bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of 16S rRNA Methylase-Producing
Acinetobacter baumannii
Clinical Strains in North America
Authors: Doi Yohei , Adams Jennifer M. , Yamane Kunikazu , Paterson David L. 
Published: September 2007

ABSTRACT

Five highly amikacin-resistant
Acinetobacter baumannii
isolates were collected at a medical center in Pennsylvania. The aminoglycoside resistance was due to the production of the 16S rRNA methylase ArmA. Two of the isolates coproduced OXA-23 β-lactamase and were highly resistant to carbapenems as well. The isolates were genetically closely related by pulsed-field gel electrophoresis.
Characterization of an Immunogenic Outer Membrane Autotransporter Protein, Arp, of
Bartonella henselae
Authors: Litwin Christine M. , Rawlins Mindy L. , Swenson Erica M. 
Published: September 2007

ABSTRACT

Bartonella henselae
is a recently recognized pathogenic bacterium associated with cat scratch disease, bacillary angiomatosis, and bacillary peliosis. This study describes the cloning, sequencing, and characterization of an antigenic autotransporter gene from
B. henselae
. A cloned 6.0-kb BclI-EcoRI DNA fragment expresses a 120-kDa
B. henselae
protein immunoreactive with 21.2% of sera from patients positive for
B. henselae
immunoglobulin G antibodies by indirect immunofluorescence, with 97.3% specificity and no cross-reactivity with antibodies against various other organisms. DNA sequencing of the clone revealed one open reading frame of 4,320 bp with a deduced amino acid sequence that shows homology to the family of autotransporters. The autotransporters are a group of proteins that mediate their own export through the outer membrane and consist of a passenger region, the α-domain, and an outer membrane transporter region, the β-domain. The passenger domain shows homology to a family of pertactin-like adhesion proteins and contains seven, nearly identical 48-amino-acid repeats not found in any other bacterial or
Bartonella
DNA sequences. The passenger α-domain has a calculated molecular mass of 117 kDa, and the transporter β-domain has a calculated molecular mass of 36 kDa. The clone expresses a 120-kDa protein and a protein that migrates at approximately 38 kDa exclusively in the outer membrane protein fraction, suggesting that the 120-kDa passenger protein remains associated with the outer membrane after cleavage from the 36-kDa transporter.
Enterococcus faecalis
Constitutes an Unusual Bacterial Model in Lysozyme Resistance
Authors: Hébert Laurent , Courtin Pascal , Torelli Riccardo , Sanguinetti Maurizio , Chapot-Chartier Marie-Pierre , Auffray Yanick , Benachour Abdellah 
Published: September 2007

ABSTRACT

Lysozyme is an important and widespread compound of the host constitutive defense system, and it is assumed that
Enterococcus faecalis
is one of the few bacteria that are almost completely lysozyme resistant. On the basis of the sequence analysis of the whole genome of
E. faecalis
V583 strain, we identified two genes that are potentially involved in lysozyme resistance, EF_0783 and EF_1843. Protein products of these two genes share significant homology with
Staphylococcus aureus
peptidoglycan
O
-acetyltransferase (OatA) and
Streptococcus pneumoniae N
-acetylglucosamine deacetylase (PgdA), respectively. In order to determine whether EF_0783 and EF_1843 are involved in lysozyme resistance, we constructed their corresponding mutants and a double mutant. The ΔEF_0783 mutant and ΔEF_0783 ΔEF_1843 double mutant were shown to be more sensitive to lysozyme than the parental
E. faecalis
JH2-2 strain and ΔEF_1843 mutant were. However, compared to other bacteria, such as
Listeria monocytogenes
or
S. pneumoniae
, the tolerance of ΔEF_0783 and ΔEF_0783 ΔEF_1843 mutants towards lysozyme remains very high. Peptidoglycan structure analysis showed that EF_0783 modifies the peptidoglycan by O acetylation of
N
-acetyl muramic acid, while the EF_1843 deletion has no obvious effect on peptidoglycan structure under the same conditions. Moreover, the EF_0783 and EF_1843 deletions seem to significantly affect the ability of
E. faecalis
to survive within murine macrophages. In all, while EF_0783 is currently involved in the lysozyme resistance of
E. faecalis
, peptidoglycan O acetylation and de-N-acetylation are not the main mechanisms conferring high levels of lysozyme resistance to
E. faecalis
.
Characterization of a New Variant of IS
257
That Has Displaced the Capsule Genes within Bovine Isolates of
Staphylococcus aureus
Authors: Tuchscherr L. P. N. , Gomez M. I. , Buzzola F. R. , Calvinho L. F. , Lee J. C. , Sordelli D. O. 
Published: September 2007

