bluuebunny/crossref_metadata_2025_split huggingface dataset:
Auditory–visual intermodal matching of small numerosities in 6‐month‐old infants
Authors: Kobayashi Tessei , Hiraki Kazuo , Hasegawa Toshikazu 
Published: July 2005

AbstractRecent studies have reported that preverbal infants are able to discriminate between numerosities of sets presented within a particular modality. There is still debate, however, over whether they are able to perform intermodal numerosity matching, i.e. to relate numerosities of sets presented with different sensory modalities. The present study investigated auditory–visual intermodal matching of small numerosities in infancy by using a violation‐of‐expectation paradigm. After being familiarized with events of a few objects impacting a surface successively, 6‐month‐old infants were alternatively presented with two and three tones while the movement of each object remained hidden behind an opaque screen. The screen was then removed to reveal either two or three objects. Results showed that the infants looked significantly longer at the numerically nonequivalent events (the three‐tone/two‐object and the two‐tone/three‐object events) than at the numerically equivalent events (the two‐tone/two‐object and the three‐tone/three‐object events) irrespective of the rate or duration of auditory tones presented. These findings suggest that infants are capable of performing intermodal matching of small numerosities and that they might possess abstract representations of numerosity beyond sensory modalities.
Expression of Scavenger Receptor CD36 in Chronic Renal Failure Patients
Authors: Chmielewski Michal , Bryl Ewa , Marzec Lukasz , Aleksandrowicz Ewa , Witkowski Jacek M. , Rutkowski Boleslaw 
Published: July 2005

Abstract:  Background:  Patients with chronic renal failure (CRF) are at increased risk of atherosclerosis development. One of the major steps in pathogenesis of atherosclerosis is formation of foam cells. Scavenger receptor CD36 is among the major receptors for oxidized low density lipoproteins (oxLDL) and therefore it plays a crucial role in foam cell formation. The aim of the present study was to investigate the expression of CD36 on blood monocytes of CRF patients.Methods:  Expression of CD36 on blood monocytes of CRF patients treated with hemodialysis (HD), peritoneal dialysis (PD), those not yet on dialysis (predialysis), and controls was assessed with the use of flow cytometry. Additionally, the major lipid peroxidation markers, malondialdehyde (MDA) and 4‐hydroxyalkenals (HAE), were measured. Further, impact of treatment with HMG‐CoA reductase inhibitors (statins) on CD36 expression in CRF patients was evaluated.Results:  Expression of monocyte CD36, measured as mean fluorescence intensity (MFI) was significantly higher in HD and PD patients, when compared to controls without renal insufficiency (respectively: 1011 ± 288 and 1000 ± 309 vs. 710 ± 313; P < 0.01 for both groups). This was not the case in predialysis group (828 ± 363 vs. 710 ± 313). Higher concentrations of lipid peroxidation indicators, MDA and HAE were observed in all three subgroups of CRF patients (2.1 ± 0.51, 2.02 ± 0.27, and 1.81 ± 0.53 µm in HD, PD, and predialysis group, respectively, vs. 1.13 ± 0.59 µm in controls; P < 0.01). Patients treated with statins showed significantly lower CD36 expression than patients without statin therapy.Conclusions:  The present study, for the first time, demonstrates increased expression of CD36 scavenger receptor in CRF patients. This may be a possible risk factor for accelerated atherogenesis observed in this group of patients.
Tissue Factor, Its Inhibitor, and the Thrombogenicity of Two New Synthetic Membranes
Authors: Zemanova Pavlina , Opatrny Karel , Vit Ladislav , Sefrna Frantisek 
Published: July 2005

Abstract:  Background:  The aim of the study was to compare the effect of new high‐flux hemodialysis membranes made from polyacrylonitrile (AN69ST) and polysulfone (Helixone) on the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) playing a key role in hemostasis. Established thrombogenicity markers were also determined.Methods:  In a clinical prospective randomized study, 10 patients were examined using either membrane at the start and at minutes 15, 60, and 240 of hemodialysis.Results:  Increases in the plasma TF levels reached significance at the end of hemodialysis with both membranes, with the Helixone also after 15 min. TFPI levels tended to rise significantly from minute 15 onward while not differing from baseline at the end of the procedure. Judging by the increase in thrombin–antithrombin III complexes, both membranes significantly activated coagulation at the end of hemodialysis. Platelet factor 4 levels, released during thrombocyte and endothelial stimulation, were elevated from the start of procedures. There were no significant differences between the AN69ST and the Helixone in any of the assessed markers.Conclusions:  The AN69ST and Helixone membranes do not differ in their effects on TF and TFPI or even in established thrombogenicity markers.
Functional Interrelationships between Cell Membrane and Cell Wall in Antimicrobial Peptide-Mediated Killing of
Staphylococcus aureus
Authors: Xiong Yan Q. , Mukhopadhyay Kasturi , Yeaman Michael R. , Adler-Moore Jill , Bayer Arnold S. 
Published: July 2005

