bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peri-Implant Tissue Is an Important Niche for
Staphylococcus epidermidis
in Experimental Biomaterial-Associated Infection in Mice
Authors: Broekhuizen Corine A. N. , de Boer Leonie , Schipper Kim , Jones Christopher D. , Quadir Shan , Feldman Roger G. , Dankert Jacob , Vandenbroucke-Grauls Christina M. J. E. , Weening Jan J. , Zaat Sebastian A. J. 
Published: December 2006

ABSTRACT

Biomaterial-associated infections (BAI), which are predominantly caused by
Staphylococcus epidermidis
, are a significant problem in modern medicine. Biofilm formation is considered the pivotal element in the pathogenesis, but in previous mouse studies we retrieved
S. epidermidis
from peri-implant tissue. To assess the kinetics and generality of tissue colonization, we investigated BAI using two
S. epidermidis
strains, two biomaterials, and two mouse strains. With small inocula all implants were culture negative, whereas surrounding tissues were positive. When higher doses were used, tissues were culture positive more often than implants, with higher numbers of CFU. This was true for the different biomaterials tested, for both
S. epidermidis
strains, at different times, and for both mouse strains.
S. epidermidis
colocalized with host cells at a distance that was >10 cell layers from the biomaterial-tissue interface. We concluded that in mouse experimental BAI
S. epidermidis
peri-implant tissue colonization is more important than biofilm formation.
Enterohemorrhagic
Escherichia coli
O157:H7
gal
Mutants Are Sensitive to Bacteriophage P1 and Defective in Intestinal Colonization
Authors: Ho Theresa Deland , Waldor Matthew K. 
Published: December 2006

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC), especially
E. coli
O157:H7, is an emerging cause of food-borne illness. Unfortunately,
E. coli
O157 cannot be genetically manipulated using the generalized transducing phage P1, presumably because its extensive O antigen obscures the P1 receptor, the lipopolysaccharide (LPS) core subunit. The GalE, GalT, GalK, and GalU proteins are necessary for modifying galactose before it can be assembled into the repeating subunit of the O antigen. Here, we constructed
E. coli
O157:H7
gal
mutants which presumably have little or no O antigen. These strains were able to adsorb P1. P1 lysates grown on the
gal
mutant strains could be used to move chromosomal markers between EHEC strains, thereby facilitating genetic manipulation of
E. coli
O157:H7. The
gal
mutants could easily be reverted to a wild-type Gal
+
strain using P1 transduction. We found that the O157:H7
galETKM
::
aad-7
deletion strain was 500-fold less able to colonize the infant rabbit intestine than the isogenic Gal
+
parent, although it displayed no growth defect in vitro. Furthermore, in vivo a Gal
+
revertant of this mutant outcompeted the
galETKM
deletion strain to an extent similar to that of the wild type. This suggests that the O157 O antigen is an important intestinal colonization factor. Compared to the wild type, EHEC
gal
mutants were 100-fold more sensitive to a peptide derived from bactericidal permeability-increasing protein, a bactericidal protein found on the surface of intestinal epithelial cells. Thus, one way in which the O157 O antigen may contribute to EHEC intestinal colonization is to promote resistance to host-derived antimicrobial polypeptides.
Proteomic Analysis of Outer Membranes and Vesicles from Wild-Type Serogroup B
Neisseria meningitidis
and a Lipopolysaccharide-Deficient Mutant
Authors: Williams Jeannette N. , Skipp Paul J. , Humphries Holly E. , Christodoulides Myron , O'Connor C. David , Heckels John E. 
Published: December 2006

