bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination Therapy with Antiangiogenic Treatment and Photodynamic Therapy for the Nude Mouse Bearing U87 Glioblastoma
Authors: Jiang Feng , Zhang Xuepeng , Kalkanis Steven N. , Zhang ZhengGang , Yang Hongyan , Katakowski Mark , Hong Xin , Zheng Xuguang , Zhu Zhenping , Chopp Michael
Published: October 2007

The objective of this study was to evaluate the effects of combination therapy with photodynamic therapy (PDT) and a novel antiangiogenic regimen using monoclonal antibodies against both vascular endothelial growth factor receptors (VEGFR)‐1 (MF1) and VEGFR‐2 (DC101) on intracranial glioblastoma xenografts in nude mice. Nude mice bearing intracerebral U87 glioblastoma were treated with PDT and the antiangiogenic regimen (MF1 and DC101) either alone or in combination, while those left untreated served as tumor controls. Tumor volume and animal survival time were analyzed to evaluate the outcome of different treatment modalities. In addition, the immunohistochemical expression of VEGF in the brain adjacent to the tumor, von Willebrand factor (vWF), apoptotic, and proliferative markers in the tumor area were examined. PDT or MF1 + DC101 alone significantly reduced the tumor volume and prolonged the survival time of glioma‐implanted animals. Combined therapy markedly reduced tumor volume and increased survival time with significantly better outcomes than both monotherapies. Both vWF and VEGF levels significantly increased after PDT while they both significantly decreased after antiangiogenic treatment, compared with no treatment. PDT plus antiangiogenic treatment led to significant decreases in both vWF and VEGF expression, compared with PDT alone. Either PDT or antiangiogenic treatment alone significantly increased tumor cell apoptosis compared with no treatment, while combination therapy resulted in further augmentation of apoptosis. Antiangiogenic treatment with or without PDT significantly decreased tumor cell proliferation, compared with either no treatment or PDT alone. In summary, we demonstrate both significant inhibition of tumor growth and extended survival of mice treated by the combination therapy with PDT and antiangiogenic agents, compared with each single treatment, suggesting that the combination therapy may be a promising strategy to improve clinical outcomes in glioblastoma.
The Photoyellowing of Stilbene‐derived Fluorescent Whitening Agents—Mass Spectrometric Characterization of Yellow Photoproducts
Authors: Dyer Jolon M. , Cornellison Charisa D. , Bringans Scott D. , Maurdev George , Millington Keith R.
Published: October 2007

The application of fluorescent whitening agents (FWAs) significantly accelerates the photoyellowing of wool and silk under exposure to the ultraviolet and visible components of sunlight <500 nm. The photochemistry involved in this process is poorly understood, particularly the role of photoproducts derived directly from the FWA itself. Hydroxylation was identified as the key initial mechanism of photodegradation leading to coloration of the solution in the irradiation of the stilbene‐derived FWA 4,4′‐bis(2‐sulfostyryl)biphenyl (DSBP) in the presence of hydrogen peroxide (H2O2). Polyhydroxylated DSBP derivatives were implicated as critical intermediates in the formation of yellow photoproducts under these conditions. The formation of trace quantities of DSBP quinone derivatives subsequent to hydroxylation was identified as the key cause of DSBP photoyellowing. These results are the first successful characterization of yellow photoproducts resulting directly from irradiation of a stilbene‐based FWA. Formation of these yellow stilbene‐based FWA‐derived photoproducts may occur on the surface of FWA‐treated wool exposed to simulated sunlight, as previous work has shown that H2O2 is photogenerated when wet FWA‐treated wool is exposed to light. These results therefore suggest that yellow FWA‐derived photoproducts contribute to the accelerated photoyellowing of FWA‐treated wool.
Thwarting the Need to Belong: Understanding the Interpersonal and Inner Effects of Social Exclusion
Authors: Baumeister Roy F. , Brewer Lauren E. , Tice Dianne M. , Twenge Jean M.
Published: October 2007

The need to belong is a powerful motivational basis for interpersonal behavior, and it is thwarted by social exclusion and rejection. Laboratory work has uncovered a destructive set of consequences of being socially excluded, such as increased aggressiveness and reduced helpfulness toward new targets. Rejected persons do, however, exhibit a cautious interest in finding new friends. Theory and intuition associate social exclusion with emotional distress, but laboratory research finds instead that the first response is a reduced sensitivity to pain and an emotional insensitivity that hampers empathy and may contribute to a variety of interpersonal behaviors. Self‐regulation and intelligent thought are also impaired as a direct result of being rejected.
A Pain Severity–Hypothalamic–Pituitary–Adrenocortical Axis Interaction: The Effects on Pain Pathways1
Authors: Garofalo John P. , Robinson Richard C. , Gatchel Robert J. , Wang Zhongyun
Published: October 2007

Recent efforts have identified psychosocial and biological factors influencing the pathogenesis of chronic pain. The present study attempted to identify whether these two variables interact and, in turn, represent an underlying mechanism in the transition from acute to chronic pain. Salivary cortisol samples were collected upon waking up and 20 minutes later daily for 2 weeks from acute pain patients. Analyses revealed a direct relationship between pain severity and hypothalamic–pituitary–adrenocortical activity for temporomandibular disorder, and a negative relationship between these variables for low back pain populations. These results highlight the possible interaction between neuroendocrine and psychological factors to increase the risk for chronic pain.
Inflammatory Markers in Acute Myocardial Infarction Patients: Preliminary Evidence of a Prospective Association With Depressive Symptoms
Authors: Hekler Eric B. , Rubenstein Jason , Coups Elliot J. , Gilligan Suzanne , Kusnecov Alexander W. , Contrada Richard J. , Steiner Matthew J. , Tannenbaum Alan K. , Leventhal Elaine A. , Krause Tyrone J.
Published: October 2007

