bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluoroquinolone Resistance in Atypical Pneumococci and Oral Streptococci: Evidence of Horizontal Gene Transfer of Fluoroquinolone Resistance Determinants from
Streptococcus pneumoniae
Authors: Ip Margaret , Chau Shirley S. L. , Chi Fang , Tang Julian , Chan Paul K. 
Published: June 2007

ABSTRACT

Atypical strains, presumed to be pneumococcus, with ciprofloxacin MICs of ≥4.0 μg/ml and unique sequence variations within the quinolone resistance-determining regions (QRDRs) of the gyrase and topoisomerase genes in comparison with the
Streptococcus pneumoniae
R6 strain, were examined. These strains were reidentified using phenotypic methods, including detection of optochin susceptibility, bile solubility, and agglutination by serotype-specific antisera, and genotypic methods, including detection of pneumolysin and autolysin genes by PCR, 16S rRNA sequencing, and multilocus sequence typing (MLST). The analysis based on concatenated sequences of the six MLST loci distinguished the “atypical” strains from pneumococci, and these strains clustered closely with
S. mitis
. However, all these strains and five of nine strains from the viridans streptococcal group possessed one to three
gyrA
,
gyrB
,
parC
, and
parE
genes whose QRDR sequences clustered with those of
S. pneumoniae
, providing evidence of horizontal transfer of the QRDRs of the gyrase and topoisomerase genes from pneumococci into viridans streptococci. These genes also conferred fluoroquinolone resistance to viridans streptococci. In addition, the fluoroquinolone resistance determinants of 32 well-characterized
Streptococcus mitis
and
Streptococcus oralis
strains from bacteremic patients were also compared. These strains have unique amino acid substitutions in GyrA and ParC that were distinguishable from those in fluoroquinolone-resistant pneumococci and the “atypical” isolates. Both recombinational events and de novo mutations play an important role in the development of fluoroquinolone resistance.
Activity against Human Immunodeficiency Virus Type 1, Intracellular Metabolism, and Effects on Human DNA Polymerases of 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine
Authors: Nakata Hirotomo , Amano Masayuki , Koh Yasuhiro , Kodama Eiichi , Yang Guangwei , Bailey Christopher M. , Kohgo Satoru , Hayakawa Hiroyuki , Matsuoka Masao , Anderson Karen S. , Cheng Yung-Chi , Mitsuya Hiroaki 
Published: June 2007

ABSTRACT

We examined the intracytoplasmic anabolism and kinetics of antiviral activity against human immunodeficiency virus type 1 (HIV-1) of a nucleoside reverse transcriptase inhibitor, 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), which has potent activity against wild-type and multidrug-resistant HIV-1 strains. When CEM cells were exposed to 0.1 μM [
3
H]EFdA or [
3
H]3′-azido-2′,3′-dideoxythymidine (AZT) for 6 h, the intracellular EFdA-triphosphate (TP) level was 91.6 pmol/10
9
cells, while that of AZT was 396.5 pmol/10
9
cells. When CEM cells were exposed to 10 μM [
3
H]EFdA, the amount of EFdA-TP increased by 22-fold (2,090 pmol/10
9
cells), while the amount of [
3
H]AZT-TP increased only moderately by 2.4-fold (970 pmol/10
9
cells). The intracellular half-life values of EFdA-TP and AZT-TP were ∼17 and ∼3 h, respectively. When MT-4 cells were cultured with 0.01 μM EFdA for 24 h, thoroughly washed to remove EFdA, further cultured without EFdA for various periods of time, exposed to HIV-1
NL4-3
, and cultured for an additional 5 days, the protection values were 75 and 47%, respectively, after 24 and 48 h with no drug incubation, while those with 1 μM AZT were 55 and 9.2%, respectively. The 50% inhibitory concentration values of EFdA-TP against human polymerases α, β, and γ were >100 μM, >100 μM, and 10 μM, respectively, while those of ddA-TP were >100 μM, 0.2 μM, and 0.2 μM, respectively. These data warrant further development of EFdA as a potential therapeutic agent for those patients who harbor wild-type HIV-1 and/or multidrug-resistant variants.
New Plasmid-Mediated Fluoroquinolone Efflux Pump, QepA, Found in an
Escherichia coli
Clinical Isolate
Authors: Yamane Kunikazu , Wachino Jun-ichi , Suzuki Satowa , Kimura Kouji , Shibata Naohiro , Kato Haru , Shibayama Keigo , Konda Toshifumi , Arakawa Yoshichika 
Published: June 2007

