bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating Toll-Like Receptor Agonists for Potential To Treat Hepatitis C Virus Infection
Authors: Thomas Amy , Laxton Carl , Rodman Joanne , Myangar Nisha , Horscroft Nigel , Parkinson Tanya 
Published: June 2007

ABSTRACTToll-like receptors (TLRs) are key mediators of innate immunity, and their activation by microbial components leads to the production of cytokines and interferons. Recombinant alpha interferon has been used to treat several viral diseases and is the current standard of care for hepatitis C virus (HCV) infection. Recently, agonists of TLR7 and TLR9 have been shown to have clinical efficacy in HCV patients, and this is correlated with their ability to induce endogenous type I interferon production. We have carried out a comprehensive study of agonists of TLRs 1 to 9 to determine if any additional TLRs can induce antiviral molecules from human peripheral blood mononuclear cells (PBMCs). The agonists were incubated with PBMCs, and the supernatant was then removed and added to HCV replicon cells to assess antiviral activity. Agonists of TLRs 3, 4, 7, 8, and 9 were found to be potent inducers of antiviral activity in PBMC supernatants, and the activity correlated with the induction of alpha interferon and the interferon-induced antiviral biomarker 2′,5′-oligoadenylate synthase. Antiviral activity of TLR7 and TLR8 agonists was blocked by an antibody that binds to the type I interferon receptor, confirming that the antiviral activity results from type I interferon induction. TLR4 and TLR8 agonists were found to strongly induce the proinflammatory cytokines interleukin 1β and tumor necrosis factor alpha at concentrations similar to those inducing antiviral activity. This raises concerns about adverse side effects if these were to be used as antiviral agents. We therefore conclude that TLRs 3, 7, and 9 represent the most attractive targets for the development of new HCV therapies.
Net Replication ofSalmonella entericaSerovars Typhimurium and Choleraesuis in Porcine Intestinal Mucosa and Nodes Is Associated with Their Differential Virulence
Authors: Paulin Susan M. , Jagannathan Aparna , Campbell June , Wallis Timothy S. , Stevens Mark P. 
Published: June 2007

ABSTRACTSalmonella entericais a facultative intracellular pathogen of worldwide importance and causes a spectrum of diseases depending on serovar- and host-specific factors. Oral infection of pigs withS. entericaserovar Typhimurium strain 4/74 produces acute enteritis but is rarely fatal, whereas serovar Choleraesuis strain A50 causes systemic disease with a high mortality rate. With a porcine ligated ileal loop model, we observed that systemic virulence of serovar Choleraesuis A50 is not associated with enhanced intestinal invasion, secretory responses, or neutrophil recruitment compared to serovar Typhimurium 4/74. The net growth in vivo of serovar Choleraesuis A50 and serovar Typhimurium 4/74 was monitored following oral inoculation of pigs with strains harboring pHSG422, which exhibits temperature-sensitive replication. Analysis of plasmid partitioning revealed that the enteric virulence of serovar Typhimurium 4/74 relative to that of serovar Choleraesuis A50 is associated with rapid replication in the intestinal wall, whereas systemic virulence of serovar Choleraesuis A50 is associated with enhanced persistence in intestinal mesenteric lymph nodes. Faster replication of serovar Typhimurium, compared to that of serovar Choleraesuis, in the intestinal mucosa was associated with greater induction of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-8 (IL-8), and IL-18 as detected by reverse transcriptase PCR analysis of transcripts from infected mucosa. During replication in batch culture and porcine alveolar macrophages, transcription of genes encoding components of type III secretion systems 1 (sipC) and 2 (sseC) was observed to be significantly higher in serovar Typhimurium 4/74 than in serovar Choleraesuis A50, and this may contribute to the differences in epithelial invasion and intracellular proliferation. The rapid induction of proinflammatory responses by strain 4/74 may explain why pigs confine serovar Typhimurium infection to the intestines, whereas slow replication of serovar Choleraesuis may enable it to evade host innate immunity and thus disseminate by stealth.
Scavenger Receptor A Dampens Induction of Inflammation in Response to the Fungal PathogenPneumocystis carinii
Authors: Hollifield Melissa , Ghanem Elsa Bou , de Villiers Willem J. S. , Garvy Beth A. 
Published: June 2007