ABSTRACT

Current experimental vaccines against serogroup B
Neisseria meningitidis
are based on meningococcal outer membrane (OM) proteins present in outer membrane vesicles (OMV) in which toxic lipopolysaccharide is depleted by detergent extraction. Knowledge of the composition of OM and OMV is essential for developing new meningococcal vaccines based on defined antigens. In the current study, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and nanocapillary liquid chromatography-tandem mass spectrometry were used to investigate the proteomes of OM and OMV from meningococcal strain MC58 and OM from a lipopolysaccharide-deficient mutant. The analysis of OM revealed a composition that was much more complex than the composition that has been reported previously; a total of 236 proteins were identified, only 6.4% of which were predicted to be located in the outer membrane. The most abundant proteins included not only the well-established major OM proteins (PorA, PorB, Opc, Rmp, and Opa) but also other proteins, such as pilus-associated protein Q (PilQ) and a putative macrophage infectivity protein. All of these proteins were also present in OMV obtained by extraction of the OM with deoxycholate. There were markedly increased levels of some additional proteins in OM from the lipopolysaccharide-deficient mutant, including enzymes that contribute to the tricarboxylic acid cycle. In all the preparations, the proteins not predicted to have an OM location were predominantly periplasmic or cytoplasmic or had an unknown location, and relatively few cytoplasmic membrane proteins were detected. However, several proteins that have previously been identified as potential vaccine candidates were not detected in either OM preparations or in OMV. These results have important implications for the development and use of vaccines based on outer membrane proteins.
Enhanced Protection against Malaria by a Chimeric Merozoite Surface Protein Vaccine
Authors: Shi Qifang , Lynch Michelle M. , Romero Margarita , Burns James M. 
Published: December 2006

ABSTRACTThe 42-kDa processed fragment ofPlasmodium falciparummerozoite surface protein 1 (MSP-142) is a prime candidate for a blood-stage malaria vaccine. Merozoite surface protein 8 contains two C-terminal epidermal growth factor (EGF)-like domains that may function similarly to those of MSP-142. Immunization with either MSP-1 or MSP-8 induces protection that is mediated primarily by antibodies against conformation-dependent epitopes. In a series of comparative immunogenicity and efficacy studies using thePlasmodium yoeliirodent model, we tested the ability of recombinantP. yoeliiMSP-8 (rPyMSP-8) to complement rPyMSP-1-based vaccines. Unlike MSP-1, PyMSP-8-dependent protection required immunization with the full-length protein and was not induced with recombinant antigens that contained only the C-terminal EGF-like domains. Unlike PyMSP-8, the immunogenicity of the PyMSP-1 EGF-like domains was low when present as part of the rPyMSP-142antigen. Immunization with a mixture of rPyMSP-142and rPyMSP-8 further inhibited the antibody response to protective epitopes of rPyMSP-142and did not improve vaccine efficacy. To improve PyMSP-1 immunogenicity, we produced a chimeric antigen containing the EGF-like domains of PyMSP-1 fused to the N terminus of PyMSP-8. Immunization with the chimeric rPyMSP-1/8 antigen induced high and comparable antibody responses against the EGF-like domains of both PyMSP-1 and PyMSP-8. This enhanced MSP-1-specific antibody response and the concurrent targeting of MSP-1 and MSP-8 resulted in improved, nearly complete protection against lethalP. yoelii17XL malaria. Unexpectedly, immunization with rPyMSP-1/8 failed to protect against challenge infection with reticulocyte-restrictedP. yoelii17X parasites. Overall, these data establish an effective strategy to improve the efficacy ofP. falciparumMSP-based vaccines.
A Novel ChimericPlasmodium vivaxCircumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites
Authors: Yadava Anjali , Sattabongkot Jetsumon , Washington Michael A. , Ware Lisa A. , Majam Victoria , Zheng Hong , Kumar Sanjai , Ockenhouse Christian F. 
Published: December 2006

ABSTRACTA successful vaccine againstPlasmodium vivaxmalaria would significantly improve the health and quality of the lives of more than 1 billion people around the world. A subunit vaccine is the only option in the absence of long-term culture ofP. vivaxparasites. The circumsporozoite protein that covers the surface ofPlasmodiumsporozoites is one of the best-studied malarial antigens and the most promising vaccine in clinical trials. We report here the development of a novel “immunologically optimal” recombinant vaccine expressed inEscherichia colithat encodes a chimeric CS protein encompassing repeats from the two major alleles, VK210 and VK247. This molecule is widely recognized by sera from patients naturally exposed toP. vivaxinfection and induces a highly potent immune response in genetically disparate strains of mice. Antibodies from immunized animals recognize both VK210 and VK247 sporozoites. Furthermore, these antibodies appear to be protective in nature since they cause the agglutination of live sporozoites, an in vitro surrogate of sporozoite infectivity. These results strongly suggest that recombinant CS is biologically active and highly immunogenic across major histocompatibility complex strains and raises the prospect that in humans this vaccine may induce protective immune responses.
Rapid Clearance of Lyme Disease Spirochetes Lacking OspC from Skin
Authors: Tilly Kit , Bestor Aaron , Jewett Mollie W. , Rosa Patricia 
Published: December 2006

