bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Sucralfate on Antibiotic Therapy for
Helicobacter pylori
Infection in Mice
Authors: Watanabe Koichiro , Murakami Kazunari , Sato Ryugo , Kashimura Koji , Miura Masahiro , Ootsu Satoshi , Miyajima Hajime , Nasu Masaru , Okimoto Tadayoshi , Kodama Masaaki , Fujioka Toshio 
Published: November 2004

ABSTRACT

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against
Helicobacter pylori
, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of
H. pylori
infection in vivo. Four weeks following induced
H. pylori
infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of
H. pylori
infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding
H. pylori
in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where
H. pylori
had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the
H. pylori
-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures
H. pylori
through the creation of an adherent mucus, which leads to bacterial clearance.
Characterization and Molecular Analysis of Macrolide-Resistant
Mycoplasma pneumoniae
Clinical Isolates Obtained in Japan
Authors: Matsuoka Mayumi , Narita Mitsuo , Okazaki Norio , Ohya Hitomi , Yamazaki Tsutomu , Ouchi Kazunobu , Suzuki Isao , Andoh Tomoaki , Kenri Tsuyoshi , Sasaki Yuko , Horino Atsuko , Shintani Miharu , Arakawa Yoshichika , Sasaki Tsuguo 
Published: November 2004

ABSTRACT

In recent years,
Mycoplasma pneumoniae
strains that are clinically resistant to macrolide antibiotics have occasionally been encountered in Japan. Of 76 strains of
M. pneumoniae
isolated in three different areas in Japan during 2000 to 2003, 13 strains were erythromycin (ERY) resistant. Of these 13 strains, 12 were highly ERY resistant (MIC, ≥256 μg/ml) and 1 was weakly resistant (MIC, 8 μg/ml). Nucleotide sequencing of domains II and V of 23S rRNA and ribosomal proteins L4 and L22, which are associated with ERY resistance, showed that 10 strains had an A-to-G transition at position 2063 (corresponding to 2058 in
Escherichia coli
numbering), 1 strain showed A-to-C transversion at position 2063, 1 strain showed an A-to-G transition at position 2064, and the weakly ERY-resistant strain showed C-to-G transversion at position 2617 (corresponding to 2611 in
E. coli
numbering) of domain V. Domain II and ribosomal proteins L4 and L22 were not involved in the ERY resistance of these clinical
M. pneumoniae
strains. In addition, by using our established restriction fragment length polymorphism technique to detect point mutations of PCR products for domain V of the 23S rRNA gene of
M. pneumoniae
, we found that 23 (24%) of 94 PCR-positive oral samples taken from children with respiratory infections showed A2063G mutation. These results suggest that ERY-resistant
M. pneumoniae
infection is not unusual in Japan.
Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers
Authors: Gattringer Rainer , Urbauer Eleonora , Traunmüller Friederike , Zeitlinger Markus , Dehghanyar Pejman , Zeleny Petra , Graninger Wolfgang , Müller Markus , Joukhadar Christian 
Published: November 2004

ABSTRACT

By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues. The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against
Streptococcus pyogenes
but not against staphylococci and human and animal bite pathogens.
Degradation of Human Antimicrobial Peptide LL-37 by
Staphylococcus aureus
-Derived Proteinases
Authors: Sieprawska-Lupa Magdalena , Mydel Piotr , Krawczyk Katarzyna , Wójcik Kinga , Puklo Magdalena , Lupa Boguslaw , Suder Piotr , Silberring Jerzy , Reed Matthew , Pohl Jan , Shafer William , McAleese Fionnuala , Foster Timothy , Travis Jim , Potempa Jan 
Published: November 2004