Inflammatory activity has been associated with both coronary disease and depressive symptoms. We sought to determine whether inflammatory markers in myocardial infarction (MI) patients are prospectively associated with depressive symptomatology. Participants were a convenience sample of MI patients. Depressive symptoms were assessed soon after the MI and again 7 months postdischarge. Inflammatory markers examined were interleukin‐6 (IL‐6) and interleukin‐1β. Results suggest no significant cross‐sectional association between inflammatory markers and depressive symptoms at baseline. However, bivariate and multiple regression analyses revealed a significant positive prospective association between baseline IL‐6 and depressive symptoms 7 months later (β = .57, p < .01). The results suggest that temporal considerations are important in understanding relationships between inflammation and depressive symptoms following MI.
The Relation Between Past Behavior, Intention, Planning, and Quitting Smoking: The Moderating Effect of Future Orientation
Authors: Kovač Velibor Bobo , Rise Jostein
Published: October 2007

The present study examined the moderating effects of two measures of future orientation on the relation between intention, planning, and past behavior on the one hand, and quitting smoking on the other. The degree of future orientation was assessed by the Consideration of Future Consequences (CFC) Scale and the Stanford Time Perspective Inventory (STPI). Both CFC and STPI significantly moderated the intention–quitting behavior and past behavior–quitting behavior relationships. CFC also moderated the relation between planning and quitting behavior, whereas STPI failed to moderate the planning–quitting relation. The results indicate that the extent to which a person is future oriented represents an important moderating variable when it comes to the relation between deliberative processes and actual behavior. The implications of the results are discussed.
Mathematics and Complex Systems
Authors: Foote Richard
Published: October 2007

Contemporary researchers strive to understand complex physical phenomena that involve many constituents, may be influenced by numerous forces, and may exhibit unexpected or emergent behavior. Often such “complex systems“ are macroscopic manifestations of other systems that exhibit their own complex behavior and obey more elemental laws. This article proposes that areas of mathematics, even ones based on simple axiomatic foundations, have discernible layers, entirely unexpected “macroscopic” outcomes, and both mathematical and physical ramifications profoundly beyond their historical beginnings. In a larger sense, the study of mathematics itself, which is increasingly surpassing the capacity of researchers to verify “by hand,” may be the ultimate complex system.
A Crisis Is a Terrible Thing to Waste
Authors: Keim Paul S.
Published: October 2007

Are We Ready?
. Public Health Since 9/11.
By David Rosner and Gerald Markowitz
. University of California Press, Berkeley, and Milbank Memorial Fund, New York, 2006. 210 pp. $45, £26.95. ISBN 9780520249202. Paper, $16.95, £9.95. ISBN 9780520250383. California/Milbank Books on Health and the Public

Rosner and Markowitz consider the effects that 9/11, the anthrax attacks that followed, and preparations for the use of smallpox as a bioterror weapon have had on the public health infrastructure in the United States.
Network Analysis of Oncogenic Ras Activation in Cancer
Authors: Stites Edward C. , Trampont Paul C. , Ma Zhong , Ravichandran Kodi S.
Published: October 2007

To investigate the unregulated Ras activation associated with cancer, we developed and validated a mathematical model of Ras signaling. The model-based predictions and associated experiments help explain why only one of two classes of activating Ras point mutations with in vitro transformation potential is commonly found in cancers. Model-based analysis of these mutants uncovered a systems-level process that contributes to total Ras activation in cells. This predicted behavior was supported by experimental observations. We also used the model to identify a strategy in which a drug could cause stronger inhibition on the cancerous Ras network than on the wild-type network. This system-level analysis of the oncogenic Ras network provides new insights and potential therapeutic strategies.
Structure of a NHEJ Polymerase-Mediated DNA Synaptic Complex
Authors: Brissett Nigel C. , Pitcher Robert S. , Juarez Raquel , Picher Angel J. , Green Andrew J. , Dafforn Timothy R. , Fox Gavin C. , Blanco Luis , Doherty Aidan J.
Published: October 2007

Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure of
Mycobacterium tuberculosis
polymerase domain of LigD mediating the synapsis of two noncomplementary DNA ends revealed a variety of interactions, including microhomology base pairing, mismatched and flipped-out bases, and 3′ termini forming hairpin-like ends. Biochemical and biophysical studies confirmed that polymerase-induced end synapsis also occurs in solution. We propose that this DNA synaptic structure reflects an intermediate bridging stage of the NHEJ process, before end processing and ligation, with both the polymerase and the DNA sequence playing pivotal roles in determining the sequential order of synapsis and remodeling before end joining.
Response to Comment on "Human Neuroblasts Migrate to the Olfactory Bulb via a Lateral Ventricular Extension"
Authors: Curtis Maurice A. , Kam Monica , Nannmark Ulf , Faull Richard L.M. , Eriksson Peter S.
Published: October 2007

