bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parametric imaging of contrast ultrasound for the evaluation of neovascularization in liver tumors
Authors: Sugimoto Katsutoshi , Moriyasu Fuminori , Kamiyama Naohisa , Metoki Ryo , Iijima Hiroko 
Published: May 2007

Aim:  To assess the efficacy of parametric imaging for the diagnosis of neovascularization in liver tumors.Methods:  The subjects were 17 rabbits (five with normal liver and 12 with VX2 tumor implanted in the liver). The contrast agents used were SonoVue (Bracco, Milan, Italy). A diagnostic ultrasound system was used with a programmable replenishment sequence. The images obtained between the initial frame after the high mechanical index (MI) scan, which diminishes microbubbles in the scan volume, and the current frame were coded in color according to the arrival and peak times. After the experiment, the tumors were excised and sectioned. Sections were prepared for light microscopy with hematoxylin–eosin (HE) staining and CD31 staining to evaluate vascular density.Results:  Arrival time imaging (ATI) delineated the fine blood vessels (100–200 μm in diameter) in all of the rabbits. Tortuous and meandering tumor vessels were visualized in the VX2 tumors. Differences of perfusion velocity between tumor tissue and tumor‐free areas were shown in peak time imaging (PTI). Vascularity evaluated on the ATI and perfusion speed recognized on the ATI and PTI were related to the vascular density measured by pathological investigation.Conclusion:  Parametric imaging is a promising new method for the visualization of perfusion and the estimation of tumor blood vessels.
Possible inhibitory effect of oral zinc supplementation on hepatic fibrosis through downregulation of TIMP‐1: A pilot study
Authors: Takahashi Masahiko , Saito Hidetsugu , Higashimoto Makiko , Hibi Toshifumi 
Published: May 2007

Aim:  To investigate the effect of oral zinc supplementation (polaprezinc) for 24 weeks (34 mg/day zinc) on liver fibrosis in patients with advanced chronic liver disease.Methods:  Various markers of liver fibrosis, and fibrogenic and fibrolytic enzyme activities were measured before and after zinc supplementation in 17 patients with early cirrhosis.Results:  Serum zinc levels were decreased in the patients as compared with healthy controls. No side‐effect was noted in any of the patients who received zinc supplementation. Serum levels of zinc increased by up to 156% over baseline levels in the group of patients who took oral zinc for 24 weeks. In patients whose serum zinc levels increased, the serum levels of type IV collagen and the activity of tissue inhibitors of metalloproteinase‐1 (TIMP‐1) were significantly reduced, but no such change was observed in the other groups of patients, and no other serum markers changed.Conclusion:  These results suggest that oral zinc supplement therapy with polaprezinc is safe and may be a novel and useful strategy for antifibrosis therapy in patients with early liver cirrhosis.
Hepatoprotective action of prostaglandin A2 analogs under CCl4‐induced liver injury in vitro
Authors: Hubich Aksana I. , Bondar Alexey Y. , Kastsiuk Tatsiana U. , Kastsiuk Uladimir A. , Lakhvich Fyodar A. , Sholukh Mikhail V. 
Published: May 2007

Aim:  The cytoprotective effects of six novel synthetic prostaglandin A2 analogs against carbon tetrachloride (CCl4) as a toxic agent were studied with isolated rat liver hepatocytes in vitro.Results:  It was found that hepatocytes treatment with CCl4 induced: (i) a significant increase of lactic dehydrogenase (LDH) release from cytoplasm; (ii) leakage of glutamate dehydrogenase (GDH) and acid phosphatase from mitochondria and lysosomes, respectively; (iii) 10‐fold increase of trien conjugates formation; and (iv) a reduction of free SH‐groups by 50%. Prostanoids U‐26, U‐9 and U‐34 decreased cytotoxic index of CCl4 on average by 1.5–2.0 times and were more effective than PGI2, the well‐known hepatoprotector of prostanoids type. The protective action of the prostanoids was not a cAMP‐ or Ca2+‐dependent process. However, prostanoids U‐26, U‐9 and U‐34 normalized intracellular content of SH‐groups, reduced trien conjugates formation by 60–80% and strongly prevented enzyme leakage through cellular membranes. They were also able to inhibit CCl4 effects via decreasing cytochrome P4502E1 activity.Conclusion:  The results obtained demonstrate that prostanoids provide cytoprotective effects on liver hepatocytes through the prevention of lipid peroxidation of the plasma and the cellular membranes and maintenance of their barrier function.
Fusion protein containing SH3 domain of c‐Abl induces hepatocarcinoma cells to apoptosis
Authors: Yin Ji Kai , Liang Ying Min , He Xian Li , Lu Jian Guo , Zhang Li , Bao Guo Qiang , Ma Qing Jiu 
Published: May 2007