ABSTRACT

Many bovine
Staphylococcus aureus
isolates from Argentina are nontypeable (NT), i.e., they do not produce serotype 5 or 8 capsular polysaccharides (CPs). Some of these NT strains have a deletion of the
cap5
(
8
) gene cluster mediated by a variant of IS
257
, now designated IS
cap
. IS
cap
showed 93% amino acid identity to
S. aureus
ORF49 but only 85% identity to IS
431
from
S. aureus
N315 and 88% identity to an IS
257
-like element from bovine strain RF122. Thirty-six (53%) of 68 bovine isolates, drawn from a previously described
S. aureus
strain collection, carried some variant of IS
257
, including IS
cap.
Of these 36 IS
+
isolates, 6 were CP5
+
, 1 was CP8
+
, and 29 were NT. Forty-four of the 68 isolates were NT, and 24 of these 44 NT isolates (55%) exhibited IS
cap
-mediated deletion of the
cap5
(
8
) gene cluster. IS
cap
was not found among 20 human NT
S. aureus
isolates bearing the
cap5HIJK
genes, which suggests that IS
cap
-mediated deletion of the capsule locus is restricted to bovine strains of
S. aureus
. We were unable to identify a precursor strain in which IS
cap
flanked the
cap5
(
8
) capsule locus, nor were we able to select for deletion of the
cap5
(
8
) locus in vitro. Our results support the hypothesis that deletion of the
cap5
locus occurred in the distant past and that the relative abundance of these NT strains may be a result of their ability to persist in subclinical mastitis infection in cows.
Maintenance of Antibody to Pathogen Epitopes Generated by Segmental Gene Conversion Is Highly Dynamic during Long-Term Persistent Infection
Authors: Zhuang Yan , Futse James E. , Brown Wendy C. , Brayton Kelly A. , Palmer Guy H. 
Published: September 2007

ABSTRACT

Multiple bacterial and protozoal pathogens utilize gene conversion to generate rapid intrahost antigenic variation. Both large- and small-genome pathogens expand the size of the variant pool via a combinatorial process in which oligonucleotide segments from distinct donor loci are recombined in various combinations into expression sites. Although the potential combinatorial diversity generated by this segmental gene conversion mechanism is quite large, the functional variant pool depends on whether immune responses against the recombined segments are generated and maintained, regardless of their specific combinatorial context. This question was addressed by tracking the
Anaplasma marginale
variant population and corresponding segment-specific immunoglobulin G (IgG) antibody responses during long-term infection. Antibody was induced early in
A. marginale
infection, predominately against the surface-exposed hypervariable region (HVR) rather than against the invariant conserved flanking domains, and these HVR oligopeptides were most immunogenic at the time of acute bacteremia, when the variant population is derived via recombination from a single donor locus. However antibody to HVR oligopeptides was not consistently maintained during persistent infection, despite reexpression of the same segment, although in a different combinatorial context. This dynamic antibody recognition over time was not attributable to the major histocompatibility complex haplotype of individual animals or use of specific
msp2
donor alleles. In contrast, the position and context of an individual oligopeptide segment within the HVR were significant determinants of antibody recognition. The results unify the genetic potential of segmental gene conversion with escape from antibody recognition and identify immunological effects of variant mosaic structure.
Siderophore-Based Iron Acquisition and Pathogen Control
Authors: Miethke Marcus , Marahiel Mohamed A. 
Published: September 2007

SUMMARYHigh-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.
Existence of Solutions and Convergence of a Multistep Iterative Algorithm for a System of Variational Inclusions with "Equation missing" -Accretive Operators
Authors: Peng Jian-Wen , Zhu Dao-Li , Zheng Xiao-Ping 
Published: September 2007