In contrast to a previous study of Sanai
et al
., our study had the advantage of using serial sagittal sections of the human basal forebrain, combined with 5-bromo-2′-deoxyuridine labeling, rigorous magnetic resonance imaging, and polymerase chain reaction analysis. We believe these methods convincingly demonstrate the presence of a rostral migratory stream in the human brain that resembles that in other mammals.
Permuted tRNA Genes Expressed via a Circular RNA Intermediate inCyanidioschyzon merolae
Authors: Soma Akiko , Onodera Akinori , Sugahara Junichi , Kanai Akio , Yachie Nozomu , Tomita Masaru , Kawamura Fujio , Sekine Yasuhiko
Published: October 2007

A computational analysis of the nuclear genome of a red alga,Cyanidioschyzon merolae, identified 11 transfer RNA (tRNA) genes in which the 3′ half of the tRNA lies upstream of the 5′ half in the genome. We verified that these genes are expressed and produce mature tRNAs that are aminoacylated. Analysis of tRNA-processing intermediates for these genes indicates an unusual processing pathway in which the termini of the tRNA precursor are ligated, resulting in formation of a characteristic circular RNA intermediate that is then processed at the acceptor stem to generate the correct termini.
Structure of Hexameric DnaB Helicase and Its Complex with a Domain of DnaG Primase
Authors: Bailey Scott , Eliason William K. , Steitz Thomas A.
Published: October 2007

The complex between the DnaB helicase and the DnaG primase unwinds duplex DNA at the eubacterial replication fork and synthesizes the Okazaki RNA primers. The crystal structures of hexameric DnaB and its complex with the helicase binding domain (HBD) of DnaG reveal that within the hexamer the two domains of DnaB pack with strikingly different symmetries to form a distinct two-layered ring structure. Each of three bound HBDs stabilizes the DnaB hexamer in a conformation that may increase its processivity. Three positive, conserved electrostatic patches on the N-terminal domain of DnaB may also serve as a binding site for DNA and thereby guide the DNA to a DnaG active site.
Genetically Capitalist?
Authors: Bowles Samuel
Published: October 2007

A Farewell to Alms
. A Brief Economic History of the World.
By Gregory Clark
. Princeton University Press, Princeton, NJ, 2007. 432 pp. $29.95, £17.95. ISBN 9780691121352

The author argues that England's take-off in the industrial revolution was caused by cultural values (such as hard work and patience) that had taken hold because the rich enjoyed higher fitness than the rest.
Failures in Clinical Treatment of
Staphylococcus aureus
Infection with Daptomycin Are Associated with Alterations in Surface Charge, Membrane Phospholipid Asymmetry, and Drug Binding
Authors: Jones Tiffanny , Yeaman Michael R. , Sakoulas George , Yang Soo-Jin , Proctor Richard A. , Sahl Hans-Georg , Schrenzel Jacques , Xiong Yan Q. , Bayer Arnold S.
Published: October 2007

Increasingly frequent reports have described the in vivo loss of daptomycin susceptibility in association with clinical treatment failures. The mechanism(s) of daptomycin resistance is not well understood. We studied an isogenic set of
Staphylococcus aureus
isolates from the bloodstream of a daptomycin-treated patient with recalcitrant endocarditis in which serial strains exhibited decreasing susceptibility to daptomycin. Since daptomycin is a membrane-targeting lipopeptide, we compared a number of membrane parameters in the initial blood isolate (parental) with those in subsequent daptomycin-resistant strains obtained during treatment. In comparison to the parental strain, resistant isolates demonstrated (i) enhanced membrane fluidity, (ii) increased translocation of the positively charged phospholipid lysyl-phosphotidylglycerol to the outer membrane leaflet, (iii) increased net positive surface charge (
P
< 0.05 versus the parental strain), (iv) reduced susceptibility to daptomycin-induced depolarization, permeabilization, and autolysis (
P
< 0.05 versus the parental strain), (v) significantly lower surface binding of daptomycin (
P
< 0.05 versus the parental strain), and (vi) increased cross-resistance to the cationic antimicrobial host defense peptides human neutrophil peptide 1 (hNP-1) and thrombin-induced platelet microbicidal protein 1 (tPMP-1). These data link distinct changes in membrane structure and function with in vivo development of daptomycin resistance in
S. aureus
. Moreover, the cross-resistance to hNP-1 and tPMP-1 may also impact the capacity of these daptomycin-resistant organisms to be cleared from sites of infection, particularly endovascular foci.
Colistin Heteroresistance in
Acinetobacter
and Its Association with Previous Colistin Therapy
Authors: Hawley Joshua S. , Murray Clinton K. , Jorgensen James H.
Published: October 2007

Colistin heteroresistance has been reported among
Acinetobacter
isolates; however, its association with prior colistin therapy has not been not described. A population analysis profile identified resistant
Acinetobacter
subpopulations from colistin-susceptible clinical isolates. The proportion of cells exhibiting heteroresistance was significantly higher among isolates recovered from patients treated with colistin.
Potential Use of Poly-
N
-Acetyl-β-(1,6)-Glucosamine as an Antigen for Diagnosis of Staphylococcal Orthopedic-Prosthesis-Related Infections
Authors: Sadovskaya Irina , Faure Stéphanie , Watier Denis , Leterme Damien , Chokr Ali , Girard Julien , Migaud Henry , Jabbouri Saïd
Published: October 2007