ABSTRACT

We previously demonstrated that
Borrelia burgdorferi
requires OspC to colonize a mammalian host. To delineate this requirement, we analyzed the clearance of
ospC
mutant spirochetes and found that they were eliminated within 48 h. We conclude that
B. burgdorferi
uses OspC to resist innate host defenses immediately after transmission.
Substance P Is Responsible for Physiological Alterations Such as Increased Chloride Ion Secretion and Glucose Malabsorption in Cryptosporidiosis
Authors: Hernandez Julio , Lackner Andrew , Aye Pyone , Mukherjee Kakali , Tweardy David J. , Mastrangelo Mary-Ann , Weinstock Joel , Griffiths Jeffrey , D'Souza Melinda , Dixit Shantu , Robinson Prema 
Published: December 2006

ABSTRACTCryptosporidiosis, caused by the protozoan parasiteCryptosporidium, causes self-limited diarrhea in immunocompetent hosts and severe life-threatening diarrhea in AIDS patients. Highly active antiretroviral therapy has been used to effectively treat cryptosporiosis in some but not all AIDS patients. Therefore, there is an urgent need for innovative drugs to treat this disease.Cryptosporidiuminfection results in intestinal pathophysiological changes such as glucose malabsorption, increased chloride ion (Cl−) secretion, and epithelial barrier disruption, leading to disease pathogenesis. In order to develop tools to combat this opportunistic pathogen, it is vital to understand mediators involved in disease pathogenesis. Substance P (SP), a neuropeptide and pain transmitter, is located in the gastrointestinal tract. SP can cause Cl−secretion in human gastrointestinal explants. However, its role in cryptosporidiosis has not been fully studied. Jejunal samples from macaques before and afterCryptosporidium parvuminfection were assayed for SP and SP receptor mRNA and protein levels by reverse transcription-PCR and by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The role of SP in pathophysiological alterations, such as Cl−secretion and glucose malabsorption, was studied using tissues derived from macaques infected withC. parvumby the Ussing chamber technique. SP and SP receptor mRNA and protein expression levels were increased in jejunal samples followingC. parvuminfection and were accompanied by increased basal ion secretion and glucose malabsorption. In vitro treatment of samples obtained from infected macaques with the SP receptor antagonist aprepitant (Emend; Merck, Whitehouse Station, NJ) completely reversed the increase in basal ion secretion and corrected the glucose malabsorption. Our findings raise the possibility of using SP receptor antagonists for the treatment of symptoms associated with cryptosporidiosis.
10 CHALLENGING PROBLEMS IN DATA MINING RESEARCH
Authors: YANG QIANG , WU XINDONG 
Published: December 2006

In October 2005, we took an initiative to identify 10 challenging problems in data mining research, by consulting some of the most active researchers in data mining and machine learning for their opinions on what are considered important and worthy topics for future research in data mining. We hope their insights will inspire new research efforts, and give young researchers (including PhD students) a high-level guideline as to where the hot problems are located in data mining. Due to the limited amount of time, we were only able to send out our survey requests to the organizers of the IEEE ICDM and ACM KDD conferences, and we received an overwhelming response. We are very grateful for the contributions provided by these researchers despite their busy schedules. This short article serves to summarize the 10 most challenging problems of the 14 responses we have received from this survey. The order of the listing does not reflect their level of importance.
Point-of-care International Normalised Ratios: UK NEQAS experience demonstrates necessity for proficiency testing of three different monitors
Authors: Kitchen Dianne , Jennings Ian , Woods Tim , Walker Isobel , Preston F. , Kitchen Stephen 
Published: December 2006