AbstractWe introduce and study a new system of variational inclusions with "Equation missing"-accretive operators, which contains variational inequalities, variational inclusions, systems of variational inequalities, and systems of variational inclusions in the literature as special cases. By using the resolvent technique for the "Equation missing"-accretive operators, we prove the existence and uniqueness of solution and the convergence of a new multistep iterative algorithm for this system of variational inclusions in real "Equation missing"-uniformly smooth Banach spaces. The results in this paper unify, extend, and improve some known results in the literature.
Foxp3 Expression in Pancreatic Carcinoma Cells as a Novel Mechanism of Immune Evasion in Cancer
Authors: Hinz Sebastian , Pagerols-Raluy Laia , Oberg Hans-Heinrich , Ammerpohl Ole , Grüssel Sandra , Sipos Bence , Grützmann Robert , Pilarsky Christian , Ungefroren Hendrik , Saeger Hans-Detlev , Klöppel Günter , Kabelitz Dieter , Kalthoff Holger 
Published: September 2007

Abstract
The forkhead transcription factor Foxp3 is highly expressed in CD4+CD25+ regulatory T cells (Treg) and was recently identified as a key player in mediating their inhibitory functions. Here, we describe for the first time the expression and function of Foxp3 in pancreatic ductal adenocarcinoma cells and tumors. Foxp3 expression was induced by transforming growth factor-β2 (TGF-β2), but not TGF-β1 stimulation in these cells, and was partially suppressed following antibody-mediated neutralization of TGF-β2. The TGF-β2 effect could be mimicked by ectopic expression of a constitutively active TGF-β type I receptor/ALK5 mutant. Down-regulation of Foxp3 with small interfering RNA (siRNA) in pancreatic carcinoma cells resulted in the up-regulation of interleukin 6 (IL-6) and IL-8 expression, providing evidence for a negative transcriptional activity of Foxp3 also in these epithelial cells. Coculture of Foxp3-expressing tumor cells with naive T cells completely inhibited T-cell proliferation, but not activation, and this antiproliferative effect was partially abrogated following specific inhibition of Foxp3 expression. These findings indicate that pancreatic carcinoma cells share growth-suppressive effects with Treg and suggest that mimicking Treg function may represent a new mechanism of immune evasion in pancreatic cancer. [Cancer Res 2007;67(17):8344–50]
Expression of a CALM-AF10 Fusion Gene Leads to Hoxa Cluster Overexpression and Acute Leukemia in Transgenic Mice
Authors: Caudell David , Zhang Zhenhua , Chung Yang Jo , Aplan Peter D. 
Published: September 2007

Abstract
To assess the role of the CALM-AF10 fusion gene in leukemic transformation in vivo, we generated transgenic mice that expressed a CALM-AF10 fusion gene. Depending on the transgenic line, at least 40% to 50% of the F1 generation mice developed acute leukemia at a median age of 12 months. Leukemic mice typically had enlarged spleens, invasion of parenchymal organs with malignant cells, and tumors with myeloid markers such as myeloperoxidase, Mac1, and Gr1. Although most leukemias were acute myeloid leukemia, many showed lymphoid features, such as CD3 staining, or clonal Tcrb or Igh gene rearrangements. Mice were clinically healthy for the first 9 months of life and had normal peripheral blood hemograms but showed impaired thymocyte differentiation, manifested by decreased CD4+/CD8+ cells and increased immature CD4−/CD8− cells in the thymus. Hematopoietic tissues from both clinically healthy and leukemic CALM-AF10 mice showed up-regulation of Hoxa cluster genes, suggesting a potential mechanism for the impaired differentiation. The long latency period and incomplete penetrance suggest that additional genetic events are needed to complement the CALM-AF10 transgene and complete the process of leukemic transformation. [Cancer Res 2007;67(17):8022–31]
Antitumor Effect of Antibody against a SEREX-Defined Antigen (UOEH-LC-1) on Lung Cancer Xenotransplanted into Severe Combined Immunodeficiency Mice
Authors: Mizukami Makiko , Hanagiri Takeshi , Yasuda Manabu , Kuroda Koji , Shigematsu Yoshiki , Baba Tetsuro , Fukuyama Takashi , Nagata Yoshika , So Tetsuya , Ichiki Yoshinobu , Sugaya Masakazu , So Tomoko , Takenoyama Mitsuhiro , Sugio Kenji , Yasumoto Kosei 
Published: September 2007