Staphylococcus aureus
and coagulase-negative staphylococci are microorganisms most frequently isolated from orthopedic-implant-associated infections. Their capacity to maintain these infections is thought to be related to their ability to form adherent biofilms. Poly-
N
-acetyl-β-(1,6)-glucosamine (PNAG) is an important constituent of the extracellular biofilm matrix of staphylococci. In the present study, we explored the possibility of using PNAG as an antigen for detecting antibodies in the blood sera of patients with staphylococcal orthopedic-prosthesis-associated infections. First, we tested the presence of anti-PNAG antibodies in an animal model, in the blood sera of guinea pigs that developed an implant-associated infection caused by biofilm-forming, PNAG-producing strains of
Staphylococcus epidermidis
. Animals infected with
S. epidermidis
RP62A showed levels of anti-PNAG immunoglobulin G (IgG) significantly higher than those of the control group. The comparative study of healthy individuals and patients with staphylococcal prosthesis-related infections showed that (i) relatively high levels of anti-PNAG IgG were present in the blood sera of the healthy control group, (ii) the corresponding levels in the infected patients were slightly but not significantly higher, and (iii) only 1 of 10 patients had a level of anti-PNAG IgM significantly higher than that of the control group. In conclusion, the encouraging results obtained in the animal study could not be readily applied for the diagnosis of staphylococcal orthopedic-prosthesis-related infections in humans, and PNAG does not seem to be an appropriate antigen for this purpose. Further studies are necessary to determine whether the developed enzyme-linked immunosorbent assay method could serve as a complementary test in the individual follow-up treatment of such infections caused by PNAG-producing staphylococci.
Therapeutic Immunization with Human Immunodeficiency Virus Type 1 (HIV-1) Peptide-Loaded Dendritic Cells Is Safe and Induces Immunogenicity in HIV-1-Infected Individuals
Authors: Connolly Nancy C. , Whiteside Theresa L. , Wilson Cara , Kondragunta Venkatswarlu , Rinaldo Charles R. , Riddler Sharon A.
Published: October 2007

Treatments for human immunodeficiency virus type 1 (HIV-1)-positive individuals that augment HIV-1 suppression and have potential for achieving long-term control of HIV-1 viremia in the absence of antiretroviral therapy (ART) are urgently needed. We therefore conducted a phase I, clinical safety trial of a dendritic cell (DC)-based vaccination strategy as immunotherapy for HIV-1-positive individuals on ART. We studied 18 HIV-1-positive subjects on ART who underwent leukapheresis to obtain peripheral blood mononuclear cells for DC generation from monocytes cultured with cytokines. Mature DC were pulsed with three HIV-1 HLA*A0201 Gag, Env, and Pol peptides and one influenza A virus matrix protein peptide. The vaccine was administered to donors randomized to receive two vaccinations, either intravenously or subcutaneously. The primary end points were safety and tolerability of two doses of peptide-DC vaccine (3 million versus 10 million). Secondary end points included gamma interferon (IFN-γ) enzyme-linked immunospot assay responses and clinical correlates of an immune response to vaccination. Autologous DC-peptide vaccine was safe, well tolerated, and feasible for use in all participants. Adverse events were rare. Although the trial was not powered to assess an immunologic response, a significantly increased frequency of HIV-1 peptide-specific IFN-γ-positive cells was observed 2 weeks following the second vaccine, with three individuals responding to all four peptides. DC vaccination was safe, was feasible, and showed promise of immunogenicity in ART-treated, HIV-1-positive individuals. Additional studies of DC immunization strategies for HIV-1 infection are warranted.
Development and Evaluation of a Real-Time Reverse Transcription-PCR Assay for Quantification of Gamma Interferon mRNA To Diagnose Tuberculosis in Multiple Animal Species
Authors: Harrington Noel P. , Surujballi Om P. , Waters W. Ray , Prescott John F.
Published: October 2007

Tuberculosis of free-ranging and captive wildlife, including species implicated in the maintenance and transmission ofMycobacterium bovis, is a difficult disease to diagnose and control. Historically, diagnosis of tuberculosis has relied largely upon assays of cell-mediated immunity (CMI), such as tuberculin skin testing. This approach, however, is problematic or impractical for use with many wildlife species. Increasingly, in vitro diagnostic tests, including gamma interferon (IFN-γ)-based assays, are replacing or complementing skin testing of cattle and humans. Analogous assays are unavailable for most wildlife because of a lack of species-specific immunological reagents. This report describes the development and validation of a whole-blood assay to quantify antigen-specific IFN-γ mRNA expression by quantitative real-time reverse transcription-PCR. Oligonucleotide primers and probes were designed and tested for reactivity towards several susceptible species of interest with respect to tuberculosis infection. The assay was subsequently optimized to quantify the IFN-γ mRNA expression in elk and red deer (Cervus elaphus) and was evaluated for its ability to detect mycobacterial antigen-specific responses of experimentally tuberculosis-infected animals. The assay was a simple, rapid, and sensitive measure of antigen-specific CMI. The IFN-γ mRNA responses correlated well with IFN-γ protein production and showed performance in determining an animal's infection status superior to that of either lymphocyte proliferation or IFN-γ protein enzyme-linked immunosorbent assay methods. An additional advantage is the ease with which the assay can be modified to reliably quantify IFN-γ expression by using consensus sequences of closely related species or of other species for which IFN-γ sequence information is available.
Enhancement of Serological Immune Responses to Foot-and-Mouth Disease Vaccine by a Supplement Made of Extract of Cochinchina Momordica Seeds
Authors: Xiao Chenwen , Rajput Zahid Iqbal , Liu Diwen , Hu Songhua
Published: October 2007

Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals. Vaccination against FMD is a routine practice in many countries where the disease is endemic. This study was designed first to investigate the extract of the seeds ofMomordica cochinchinensis(Lour.) Spreng. (ECMS) for its adjuvant effect on vaccination of inactivated FMDV antigens in a guinea pig model and then to evaluate the supplement of ECMS in oil-emulsified FMD vaccines for its immunopotentiation in pigs. The results indicated that ECMS and oil emulsion act synergistically as adjuvants to promote the production of FMDV- and VP1-specific immunoglobulin G (IgG) and subclasses in guinea pigs. A supplement of ECMS in a commercial FMD vaccine significantly enhanced FMDV-specific indirect hemagglutination assay titers as well as VP1-specific IgG and subclasses in pigs. Therefore, ECMS could be an alternative approach to improving swine FMD vaccination when the vaccine is poor to induce an effective immune response.
Use of Recombinant Antigens To Detect Antibodies againstMycoplasma suis, with Correlation of Serological Results to Hematological Findings
Authors: Hoelzle Katharina , Grimm Julia , Ritzmann Mathias , Heinritzi Karl , Torgerson Paul , Hamburger Anja , Wittenbrink Max M. , Hoelzle Ludwig E.
Published: October 2007

Porcine eperythrozoonosis is a disease with worldwide distribution caused by the unculturable hemotrophic bacteriumMycoplasma suis. Current serological testing utilizes crudeM. suisantigens purified from the blood of experimentally infected pigs. These antigens show high variability and are restricted to specialized laboratories. We evaluated a novel serological assay based on two recombinantM. suisantigens (rMSG1 and rHspA1). Antigen specificity was proven by means of sera raised against nonhemotrophic mycoplasma and other relevant bacteria. Using experimental and convalescent-phase sera, rMSG1 and rHspA1 enzyme-linked immunosorbent assays (ELISAs) demonstrated sensitivities, specificities, and predictive values (94.0 to 100.0%) equal to or higher than those of theM. suiswhole-cell ELISA. Field samples from 120 weaning piglets grouped by quantitative PCR results were used to evaluate the diagnostic capability of the new ELISA systems in comparison to that of the whole-cell ELISA. Assuming a 100.0% specificity of the PCR, the whole-cell ELISA, rHspA1 ELISA, and rMSG1 ELISA showed specificities of 84.8%, 83.8%, and 90.6% and sensitivities of 61.5%, 74.0% and 58.1%, respectively. Cohen's kappa coefficients comparing the recombinant ELISAs to the whole-cell ELISA indicate moderate to substantial agreement. The detection of anti-MSG1 and/or anti-HspA1 antibodies in pigs was significantly correlated with decreased hematocrit, erythrocyte numbers, and hemoglobin concentrations, indicating that a single seropositive result is connected with clinical and etiological significance. In conclusion, rMSG1 and rHspA1 are sensitive and specific serological and infection markers which are for the first time used independently of animal experiments. They are especially fit to be used in routine diagnosis, pathogenesis studies, and large-scale epidemiological investigations.
Clonal Spread of Imipenem-Resistant
Acinetobacter baumannii
among Different Cities of China
Authors: Zhou Hua , Yang Qing , Yu Yun-Song , Wei Ze-Qing , Li Lan-Juan
Published: October 2007

A total of 342 imipenem-resistant
Acinetobacter baumannii
isolates (IRABs) were collected from 16 Chinese cities. Six predominant clones had spread widely, and four clones were detected in distant hospitals. The majority of the IRABs contain
bla
OXA-23
, with IS
Aba1
upstream of the gene. These results suggested that clonal spread played an important role in the outbreak of IRABs in China.
Hepatitis B Virus Core-Related Antigens as Markers for Monitoring Chronic Hepatitis B Infection
Authors: Wong Danny Ka-Ho , Tanaka Yasuhito , Lai Ching-Lung , Mizokami Masashi , Fung James , Yuen Man-Fung
Published: October 2007