ABSTRACT

Plasmid-mediated Qnr and AAC(6′)-Ib-cr have been recognized as new molecular mechanisms affecting fluoroquinolone (FQ) resistance. C316, an
Escherichia coli
strain demonstrating resistance to various FQs, was isolated in Japan. Resistance to FQs was augmented in an
E. coli
CSH2 transconjugant, but PCR failed to detect
qnr
genes, suggesting the presence of novel plasmid-mediated FQ resistance mechanisms. Susceptibility tests, DNA manipulation, and analyses of the gene and its product were performed to characterize the genetic determinant. A novel FQ-resistant gene,
qepA
, was identified in a plasmid, pHPA, of
E. coli
C316, and both
qepA
and
rmtB
genes were mediated by a probable transposable element flanked by two copies of IS
26
. Levels of resistance to norfloxacin, ciprofloxacin, and enrofloxacin were significantly elevated in
E. coli
transformants harboring
qepA
under AcrB-TolC-deficient conditions. QepA showed considerable similarities to transporters belonging to the 14-transmembrane-segment family of environmental actinomycetes. The effect of carbonyl cyanide
m
-chlorophenylhydrazone (CCCP) on accumulation of norfloxacin was assayed in a
qepA
-harboring
E. coli
transformant. The intracellular accumulation of norfloxacin was decreased in a
qepA
-expressing
E. coli
transformant, but this phenomenon was canceled by CCCP. The augmented FQ resistance level acquired by the probable intergeneric transfer of a gene encoding a major facilitator superfamily-type efflux pump from some environmental microbes to
E. coli
was first identified. Surveillance of the
qepA
-harboring clinical isolates should be encouraged to minimize further dissemination of the kind of plasmid-dependent FQ resistance determinants among pathogenic microbes.
Cross-Resistance to Medical and Agricultural Azole Drugs in Yeasts from the Oropharynx of Human Immunodeficiency Virus Patients and from Environmental Bavarian Vine Grapes
Authors: Müller Frank-Michael C. , Staudigel Andrea , Salvenmoser Stefanie , Tredup Antje , Miltenberger Rudolf , Herrmann Josef V. 
Published: June 2007

ABSTRACT

Cross-resistance among
Candida albicans
isolates from the oropharynges of human immunodeficiency virus-infected patients (
n
= 16) and environmental yeast strains of various species (
n
= 54) to medical and agricultural azole drugs was observed. Precautions against the unnecessary widespread use of azoles in the environment and human medicine are strongly recommended to prevent patients from acquiring azole-resistant yeasts.
Synergistic Activity of Dispersin B and Cefamandole Nafate in Inhibition of Staphylococcal Biofilm Growth on Polyurethanes
Authors: Donelli G. , Francolini I. , Romoli D. , Guaglianone E. , Piozzi A. , Ragunath C. , Kaplan J. B. 
Published: June 2007

ABSTRACT

Antibiotic therapies to eradicate medical device-associated infections often fail because of the ability of sessile bacteria, encased in their exopolysaccharide matrix, to be more drug resistant than planktonic organisms. In the last two decades, several strategies to prevent microbial adhesion and biofilm formation on the surfaces of medical devices, based mainly on the use of antiadhesive, antiseptic, and antibiotic coatings on polymer surfaces, have been developed. More recent alternative approaches are based on molecules able to interfere with quorum-sensing phenomena or to dissolve biofilms. Interestingly, a newly purified β-
N
-acetylglucosaminidase, dispersin B, produced by the gram-negative periodontal pathogen
Actinobacillus actinomycetemcomitans
, is able to dissolve mature biofilms produced by
Staphylococcus epidermidis
as well as some other bacterial species. Therefore, in this study, we developed new polymeric matrices able to bind dispersin B either alone or in combination with an antibiotic molecule, cefamandole nafate (CEF). We showed that our functionalized polyurethanes could adsorb a significant amount of dispersin B, which was able to exert its hydrolytic activity against the exopolysaccharide matrix produced by staphylococcal strains. When microbial biofilms were exposed to both dispersin B and CEF, a synergistic action became evident, thus characterizing these polymer-dispersin B-antibiotic systems as promising, highly effective tools for preventing bacterial colonization of medical devices.
Disease Burden Due to Enterotoxigenic
Escherichia coli
in the First 2 Years of Life in an Urban Community in Bangladesh
Authors: Qadri Firdausi , Saha Amit , Ahmed Tanvir , Al Tarique Abdullah , Begum Yasmin Ara , Svennerholm Ann-Mari 
Published: June 2007