ABSTRACTAlveolar macrophages are the effector cells largely responsible for clearance ofPneumocystis cariniifrom the lungs. Binding of organisms to β-glucan and mannose receptors has been shown to stimulate phagocytosis of the organisms. To further define the mechanisms used by alveolar macrophages for clearance ofP. carinii, mice deficient in the expression of scavenger receptor A (SRA) were infected withP. carinii, and clearance of organisms was monitored over time. SRA-deficient (SRAKO) mice consistently clearedP. cariniifaster than did wild-type control mice. Expedited clearance corresponded to elevated numbers of activated CD4+T cells in the alveolar spaces of SRAKO mice compared to wild-type mice. Alveolar macrophages from SRAKO mice had increased expression of CD11b on their surfaces, consistent with an activated phenotype. However, they were not more phagocytic than macrophages expressing SRA, as measured by an in vivo phagocytosis assay. SRAKO alveolar macrophages produced significantly more tumor necrosis factor alpha (TNF-α) than wild-type macrophages when stimulated with lipopolysaccharide in vitro but less TNF-α in response toP. cariniiin vitro. However, upon in vivo stimulation, SRAKO mice produced significantly more TNF-α, interleukin 12 (IL-12), and IL-18 in response toP. cariniiinfection than did wild-type mice. Together, these data indicate that SRA controls inflammatory cytokines produced by alveolar macrophages in the context ofP. cariniiinfection.
The Secreted Pyomelanin Pigment of
Legionella pneumophila
Confers Ferric Reductase Activity
Authors: Chatfield Christa H. , Cianciotto Nicholas P. 
Published: June 2007

ABSTRACT

The virulence of
Legionella pneumophila
is dependent upon its capacity to acquire iron. To identify genes involved in expression of its siderophore, we screened a mutagenized population of
L. pneumophila
for strains that were no longer able to rescue the growth of a ferrous transport mutant. However, an unusual mutant was obtained that displayed a strong inhibitory effect on the
feoB
mutant. Due to an insertion in
hmgA
that encodes homogentisate 1,2-dioxygenase, the mutant secreted increased levels of pyomelanin, the
L. pneumophila
pigment that is derived from secreted homogentisic acid (HGA). Thus, we hypothesized that
L. pneumophila
-secreted HGA-melanin has intrinsic ferric reductase activity, converting Fe
3+
to Fe
2+
, but that hyperpigmentation results in excessive reduction of iron that can, in the case of the
feoB
mutant, be inhibitory to growth. In support of this hypothesis, we demonstrated, for the first time, that wild-type
L. pneumophila
secretes ferric reductase activity. Moreover, whereas the hyperpigmented mutant had increased secreted activity, an
lly
mutant specifically impaired for pigment production lacked the activity. Compatible with the nature of HGA-melanins, the secreted ferric reductase activity was positively influenced by the amount of tyrosine in the growth medium, resistant to protease, acid precipitable, and heterogeneous in size. Together, these data represent the first demonstration of pyomelanin-mediated ferric reduction by a pathogenic bacterium.
Mutation of
traP
in
Staphylococcus aureus
Has No Impact on Expression of
agr
or Biofilm Formation
Authors: Tsang Laura H. , Daily Sonja T. , Weiss Elizabeth C. , Smeltzer Mark S. 
Published: June 2007

ABSTRACT

To investigate the regulatory role of
traP
(
t
arget of
R
NAIII-
a
ctivating
p
eptide) in
Staphylococcus aureus
, we generated
traP
mutations in the clinical isolates UAMS-1 and USA300. In neither case did mutation of
traP
affect expression of the accessory gene regulator (
agr
) or the ability to form a biofilm. We were also unable to confirm that mutation of
traP
in the prototype 8325-4 laboratory strain RN6390 results in reduced expression of
agr
, reduced hemolytic activity, or an altered capacity to form a biofilm.
Assessing basketball ability in players with mental retardation
Authors: Guidetti L , Franciosi E , Emerenziani G P , Gallotta M C , Baldari C 
Published: June 2007