Aim:  Through a preliminary test on a novel protein containing an HIV1‐TAT domain and a SH3 domain of oncoprotein P210BCR‐ABL (we named it after PTD‐BCR/ABL SH3), we found that this protein shows inhibition activity of hepatocarcinoma cell HepG‐2. The purpose of the present study is to explore the biological behavior of PTD‐BCR/ABL SH3 fusion protein in hepatocarcinoma cells in vitro and in vivo.Methods:  HepG‐2 cells were cocultured with the fusion protein for the indicated time and studied in vitro by immunocytochemistry staining to demonstrate the localization of the protein, light and electron microscope observation in morphology research, MTT assay to draw a growth curve and to analyze inhibition ratio, DNA ladder and TUNEL staining to study apoptosis. Nude mice bearing HepG‐2 tumors were used to test the antitumor activity of the fusion protein.Results:  PTD‐BCR/ABL SH3 fusion protein successfully entered into HepG‐2 cells and localized in the nucleus. The protein had shown high cytotoxity through inducing HepG‐2 cells to apoptosis, and in vivo. The growth speed of tumors in the treatment group was distinctly slower than those in the control group, and the survival time of mice in the treatment group was longer than those in the control group. The growth of the tumors had been inhibited in the treatment group, while other tissues, such as heart, liver, lung and kidney displayed normal morphology.Conclusion:  PTD‐BCR/ABL SH3 fusion protein displays significant inhibitory activity of inducing hepatocarcinoma HepG‐2 cells to apoptosis in vitro. It also showed therapeutic effects in vivo.
A prospective study of acute drug‐induced liver injury in patients suffering from non‐alcoholic fatty liver disease
Authors: Tarantino Giovanni , Conca Paolo , Basile Vincenzo , Gentile Antonio , Capone Domenico , Polichetti Giuliano , Leo Emilio 
Published: May 2007

Aim:  Liver damage due to facultative hepatotoxins is scarcely foreseeable. We evaluated the prevalence of acute drug‐induced liver injury (DILI) in a specific setting, assessing eventual interactions with pre‐existing hepatic illnesses.Methods:  The research was carried out in an Italian tertiary care hospital, by analyzing 248 patients with non‐advanced liver disease, divided into two well‐matched groups: 174 patients (median age 53, 94 females) with hepatitis C virus‐related chronic hepatitis; and 74 (median age 55, 39 females) with non‐alcoholic fatty liver disease (NAFLD).Results:  Six patients (2.4% of the whole population) belonging to the NAFLD group (χ2‐test, P = 0.004) suffered from acute hepatoxicity related to the following drugs, that is antihypertensive, acting on platelet aggregation, antimicrobial, non‐steroidal anti‐inflammatory and proton pump inhibitor. The NAFLD presence was an independent risk factor in determining drug‐related acute hepatitis, with an odds ratio of 3.95 (95% confidence intervals: 11.48–1.35). Central obesity was relevant in every patient with acute toxicity. Alcohol consumption and drug association did not influence the acute drug‐induced liver damage.Conclusion:  NAFLD conveys a nearly fourfold increase of DILI risk in obese middle‐aged patients. NAFLD, characterized by mitochondrial dysfunction, could predispose to drug‐induced hepatotoxicity that probably shares the same pathophysiological mechanism.
SB-431542, a Transforming Growth Factor β Inhibitor, ImpairsTrypanosoma cruziInfection in Cardiomyocytes and Parasite Cycle Completion
Authors: Waghabi Mariana C. , Keramidas Michelle , Calvet Claudia M. , Meuser Marcos , Soeiro Maria de Nazaré C. , Mendonça-Lima Leila , Araújo-Jorge Tania C. , Feige Jean-Jacques , Bailly Sabine 
Published: May 2007