ABSTRACT

A cohort of 321 children was followed from birth up to 2 years of age to determine the incidence of enterotoxigenic
Escherichia coli
(ETEC) in Bangladesh. The average number of diarrheal days and incidence rates were 6.6 and 2.3/child/year, respectively. ETEC was the most common pathogen and was isolated in 19.5% cases, with an incidence of 0.5 episode/child/year. The prevalence of rotavirus diarrhea was lower (10%). ETEC expressing the heat-stable enterotoxin (ST) was predominant. Strains isolated from diarrheal cases were positive for colonization factors (CFs) in higher frequency (66%) than from healthy children (33%) (
P
< 0.001). The heat-labile toxin (LT)-positive strains from healthy children were more often CF negative (92%) than those isolated from children with diarrhea (73%) (
P
< 0.001). In children with symptomatic or asymptomatic infections by CFA/I, CS1 plus CS3, CS2 plus CS3, or CS5 plus CS6 strains, a repeat episode of diarrhea or infection by the homologous CF type was uncommon. Repeat symptomatic infections were noted mostly for LT- and ST-expressing ETEC. ETEC diarrhea was more prevalent in children in the A and AB groups than in those in the O blood group (
P
= 0.032 to 0.023). Children with ETEC diarrhea were underweight and growth stunted at the 2-year follow-up period, showing the importance of strategies to prevent and decrease ETEC diarrheal morbidity in children.
Inactivation of
traP
Has No Effect on the Agr Quorum-Sensing System or Virulence of
Staphylococcus aureus
Authors: Shaw Lindsey N. , Jonsson Ing-Marie , Singh Vineet K. , Tarkowski Andrej , Stewart George C. 
Published: June 2007

ABSTRACT

The success of
Staphylococcus aureus
as a pathogen can largely be attributed to the plethora of genetic regulators encoded within its genome that temporally regulate its arsenal of virulence determinants throughout its virulence lifestyle. Arguably the most important of these is the two-component, quorum-sensing system
agr
. Over the last decade, the controversial presence of a second quorum-sensing system (the TRAP system) has been proposed, and it has been mooted to function as the master regulator of virulence in
S. aureus
by modulating
agr
. Mutants defective in TRAP are reported to be devoid of
agr
expression, lacking in hemolytic activity, essentially deficient in the secretion of virulence determinants, and avirulent in infection models. A number of research groups have questioned the validity of the TRAP findings in recent years; however, a thorough and independent analysis of its role in
S. aureus
physiology and pathogenesis has not been forthcoming. Therefore, we have undertaken such an analysis of the TRAP locus of
S. aureus
. We found that a
traP
mutant was equally hemolytic as the wild-type strain. Furthermore, transcriptional profiling found no alterations in the
traP
mutant in expression levels of
agr
or in expression levels of multiple
agr
-regulated genes (
hla
,
sspA
, and
spa
). Analysis of secreted and surface proteins of the
traP
mutant revealed no deviation in comparison to the parent. Finally, analysis conducted using a murine model of
S. aureus
septic arthritis revealed that, in contrast to an
agr
mutant, the
traP
mutant was just as virulent as the wild-type strain.
Forget me not: palliative care for people with dementia
Authors: Harris Dylan 
Published: June 2007

Abstract
Dementia is a progressive life limiting condition with increasing prevalence and complex needs. Palliative care needs of patients with dementia are often poorly addressed; symptoms such as pain are under treated while these patients are over subjected to burdensome interventions. Research into palliative care in dementia remains limited but recent developments together with national guidelines and policies set foundations for improving the delivery of palliative care to this group of the population.
Acute rhinosinusitis in adults: an update on current management
Authors: Masood Ajmal , Moumoulidis Ioannis , Panesar Jaan 
Published: June 2007

Abstract
Acute rhinosinusitis is a common disease with worldwide prevalence. It is a significant burden on the health services. It is most commonly caused by viruses and is self-limiting in nature. The diagnosis of acute rhinosinusitis is clinical and sinus radiography is not indicated routinely. Most cases of acute rhinosinusitis are treated symptomatically. However, symptoms may persist beyond 10 days when secondary bacterial infection prevails. Antibiotics are reserved for moderate or severe cases or when there is development of complications of acute rhinosinusitis. This paper provides an update on the current management of acute rhinosinusitis.
Sir Henry Halford, president of the Royal College of Physicians, with a note on his involvement in the exhumation of King Charles I
Authors: Morris John S 
Published: June 2007