Background:Although athletes with mental retardation (MR) have achieved an important role, literature concerning the evaluation tests in basketball is still poor.Objective:To assess basketball ability before and after a 4-month training performed before championship for athletes with MR and to correlate ability variations with MR levels.Methods:15 trained basketball players with MR (11 men and 4 women; age range 21–43 years; MR: 3 mild, 8 moderate, 8 severe and 1 profound). Athletes were tested before (pre) and after (post) 4 month training preceding the championship. The tests assessed 4levels of ability, each one characterised by 4fundamental areasof this game: ball handling, reception, passing and shooting. Each area was divided into 5specific components.Results:The team average score, based on the score of each athlete’s 4levels, improved by 6.6 points (41.6 (SD 11.9) vs 48.2 (14.7)). The comparison between pre and post scores in each level showed increases (p<0.01), especially in level II (14.4 (3.5) vs 16.5 (3.3)) and in level III (7.1 (5.7) vs 9.2 (6.6)). Within level II, ball handling (3.67 (1.2) vs 4.37 (0.5); p<0.05) and passing (3.20 (1.2) vs 3.97 (1.3); p<0.01) improved; in level III reception (3.21 (1.1) vs 3.73 (1.1); p = 0.01) and shooting (1.82 (1.1) vs 2.45 (1.3); p<0.05) increased.Conclusions:A 4 month training caused a general improvement, especially evident in levels II and III. Total score reached in level II was negatively correlated with MR level (r = −0.56; p<0.05), indicating that athletes with lower MR obtained higher scores.
Consumption of anabolic steroids in sport, physical activity and as a drug of abuse: an analysis of the scientific literature and areas of research
Authors: Agulló-Calatayud V , González-Alcaide G , Valderrama-Zurián J C , Aleixandre-Benavent R 
Published: June 2007

Objective:The consumption of anabolic steroids (AS) has been growing continuously in recent years. It has gone beyond the sports world; AS are now widely used as drugs of abuse in connection with bodybuilding. This study sets out to assess the state of scientific research in the area.Design:Bibliometrics were employed to evaluate the literature retrieved from the principal relevant bibliographic databases: MEDLINE, SportDiscus, the Science Citation Index Expanded and the Social Sciences Citation Index. The core journals were identified along with the leading authors and research groups and their institutional affiliations. Techniques based on social network analysis were applied in order to build up a concept map of research.Results:1325 documents were retrieved. They were produced by 3131 different researchers giving a Collaboration Index of 3.32. The institutions with the most productive authors were Ball State University (Muncie, IN, USA), the École Nationale Vétérinaire de Nantes (ENVN), the Institut Municipal dInvestigació Mèdica (IMIM) (Barcelona, Spain), the Institute of Biochemistry of the German Sport University Cologne (DSHS), Iowa State University, Maastricht University and the University of Iowa.Conclusions:It was concluded that there has been an upward trend in the number of research projects. The sources used complemented one another, as 78.04% of the documents retrieved were unique to one source. The productivity ranking was headed by sports medicine journals, followed by journals of chemistry, physiology, endocrinology and substance abuse. Besides sporting activities, the most important research clusters were those connected with bodybuilding and with youth groups.
Management of end stage cardiac failure
Authors: Johnson Miriam J 
Published: June 2007

Abstract
Optimum heart failure medication and an increasing array of interventions have had an enormous effect on morbidity and mortality over the past 10 years. However, patients with end stage disease can still be highly symptomatic. Moreover, such patients are disadvantaged compared with patients with malignant disease. They are less likely to have an understanding of their illness or have access to supportive care. They are also less likely to have the opportunity to plan for care with regard to death and dying. There is increasing demand that the multi-professional clinical team gain good communication and supportive care skills, and that appropriate access to specialist palliative care services is available.
Cocaine use and stroke
Authors: Treadwell Sean D , Robinson Tom G 
Published: June 2007

Abstract
Stroke is the third most common cause of death in developed countries. In England and Wales, 1000 people under the age of 30 have a stroke each year. Cocaine is the most commonly used class A drug, and the first report of cocaine-induced stroke was in 1977. Since the development of alkaloidal “crack” cocaine in the 1980s, there has been a significant rise in the number of case reports describing both ischaemic and haemorrhagic stroke associated with cocaine use. Cocaine is a potent central nervous system stimulant, and acts by binding to specific receptors at pre-synaptic sites preventing the reuptake of neurotransmitters. The exact mechanism of cocaine-induced stroke remains unclear and there are likely to be a number of factors involved including vasospasm, cerebral vasculitis, enhanced platelet aggregation, cardioembolism, and hypertensive surges associated with altered cerebral autoregulation. The evidence surrounding each of these factors will be considered here.
Hyponatraemia in clinical practice
Authors: Biswas M , Davies J S 
Published: June 2007