ABSTRACTThe antiinflammatory cytokine transforming growth factor β (TGF-β) plays an important role in Chagas disease, a parasitic infection caused by the protozoanTrypanosoma cruzi. In the present study, we show that SB-431542, an inhibitor of the TGF-β type I receptor (ALK5), inhibitsT. cruzi-induced activation of the TGF-β pathway in epithelial cells and in cardiomyocytes. Further, we demonstrate that addition of SB-431542 greatly reduces cardiomyocyte invasion byT. cruzi. Finally, SB-431542 treatment significantly reduces the number of parasites per infected cell and trypomastigote differentiation and release. Taken together, these data further confirm the major role of the TGF-β signaling pathway in bothT. cruziinfection andT. cruzicell cycle completion. Our present data demonstrate that small inhibitors of the TGF-β signaling pathway might be potential pharmacological tools for the treatment of Chagas disease.
Deoxyribonucleoside Kinases Activate Nucleoside Antibiotics in Severely Pathogenic Bacteria
Authors: Sandrini Michael P. B. , Shannon Oonagh , Clausen Anders R. , Björck Lars , Piškur Jure 
Published: May 2007

ABSTRACT

Common bacterial pathogens are becoming progressively more resistant to traditional antibiotics, representing a major public-health crisis. Therefore, there is a need for a variety of antibiotics with alternative modes of action. In our study, several nucleoside analogs were tested against pathogenic staphylococci and streptococci. We show that pyrimidine-based nucleoside analogs, like 3′-azido-3′-deoxythymidine (AZT) and 2′,2′-difluoro-2′deoxycytidine (gemcitabine), are specifically activated by the endogenous bacterial deoxyribonucleoside kinases, leading to cell death. Deoxyribonucleoside kinase-deficient
Escherichia coli
strains become highly susceptible to nucleoside analogs when they express recombinant kinases from
Staphylococcus aureus
or
Streptococcus pyogenes
. We further demonstrate that recombinant
S. aureus
deoxyadenosine kinase efficiently phosphorylates the anticancer drug gemcitabine in vitro and is therefore the key enzyme in the activation pathway. When adult mice were infected intraperitoneally with a fatal dose of
S. pyogenes
strain AP1 and afterwards received gemcitabine, they failed to develop a systemic infection. Nucleoside analogs may therefore represent a promising alternative for combating pathogenic bacteria.
Chloramphenicol Is a Substrate for a Novel Nitroreductase Pathway in
Haemophilus influenzae
Authors: Smith Arnold L. , Erwin Alice L. , Kline Toni , Unrath William C. T. , Nelson Kevin , Weber Allan , Howald William N. 
Published: May 2007