ABSTRACT

Cathelicidin LL-37 is one of the few human bactericidal peptides with potent antistaphylococcal activity. In this study we examined the susceptibility of LL-37 to proteolytic degradation by two major proteinases produced by
Staphylococcus aureus
, a metalloproteinase (aureolysin) and a glutamylendopeptidase (V8 protease). We found that aureolysin cleaved and inactivated LL-37 in a time- and concentration-dependent manner. Analysis of the generated fragments by mass spectroscopy revealed that the initial cleavage of LL-37 by aureolysin occurred between the Arg19-Ile20, Arg23-Ile24, and Leu31-Val32 peptide bonds, instantly annihilating the antibacterial activity of LL-37. In contrast, the V8 proteinase hydrolyzed efficiently only the Glu16-Phe17 peptide bond, rendering the C-terminal fragment refractory to further degradation. This fragment (termed LL-17-37) displayed antibacterial activity against
S. aureus
at a molar level similar to that of the full-length LL-37 peptide, indicating that the antibacterial activity of LL-37 resides in the C-terminal region. In keeping with LL-37 degradation by aureolysin,
S. aureus
strains that produce significant amounts of this metalloprotease were found to be less susceptible to LL-17-37 than strains expressing no aureolysin activity. Taken together, these data suggest that aureolysin production by
S. aureus
contributes to the resistance of this pathogen to the innate immune system of humans mediated by LL-37.
Integron Carrying a Novel Metallo-β-Lactamase Gene,
bla
IMP-16
, and a Fused Form of Aminoglycoside-Resistant Gene
aac(6′)-30/aac(6′)-Ib′
: Report from the SENTRY Antimicrobial Surveillance Program
Authors: Mendes Rodrigo E. , Toleman Mark A. , Ribeiro Julival , Sader Helio S. , Jones Ronald N. , Walsh Timothy R. 
Published: November 2004

ABSTRACT

Since January 2002
Pseudomonas
sp. strains resistant to carbapenems and ceftazidime have been routinely screened as part of the SENTRY Antimicrobial Surveillance Program for metallo-β-lactamase production, and their resistance determinants have been analyzed.
Pseudomonas aeruginosa
index strain 101-4704, which harbors a novel
bla
IMP
variant,
bla
IMP-16
, was isolated in April 2002 from a 60-year-old man in Brasília, Brazil.
bla
IMP-16
was found on the chromosome of the
P. aeruginosa
index strain, and the deduced amino acid sequence (IMP-16) showed the greatest identities to IMP-11 (90.3%) and IMP-8 (89.5%). Sequence analysis revealed that
bla
IMP-16
was associated with a class 1 integron, which also encoded aminoglycoside-modifying enzymes. Downstream of
bla
IMP-16
resided an open reading frame, which consisted of a new aminoglycoside-modifying gene, namely,
aac(6′)-30
, which was fused with
aac(6′)-Ib′
. The amino acid sequence of the
aac(6′)-30
putative protein showed the most identity (52.7%) to the sequence of AAC(6′)-29b described previously. The fourth gene cassette constituted
aadA1
. The steady-state kinetics of IMP-16 demonstrated that the enzyme preferred cephalosporins and carbapenems to penicillins. The main functional difference observed among the kinetic values for IMP-16 compared to those for other IMPs was a lack of cefoxitin hydrolysis and a lower
k
cat
/

K
m

value for imipenem (0.36 μM
−1
· s
−1
). This report further emphasizes the spread of metallo-β-lactamase genes and their close association with various aminoglycoside resistance genes.
Liposomal Nystatin in Patients with Invasive Aspergillosis Refractory to or Intolerant of Amphotericin B
Authors: Offner Fritz , Krcmery Vladimir , Boogaerts Marc , Doyen Chantal , Engelhard Dan , Ribaud Patricia , Cordonnier Catherine , de Pauw Ben , Durrant Simon , Marie Jean-Pierre , Moreau Philippe , Guiot Harry , Samonis George , Sylvester Richard , Herbrecht Raoul 
Published: November 2004

ABSTRACT
We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.
Novel Nonnucleoside Inhibitor of Hepatitis C Virus RNA-Dependent RNA Polymerase
Authors: Howe Anita Y. M. , Bloom Johnathan , Baldick Carl J. , Benetatos Christopher A. , Cheng Huiming , Christensen Joel S. , Chunduru Srinivas K. , Coburn Glen A. , Feld Boris , Gopalsamy Ariamala , Gorczyca William P. , Herrmann Steve , Johann Stephen , Jiang Xiaoqun , Kimberland Michelle L. , Krisnamurthy Girija , Olson Matthew , Orlowski Mark , Swanberg Steve , Thompson Ian , Thorn Megan , Del Vecchio Alfred , Young Dorothy C. , van Zeijl Marja , Ellingboe John W. , Upeslacis Janis , Collett Marc , Mansour Tarek S. , O'Connell John F. 
Published: November 2004