Abstract
Hyponatraemia is defined as a serum sodium concentration below 135 mmol/l. It causes major diagnostic and management problems in practice. Hyponatraemic disorders are divided into euvolaemic, hypervolaemic and hypovolaemic. In the evaluation of the hyponatraemic patient, history taking should focus on identifying the potential cause, duration and symptomatology. Clinical examination should include assessment of volume status. Acute hyponatraemia of less than 48 h duration requires prompt correction. Treatment may involve hypertonic saline, isotonic saline and appropriate hormone replacement therapy depending on the aetiology. Chronic hyponatraemia should be treated with caution because of the risk of central pontine myelinolysis.
Effect of serum creatine kinase-MBmass on the early and hierarchical diagnosis of related artery reperfusion in acute myocardial infarction
Authors: Xing Shan-Shan , Xing Qi-Chong , Zhang Yun , Zhang Wei 
Published: June 2007

Abstract

Aim
To evaluate creatine kinase-MBmass (CK-MBmass) for the early diagnosis of infarct-related artery (IRA) patency after thrombolysis and the hierarchical diagnosis of related artery reperfusion (RAR).

Patients and methods
CK-MBmass and creatine kinase-MBactivity (CK-MBactivity) were measured kinetically in 48 patients treated with thrombolysis and 96 patients treated with routine drugs.

Results
In the continuous-RAR (CRAR) group, the peak values of CK-MBmass and CK-MBactivity appeared at ⩽12 h, the peak durations were maintained for ⩽8 h before decreasing to normal at ⩽42 h, which occurred more quickly than those values in the non-RAR (NRAR) group. In the temporary-RAR (TRAR) group, the peak values appeared at ⩽12 h, but no significant differences were found between the TRAR and NRAR groups in the time that the peak durations lasted before decreasing to normal values. In the reobliteration group after RAR, the peak values appeared at ⩽12 h, and the peak durations were maintained for ⩽8 h. After returning to the normal, a second peak appeared, and the time required for the values to return to normal was prolonged significantly.

Conclusions
CK-MBmass could be used as an indicator of RAR after thrombolysis; and the kinetic changes of serum CK-MBmass could be used for the hierarchical diagnosis of RAR in acute myocardial infarction.
Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia
Authors: Likhari Taruna , Magzoub Saeed , Griffiths Melanie J , Buch Harit N , Gama R 
Published: June 2007

Abstract

Background
Addison's disease may present with recurrent hypoglycaemia in subjects with type 1 diabetes mellitus. There are no data, however, on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with diabetes mellitus.

Methods
Three year retrospective study of diabetic patients with “unexplained” recurrent hypoglycaemia investigated with a short Synacthen test to exclude adrenocortical insufficiency.

Results
95 patients with type 1 diabetes mellitus were studied. Addison's disease was identified as the cause of recurrent hypoglycaemia in one patient with type 1 diabetes mellitus.

Conclusion
Addison's disease is a relatively rare but remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes mellitus. A low threshold for investigating patients with type 1 diabetes mellitus and recurrent hypoglycaemia to detect Addison's disease is therefore suggested.
Peroxisome proliferator-activated receptor γ agonists inhibit the proliferation and invasion of human colon cancer cells
Authors: Shen Dan , Deng Changsheng , Zhang Ming 
Published: June 2007

Abstract

Background and aims
Data regarding the effect of peroxisome proliferator-activated receptor γ (PPAR-γ) ligands on the invasive ability of colon cancer cells are currently limited. This study was designed to examine the effects of PPAR-γ agonists on the proliferation and invasion of two colon cancer cells to identify the role of PPAR-γ in colon cancer growth and metastasis.

Methods
SW480 and LS174T cells were treated with PPAR-γ ligands, pioglitazone and 15-deoxy-δ(12,14)-prostaglandin J2 (15d-PGJ2), as well as their combinations with the PPAR-γ antagonist GW9662. MTT assay was used to determine the antiproliferative effects. Cell cycle analysis was conducted by flow cytometry. The mRNA and protein expression were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot, respectively. The invasive ability of cells was determined by the BD BioCoat Matrige invasion chamber.

Results
Pioglitazone and 15d-PGJ2 inhibited the proliferation of both colon cancer cell lines in a dose-dependent manner. This growth inhibitory effect was reversed by GW9662. Results from flow cytometry demonstrated G1 arrest following treatment with pioglitazone and 15d-PGJ2. The expression of matrix metalloproteinase-7 (MMP-7) was only detected in LS174T cells, while its tissue inhibitor-1 (TIMP-1) was expressed in both colon cancer cells. 15d-PGJ2 and pioglitazone downregulated MMP-7 expression and upregulated TIMP-1 expression. PPAR-γ agonists can only inhibit invasive activity of LS174T cells.

