bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Macrolide Resistance of
Mycoplasma pneumoniae
in Pediatric Patients with Community-Acquired Pneumonia
Authors: Morozumi Miyuki , Iwata Satoshi , Hasegawa Keiko , Chiba Naoko , Takayanagi Reiko , Matsubara Keita , Nakayama Eiichi , Sunakawa Keisuke , Ubukata Kimiko 
Published: October 2007

ABSTRACT

Among 380
Mycoplasma pneumoniae
isolates from 3,678 pediatric patients with community-acquired pneumonia, 50 macrolide-resistant strains had an A2063G transition in domain V of the 23S rRNA, whereas 5 had an A2064G transition. These resistant strains increased rapidly from April 2002 to December 2006.
Exposure-Response Analyses of Tigecycline Efficacy in Patients with Complicated Intra-Abdominal Infections
Authors: Passarell J. A. , Meagher A. K. , Liolios K. , Cirincione B. B. , Van Wart S. A. , Babinchak T. , Ellis-Grosse E. J. , Ambrose P. G. 
Published: October 2007

ABSTRACT

Exposure-response analyses were performed to test the microbiological and clinical efficacies of tigecycline in complicated intra-abdominal infections where
Escherichia coli
and
Bacteroides fragilis
are the predominant pathogens. Data from evaluable patients enrolled in three clinical trials were pooled. Patients received intravenous tigecycline (100-mg loading dose followed by 50 mg every 12 h or 50-mg loading dose followed by 25 mg every 12 h). At the test-of-cure visit, microbiological and clinical responses were evaluated. Patients were prospectively classified into cohorts based on infection with a baseline pathogen(s):
E. coli
only (cohort 1), other mono- or polymicrobial
Enterobacteriaceae
(cohort 2), at least one
Enterobacteriaceae
pathogen plus an anaerobe(s) (cohort 3), at least one
Enterobacteriaceae
pathogen plus a gram-positive pathogen(s) (cohort 4), and all other pathogens (cohort 5). The cohorts were prospectively combined to increase sample size. Logistic regression was used to evaluate ratio of steady-state 24-hour area under the concentration-time curve (AUC) to MIC as a response predictor, and classification-and-regression-tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with cohorts 1, 2, and 3 pooled, which included 71 patients, with 106 pathogens. The small sample size precluded evaluation of cohorts 1 (34 patients, 35
E. coli
pathogens) and 2 (16 patients, 24
Enterobacteriaceae
). CART analyses identified a significant AUC/MIC breakpoint of 6.96 for microbiological and clinical responses (
P
values of 0.0004 and 0.399, respectively). The continuous AUC/MIC ratio was also borderline predictive of microbiological response (
P
= 0.0568). Cohort 4 (21 patients, 50 pathogens) was evaluated separately; however, an exposure-response relationship was not detected; cohort 5 (31 patients, 60 pathogens) was not evaluated. The prospective approach of creating homogenous populations of pathogens was critical for identifying exposure-response relationships in complicated intra-abdominal infections.
Bile and Unsaturated Fatty Acids Inhibit the Binding of Cholera Toxin andEscherichia coliHeat-Labile Enterotoxin to GM1 Receptor
Authors: Chatterjee Arpita , Chowdhury Rukhsana 
Published: October 2007

ABSTRACTCholera toxin (CT) is an archetypal bacterial toxin that binds with a high affinity to the receptor ganglioside GM1 on the intestinal epithelial surface and that causes the severe watery diarrhea characteristic of the disease cholera. Blockage of the interaction of CT with the GM1 receptor is an attractive approach for therapeutic intervention. We report here that crude bile prevents the interaction of CT with GM1 and reduces CT-mediated fluid accumulation in the rabbit intestine. The unsaturated fatty acids detected in crude bile, arachidonic, linoleic, and oleic acids, were found to be the most effective. Crude bile and the unsaturated fatty acids interacted with CT but not GM1 to prevent CT-GM1 binding. Neither crude bile nor the unsaturated fatty acids had any effect on the subunit structure of CT. The binding of CT to unsaturated fatty acids resulted in a shift of the apparent pI of CT from 6.8 to 8.2 and a marked decrease in intrinsic fluorescence. TheKdwas calculated from fluorescence quenching assays. It was demonstrated by the rabbit ileal loop model that practically no fluid accumulated in the intestinal loops when CT was administered together with inhibitory concentrations of linoleic acid. The bile present in the intestine was sufficient to inhibit the activity of up to 300 ng CT. Bile and unsaturated fatty acids also inhibited the binding ofEscherichia coliheat-labile enterotoxin (LT) to GM1, and no fluid accumulation was observed in rabbit ileal loops when LT was administered together with linoleic acid.
Tetracycline-Inducible Expression of Individual Secreted Aspartic Proteases in
Candida albicans
Allows Isoenzyme-Specific Inhibitor Screening
Authors: Staib Peter , Lermann Ulrich , Blaβ-Warmuth Julia , Degel Björn , Würzner Reinhard , Monod Michel , Schirmeister Tanja , Morschhäuser Joachim 
Published: October 2007