Abstract
Henry Halford (formerly Vaughan) (1766–1844) was president of the Royal College of Physicians for an unprecedented 24 years. A successful physician, he had to resign his post at the Middlesex Hospital because of his growing private practice. He was physician to four reigning monarchs and had many famous patients including Geogiana Duchess of Devonshire in whom he correctly diagnosed a liver abscess when other physicians had failed. He was also involved in the exhumation of King Charles I, and the fourth cervical vertebra, through which the King had been executed, came into his possession.
Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential
Authors: Whitaker Iain S , Twine Christopher , Whitaker Michael J , Welck Mathew , Brown Charles S , Shandall Ahmed 
Published: June 2007

Abstract
When modern medicine fails, it is often useful to draw ideas from ancient treatments. The therapeutic use of fly larvae to debride necrotic tissue, also known as larval therapy, maggot debridement therapy or biosurgery, dates back to the beginnings of civilisation. Despite repeatedly falling out of favour largely because of patient intolerance to the treatment, the practice of larval therapy is increasing around the world because of its efficacy, safety and simplicity. Clinical indications for larval treatment are varied, but, in particular, are wounds infected with multidrug-resistant bacteria and the presence of significant co-morbidities precluding surgical intervention. The flies most often used in larval therapy are the facultative calliphorids, with the greenbottle blowfly (Lucilia sericata) being the most widely used species. This review summarises the fascinating and turbulent history of larval therapy from its origin to the present day, including mechanisms of action and evidence for its clinical applications. It also explores future research directions.
Long term prognosis of women with gestational diabetes in a multiethnic population
Authors: Oldfield Matthew D , Donley Penelope , Walwyn Linda , Scudamore Ian , Gregory Robert 
Published: June 2007

Abstract

Aim
To assess the glucose tolerance of South Asian and Caucasian women with previous gestational diabetes mellitus (GDM).

Method
A retrospective follow-up study of 189 women diagnosed with GDM between 1995 and 2001. Glucose tolerance was reassessed by oral glucose tolerance test at a mean duration since pregnancy of 4.38 years.

Results
South Asian women comprised 65% of the GDM population. Diabetes developed in 36.9% of the population, affecting more South Asian (48.6%) than Caucasian women (25.0%). Women developing diabetes were older at follow-up (mean (SD) 38.8 (5.7) vs 35.9 (5.6) years; p&lt;0.05) and had been heavier (body mass index 31.4 (6.3) vs 27.7 (6.7) kg/m2; p&lt;0.05), more hyperglycaemic (Gl0 6.5 (1.7) vs 5.2 (1.1) mmol/l; p&lt;0.01: G120 11.4 (3.3) vs 9.6 (1.8) mmol/l; p&lt;0.01: HbA1c 6.4 (1.0) vs 5.6 (0.7); p&lt;0.01) and more likely to require insulin during pregnancy (88.1% vs 34.0%; p&lt;0.01). Future diabetes was associated with and predicted by HbA1c taken at GDM diagnosis in both South Asian (odds ratio 4.09, 95% confidence interval 1.35 to 12.40; p&lt;0.05) and Caucasian women (OR 9.15, 95% CI 1.91 to 43.87; p&lt;0.01) as well as by previously reported risk factors of increasing age at follow-up, pregnancy weight, increasing hyperglycaemia and insulin requirement during pregnancy.

Conclusion
GDM represents a significant risk factor for future DM development regardless of ethnicity. Glycated haemoglobin values at GDM diagnosis have value in predicting future diabetes mellitus.
Cerebral haemodynamics during hypo- and hypercapnia
Authors: Terborg C. , Hautzel H. , Herzog H. , Witte O. W. , Mueller H.-W. , Krause B. J. , Poeppel T. D. 
Published: June 2007