ABSTRACT

The
p
-nitroaromatic antibiotic chloramphenicol has been used extensively to treat life-threatening infections due to
Haemophilus influenzae
and
Neisseria meningitidis
; its mechanism of action is the inhibition of protein synthesis. We found that during incubation with
H. influenzae
cells and lysates, chloramphenicol is converted to a 4-aminophenyl allylic alcohol that lacks antibacterial activity. The allylic alcohol moiety undergoes facile re-addition of water to restore the 1,3-diol, as well as further dehydration driven by the aromatic amine to form the iminoquinone. Several
Neisseria
species and most chloramphenicol-susceptible
Haemophilus
species, but not
Escherichia coli
or other gram-negative or gram-positive bacteria we examined, were also found to metabolize chloramphenicol. The products of chloramphenicol metabolism by species other than
H. influenzae
have not yet been characterized. The strains reducing the antibiotic were chloramphenicol susceptible, indicating that the pathway does not appear to mediate chloramphenicol resistance. The role of this novel nitroreductase pathway in the physiology of
H. influenzae
and
Neisseria
species is unknown. Further understanding of the
H. influenzae
chloramphenicol reduction pathway will contribute to our knowledge of the diversity of prokaryotic nitroreductase mechanisms.
Sequencing and Comparative Genomic Analysis of pK29, a 269-Kilobase Conjugative Plasmid Encoding CMY-8 and CTX-M-3 β-Lactamases in
Klebsiella pneumoniae
Authors: Chen Ying-Tsong , Lauderdale Tsai-Ling , Liao Tsai-Lien , Shiau Yih-Ru , Shu Hung-Yu , Wu Keh-Ming , Yan Jing-Jou , Su Ih-Jen , Tsai Shih-Feng 
Published: May 2007

ABSTRACT

A 269-kilobase conjugative plasmid, pK29, from a
Klebsiella pneumoniae
strain was sequenced. The plasmid harbors multiple antimicrobial resistance genes, including those encoding CMY-8 AmpC-type and CTX-M-3 extended-spectrum β-lactamases in the common backbone of IncHI2 plasmids. Mechanisms for dissemination of the resistance genes are highlighted in comparative genomic analyses.
Changes in
qnr
Prevalence and Fluoroquinolone Resistance in Clinical Isolates of
Klebsiella pneumoniae
and
Enterobacter
spp. Collected from 1990 to 2005
Authors: Strahilevitz Jacob , Engelstein Dalia , Adler Amos , Temper Violeta , Moses Allon E. , Block Colin , Robicsek Ari 
Published: May 2007

ABSTRACT

Clinical isolates of
Klebsiella pneumoniae
and
Enterobacter
spp. collected from 1990 through 2005 at a tertiary care center were studied for
qnr
genes. Isolates bearing these genes emerged in the mid-1990s, coinciding with the time of a rapid increase in fluoroquinolone resistance. Sixty percent of these isolates were ciprofloxacin susceptible by CLSI breakpoints.
Rifaximin Does Not Induce Toxin Production or Phage-Mediated Lysis of Shiga Toxin-Producing
Escherichia coli
Authors: Ochoa Theresa J. , Chen Jane , Walker Christopher M. , Gonzales Elsa , Cleary Thomas G. 
Published: May 2007

ABSTRACT

Diarrhea in children is often caused by enteropathogen infections that might benefit from early empirical antibiotic therapy. However, when the definition of the pathogen requires sophisticated laboratory studies, the etiology of enteritis is not known early in illness. Empirical therapy may be dangerous if the child is infected with a Shiga toxin-producing
Escherichia coli
(STEC) strain because antimicrobials may increase Shiga toxin (Stx) release, resulting in increased risk of microangiopathic hemolytic anemia with acute renal failure (hemolytic-uremic syndrome [HUS]) and death. There is a need for antimicrobials that would be effective against multiple bacterial enteropathogens yet not induce Stx release or increase the risk of HUS. Rifaximin has been evaluated in adults for treatment of bacterial enteritis and has a good record for safety and efficacy, but it has not been evaluated extensively in children with gastroenteritis. We therefore evaluated rifaximin's potential for phage induction, drug-induced bacteriolysis, and toxin release in 57 STEC strains (26 O157 and 31 non-O157 strains). Growth in ciprofloxacin, a known Stx phage inducer, caused bacteriolysis and release of toxin in 25/26 (96%) O157 strains and 15/31 (48%) non-O157 strains. In contrast, rifaximin did not induce phage replication or lysis in any strain. Toxin release in the presence of rifaximin was not different from release in the absence of antibiotic. Rifaximin, unlike many antibiotics used to treat pediatric gastroenteritis, does not induce phage-mediated bacteriolysis and Stx release.
Bacteriophage Therapy To Reduce
Salmonella
Colonization of Broiler Chickens
Authors: Atterbury R. J. , Van Bergen M. A. P. , Ortiz F. , Lovell M. A. , Harris J. A. , De Boer A. , Wagenaar J. A. , Allen V. M. , Barrow P. A. 
Published: May 2007