ABSTRACT

The yeast
Candida albicans
possesses a gene family that encodes secreted aspartic proteases (Saps), which are important for the virulence of this human fungal pathogen. Inhibitors of the Saps could therefore be used as novel antimycotic agents for the treatment of
C. albicans
infections. In the present study, we established a bioassay which allows testing of the activity of potential protease inhibitors against specific Sap isoenzymes by their ability to inhibit protease-dependent growth of
C. albicans
. In a medium containing bovine serum albumin (BSA) as the sole source of nitrogen,
C. albicans
specifically expresses the Sap2p isoenzyme, which degrades the BSA and thereby enables the fungus to grow. As the other
SAP
genes are not significantly expressed under these conditions, mutants lacking
SAP2
are unable to utilize BSA as a nitrogen source and cannot grow in such a medium. To investigate whether forced expression of
SAP
genes other than
SAP2
would also allow growth on BSA, we constructed a set of strains expressing each of the 10
SAP
genes from a tetracycline-inducible promoter in a
sap2
Δ mutant background. Expression of Sap1p, Sap2p, Sap3p, Sap4p, Sap5p, Sap6p, Sap8p, and a C-terminally truncated, secreted Sap9p restored the growth of the
sap2
Δ mutant with different efficiencies. This set of strains was then used to test the activities of various aspartic protease inhibitors against specific Sap isoenzymes by monitoring growth on BSA in the presence of the inhibitors. While pepstatin blocked the activity of all of the Saps tested, the human immunodeficiency virus protease inhibitors ritonavir and saquinavir inhibited growth of the strains expressing Sap1p to Sap3p and Sap1p, respectively, but not that of strains expressing other Saps. Therefore, the strain set can be used to test the activity of new protease inhibitors against individual
C. albicans
Sap isoenzymes by their ability to block the growth of the pathogen.
Staphylococcus epidermidis saeR
Is an Effector of Anaerobic Growth and a Mediator of Acute Inflammation
Authors: Handke L. D. , Rogers K. L. , Olson M. E. , Somerville G. A. , Jerrells T. J. , Rupp M. E. , Dunman P. M. , Fey P. D. 
Published: October 2007

ABSTRACT

The
saeRS
two-component regulatory system regulates transcription of multiple virulence factors in
Staphylococcus aureus
. In the present study, we demonstrated that the
saePQRS
region in
Staphylococcus epidermidis
is transcriptionally regulated in a temporal manner and is arranged in a manner similar to that previously described for
S. aureus
. Studies using a mouse foreign body infection model demonstrated that the virulence of strain 1457 and the virulence of a mutant, strain 1457
saeR
, were statistically equivalent. However, histological analyses suggested that the polymorphonuclear neutrophil response at 2 days postinfection was significantly greater in 1457-infected mice than in 1457
saeR
-infected mice, demonstrating that SaeR influences the early, acute phases of infection. Microarray analysis demonstrated that a
saeR
mutation affected the transcription of 65 genes (37 genes were upregulated and 28 genes were downregulated); in particular, 8 genes that facilitate growth under anaerobic conditions were downregulated in 1457
saeR
. Analysis of growth under anaerobic conditions demonstrated that 1457
saeR
had a decreased growth rate compared to 1457. Further metabolic experiments demonstrated that 1457
saeR
had a reduced capacity to utilize nitrate as a terminal electron acceptor and exhibited increased production of lactic acid in comparison to 1457. These data suggest that in
S. epidermidis
SaeR functions to regulate the transition between aerobic growth and anaerobic growth. In addition, when grown anaerobically, 1457
saeR
appeared to compensate for the redox imbalance created by the lack of electron transport-mediated oxidation of NADH to NAD
+
by increasing lactate dehydrogenase activity and the subsequent oxidation of NADH.
Critical Role of RecN in Recombinational DNA Repair and Survival of
Helicobacter pylori
Authors: Wang Ge , Maier Robert J. 
Published: October 2007