ABSTRACT

Perturbation of the
Staphylococcus aureus
cytoplasmic membrane (CM) is felt to play a key role in the microbicidal mechanism of many antimicrobial peptides (APs). However, it is not established whether membrane permeabilization (MP) alone is sufficient to kill susceptible staphylococci or if the cell wall (CW) and/or intracellular targets contribute to AP-induced lethality. We hypothesized that the relationships between MP and killing may differ for distinct APs. In this study, we investigated the association between AP-induced MP and lethality in
S. aureus
whole cells versus CW-free protoplasts, and in comparison to the MP of liposomes modeled after whole CMs in terms of phospholipid composition, fluidity and charge. Four APs with different structure-activity relationships were examined: thrombin-induced platelet microbicidal protein 1 (tPMP-1), human neutrophil protein 1 (hNP-1), gramicidin D, and polymyxin B. MP was quantified fluorometrically by calcein release. All APs tested, except polymyxin B, caused concentration-dependent MP and killing of whole cells, but not of protoplasts. The reduced AP susceptibility of protoplasts was associated with increased cardiolipin and lysyl-phosphatidylglycerol content and reduced fluidity of their CMs. However, liposomal MP induced by tPMP-1, hNP-1, and gramicidin D paralleled that of whole cells. Collectively, these results indicate that (i) structurally distinct APs likely exert their staphylocidal effects by differing mechanisms, (ii) MP is not the sole event leading to AP-induced staphylocidal activity, (iii) a complex interrelationship exists between the CM and CW in AP-induced killing, and (iv) liposomes modeled upon whole cell or protoplast CMs can recapitulate the respective susceptibilities to killing by distinct APs.
Neopeptide Antibiotics That Function as Opsonins and Membrane-Permeabilizing Agents for Gram-Negative Bacteria
Authors: Tsubery Haim , Yaakov Hertzig , Cohen Sofia , Giterman Tal , Matityahou Ariella , Fridkin Mati , Ofek Itzhak 
Published: July 2005

ABSTRACTWe suggest a novel approach to enhancing antimicrobial drug action by utilizing engineered peptide conjugates. Our most potent conjugates, [fMLF]PMBN and [fMLF]PMEN, are nonapeptides derived from polymyxin B's (PMB's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Phe-Leu-Dab-Dab-Thr], where Dab is 2,4-diaminobutyric acid) and polymyxin E's (PME's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Leu-Leu-Dab-Dab-Thr]), respectively, attached to a linear tail comprised of formyl-Met-Leu-Phe (fMLF). The cyclic part binds to gram-negative lipopolysaccharides, rendering the bacterial outer membrane permeable to hydrophobic antibiotics. The tail confers chemotactic and opsonic activities upon the conjugates. These two activities appear to be the basis for the conjugates' antibacterial activities. The conjugates are 8 to 10 times less toxic than the parent PMB or PME antibiotics. Fourteen of 18 mice lethally challenged with erythromycin-resistantKlebsiella pneumoniaesurvived following intraperitoneal administration of erythromycin and [fMLF]PMBN, whereas erythromycin or the peptide conjugate alone had no effect. Moreover, the clearance ofKlebsiellafrom blood was markedly enhanced by intravenous injection of the [fMLF]PMEN peptide conjugate compared to the clearance of the organism from the mice treated with buffer alone as a control and was similar to that achieved by the PME antibiotic. Blood clearance was also significantly enhanced by administration of PMEN either alone or in a mixture with fMLF, although the effect was less than that produced by the peptide conjugate. Since resistance to polymyxins, the parent molecules of the synthetic cyclic peptides, is rare, the emergence of bacteria resistant to the antimicrobial properties of the peptide conjugates may be precluded as well.
Combination Therapy with Intravenous Colistin for Management of Infections Due to Multidrug-Resistant Gram-Negative Bacteria in Patients without Cystic Fibrosis
Authors: Kasiakou Sofia K. , Michalopoulos Argyris , Soteriades Elpidoforos S. , Samonis George , Sermaides George J. , Falagas Matthew E. 
Published: July 2005