ABSTRACT

Acute enteric infections caused by salmonellas remain a major public health burden worldwide. Poultry, particularly chickens, are known to be the main reservoir for this zoonotic pathogen. Although some progress has been made in reducing
Salmonella
colonization of broiler chickens by using biosecurity and antimicrobials, it still remains a considerable problem. The use of host-specific bacteriophages as a biocontrol is one possible intervention by which
Salmonella
colonization could be reduced. A total of 232
Salmonella
bacteriophages were isolated from poultry farms, abattoirs, and wastewater in 2004 and 2005. Three phages exhibiting the broadest host ranges against
Salmonella enterica
serotypes Enteritidis, Hadar, and Typhimurium were characterized further by determining their morphology and lytic activity in vitro. These phages were then administered in antacid suspension to birds experimentally colonized with specific
Salmonella
host strains. The first phage reduced
S. enterica
serotype Enteritidis cecal colonization by ≥4.2 log
10
CFU within 24 h compared with controls. Administration of the second phage reduced
S. enterica
serotype Typhimurium by ≥2.19 log
10
CFU within 24 h. The third bacteriophage was ineffective at reducing
S. enterica
serotype Hadar colonization. Bacteriophage resistance occurred at a frequency commensurate with the titer of phage being administered, with larger phage titers resulting in a greater proportion of resistant salmonellas. The selection of appropriate bacteriophages and optimization of both the timing and method of phage delivery are key factors in the successful phage-mediated control of salmonellas in broiler chickens.
“Mark the Gene”: a Method for Nondestructive Introduction of Marker Sequences Inside the Gene Frame of Transgenes
Authors: Morono Yuki , Kitagawa Wataru , Kimura Nobutada , Noda Naohiro , Nakamura Kazunori , Kamagata Yoichi 
Published: May 2007

ABSTRACT

A specific marking and detection technique is a fundamental requirement for the safer use of genetically modified (GM) organisms. Here we propose a simple and effective method for directly marking functional transgenes in GM organisms. For that purpose, we introduced nucleotide substitutions (NS), based on the degeneracy of codons as markers (NS markers), into the
bphC
(2,3-dihydroxybiphenyl dioxygenase) and
tomA3
(toluene-
ortho
-monooxygenase) gene frames using a PCR-based method. No change was observed in the enzyme activity of translated proteins, and alignments with homologous genes showed the uniqueness of the NS markers. Furthermore, we constructed
tomA3
variations harboring NS markers in different positions. Although the translational products were identical, the constructed variation genes could be distinguished through their marker patterns by multiplex PCR, showing that NS markers could serve as product-specific tags for identifying individual GM organisms. This direct method of marking the functional transgene provides a simple, low-risk, and robust marking method without causing the gene functions to deteriorate.
Comparative Sequence Analysis of Plasmids from
Lactobacillus delbrueckii
and Construction of a Shuttle Cloning Vector
Authors: Lee Ju-Hoon , Halgerson Jamie S. , Kim Jeong-Hwan , O'Sullivan Daniel J. 
Published: May 2007