ABSTRACT

A novel nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp), [(1
R
)-5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyano[3,4-b]indol-1-yl] acetic acid (HCV-371), was discovered through high-throughput screening followed by chemical optimization. HCV-371 displayed broad inhibitory activities against the NS5B RdRp enzyme, with 50% inhibitory concentrations ranging from 0.3 to 1.8 μM for 90% of the isolates derived from HCV genotypes 1a, 1b, and 3a. HCV-371 showed no inhibitory activity against a panel of human polymerases, including mitochondrial DNA polymerase gamma, and other unrelated viral polymerases, demonstrating its specificity for the HCV polymerase. A single administration of HCV-371 to cells containing the HCV subgenomic replicon for 3 days resulted in a dose-dependent reduction of the steady-state levels of viral RNA and protein. Multiple treatments with HCV-371 for 16 days led to a >3-log
10
reduction in the HCV RNA level. In comparison, multiple treatments with a similar inhibitory dose of alpha interferon resulted in a 2-log
10
reduction of the viral RNA level. In addition, treatment of cells with a combination of HCV-371 and pegylated alpha interferon resulted in an additive antiviral activity. Within the effective antiviral concentrations of HCV-371, there was no effect on cell viability and metabolism. The intracellular antiviral specificity of HCV-371 was demonstrated by its lack of activity in cells infected with several DNA or RNA viruses. Fluorescence binding studies show that HCV-371 binds the NS5B with an apparent dissociation constant of 150 nM, leading to high selectivity and lack of cytotoxicity in the antiviral assays.
Distribution of Antibiotic MICs for
Helicobacter pylori
Strains over a 16-Year Period in Patients from Seoul, South Korea
Authors: Kim Jung Mogg , Kim Joo Sung , Jung Hyun Chae , Kim Nayoung , Kim Young-Jeon , Song In Sung 
Published: November 2004

ABSTRACT

Recently, the development of antibiotic resistance emerged as a significant clinical problem in the eradication of
Helicobacter pylori
. We investigated the MICs of antibiotics for 135
H. pylori
isolates from adults in Seoul, South Korea, over the past 16 years. The MICs of amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, and ciprofloxacin increased from 1987 to 2003. Rates of primary resistance to clarithromycin increased from 2.8% in 1994 to 13.8% in 2003. The A2144G mutation was frequently observed in the 23S rRNA gene in clarithromycin-resistant isolates. The increase in resistance to clarithromycin seems to result in a decrease in eradication efficacy for
H. pylori
. These results suggest that the MICs of several antibiotics for
H. pylori
have increased over the past 16 years in Seoul.
Association of a Novel Human Immunodeficiency Virus Type 1 Protease Substrate Cleft Mutation, L23I, with Protease Inhibitor Therapy and In Vitro Drug Resistance
Authors: Johnston Elizabeth , Winters Mark A. , Rhee Soo-Yon , Merigan Thomas C. , Schiffer Celia A. , Shafer Robert W. 
Published: November 2004

ABSTRACT
We observed a previously uncharacterized mutation in the protease substrate cleft, L23I, in 31 of 4,303 persons undergoing human immunodeficiency virus type 1 genotypic resistance testing. In combination with V82I, L23I was associated with a sevenfold reduction in nelfinavir susceptibility and a decrease in replication capacity. In combination with other drug resistance mutations, L23I was associated with multidrug resistance and a compensatory increase in replication capacity.
PCR-Restriction Fragment Length Polymorphism Assay for Detection of
gyrA
Mutations Associated with Fluoroquinolone Resistance in
Campylobacter coli
Authors: Alonso Rodrigo , Mateo Estibaliz , Girbau Cecilia , Churruca Estibaliz , Martinez Irati , Fernández-Astorga Aurora 
Published: November 2004