ABSTRACT

Colistin,
an antibiotic almost abandoned for intravenous administration for many
years due to its reported toxicity, has been recently reintroduced in
clinical practice due to the emergence of multidrug-resistant
gram-negative bacteria and the lack of development of new antibiotics
to combat them. To assess the safety and effectiveness of intravenous
colistin, in combination with other antimicrobial agents, in the
treatment of serious infections in patients without cystic fibrosis, a
retrospective cohort study in a 450-bed tertiary-care hospital in
Athens, Greece, was performed. Patients who were hospitalized from 1
October 2000 to 31 January 2004 and received intravenous colistin for
more than 72 h were further analyzed. The primary outcome
measure was the in-hospital mortality; secondary end points were the
clinical outcome of the infections and the occurrence of colistin
toxicity. Fifty patients received intravenous colistin with a median
(mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the
management of 54 episodes of infections due to multidrug-resistant
gram-negative bacteria. The predominant infections were pneumonia
(33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and
intra-abdominal infection (11.1%). The responsible pathogens were
Acinetobacter baumannii
(51.9%),
Pseudomonas
aeruginosa
(42.6%), and
Klebsiella pneumoniae
(3.7%)
strains (no pathogen was isolated from one case). In-hospital mortality
was 24% (12/50 patients). Clinical response (cure or improvement) of
the infection was observed in 66.7% of episodes (36/54). In the studied
group, serum creatinine levels were decreased, at the end of colistin
treatment, by an average of 0.2 ± 1.3 mg/dl compared to
baseline levels. Deterioration of renal function during colistin
therapy was observed in 4/50 patients (8%). Coadministration of other
antimicrobial agents with spectrum against gram-negative microorganisms
and the absence of a control group constitute the major limitations of
this study. The use of intravenous colistin for the treatment of
infections due to multidrug-resistant gram-negative bacteria appears to
be safe and
effective.
Countrywide Survey Shows Very High Prevalence of
Plasmodium falciparum
Multilocus Resistance Genotypes in Cambodia
Authors: Khim Nimol , Bouchier Christiane , Ekala Marie-Thérèse , Incardona Sandra , Lim Pharath , Legrand Eric , Jambou Ronan , Doung Socheat , Puijalon Odile Mercereau , Fandeur Thierry 
Published: July 2005

ABSTRACT

Cambodia is located in an area of resistance to multiple antimalarials and has been the first country to implement the systematic use of an artesunate-mefloquine combination as first-line treatment for
Plasmodium falciparum
malaria. Little is known, however, about the prevalence of resistance mutations within the natural parasite populations, impeding rational drug policy in this context. Using direct sequencing of PCR products, we have analyzed sequence polymorphism of the dihydrofolate reductase-thymidylate synthase, dihydropteroate synthetase, and multidrug resistance 1 genes in a large number of clinical
P. falciparum
isolates collected in various areas of Cambodia. This highlighted a 100% prevalence of haplotypes with multiple mutations in the target genes of antifolates after more than a decade without use of antifolates for malaria therapy. A high prevalence of mutations in
Pfmdr1
, including mutations associated with decreased in vitro susceptibility to mefloquine and quinine, was also observed. In addition, novel, low-frequency mutations were detected in
Pfmdr1
. Our findings show an alarming rate of multilocus resistance genotypes in Cambodia, requiring diligent surveillance and imposing limitations on possible future drug combinations.
Mechanism of Inhibition of Vaccinia Virus DNA Polymerase by Cidofovir Diphosphate
Authors: Magee Wendy C. , Hostetler Karl Y. , Evans David H. 
Published: July 2005

ABSTRACT
Cidofovir (CDV) is a broad-spectrum antiviral agent that has been approved for clinical use in the treatment of cytomegalovirus retinitis. It has also been used off label to treat a variety of other viral infections, including those caused by orf and molluscum contagiosum poxviruses. Because it is a dCMP analog, CDV is thought to act by inhibiting viral DNA polymerases. However, the details of the inhibitory mechanism are not well established and nothing is known about the mechanism by which the drug inhibits poxvirus DNA polymerases. To address this concern, we have studied the effect of the active intracellular metabolite of CDV, CDV diphosphate (CDVpp), on reactions catalyzed by vaccinia virus DNA polymerase. Using different primer-template pairs and purified vaccinia virus polymerase, we observed that CDV is incorporated into the growing DNA strand opposite template G's but the enzyme exhibits a lower catalytic efficiency compared with dCTP. CDV-terminated primers are also good substrates for the next deoxynucleoside monophosphate addition step, but these CDV + 1 reaction products are poor substrates for further rounds of synthesis. We also noted that although CDV can be excised from the primer 3′ terminus by the 3′-to-5′ proofreading exonuclease activity of vaccinia virus polymerase, DNAs bearing CDV as the penultimate 3′ residue are completely resistant to exonuclease attack. These results show that vaccinia virus DNA polymerase can use CDVpp as a dCTP analog, albeit one that slows the rate of primer extension. By inhibiting the activity of the proofreading exonuclease, the misincorporation of CDV could also promote error-prone DNA synthesis during poxvirus replication.
Real-Time PCR Screening for 16S rRNA Mutations Associated with Resistance to Tetracycline in
Helicobacter pylori
Authors: Glocker Erik , Berning Marco , Gerrits Monique M. , Kusters Johannes G. , Kist Manfred 
Published: July 2005