A sensitive chemiluminescence enzyme immunoassay has been developed for hepatitis B virus (HBV) core-related antigen (HBcrAg) detection. We aimed to investigate the usefulness of HBcrAg measurement for monitoring chronic hepatitis B disease. HBcrAg levels were measured by a chemiluminescence enzyme immunoassay in 54 untreated patients and 39 patients treated with either entecavir or lamivudine. The HBcrAg concentration correlated positively with the levels of serum HBV DNA (
r
= 0.820), intrahepatic total HBV DNA (
r
= 0.700), and covalently closed circular DNA (cccDNA) (
r
= 0.664; for all,
P
values were <0.001). A higher HBcrAg concentration was associated with a greater proportion of hepatitis B core antigen immunostaining. Although the differences were not statistically significant, patients with higher Knodell necroinflammation and fibrosis scores tended to have higher serum HBcrAg concentration levels. In the treated patients, the logarithmic reduction in HBcrAg at week 48 correlated positively with the logarithmic reduction of serum HBV DNA, intrahepatic total HBV DNA, and cccDNA. Of the 31 patients with undetectable serum HBV DNA (<300 copies/ml) at the end of treatment, 20 (65%) still had detectable HBcrAg. A greater reduction in posttreatment HBcrAg concentration was associated with histological improvement and a decrease in hepatitis B core antigen immunostaining. HBcrAg concentrations of <40,000 kU/ml at baseline and <200 kU/ml at week 24 were associated with a higher chance of having undetectable HBV DNA at week 48. In conclusion, serum HBcrAg levels correlated with HBV virological markers and reflected the chronic hepatitis B disease activity in the liver.
Clinical Impact of a PCR Assay for Rapid Identification of
Klebsiella pneumoniae
in Blood Cultures
Authors: Neuberger A. , Oren I. , Sprecher H.
Published: October 2007

The clinical impact of a rapid PCR identification assay for
Klebsiella pneumoniae
in positive blood cultures was prospectively evaluated. Multivariate analysis identified the rapid PCR assay as the only significant factor in decreasing the time lapse preceding the initiation of appropriate antimicrobial therapy (hazards ratio, 3.03; confidence interval, 1.62 to 5.68;
P
, 0.001).
Changing Antimicrobial Susceptibility Epidemiology of
Helicobacter pylori
Strains in Japan between 2002 and 2005
Authors: Kobayashi Intetsu , Murakami Kazunari , Kato Mototsugu , Kato Seiichi , Azuma Takeshi , Takahashi Shin'ichi , Uemura Naomi , Katsuyama Tsutomu , Fukuda Yoshihiro , Haruma Ken , Nasu Masaru , Fujioka Toshio
Published: October 2007

Surveillance of
Helicobacter pylori
antimicrobial susceptibility reflecting the general population in Japan is limited. The antimicrobial susceptibilities of 3,707
H. pylori
strains isolated from gastric mucosa samples of previously untreated patients diagnosed with gastroduodenal diseases at 36 medical facilities located throughout Japan between October 2002 and September 2005 were evaluated. Using an agar dilution method for antimicrobial susceptibility testing of
H. pylori
, the MIC distributions and trends during the study period for clarithromycin, amoxicillin, and metronidazole were studied. While the MIC
50
and MIC
90
for clarithromycin did not change during the 3-year period, the MIC
80
showed a 128-fold increase. Furthermore, the rate of resistance increased yearly from 18.9% (2002 to 2003) to 21.1% (2003 to 2004) and 27.7% (2004 to 2005). With a resistance rate of 19.2% among males compared to 27.0% among females, a significant gender difference was observed (
P
< 0.0001). Our study shows that in Japan, there is an evolving trend towards increased resistance to clarithromycin with geographical and gender differences as well as between clinical disease conditions. No significant changes in resistance were observed for amoxicillin and metronidazole during the period. While the benefit of
H. pylori
antimicrobial susceptibility testing has been debated in Japan, current empirical regimens are not based on susceptibility data representative of the general population. The development of an effective
H. pylori
eradication regimen in Japan will require continued resistance surveillance as well as a better understanding of the epidemiology of resistance.
Up-Converting Phosphor Technology-Based Lateral Flow Assay for Detection of
Schistosoma
Circulating Anodic Antigen in Serum
Authors: Corstjens Paul L. A. M. , van Lieshout Lisette , Zuiderwijk Michel , Kornelis Dieuwke , Tanke Hans J. , Deelder Andre M. , van Dam Govert J.
Published: October 2007

Schistosoma
sp. circular anodic antigen (CAA) serum concentrations reflect actual worm burden in a patient and are a valuable tool for population screening and epidemiological research. However, for the diagnosis of individual imported schistosomiasis cases, the current enzyme-linked immunosorbent assay (ELISA) lacks sensitivity and robustness. Therefore, a lateral flow (LF) assay was developed to test CAA in serum for individual diagnosis of imported active schistosome infections. Application of fluorescent submicron-sized up-converting phosphor technology (UPT) reporter particles increased analytical sensitivity compared to that of the standard ELISA method. Evaluation of the UPT-LF test with a selection of 40 characterized epidemiologic samples indicated a good correlation between signal intensity and infection intensity. Subsequently, the UPT-LF assay was applied to 166 serum samples of Dutch residents (immigrants and travelers) suspected of schistosomiasis, a case in which group routine antibody detection frequently fails straightforward diagnosis. The UPT-LF assay identified 36 CAA-positive samples, compared to 15 detected by CAA-ELISA. In conclusion, the UPT-LF assay is a low-complexity test with higher sensitivity than the CAA-ELISA, well suited for laboratory diagnosis of individual active
Schistosoma
infections.
Comparison of Multiple-Locus Variable-Number Tandem-Repeat Analysis with Other PCR-Based Methods for Typing
Brucella suis
Isolates
Authors: García-Yoldi David , Le Fleche Philippe , De Miguel María J. , Muñoz Pilar M. , Blasco José M. , Cvetnic Zeljko , Marín Clara M. , Vergnaud Gilles , López-Goñi Ignacio
Published: October 2007