SummaryExternal quality assessment (EQA) or proficiency testing is widely considered to be necessary for International Normalised Ratio (INR) determinations performed in conventional laboratory settings. There is increasing use of near-patient-test (NPT) or point-of-care (POC) INR devices and it is not known whether EQA is also necessary for these monitors. We report here on six years experience of proficiency testing for POC monitors used by health care professionals. Three devices were used by >10 centres who participated in the programme, the CoaguChek (CUC), the CUC-S and the TAS or Rapidpoint Coag. Not all users of the same type of monitor obtained the same INR result when analysing the same plasma sample. For the three monitors the CV of results in different centres was 11–14%. The variation between results in different centres could relate to inappropriately handled proficiency testing material, inaccuracies in the calibration of the system by the manufacturer or deterioration during transport/storage of the test strips. In each survey 10–11% of centres using POC monitors obtained INR results which were >15% different from those in other centres using the same monitors. For hospital laboratories using conventional INR techniques this figure was 12%. The relationship between INR results obtained by users of the Rapidpoint Coag orTAS monitor and results obtained by conventional techniques was not constant over the period of study. During one period INRs with TAS were 13.7% greater than with conventional methods. For the remaining three time periods results were similar. Our data suggest that the variation between INR results determined with three POC monitors show similar variation to that observed in hospital laboratories using conventional methods. Based on our data we recommend that users of these POC monitors participate regularly in an independent external proficiency testing programme.
Rat models of myocardial infarction
Authors: Bhindi Ravinay , Witting Paul , McMahon Aisling , Khachigian Levon , Lowe Harry 
Published: December 2006

SummaryAnimal models of cardiovascular pathology contribute towards understanding and treatment of a broad range of conditions. Specifically in the context of acute myocardial infarction (AMI), rat models have been commonly used in studies of pathogenesis, investigation and novel therapies, although there has often been difficulty in translating experimental findings to clinical benefit. However, recent years have seen two important changes to our clinical approaches to AMI. First, there is increasing recognition that the pathophysiology of human AMI is a process occurring at many levels, not just within the epicardial coronary artery, but also within the microvasculature and the myocardium. Second, contemporary treatments are shifting away from thrombolytic dissolution of epicardial coronary thrombus to direct mechanical approaches using angioplasty and stents. These changes in our understanding of AMI have implications for the relevance of these animal models. The following discussion therefore reviews and examines the current rat models of AMI, places them in a clinical context, discusses their advantages and limitations, and outlines likely future developments, providing an overview of the place of these important models of AMI.
A multi-dose pharmacokinetic study of dalteparin in haemodialysis patients
Authors: Byrne Stephen , Szczech Lynda , Ortel Thomas , Perry Stephanie , O’Shea Susan 
Published: December 2006

SummaryLow-molecular-weight heparins undergo renal elimination, and therefore the proper dosing in hemodialysis (HD) patients is unclear. It was the objective of this study to evaluate the pharmacokinetic (PK) parameters of dalteparin in patients receiving chronic HD for end-stage renal disease. We performeda multidose PK study with prophylactic doses of dalteparin in twelve HD patients. Dalteparin 5,000 IU was administered subcutaneously daily for four consecutive days, with HD performed on day2 and day 4. Anti-factor Xa activity was determined daily and at multiple blood samples after the 3rd and 4th dose. Eleven of 12 patients completed the study. The mean (range) PK parameters determined after the 4th dose were as follows: i) maximum concentration (Cmax) was 0.31 IU/ml (0.06 to 0.55 IU/ml); ii) time to Cmax was 3.55 hours (2.59 to 4.96 hr); iii) area under the curve was 3.24 IU*hr/ml (0.64 to 6.44 IU*hr/ml); iv) half-life was 3.82 hr (2.03 to 9.63 hr); and v) trough anti-factor Xa activity 0.04 IU/ml (0.02 to 0.08 IU/ml). No major bleeding was observed. In general, patients with lower body weight exhibited a higher Cmax. From this pilot PK study, we have determined initial PK parameters for dalteparin in HD patients. Although a standard prophylactic dose was used, we found that in this patient population differences in body weight influenced the Cmax. Future studies to evaluate the PK parameters of dalteparin in patients receiving chronic HD may have to use weight-based dosing and will need to be performed over a longer period of time.
Platelet-induced growth of human fibroblasts is associated with an increased expression of 5-lipoxygenase
Authors: Berg Cecilia , Hammarström Sven , Herbertsson Helena , Lindström Eva , Svensson Ann-Charlotte , Söderström Mats , Tengvall Pentti , Bengtsson Torbjörn 
Published: December 2006