Abstract
We previously reported the humoral immune response of tumor-infiltrating B lymphocytes in a lung cancer patient and 22 genes coding tumor-associated antigens identified using the serological identification of antigens by recombinant expression cloning method. In this study, we investigated one of these genes, designated University of Occupational and Environmental Health—Lung cancer antigen-1 (UOEH-LC-1), which has an extracellular domain. Quantitative reverse transcription-PCR revealed that UOEH-LC-1 was expressed ubiquitously in the normal tissues tested. However, it was overexpressed in 5 of 11 (45.5%) lung cancer cell lines and also in 9 of 15 (60%) lung cancer tissues compared with the paired normal lung tissues. A sequence analysis revealed that UOEH-LC-1 has a transmembrane domain. Flow cytometry analysis using a polyclonal antibody against UOEH-LC-1 revealed positive staining on lung cancer cell lines that were positive for expression of mRNA of UOEH-LC-1. Phage plaque assay showed the specific reactivity of anti–UOEH-LC-1 antibody against UOEH-LC-1 protein derived from the antigen encoding phage. By immunohistochemical staining with the anti–UOEH-LC-1 antibody, 7 of 28 (25.0%) lung cancer specimens showed positive staining on the cell surface. The administration of anti–UOEH-LC-1 antibody inhibited the growth of the UOEH-LC-1–positive tumors that were xenotransplanted into severe combined immunodeficiency mice. Complement-dependent cytotoxicity was one of the mechanisms to suppress the tumor growth. These results suggest that the antibody against UOEH-LC-1 therefore seems to have a promising therapeutic potential as a treatment for lung cancer. [Cancer Res 2007;67(17):8351–7]
Inhibition of Prostate Cancer Growth by Muscadine Grape Skin Extract and Resveratrol through Distinct Mechanisms
Authors: Hudson Tamaro S. , Hartle Diane K. , Hursting Stephen D. , Nunez Nomeli P. , Wang Thomas T.Y. , Young Heather A. , Arany Praveen , Green Jeffrey E. 
Published: September 2007

Abstract
The phytochemical resveratrol contained in red grapes has been shown to inhibit prostate cancer cell growth, in part, through its antioxidant activity. Muscadine grapes contain unique phytochemical constituents compared with other grapes and are potentially a source for novel compounds with antitumor activities. We compared the antitumor activities of muscadine grape skin extract (MSKE), which we show contains no resveratrol, with that of resveratrol using primary cultures of normal prostate epithelial cells (PrEC) and the prostate cancer cell lines RWPE-1, WPE1-NA22, WPE1-NB14, and WPE1-NB26, representing different stages of prostate cancer progression. MSKE significantly inhibited tumor cell growth in all transformed prostate cancer cell lines but not PrEC cells. Prostate tumor cell lines, but not PrEC cells, exhibited high rates of apoptosis in response to MSKE through targeting of the phosphatidylinositol 3-kinase–Akt and mitogen-activated protein kinase survival pathways. The reduction in Akt activity by MSKE is mediated through a reduction in Akt transcription, enhanced proteosome degradation of Akt, and altered levels of DJ-1, a known regulator of PTEN. In contrast to MSKE, resveratrol did not induce apoptosis in this model but arrested cells at the G1-S phase transition of the cell cycle associated with increased expression of p21 and decreased expression of cyclin D1 and cyclin-dependent kinase 4 proteins. These results show that MSKE and resveratrol target distinct pathways to inhibit prostate cancer cell growth in this system and that the unique properties of MSKE suggest that it may be an important source for further development of chemopreventive or therapeutic agents against prostate cancer. [Cancer Res 2007;67(17):8396–405]
Inactivation of Smad4 Accelerates KrasG12D-Mediated Pancreatic Neoplasia
Authors: Kojima Kyoko , Vickers Selwyn M. , Adsay N. Volkan , Jhala Nirag C. , Kim Hyung-Gyoon , Schoeb Trenton R. , Grizzle William E. , Klug Christopher A. 
Published: September 2007