Multiple-locus variable-number tandem-repeat analysis (MLVA), multiplex PCR, and PCR-restriction fragment length polymorphism analysis were compared for typing
Brucella suis
isolates. A perfect concordance was obtained among these molecular assays. However, MLVA was the only method to demonstrate brucellosis outbreaks and to confirm that wildlife is a reservoir for zoonotic brucellosis.
Predominance of Community-Associated Methicillin-Resistant
Staphylococcus aureus
Strains Carrying Staphylococcal Chromosome Cassette
mec
Type IVA in South Korea
Authors: Park Chulmin , Lee Dong-Gun , Kim Sun Woo , Choi Su-Mi , Park Sun Hee , Chun Hye-Sun , Choi Jung-Hyun , Yoo Jin-Hong , Shin Wan Shik , Kang Jin Han , Kim Jong Hyun , Lee Soo Young , Kim Sun Mi , Pyun Bok Yang
Published: October 2007

Studies on the molecular epidemiologic characteristics of methicillin-resistant
Staphylococcus aureus
(MRSA) strains have demonstrated their genetic and geographical diversity. In addition, it has been reported that there are genetic differences between community-associated (CA) and health care-associated (HA) MRSA strains. Therefore, we investigated the major epidemiologic characteristics of CA MRSA isolates in South Korea and compared them with those of HA MRSA strains. Distributions of staphylococcal chromosome cassette
mec
(SCC
mec
) types and other molecular features, including the Panton-Valentine leukocidin (PVL) gene, were studied in 138 invasive MRSA isolates. Multiplex type IVA SCC
mec
was identified as the major CA MRSA infection type (53.1%), with a significantly higher prevalence than in HA MRSA (
P
< 0.001). One major group of type IVA strains carried a larger atypical class B
mec
element and new subtypes of
ccrA2
(96% amino acid homology). The PVL gene was detected in one USA300-like isolate only. Seven major clone types determined by combinational grouping (genetic background SCC
mec
typing) showed representative patterns of antimicrobial susceptibilities. We concluded that less multi-drug-resistant strains of clone types B-I and D-1 (genetic background, B and D complexes; type IVA SCC
mec
) predominate in CA MRSA and that international PVL-positive strains have not spread in South Korea as yet.
Agar Dilution Method for Detection of Inducible Clindamycin Resistance in
Staphylococcus
spp
Authors: Fernandes Clarence J. , O'Sullivan Matthew V. N. , Cai Yongwei , Kong Fanrong , Zeng Xianyu , Gilbert Gwendolyn L. , Kotsiou George
Published: October 2007

We describe the development and validation of an agar dilution method for the detection of inducible clindamycin resistance by using 227 previously characterized erythromycin-resistant, clindamycin-susceptible
Staphylococcus
sp. isolates. Mueller-Hinton agar with defibrinated horse blood containing a range of erythromycin concentrations (1 to 8 mg/liter) combined with clindamycin at 0.5 mg/liter was used to determine the optimal concentration that produced growth of inducible isolates while inhibiting that of isolates without the inducible phenotype. A concentration of clindamycin of 0.5 mg/liter with erythromycin at 1 mg/liter was the optimal combination for detection of inducible resistance and resulted in a sensitivity of 100% (95% confidence interval [CI], 97.9 to 100) and a specificity of 100% (95% CI, 93.0 to 100). Attention must be paid to ensuring that a sufficient inoculum has been used, since an inoculum below the standard 10
7
bacteria/ml may result in false-negative results. This method has been incorporated into routine use in our laboratory.
Characterization of a New Sensitive PCR Assay for Quantification of Viral DNA Isolated from Patients with Hepatitis B Virus Infections
Authors: Thibault Vincent , Pichoud Christian , Mullen Carolyn , Rhoads James , Smith Jane B. , Bitbol Alain , Thamm Sven , Zoulim Fabien
Published: October 2007

Sensitive and accurate quantification of hepatitis B virus (HBV) DNA is necessary for monitoring patients with chronic hepatitis receiving antiviral therapy in order to determine treatment response and to adapt therapy in case of inadequate virologic control. The development of quantitative PCR assays has been crucial in meeting these needs. The objective of this study was to compare the performance of a new real-time PCR assay (Abbott RealTime) for HBV DNA with that of three other commercial assays for the detection of HBV DNA. These were the Versant 3.0 branched-chain DNA assay, the Cobas Amplicor HBV Monitor test, and the Cobas AmpliPrep-Cobas TaqMan hepatitis B virus assay (CAP-CTM). HBV DNA was measured in blood samples taken from two cohorts of patients with chronic hepatitis. HBV DNA levels measured with the Abbott RealTime assay were highly correlated with those measured with the other three tests over their respective dynamic ranges (
r
, 0.88 to 0.96). The sensitivity (detection limit, 10 IU/ml) and dynamic range of the Abbott RealTime assay (10
1
to 10
9
IU/ml) was superior to that of the Versant assay. The RealTime assay recognized both HBV strains belonging to genotypes A to G and those bearing polymerase gene mutations equivalently. In conclusion, this study demonstrates the utility of the Abbott RealTime assay for monitoring HBV DNA levels in patients with chronic hepatitis B. Its sensitivity and wide dynamic range should allow optimal monitoring of antiviral therapy and timely treatment adaptation.
Molecular Characteristics of the
Mycobacterium tuberculosis
LAM-RUS Family Prevalent in Central Russia
Authors: Dubiley Svetlana , Kirillov Eugene , Ignatova Anna , Stepanshina Valentina , Shemyakin Igor
Published: October 2007