SummaryProliferation of fibroblasts is vital for adequate wound healing but is probably also involved in different hyperproliferative disorders such as atherosclerosis and cancer. The regeneration of tissue usually starts with coagulation, involving release of mitogenic and inflammatory factors from activated platelets. This study focuses on the role of eicosanoids in the proliferative effects of platelets on human fibroblasts. We show that the phospholipase A2 inhibitor 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), the combined cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) and the LOX inhibitor 5,8,11-eicosatriynoic acid (ETI) block the platelet-induced proliferation of serum starved subconfluent human fibroblasts. Anti-proliferative effects were also obtained by specific inhibition of 5-LOX with 5,6-dehydro arachidonic acid (5,6-dAA), whereas the 12-LOX inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) did not affect the platelet-stimulated growth of fibroblasts. The expression of 5-LOX was analyzed by reverse-transcriptase-mediated PCR (RT-PCR), Western blotting and HPLC. 5-LOX message and protein was detected in fibroblasts but not in platelets. Incubation with platelets markedly increased, already after one hour, the expression of 5-LOX in the fibroblast culture. The increased 5-LOX activity was associated with an elevated level of the 5-LOX metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) reaching its maximum after 1–2 hours of co-incubation of fibroblasts and platelets. The 5-HETE production was reduced by the inhibitors DMDA, ETYA and ETI. In conclusion, this study suggests that platelet-stimulated proliferation of fibroblasts is mediated by an increased 5-LOX activity, which supports recent findings indicating a crucial role for this enzyme in proliferative disorders such as atherosclerosis.
LFA-1 and VLA-4 involved in human high proliferative potentialendothelial progenitor cells homing to ischemic tissue
Authors: Duan Huaxin , Cheng Lamei , Sun Xuan , Wu Yonggang , Hu Liangshan , Wang Jian , Zhao Huiping , Lu Guangxiu 
Published: December 2006

SummaryCumulative evidences have revealed that endothelial progenitor cell (EPC) transplantation can promote the neovascularization in ischemic tissue, but the mechanism of EPCs homing to the site of ischemia is poorly understood. In this study, to investigate the mechanism of human umbilical cord blood-derived high proliferative potential-endothelial progenitor cells (HPP-EPCs) homing to ischemic tissue we evaluated the expression of lymphocyte function-associated antigen-1 (LFA-1, or CD11a/CD18) and very late antigen-4 (VLA-4, or CD49d/CD29) in EPCs and the changes of expression level of their ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in ischemic tissue and performed the adhesion and migration assays to analyze the interaction between the receptors and ligands. Furthermore, we studied the roles of LFA-1 and VLA-4 in EPC homing in an ischemic model of mice. The results show that LFA-1 andVLA-4 were expressed in HPPEPCs and ICAM-1 and VCAM-1 were expressed in vessel endothelium in ischemic tissues. The pre-incubation of HPP-EPCs with neutralizing antibodies against CD11a or CD49d reduced adhesion and migration of HPP-EPCs in vitro and reduced recovery of hind-limb blood flow, capillary density and incorporation of HPP-EPC into ischemic tissues in vivo. Furthermore, the pre-incubation of HPP-EPCs with the combination of CD11a and CD49d antibodies led to synergistically negative effects on adhesion and transmigration of HPP-EPCs in vitro, and on the homing of HPP-EPCs to ischemic tissue and on neovascularization capacity in vivo. These results indicate that LFA-1 andVLA-4 are involved in HPP-EPC homing to ischemic tissues.