ABSTRACT

A fragment of the
gyrA
gene was sequenced from 34 isolates of
Campylobacter coli
, including 23 isolates resistant to ciprofloxacin. All ciprofloxacin-resistant isolates examined by DNA sequencing carried a point mutation at position Thr-86 on the
gyrA
gene product, involving the replacement of Thr-86 by Ile. A combined PCR-restriction fragment length polymorphism technique using RsaI was developed to detect this mutation.
The Synthetic N-Terminal Peptide of Human Lactoferrin, hLF(1-11), Is Highly Effective against Experimental Infection Caused by Multidrug-Resistant
Acinetobacter baumannii
Authors: Dijkshoorn Lenie , Brouwer Carlo P. J. M. , Bogaards Sylvia J. P. , Nemec Alexandr , van den Broek Peterhans J. , Nibbering Peter H. 
Published: November 2004

ABSTRACT

The lactoferrin-derived peptide hLF(1-11), but not its control peptide, was highly effective against five multidrug-resistant
Acinetobacter baumannii
strains in vitro (3 to 4 log reduction) and against four of these strains in an experimental infection in mice (2 to 3 log reduction). Therefore, this peptide is a promising candidate as a novel agent against infections with multidrug-resistant
A. baumannii
.
Two Amino Acid Mutations in the Capsid Protein of Type 2 Porcine Circovirus (PCV2) Enhanced PCV2 Replication In Vitro and Attenuated the Virus In Vivo
Authors: Fenaux M. , Opriessnig T. , Halbur P. G. , Elvinger F. , Meng X. J. 
Published: November 2004

ABSTRACT

Porcine circovirus type 2 (PCV2) is the primary causative agent of postweaning multisystemic wasting syndrome (PMWS) in pigs. To identify potential genetic determinants for virulence and replication, we serially passaged a PCV2 isolate 120 times in PK-15 cells. The viruses harvested at virus passages 1 (VP1) and 120 (VP120) were biologically, genetically, and experimentally characterized. The PCV2 VP120 virus replicated in PK-15 cells to a titer similar to that of the PK-15 cell line-derived nonpathogenic PCV1 but replicated more efficiently than PCV2 VP1 with a difference of about 1 log unit in the titers. The complete genomic sequences of viruses at passages 0, 30, 60, 90, and 120 were determined. After 120 passages, only two nucleotide mutations were identified in the entire genome, and both were located in the capsid gene: the mutations were located at nucleotide positions 328 (C328G) and 573 (A573C). The C328G mutation, in which a proline at position 110 of the capsid protein changed to an alanine (P110A), occurred at passage 30 and remained in the subsequent passages. The second mutation, A573C, resulting in a change from an arginine to a serine at position 191 (R191S), appeared at passage 120. To experimentally characterize the VP120 virus, 31 specific-pathogen-free pigs were randomly divided into three groups. Ten pigs in group 1 received phosphate-buffered saline as negative controls. Each pig in group 2 (11 pigs) was inoculated intramuscularly and intranasally with 10
4.9
50% tissue culture infective doses (TCID
50
) of PCV2 VP120. Each pig in group 3 (10 pigs) was similarly inoculated with 10
4.9
TCID
50
of PCV2 VP1. Viremia was detected in 9 of 10 pigs in the PCV2 VP1 group with a mean duration of 3 weeks, but in only 4 of 11 pigs in the PCV2 VP120 group with a mean duration of 1.6 weeks. The PCV2 genomic copy numbers in serum in the PCV2 VP1 group were significantly higher than those in the PCV2 VP120 group (
P
< 0.0001). Gross and histopathologic lesions in pigs inoculated with PCV2 VP1 were more severe than those inoculated with PCV2 VP120 at both day 21 and 42 necropsies (
P
= 0.0032 and
P
= 0.0274, respectively). Taken together, the results from this study indicated that the P110A and R191S mutations in the capsid of PCV2 enhanced the growth ability of PCV2 in vitro and attenuated the virus in vivo. This finding has important implications for PCV2 vaccine development.
The Positively Charged Termini of L2 Minor Capsid Protein Required for Bovine Papillomavirus Infection Function Separately in Nuclear Import and DNA Binding
Authors: Fay Alyson , Yutzy William H. , Roden Richard B. S. , Moroianu Junona 
Published: November 2004