ABSTRACT

Homologous recombination is one of the key mechanisms responsible for the repair of DNA double-strand breaks. Recombinational repair normally requires a battery of proteins, each with specific DNA recognition, strand transfer, resolution, or other functions.
Helicobacter pylori
lacks many of the proteins normally involved in the early stage (presynapsis) of recombinational repair, but it has a RecN homologue with an unclear function. A
recN
mutant strain of
H. pylori
was shown to be much more sensitive than its parent to mitomycin C, an agent predominantly causing DNA double-strand breaks. The
recN
strain was unable to survive exposure to either air or acid as well as the parent strain, and air exposure resulted in no viable
recN
cells recovered after 8 h. In oxidative stress conditions (i.e., air exposure), a
recN
strain accumulated significantly more damaged (multiply fragmented) DNA than the parent strain. To assess the DNA recombination abilities of strains, their transformation abilities were compared by separately monitoring transformation using
H. pylori
DNA fragments containing either a site-specific mutation (conferring rifampin resistance) or a large insertion (kanamycin resistance cassette). The transformation frequencies using the two types of DNA donor were 10- and 50-fold lower, respectively, for the
recN
strain than for the wild type, indicating that RecN plays an important role in facilitating DNA recombination. In two separate mouse colonization experiments, the
recN
strain colonized most of the stomachs, but the average number of recovered cells was 10-fold less for the mutant than for the parent strain (a statistically significant difference). Complementation of the
recN
strain by chromosomal insertion of a functional
recN
gene restored both the recombination frequency and mouse colonization ability to the wild-type levels. Thus,
H. pylori
RecN, as a component of DNA recombinational repair, plays a significant role in
H. pylori
survival in vivo.
Mycoplasma gallisepticum
Invades Chicken Erythrocytes during Infection
Authors: Vogl Gunther , Plaickner Astrid , Szathmary Susan , Stipkovits László , Rosengarten Renate , Szostak Michael P. 
Published: October 2007

ABSTRACT

Recently, it was demonstrated using in vitro assays that the avian pathogen
Mycoplasma gallisepticum
is able to invade nonphagocytic cells. It was also shown that this mycoplasma can survive and multiply intracellularly for at least 48 h and that this cell invasion capacity contributes to the systemic spread of
M. gallisepticum
from the respiratory tract to the inner organs. Using the gentamicin invasion assay and a differential immunofluorescence technique combined with confocal laser scanning microscopy, we were able to demonstrate in in vitro experiments that
M. gallisepticum
is also capable of invading sheep and chicken erythrocytes. The frequencies of invasion of three well-defined
M. gallisepticum
strains were examined over a period of 24 h, and a significant increase in invasiveness occurred after 8 h of infection. In addition, blood samples derived from chickens experimentally infected via the aerosol route with the virulent strain
M. gallisepticum
R
low
were analyzed. Surprisingly,
M. gallisepticum
R
low
was detected in the bloodstream of infected chickens by nested PCR, as well as by differential immunofluorescence and interference contrast microscopy that showed that mycoplasmas were not only on the surface but also inside chicken erythrocytes. This finding provides novel insight into the pathomechanism of
M. gallisepticum
and may have implications for the development of preventive strategies.
Mycoplasma pneumoniae-Derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice
Authors: Shimizu Takashi , Kida Yutaka , Kuwano Koichi 
Published: October 2007

ABSTRACTThe pathogenesis ofMycoplasma pneumoniaeinfection is considered to be in part attributable to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F0F1-type ATPase (F0F1-ATPase), NF-κB-activating lipoprotein 1 (N-ALP1), and N-ALP2 (named FAM20, sN-ALP1, and sN-ALP2, respectively) derived fromM. pneumoniaeinduce cytokine and chemokine production and leukocyte infiltration in vivo. Intranasal administration of FAM20 and sN-ALP2 induced infiltration of leukocyte cells and production of chemokines and cytokines in bronchoalveolar lavage fluid, but sN-ALP1 failed to do so. The activity of FAM20 was notably higher than that of sN-ALP2. FAM20 and sN-ALP2 induced tumor necrosis factor alpha (TNF-α) through Toll-like receptor 2 in mouse peritoneal macrophages. Moreover, in the range of low concentrations of lipopeptides, FAM20 showed relatively high activity of inducing TNF-α in mouse peritoneal macrophages compared to synthetic lipopeptides such as MALP-2 and FSL-1, derived fromMycoplasma fermentansandMycoplasma salivarium, respectively. These findings indicate that the F0F1-ATPase might be a key molecule in inducing cytokines and chemokines contributing to inflammatory responses duringM. pneumoniaeinfection in vivo.
Lipoteichoic Acid Is Important in Innate Immune Responses to Gram-Positive Bacteria
Authors: Seo Ho Seong , Michalek Suzanne M. , Nahm Moon H. 
Published: October 2007