Conclusions
PPAR-γ agonists have inhibitory effects on the proliferation of colon cancer cell lines associated with G1 cell cycle arrest and invasive activity. The latter effect is demonstrated in certain cell lines through the down-regulation of MMP-7 synthesis.
Effect of scatter and attenuation correction in ROI analysis of brain perfusion scintigraphy
Authors: Hashimoto J. , Ogawa K. , Kubo A. , Fukunaga A. , Onozuka S. , Bai J. 
Published: June 2007

SummaryThe aim of this study was to evaluate the effect of scatter and attenuation correction in region of interest (ROI) analysis of brain perfusion single-photon emission tomography (SPECT), and to assess the influence of selecting the reference area on the calculation of lesion-to-reference count ratios. Patients, methods: Data were collected from a brain phantom and ten patients with unilateral internal carotid artery stenosis. A simultaneous emission and transmission scan was performed after injecting 123I-iodoamphetamine. We reconstructed three SPECT images from common projection data: with scatter correction and nonuniform attenuation correction, with scatter correction and uniform attenuation correction, and with uniform attenuation correction applied to data without scatter correction. Regional count ratios were calculated by using four different reference areas (contralateral intact side, ipsilateral cerebellum, whole brain and hemisphere). Results: Scatter correction improved the accuracy of measuring the count ratios in the phantom experiment. It also yielded marked difference in the count ratio in the clinical study when using the cerebellum, whole brain or hemisphere as the reference. Difference between nonuniform and uniform attenuation correction was not significant in the phantom and clinical studies except when the cerebellar reference was used. Calculation of the lesion-to-normal count ratios referring the same site in the contralateral hemisphere was not dependent on the use of scatter correction or transmission scan-based attenuation correction. Conclusion: Scatter correction was indispensable for accurate measurement in most of the ROI analyses. Nonuniform attenuation correction is not necessary when using the reference area other than the cerebellum.
Administration of additional inactive iodide during radioiodine therapy for Graves' disease
Authors: Moka D. , Reinholz U. , Schmidt M. , Schomäcker K. , Schicha H. , Wellner U. , Dietlein M. 
Published: June 2007

Summary
Aim: Graves' hyperthyroidism and antithyroid drugs empty the intrathyroid stores of hormones and iodine. The consequence is rapid 131I turnover and impending failure of radioiodine therapy. Can administration of additional inactive iodide improve 131I kinetics? Patients, methods: Fifteen consecutive patients, in whom the 48 h post-therapeutically calculated thyroid dose was between 150 and 249 Gy due to an unexpectedly short half-life, received 3 × 200 μg inactive potassium-iodide (127I) daily for 3 days (Group A), while 17 consecutive patients with a thyroid dose of ≥ 250 Gy (Group B) served as the non-iodide group. 48 hours after 131I administration (M1) and 4 or 5 days later (M2) the following parameters were compared: effective 131I half-life, thyroid dose, total T3, total T4, 131I-activity in the T3- and T4-RIAs. Results: In Group A, the effective 131I half-life M1 before iodine (3.81 ± 0.93 days) was significantly (p <0.01) shorter than the effective 131I half-life M2 (4.65 ± 0.79 days). Effective 131I half-life M1 correlated with the benefit from inactive 127I (r = –0.79): Administration of 127I was beneficial in patients with an effective 131I half-life M1 of <3 or 4 days. Patients from Group A with high initial specific 131I activity of T3 and T4 showed lower specific 131I activity after addition of inactive iodine compared with patients from the same group with a lower initial specific 131I activity of T3 and T4 and compared with the patient group B who was given no additional inactive iodide. This correlation was mathematically described and reflected in the flatter gradient in Group A (y = 0.5195x + 0.8727 for 131I T3 and y = 1.0827x – 0.4444 for 131I T4) and steeper gradient for Group B (y = 0.6998x + 0.5417 for 131I T3 and y = 1.3191x – 0.2901 for 131I T4). Radioiodine therapy was successful in all 15 patients from Group A. Conclusion: The administration of 600 μg inactive iodide for three days during radioiodine therapy in patients with Graves' hyperthyroidism and an unexpectedly short half-life of <3 or 4 days was a safe and effective alternative to the administration of a second radioiodine capsule