutic targets, vaccine candidates, or virulence-related genes may be discovered utilizing classical genetic approaches inFrancisella.
Overproduction of DNA Adenine Methyltransferase Alters Motility, Invasion, and the Lipopolysaccharide O-Antigen Composition of
Yersinia enterocolitica
Authors: Fälker Stefan , Schilling Jennifer , Schmidt M. Alexander , Heusipp Gerhard 
Published: August 2007

ABSTRACT

DNA adenine methyltransferase (Dam) not only regulates basic cellular functions but also interferes with the proper expression of virulence factors in various pathogens. We showed previously that for the human pathogen
Yersinia enterocolitica
, overproduction of Dam results in increased invasion of epithelial cells. Since invasion and motility are coordinately regulated in
Y. enterocolitica
, we analyzed the motility of a Dam-overproducing (Dam
OP
) strain and found it to be highly motile. In Dam
OP
strains, the operon encoding the master regulator of flagellum biosynthesis,
flhDC
, is upregulated. We show that the increased invasion is not due to enhanced expression of known and putative
Y. enterocolitica
invasion and adhesion factors, such as Inv, YadA, Ail, Myf fibrils, Pil, or Flp pili. However, overproduction of Dam no longer results in increased invasion for an
inv
mutant strain, indicating that Inv is necessary for increased invasion after overproduction of Dam. Since we show that overproduction of Dam results in an increased amount of rough lipopolysaccharide (LPS) molecules lacking O-antigen side chains, this implies that reduced steric hindrance by LPS might contribute to increased invasion by a
Y. enterocolitica
Dam
OP
strain. Our data add an important new aspect to the various virulence-associated phenotypes influenced by DNA methylation in
Y. enterocolitica
and indicate that Dam targets regulatory processes modulating the composition and function of the bacterial surface.
Mannheimia haemolytica
Leukotoxin Binds to Lipid Rafts in Bovine Lymphoblastoid Cells and Is Internalized in a Dynamin-2- and Clathrin-Dependent Manner
Authors: Atapattu Dhammika N. , Czuprynski Charles J. 
Published: August 2007

ABSTRACT

Mannheimia haemolytica
is the principal bacterial pathogen of the bovine respiratory disease complex. Its most important virulence factor is a leukotoxin (LKT), which is a member of the RTX family of exotoxins produced by many gram-negative bacteria. Previous studies demonstrated that LKT binds to the β
2
-integrin LFA-1 (CD11a/CD18) on bovine leukocytes, resulting in cell death. In this study, we demonstrated that depletion of lipid rafts significantly decreases LKT-induced bovine lymphoblastoid cell (BL-3) death. After binding to BL-3 cells, some of the LKT relocated to lipid rafts in an LFA-1-independent manner. We hypothesized that after binding to LFA-1 on BL-3 cells, LKT moves to lipid rafts and clathrin-coated pits via a dynamic process that results in LKT internalization and cytotoxicity. Knocking down dynamin-2 by small interfering RNA reduced both LKT internalization and cytotoxicity. Similarly, expression of dominant negative Eps15 protein expression, which is required for clathrin coat formation, reduced LKT internalization and LKT-mediated cytotoxicity to BL-3 cells. Finally, we demonstrated that inhibiting actin polymerization reduced both LKT internalization and LKT-mediated cytotoxicity. These results suggest that both lipid rafts and clathrin-mediated mechanisms are important for LKT internalization and cytotoxicity in BL-3 cells and illustrate the complex nature of LKT internalization by the cytoskeletal network.
Rapid Elimination ofToxoplasma gondiiby Gamma Interferon-Primed Mouse Macrophages Is Independent of CD40 Signaling
Authors: Zhao Yanlin , Wilson Douglas , Matthews Suzanne , Yap George S. 
Published: August 2007

ABSTRACTAutophagy has been implicated in the intracellular destruction ofToxoplasma gondiiby primed macrophages following gamma interferon (IFN-γ) activation of p47 GTPases. CD40 ligation has also been shown to trigger autophagic elimination ofT. gondiiindependent of IFN-γ and p47 GTPases. Here we demonstrate that IFN-γ/p47 GTPase-dependent elimination ofT. gondiiby strain CPS vaccine-primed macrophages is independent of CD40/tumor necrosis factor signaling. Similar to wild-type controls, both CD40-deficient and tumor necrosis factor receptor 1/2 (TNFR1/2)-deficient macrophages can efficiently eliminate invaded strain GFP-PTG and restrain its replication following priming. In contrast, macrophages from mice lacking the IFN-γ receptor gene neither clear the parasites nor repress their proliferation. Thus, CD40 and IFN-γ-induced pathogen elimination might represent two independent resistance pathways, the latter of which plays a primary role in anti-Toxoplasmaimmunity in mice.
Quantification of the physiological and performance characteristics of on-court tennis drills
Authors: Reid M , Duffield R , Dawson B , Baker J , Crespo M 
Published: August 2007

Objective:To determine the physiological responses and stroke characteristics of common on-court tennis training drills.Methods:Six high-performance players performed 1×6 repetitions of four common on-court training drills on two separate occasions; once with 30:30 seconds work:rest, and once with 60:30 seconds work:rest. Heart rate (HR), blood lactate [La−], distance covered by the player (GPS) and rate of perceived exertion (RPE) were measured before the start of each drill and after the first and last repetition. Measures of shot count and accuracy and post-impact ball velocity per drill were also recorded.Results:Significant differences were observed between drills in measures of [La−] and RPE both during ([La−] 2.1–4.4 mmol/l; RPE 2.6–5.1) and after ([La−] 4.4–10.6 mmol/l; RPE 4.3–7.6) drills, yet individual HR responses (160–182 beats/minute) were similar. Increased work times (60v30 seconds) also produced consistently raised [La−] and RPE responses, yet players’ average movement velocities and forehand ball speed and accuracy remained consistent. Significant decreases in forehand ball speed and accuracy were observed during higher-intensity training drills, whereas significantly lower mean movement velocities underpinned performance of less intensive drills.Conclusions:The four drills produced physiological responses that reflect previously reported normal or maximal matchplay demands. These results point to the adaptations possible with adjustment of training drill type and load specific to matchplay demands or training phase.