ABSTRACT

The effectiveness of recommended first-line therapies for
Helicobacter pylori
infections is decreasing due to the occurrence of resistance to metronidazole and/or clarithromycin. Quadruple therapies, which include tetracycline and a bismuth salt, are useful alternative regimens. However, resistance to tetracycline, mainly caused by mutations in the 16S rRNA genes (
rrnA
and
rrnB
) affecting nucleotides 926 to 928, are already emerging and can impair the efficacies of such second-line regimens. Here, we describe a novel real-time PCR for the detection of 16S rRNA gene mutations associated with tetracycline resistance. Our PCR method was able to distinguish between wild-type strains and resistant strains exhibiting single-, double, or triple-base-pair mutations. The method was applicable both to DNA extracted from pure cultures and to DNA extracted from fresh or frozen
H. pylori
-infected gastric biopsy samples. We therefore conclude that this real-time PCR is an excellent method for determination of
H. pylori
tetracycline resistance even when live bacteria are no longer available.
Efficacy of the Combination Rifampin-Streptomycin in Preventing Growth of
Mycobacterium ulcerans
in Early Lesions of Buruli Ulcer in Humans
Authors: Etuaful S. , Carbonnelle B. , Grosset J. , Lucas S. , Horsfield C. , Phillips R. , Evans M. , Ofori-Adjei D. , Klustse E. , Owusu-Boateng J. , Amedofu G. K. , Awuah P. , Ampadu E. , Amofah G. , Asiedu K. , Wansbrough-Jones M. 
Published: July 2005

ABSTRACT

Mycobacterium ulcerans
disease is common in some humid tropical areas, particularly in parts of West Africa, and current management is by surgical excision of skin lesions ranging from early nodules to extensive ulcers (Buruli ulcer). Antibiotic therapy would be more accessible to patients in areas of Buruli ulcer endemicity. We report a study of the efficacy of antibiotics in converting early lesions (nodules and plaques) from culture positive to culture negative. Lesions were excised either immediately or after treatment with rifampin orally at 10 mg/kg of body weight and streptomycin intramuscularly at 15 mg/kg of body weight daily for 2, 4, 8, or 12 weeks and examined by quantitative bacterial culture, PCR, and histopathology for
M. ulcerans
. Lesions were measured during treatment. Five lesions excised without antibiotic treatment and five lesions treated with antibiotics for 2 weeks were culture positive, whereas three lesions treated for 4 weeks, five treated for 8 weeks, and three treated for 12 weeks were culture negative. No lesions became enlarged during antibiotic treatment, and most became smaller. Treatment with rifampin and streptomycin for 4 weeks or more inhibited growth of
M. ulcerans
in human tissue, and it provides a basis for proceeding to a trial of antibiotic therapy as an alternative to surgery for early
M. ulcerans
disease.
Contribution of Acquired Carbapenem-Hydrolyzing Oxacillinases to Carbapenem Resistance in
Acinetobacter baumannii
Authors: Héritier Claire , Poirel Laurent , Lambert Thierry , Nordmann Patrice 
Published: July 2005