ABSTRACTTo define the role of lipoteichoic acid (LTA) in innate immunity to gram-positive bacteria, we investigated the production of tumor necrosis factor alpha (TNF-α) by macrophages stimulated with gram-positive bacterial culture supernatants (GPCSs) after their LTA was removed or inactivated. GPCSs were obtained from three gram-positive species (pneumococci, staphylococci, and group B streptococci) during the exponential growth phase (designated early GPCSs) or at the senescent stage (designated late GPCSs). LTA was removed using an anti-LTA antibody or was inactivated by alkaline hydrolysis or platelet-activating factor acetylhydrolase (PAF-AH) treatment. Both early and late GPCSs from the three gram-positive bacteria stimulated macrophages to produce TNF-α primarily via Toll-like receptor 2 (TLR2), although late pneumococcal supernatant could stimulate macrophages via TLR4 as well. Following LTA inactivation by both methods, early GPCS lost about 85 to 100% of its activity and late GPCS lost about 50 to 90%. Both early and late culture supernatants fromEscherichia colicould be inactivated by alkali hydrolysis but not by PAF-AH. In addition, removal of LTA from an early staphylococcal culture supernatant with a monoclonal antibody reduced about 70 to 85% of its potency. Reconstitution of inactivated early GPCS with a highly purified LTA restored its inflammatory activity, but the restored GPCS had higher activity than the pure LTA alone. These findings indicate that LTA is the primary TLR2 ligand in the early phase of gram-positive bacterial infection and remains a major ligand in the late phase when another TLR2 and TLR4 ligand(s) appears. In addition, our findings suggest that another gram-positive bacterial factor(s) synergizes with LTA in inducing inflammatory responses.
STAGES OF SMALL ENTERPRISE DEVELOPMENT: A COMPARISON OF CANADIAN FEMALE AND MALE ENTREPRENEURS
Authors: ZINGER J TERENCE , LEBRASSEUR ROLLAND , ROBICHAUD YVES , RIVERIN NATHALY 
Published: October 2007

The explosive growth in the rate of new business formation by women has spurred renewed research interest in the area of female entrepreneurship and its related economic impact. Yet, there has been a dearth of research into the influence of gender on new venture formation and development. This study draws on data from the annual survey of the Global Entrepreneurship Monitor to examine the differences between female and male entrepreneurs in the early stages of small enterprise development. The data was aggregated for the period 2002 through 2004, and consisted of 444 Canadian entrepreneurs: 164 females and 280 males. Gender differences are explored within the context of a variety of personal as well as business-related variables. Women entrepreneurs had a much greater propensity to have established a consumer or business services enterprise, and reported significantly lower income levels. In addition, they were less likely than their male counterparts to work full time at their business, to utilize new technology or to anticipate new business opportunities in the near term. In terms of the enterprise's stage of development, it was found that 62 percent of the enterprises operated by females were ‘nascent’ small firms, while 38 percent were ‘new;’ the respective proportions for males were 55 percent and 45 percent. The analysis revealed that the difference between genders on business-related variables strengthens as the firm evolves through the stages of development from nascent to new; however, there was mixed support for the corollary hypothesis that differences in personal characteristics and attitudes diminish during this progression: even for ventures that have reached the ‘new’ phase, personal variables continue to act as important discriminators between genders. The paper provides a discussion of the implications of these empirical findings, as well as some directions for future research.
Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML
Authors: Gondek Lukasz P. , Tiu Ramon , O'Keefe Christine L. , Sekeres Mikkael A. , Theil Karl S. , Maciejewski Jaroslaw P. 
Published: October 2007