Summary
Aim: Transcranial Doppler sonography (TCD) is increasingly used in cerebrovascular disease for monitoring brain perfusion. It allows estimation of cerebral blood flow (CBF) by the measurement of cerebral blood flow velocity (CBFV). The CBFV as well as CBF are intimately associated with the intravascular CO2-concentration. Thus, hyper- or hypocapnia can be used to induce a defined range of blood flows. The aim of our study was the comparison of vasomotor reactivity assessed with simultaneous TCD and quantitative regional CBFmeasurements (rCBF) by PET (serving as the reference method for in-vivo quantification of rCBF). Patients, methods: Six healthy young volunteers participated in this study. CBF was measured using 15O-butanol PET. A flow and dispersion- model was fitted to the measured time activity curves using arterial input curves. Each subject underwent five scans at five different end-tidal CO2 levels (EtCO2): 25, 32, 40, 48, and 55 mmHg. CBFV was assessed by continuous bilateral TCD of the middle cerebral artery (MCA). Volumes of interest for rCBF determination were placed in grey matter of the prefrontal cortex (PFC) as determined from individual MRIs. Comparisons between the rCBF, EtCO2 and CBFV were carried out with regression and correlation analysis and paired t-tests. Results: Strong positive linear correlations of rCBF and CBFV with the CO2-concentration and linear relationships between rCBF and CBFV were found in each individual. Normalised CO2-reactivities measured by TCD and PET were closely correlated. Conclusions: TCD-measurements of vascular reactivity in healthy volunteers show a high correlation to those acquired with PET that serves as the reference method of quantitative rCBF-measurement. The results of the MCA insonation are a close approximation of the rCBF changes induced by variations of EtCO2.
Proteomic discovery of 21 proteins expressed in human plasma-derived but not platelet-derived microparticles
Authors: Smalley David M. , Root Karen E. , Cho HyungJun , Ross Mark M. , Ley Klaus 
Published: June 2007

SummaryMicroparticles (MPs) are small membrane vesicles generated by essentially all cell types. In the plasma, most MPs are derived from platelets, but those from other sources, particularly leukocytes (macrophages, lymphocytes, and neutrophils), endothelial cells, and even smooth muscle cells can be detected and appear to play an important role in normal physiology and various diseases. In previous work we analyzed the proteome of MPs generated from isolated platelets (platelet MPs). Here, we report on a comparative analysis of microparticles isolated from plasma (plasma MPs) versus platelet MP using two complementary methods of comparative analysis. The first method, spectral count analysis, yielded 21 proteins detected in plasma MPs (with a total spectral count of 10 or greater) that were essentially absent in platelet MPs (with a total spectral count of 1 or 0). An additional two proteins (von Willebrand Factor, albumin) were present in both types of MPs but enriched in the plasma MPs. The second method, isotope-coded affinity tag (ICAT) labeling of proteins, supported the spectral count results for the more abundant proteins and provided better relative quantitation of differentially expressed proteins. Proteins present only in the plasma MPs include several associated with apoptosis (CD5-like antigen, galectin 3 binding protein, several complement components), iron transport (transferrin, transferrin receptor, haptoglobin), immune response (complement components, immunoglobulin J and kappa chains), and the coagulation process (protein S, coagulation factor VIII).
Relatively increased von Willebrand factor activity after off-pump coronary artery bypass graft surgery
Authors: Nierich Arno P. , Kalkman Cor J. , Fijnheer Rob , Lo Bernard 
Published: June 2007

SummaryHigh shear forces can induce structural changes in the shape of the von Willebrand factor (VWF) molecule, making it more sensitive for ADAMTS-13, a specific VWF protease. This leads to proteolysis of the highest-molecular-weight multimers, which are the most effective in platelet-mediated hemostasis under conditions of high shear stress. The use of cardiopulmonary bypass (CPB) is accompanied with high shear forces and could therefore lead to diminished VWF activity. Therefore, we studied VWF activity in patients undergoing myocardial revascularization. We enrolled 60 patients undergoing coronary artery bypass graft (CABG) surgery with and without CPB (30 in each group). ADAMTS-13 activity, VWF antigen (VWF:Ag) and propeptide levels were measured directly before and after the procedure. VWF activity was determined using both the ristocetin cofactor activity (VWF:Rcof) and collagen binding (VWF:CB) assays. VWF:Rcof and VWF:CB, both corrected for VWF:Ag, were significantly increased after the procedure in the off-pump group (p<0.001 and p=0.05, respectively), but not in the CPB group. Postoperative VWF:Ag and VWF-propeptide levels significantly increased in both groups. ADAMTS-13 activity increased after both types of surgery after correction for hemodilution. Postoperative VWF: Rcof levels correlated with postoperative D-dimer levels (p=0.025) and were associated with early cognitive decline in the off-pump group (p=0.025). Our data indicate that VWF activity is increased after off-pump CABG, but not after CABG with CPB. Since release of VWF is comparable in both groups, shear stress-induced proteolysis due to the use of CPB may be responsible for the decreased VWF activity.