ABSTRACT

Carbapenem-hydrolyzing oxacillinases are reported increasingly in
Acinetobacter baumannii
. Since they hydrolyze carbapenems at low levels, the roles of carbapenem-hydrolyzing oxacillinases OXA-23, OXA-40, and OXA-58 in
A. baumannii
were determined. The
bla
OXA-23
,
bla
OXA-40
, and
bla
OXA-58
genes were inserted in broad-host-range plasmid pAT801 and transformed in
Escherichia coli
DH10B and in
A. baumannii
CIP 70.10 and its point mutant derivative
A. baumannii
BM4547, which overexpresses the efflux pump AdeABC. Natural plasmids harboring the
bla
OXA-23
and
bla
OXA-58
genes were also transformed in
A. baumannii
CIP 70.10. In addition, the
bla
OXA-40
gene was inactivated at its chromosome location in
A. baumannii
CLA-1. Intermediate levels of resistance or reduced susceptibilities to carbapenems were observed for
A. baumannii
transformants expressing OXA-23, OXA-40, and OXA-58. The inactivation of
bla
OXA-40
in
A. baumannii
CLA-1 yielded reduced susceptibilities to carbapenems. Carbapenem-hydrolyzing oxacillinases OXA-23, OXA-40, and to a lesser extent OXA-58 play a role in carbapenem resistance in
A. baumannii
, and overexpression of efflux pump AdeABC may also contribute to higher levels of resistance to β-lactams, including carbapenems.
Acquisition of Resistant Bowel Flora during a Double-Blind Randomized Clinical Trial of Ertapenem versus Piperacillin-Tazobactam Therapy for Intraabdominal Infections
Authors: DiNubile Mark J. , Chow Joseph W. , Satishchandran Vilas , Polis Adam , Motyl Mary R. , Abramson Murray A. , Teppler Hedy 
Published: July 2005

ABSTRACT

Bowel colonization with resistant bacteria can develop in patients receiving broad-spectrum antimicrobial therapy. We compared the impact of two antimicrobial regimens often used to treat intraabdominal infections on susceptibility patterns of bowel flora at the end of therapy. In a double-blind clinical trial, adults with complicated intraabdominal infection requiring surgery were randomized to receive piperacillin-tazobactam (3.375 g every 6 h) or ertapenem (1 g once a day) for 4 to 14 days. Rectal swabs were obtained at baseline and at the end of study therapy to determine the acquisition rates of
Enterobacteriaceae
resistant to the study drug, extended-spectrum β-lactamase (ESBL)-producing
Escherichia coli
or
Klebsiella
species,
Pseudomonas aeruginosa
resistant to imipenem or piperacillin-tazobactam, and vancomycin-resistant
Enterococcus faecalis
or
Enterococcus faecium
. Treated patients were assessable for the acquisition of resistant bacteria if appropriate specimens were obtained at both time points.
Enterobacteriaceae
resistant to the treatment received were acquired during study therapy by 8/122 assessable piperacillin-tazobactam recipients (6.6%) compared to 0/122 assessable ertapenem recipients (
P
= 0.007). Neither ESBL-producing
E. coli
or
Klebsiella
species nor
P. aeruginosa
resistant to piperacillin-tazobactam was isolated from patients in either treatment group. Imipenem-resistant
P. aeruginosa
was acquired by two of the ertapenem recipients (1.6%) versus zero of the piperacillin-tazobactam recipients (
P
= 0.50). Vancomycin-resistant enterococci were acquired during therapy by 8/125 assessable ertapenem recipients (6.4%) versus 2/123 assessable piperacillin-tazobactam recipients (1.6%;
P
= 0.10). In this study, the acquisition of resistant
Enterobacteriaceae
occurred significantly more often in patients treated with piperacillin-tazobactam than in those treated with ertapenem.
Lipophilic Antifolate Trimetrexate Is a Potent Inhibitor of
Trypanosoma cruzi
: Prospect for Chemotherapy of Chagas' Disease
Authors: Senkovich Olga , Bhatia Vandanajay , Garg Nisha , Chattopadhyay Debasish 
Published: July 2005

ABSTRACT

Trypanosoma cruzi
, a protozoan parasite, is the causative agent for Chagas' disease, which poses serious public health problem in Latin America. The two drugs available for the treatment of this disease are effective only against recent infections and are toxic. Dihydrofolate reductase (DHFR) has a proven track record as a drug target. The lipophilic antifolate trimetrexate (TMQ), which is an FDA-approved drug for the treatment of
Pneumocystis carinii
infection in AIDS patients, is a potent inhibitor of
T. cruzi
DHFR activity, with an inhibitory constant of 6.6 nM. The compound is also highly effective in killing
T. cruzi
parasites. The 50 and 90% lethal dose values against the trypomastigote are 19 and 36 nM, and the corresponding values for the amastigote form are 26 and 72 nM, respectively. However, as TMQ is also a good inhibitor of human DHFR, further improvement of the selectivity of this drug would be preferable. Identification of a novel antifolate selective against
T. cruzi
would open up new therapeutic avenues for treatment of Chagas' disease.