Abstract
Using metaphase cytogenetics (MC), chromosomal abnormalities are found in only a proportion of patients with myelodysplastic syndrome (MDS). We hypothesized that with new precise methods more cryptic karyotypic lesions can be uncovered that may show important clinical implications. We have applied 250K single nucleotide polymorphisms (SNP) arrays (SNP-A) to study chromosomal lesions in samples from 174 patients (94 MDS, 33 secondary acute myeloid leukemia [sAML], and 47 myelodysplastic/myeloproliferative disease [MDS/MPD]) and 76 controls. Using SNP-A, aberrations were found in around three-fourths of MDS, MDS/MPD, and sAML (vs 59%, 37%, 53% by MC; in 8% of patients MC was unsuccessful). Previously unrecognized lesions were detected in patients with normal MC and in those with known lesions. Moreover, segmental uniparental disomy (UPD) was found in 20% of MDS, 23% of sAML, and 35% of MDS/MPD patients, a lesion resulting in copy-neutral loss of heterozygosity undetectable by MC. The potential clinical significance of abnormalities detected by SNP-A, but not seen on MC, was demonstrated by their impact on overall survival. UPD involving chromosomes frequently affected by deletions may have prognostic implications similar to the deletions visible by MC. SNP-A–based karyotyping shows superior resolution for chromosomal defects, including UPD. This technique further complements MC to improve clinical prognosis and targeted therapies.
Increasing Use of Contralateral Prophylactic Mastectomy for Breast Cancer Patients: A Trend Toward More Aggressive Surgical Treatment
Authors: Tuttle Todd M. , Habermann Elizabeth B. , Grund Erin H. , Morris Todd J. , Virnig Beth A. 
Published: October 2007

Purpose Many patients with unilateral breast cancer choose contralateral prophylactic mastectomy to prevent cancer in the opposite breast. The purpose of our study was to determine the use and trends of contralateral prophylactic mastectomy in the United States. Patients and Methods We used the Surveillance, Epidemiology and End Results database to review the treatment of patients with unilateral breast cancer diagnosed from 1998 through 2003. We determined the rate of contralateral prophylactic mastectomy as a proportion of all surgically treated patients and as a proportion of all mastectomies. Results We identified 152,755 patients with stage I, II, or III breast cancer; 4,969 patients chose contralateral prophylactic mastectomy. The rate was 3.3% for all surgically treated patients; 7.7%, for patients undergoing mastectomy. The overall rate significantly increased from 1.8% in 1998 to 4.5% in 2003. Likewise, the contralateral prophylactic mastectomy rate for patients undergoing mastectomy significantly increased from 4.2% in 1998 to 11.0% in 2003. These increased rates applied to all cancer stages and continued to the end of our study period. Young patient age, non-Hispanic white race, lobular histology, and previous cancer diagnosis were associated with significantly higher rates. Large tumor size was associated with a higher overall rate, but with a lower rate for patients undergoing mastectomy. Conclusion The use of contralateral prophylactic mastectomy in the United States more than doubled within the recent 6-year period of our study. Prospective studies are needed to understand the decision-making processes that have led to more aggressive breast cancer surgery.
Cancer Care Ontario and American Society of Clinical Oncology Adjuvant Chemotherapy and Adjuvant Radiation Therapy for Stages I-IIIA Resectable Non–Small-Cell Lung Cancer Guideline
Authors: Pisters Katherine M.W. , Evans William K. , Azzoli Christopher G. , Kris Mark G. , Smith Christopher A. , Desch Christopher E. , Somerfield Mark R. , Brouwers Melissa C. , Darling Gail , Ellis Peter M. , Gaspar Laurie E. , Pass Harvey I. , Spigel David R. , Strawn John R. , Ung Yee C. , Shepherd Frances A. 
Published: October 2007

Purpose To determine the role of adjuvant chemotherapy and radiation therapy in patients with completely resected stage IA-IIIA non–small-cell lung cancer (NSCLC). Methods The Cancer Care Ontario Program in Evidence-Based Care and the American Society of Clinical Oncology convened a Joint Expert Panel in August 2006 to review the evidence and draft recommendations for these therapies. Results Available data support the use of adjuvant cisplatin-based chemotherapy in completely resected NSCLC; however, the strength of the data and consequent recommendations vary by disease stage. Adjuvant radiation therapy appears detrimental to survival in stages IB and II, with a possible modest benefit in stage IIIA. Conclusion Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA disease. Although there has been a statistically significant overall survival benefit seen in several randomized clinical trials (RCTs) enrolling a range of people with completely resected NSCLC, results of subset analyses for patient populations with stage IB disease were not significant, and adjuvant chemotherapy in stage IB disease is not currently recommended for routine use. To date, very few patients with stage IA NSCLC have been enrolled onto RCTs of adjuvant therapy; adjuvant chemotherapy is not recommended in these cases. Evidence from RCTs demonstrates a survival detriment for adjuvant radiotherapy with limited evidence for a reduction in local recurrence. Adjuvant radiation therapy appears detrimental to survival in stage IB and II, and may possibly confer a modest benefit in stage IIIA.