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human malignancies, with an overall 5-year survival rate of &lt;5%. Genetic analysis of PDAC patient samples has shown that specific disease-associated mutations are correlated with histologically defined stages of neoplastic progression in the ductal epithelium. Activating mutations in KRAS are almost uniformly present in early-stage disease, with subsequent inactivating mutations in p16INK4A, p53, and SMAD4 occurring in more advanced lesions. In this study, we have tested whether the loss of Smad4 would cooperate with an activating KrasG12D mutation to promote progression to PDAC using the Pdx1-Cre transgenic system to activate KrasG12D and delete Smad4 in all pancreatic lineages including the ductal epithelium. Analysis of double-mutant mice showed that loss of Smad4 significantly accelerated the progression of pancreatic intraepithelial neoplasias (mPanIN) and promoted a high incidence of intraductal papillary mucinous neoplasia and active fibrosis compared with Pdx1-Cre;KrasG12D or Pdx1-Cre;Smad4lox/lox mice. Occasionally, double-mutant mice progressed to locally invasive PDAC with little evidence of metastases by 6 months of age and without the detectable loss of p53 or p16Ink4A expression or function. The loss of Smad4 only seemed to promote disease progression in the presence of the activated KrasG12D allele because we observed no abnormal pathology within the pancreata of 23 Pdx1-Cre;Smad4lox/lox animals that were analyzed up to 8 months of age. This indicates that Smad4 is dispensable for normal pancreatic development but is critical for at least partial suppression of multiple KrasG12D-dependent disease-associated phenotypes. [Cancer Res 2007;67(17):8121–30]
Gene-Engineered Varicella-Zoster Virus–Reactive CD4+ Cytotoxic T Cells Exert Tumor-Specific Effector Function
Authors: Landmeier Silke , Altvater Bianca , Pscherer Sibylle , Eing Bodo R. , Kuehn Joachim , Rooney Cliona M. , Juergens Heribert , Rossig Claudia 
Published: September 2007

AbstractT cells with grafted specificities for surface antigens provide an avenue for rapidly producing immune effector cells with tumor specificity. However, the function of chimeric receptor (chRec) gene-modified T cells is limited by lack of T-cell expansion and persistence. We propose to use varicella zoster virus (VZV)–reactive T cells as host for the chRec because these cells can be expanded both in vitro and in vivo by stimulation of their native receptor during endogenous reexposure to the virus or by administration of VZV vaccine. We obtained human T cells reactive with VZV from the peripheral blood of seropositive donors by stimulation with VZV lysate and evaluated their characteristics after genetic modification with two tumor-specific model chRecs. Cultures dominated by cytolytic CD4+ T cells (VZV-CTL) could be expanded and maintained in vitro. Gene-modified VZV-CTL recognized and lysed tumor targets in a MHC-independent manner while maintaining functional, MHC-restricted interaction with VZV antigen through their native receptor. Thus, chRec-transduced VZV-CTL may provide a source of potent tumor-reactive cells for adoptive immunotherapy of cancer. The availability of a safe and effective VZV vaccine provides the option of repeated in vivo stimulation to maintain high T-cell numbers until the tumor is eliminated. [Cancer Res 2007;67(17):8335–43]
Bone Morphogenetic Protein Signaling Suppresses Tumorigenesis at Gastric Epithelial Transition Zones in Mice
Authors: Bleuming Sylvia A. , He Xi C. , Kodach Liudmila L. , Hardwick James C. , Koopman Frieda A. , ten Kate Fiebo J. , van Deventer Sander J.H. , Hommes Daniel W. , Peppelenbosch Maikel P. , Offerhaus G. Johan , Li Linheng , van den Brink Gijs R. 
Published: September 2007

Abstract
Bone morphogenetic protein (BMP) signaling is known to suppress oncogenesis in the small and large intestine of mice and humans. We examined the role of Bmpr1a signaling in the stomach. On conditional inactivation of Bmpr1a, mice developed neoplastic lesions specifically in the squamocolumnar and gastrointestinal transition zones. We hypothesized that the regulation of epithelial cell fate may be less well defined in these junctional zones than in the adjacent epithelium and found that the mucosa at the squamocolumnar junction in mice shows a lack of differentiated fundic gland cell types and that foveolar cells at the gastrointestinal junctional zone lack expression of the foveolar cell marker Muc5ac. Precursor cell proliferation in both transition zones was higher than in the surrounding epithelium. Our data show that BMP signaling through Bmpr1a suppresses tumorigenesis at gastric epithelial junctional zones that are distinct from the adjacent gastric epithelium in both cellular differentiation and proliferation. [Cancer Res 2007;67(17):8149–55]