ABSTRACT

While plasmids are very commonly associated with the majority of the lactic acid bacteria, they are only very rarely associated with
Lactobacillus delbrueckii
, with only four characterized to date. In this study, the complete sequence of a native plasmid, pDOJ1, from a strain of
Lactobacillus delbrueckii
subsp.
bulgaricus
was determined. It consisted of a circular DNA molecule of 6,220 bp with a G+C content of 44.6% and a characteristic
ori
and encoded six open reading frames (ORFs), of which functions could be predicted for three—a mobilization (Mob) protein, a transposase, and a fused primase-helicase replication protein. Comparative analysis of pDOJ1 and the other available
L. delbrueckii
plasmids (pLBB1, pJBL2, pN42, and pLL1212) revealed a very similar organization and amino acid identities between 85 and 98% for the putative proteins of all six predicted ORFs from pDOJ1, reflecting a common origin for
L. delbrueckii
plasmids. Analysis of the fused primase-helicase replication gene found a similar fused organization only in the theta replicating group B plasmids from
Streptococcus thermophilus
. This observation and the ability of the replicon to function in
S. thermophilus
support the idea that the origin of plasmids in
L. delbrueckii
was likely from
S. thermophilus
. This may reflect the close association of these two species in dairy fermentations, particularly yogurt production. As no vector based on plasmid replicons from
L. delbrueckii
has previously been constructed, an
Escherichia coli-L. delbrueckii
shuttle cloning vector, pDOJ4, was constructed from pDOJ1, the p15A
ori
, the chloramphenicol resistance gene of pCI372, and the
lacZ
polylinker from pUC18. This cloning vector was successfully introduced into
E. coli
,
L. delbrueckii
subsp.
bulgaricus
,
S. thermophilus
, and
Lactococcus lactis
. This shuttle cloning vector provides a new tool for molecular analysis of
Lactobacillus delbrueckii
and other lactic acid bacteria.
A General Framework for Designing and Validating Oligomer-Based DNA Microarrays and Its Application to
Clostridium acetobutylicum
Authors: Paredes Carlos J. , Senger Ryan S. , Spath Iwona S. , Borden Jacob R. , Sillers Ryan , Papoutsakis Eleftherios T. 
Published: May 2007

ABSTRACT

While DNA microarray analysis is widely accepted as an essential tool for modern biology, its use still eludes many researchers for several reasons, especially when microarrays are not commercially available. In that case, the design, construction, and use of microarrays for a sequenced organism constitute substantial, time-consuming, and expensive tasks. Recently, it has become possible to construct custom microarrays using industrial manufacturing processes, which offer several advantages, including speed of manufacturing, quality control, no up-front setup costs, and need-based microarray ordering. Here, we describe a strategy for designing and validating DNA microarrays manufactured using a commercial process. The 22K microarrays for the solvent producer
Clostridium acetobutylicum
ATCC 824 are based on in situ-synthesized 60-mers employing the Agilent technology. The strategy involves designing a large library of possible oligomer probes for each target (i.e., gene or DNA sequence) and experimentally testing and selecting the best probes for each target. The degenerate
C. acetobutylicum
strain M5 lacking the pSOL1 megaplasmid (with 178 annotated open reading frames [genes]) was used to estimate the level of probe cross-hybridization in the new microarrays and to establish the minimum intensity for a gene to be considered expressed. Results obtained using this microarray design were consistent with previously reported results from spotted cDNA-based microarrays. The proposed strategy is applicable to any sequenced organism.
SIMPLE Approach for Isolating Mutants Expressing Fimbriae
Authors: Nuccio Sean-Paul , Chessa Daniela , Weening Eric H. , Raffatellu Manuela , Clegg Steven , Bäumler Andreas J. 
Published: May 2007

ABSTRACT

Genomes of members of the family
Enterobacteriaceae
contain large repertoires of putative fimbrial operons. Since many of these operons are poorly expressed in vitro, a convenient method for inducing elaboration of the encoded fimbriae would greatly facilitate their functional characterization. Here we describe a new technique for identifying fimbriated bacteria from a library of transposon mutants by screening with immunomagnetic particles for ligand expression (SIMPLE). The SIMPLE method was applied to identify the T-POP mutants of
Salmonella enterica
serotype Typhimurium carrying on their surfaces filaments composed of PefA, the major subunit product of a fimbrial operon (
pef
) that is not expressed during growth in Luria-Bertani broth. Four such mutants were identified from a library of 24,000 mutants, each of which carried a T-POP insertion within the
hns
gene, which encodes a global silencer of horizontally acquired genes. Our data suggest that the SIMPLE method is an effective approach for isolating fimbriated bacteria, which can be readily applied to fimbrial operons identified by whole-genome sequencing.