ABSTRACT
During the papillomavirus (PV) life cycle, the L2 minor capsid protein enters the nucleus twice: in the initial phase after entry of virions into cells and in the productive phase to mediate encapsidation of the newly replicated viral genome. Therefore, we investigated the interactions of the L2 protein of bovine PV type 1 (BPV1) with the nuclear import machinery and the viral DNA. We found that BPV1 L2 bound to the karyopherin α2 (Kap α2) adapter and formed a complex with Kap α2β1 heterodimers. Previous data have shown that the positively charged termini of BPV1 L2 are required for BPV1 infection after the binding of the virions to the cell surface. We determined that these BPV1 L2 termini function as nuclear localization signals (NLSs). Both the N-terminal NLS (nNLS) and the C-terminal NLS (cNLS) interacted with Kap α2, formed a complex with Kap α2β1 heterodimers, and mediated nuclear import via a Kap α2β1 pathway. Interestingly, the cNLS was also the major DNA binding site of BPV1 L2. Consistent with the promiscuous DNA encapsidation by BPV1 pseudovirions, this DNA binding occurred without nucleotide sequence specificity. Moreover, an L2 mutant encoding a scrambled version of the cNLS, which supports production of virions, rescued the DNA binding but not the Kap α2 interaction. These data support a model in which BPV1 L2 functions as an adapter between the viral DNA via the cNLS and the Kaps via the nNLS and facilitates nuclear import of the DNA during infection.
Immunogenicity Study of Glycoprotein-Deficient Rabies Virus Expressing Simian/Human Immunodeficiency Virus SHIV89.6PEnvelope in a Rhesus Macaque
Authors: McKenna Philip M. , Aye Pyone Pyone , Dietzschold Bernhard , Montefiori David C. , Martin Louis N. , Marx Preston A. , Pomerantz Roger J. , Lackner Andrew , Schnell Matthias J. 
Published: November 2004

ABSTRACTRabies virus (RV) has recently been developed as a novel vaccine candidate for human immunodeficiency virus type 1 (HIV-1). The RV glycoprotein (G) can be functionally replaced by HIV-1 envelope glycoprotein (Env) if the gp160 cytoplasmic domain (CD) of HIV-1 Env is replaced by that of RV G. Here, we describe a pilot study of the in vivo replication and immunogenicity of an RV with a deletion of G (ΔG) expressing a simian/human immunodeficiency virus SHIV89.6PEnv ectodomain and transmembrane domain fused to the RV G CD (ΔG-89.6P-RVG) in a rhesus macaque. An animal vaccinated with ΔG-89.6P-RVG developed SHIV89.6Pvirus-neutralizing antibodies and SHIV89.6P-specific cellular immune responses after challenge with SHIV89.6P. There was no evidence of CD4+T-cell loss, and plasma viremia was controlled to undetectable levels by 6 weeks postchallenge and has remained suppressed out to 22 weeks postchallenge.
Lytic Cycle Gene Regulation of Epstein-Barr Virus
Authors: Amon Wolfgang , Binné Ulrich K. , Bryant Helen , Jenkins Peter J. , Karstegl Claudio Elgueta , Farrell Paul J. 
Published: November 2004

ABSTRACT

Episomal reporter plasmids containing the Epstein-Barr virus (EBV) oriP sequence stably transfected into Akata Burkitt's lymphoma cells were used to analyze EBV lytic cycle gene regulation. First, we found that the Zp promoter of EBV, but not the Rp promoter, can be activated in the absence of protein synthesis in these oriP plasmids, casting doubt on the immediate early status of Rp. An additional level of regulation of Zp was implied by analysis of a mutation of the ZV element. Second, our analysis of late lytic cycle promoters revealed that the correct relative timing, dependence on ori lyt in
cis
, and sensitivity to inhibitors of DNA replication were reconstituted on the oriP plasmids. Late promoter luciferase activity from oriP plasmids also incorporating replication-competent ori lyt was phosphonoacetic acid sensitive, a hallmark of EBV late genes. A minimal ori lyt, which only replicates weakly, was sufficient to confer late timing of expression specifically on late promoters. Finally, deletion analysis of EBV late promoter sequences upstream of the transcription start site confirmed that sequences between −49 and +30 are sufficient for late gene expression, which is dependent on ori lyt in
cis
. However, the TATT version of the TATA box found in many late genes was not essential for late expression.