We analyzed IS
6110
-associated polymorphisms in the phospholipase C genes of 107 isolates of
Mycobacterium tuberculosis
selected to be representative of isolates circulating in central Russia. We found that the majority of Latin American-Mediterranean family strains contained an insertion in a unique position in the
plcA
gene, suggesting a common ancestor. This insertion can serve as a specific genetic marker for this group, which we designate the LAM-RUS family.
Cystic Fibrosis Patient with
Burkholderia pseudomallei
Infection Acquired in Brazil
Authors: Barth Afonso Luís , de Abreu e Silva Fernando Antonio , Hoffmann Anneliese , Vieira Maria Izolete , Zavascki Alexandre Prehn , Ferreira Alex Guerra , da Cunha Luiz Gonzaga , Albano Rodolpho Mattos , de Andrade Marques Elizabeth
Published: October 2007

Burkholderia pseudomallei
is rarely isolated from cystic fibrosis patients outside known areas of endemicity. We report the recovery of
B. pseudomallei
from the sputum of a cystic fibrosis patient who lives in Brazil. We highlight the importance of careful attention to unusual nonfermentative gram-negative rods in cystic fibrosis patients.
Detection of Inducible Clindamycin Resistance in Staphylococci by Broth Microdilution Using Erythromycin-Clindamycin Combination Wells
Authors: Swenson Jana M. , Brasso William B. , Ferraro Mary Jane , Hardy Dwight J. , Knapp Cynthia C. , McDougal Linda K. , Reller L. Barth , Sader Helio S. , Shortridge Dee , Skov Robert , Weinstein Melvin P. , Zimmer Barbara L. , Patel Jean B.
Published: October 2007

A study conducted by 11 laboratories investigated the ability of four combinations of erythromycin (ERY) and clindamycin (CC) (ERY and CC at 4 and 0.5, 6 and 1, 8 and 1.5, and 0.5 and 2 μg/ml) in a single well of a broth microdilution panel to predict the presence of inducible CC resistance. Each laboratory tested approximately 30
Staphylococcus aureus
isolates and 20 coagulase-negative staphylococcus (CoNS) isolates in a panel using cation-adjusted Mueller-Hinton broth from three different manufacturers. Only the strains resistant to ERY and those susceptible or intermediate to CC were included in the analysis (
S. aureus
,
n
= 333; CoNS,
n
= 97). Results of the D-zone test were used as the gold standard. After an 18-h incubation, the combination of 4 μg/ml ERY and 0.5 μg/ml CC performed the best, with 98 to 100% sensitivity and 100% specificity for both organism groups. After a 24-h incubation, the ERY-CC combinations of 4 and 0.5, 6 and 1, and 8 and 1.5 μg/ml correlated well with the D-zone test.
Trends in Prescribing β-Lactam Antibiotics for Treatment of Community-Associated Methicillin-Resistant
Staphylococcus aureus
Infections
Authors: Gupta Kalpana , MacIntyre Ann , Vanasse Gary , Dembry Louise-Marie
Published: October 2007

Rates of prescribing of β-lactam antibiotics as initial empirical therapy for patients with skin and soft tissue infections (SSTIs) caused by molecularly and epidemiologically characterized community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) isolates were assessed over a 3-year period. A prospectively developed database was used to calculate the prevalence of CA-MRSA SSTIs from 2004 to 2006. Molecular characterization of the MRSA isolate and medical record review for assessment of initial antimicrobial therapy were performed on a subset of patients. Among 2,636 patients with
S. aureus
SSTIs, the prevalence of CA-MRSA was 9% in 2004, 16% in 2005, and 21% in 2006 (
P
< 0.0001, chi-square test for trend). Seventy-five percent of CA-MRSA isolates tested were of the USA 300 or 400 clone type. Ninety-two percent of CA-MRSA isolates tested were positive for Panton-Valentine leukocidin, of which 90% carried staphylococcal chromosomal cassette
mec
type IV. The rate of use of a β-lactam antibiotic as initial empirical therapy for patients with CA-MRSA SSTIs was 86%, 77%, and 60% in 2004, 2005, and 2006, respectively (
P
= 0.04, chi-square test for trend). Thirty percent of β-lactam-treated patients had a documented risk factor for CA-MRSA infection. The use of a β-lactam antibiotic as initial empirical therapy for CA-MRSA SSTIs has decreased significantly over the past 3 years. However, even as the prevalence of CA-MRSA SSTIs approaches 25%, the majority of patients are still receiving inactive antimicrobial therapy. Further evaluation of the outcomes associated with discordant therapy for CA-MRSA SSTIs is needed.
Genetic Analysis of Influenza A/H3N2 and A/H1N1 Viruses Circulating in Vietnam from 2001 to 2006
Authors: Li Danjuan , Saito Reiko , Le Mai T. Q. , Nguyen Hang L. K. , Suzuki Yasushi , Shobugawa Yugo , Dinh Duc T. , Hoang Phuong V. M. , Tran Huong T. T. , Nghiem Ha K. , Hoang Long T. , Huynh Lien P. , Nguyen Hien T. , Nishikawa Makoto , Suzuki Hiroshi
Published: October 2007

Influenza A virus has the ability to overcome immunity from previous infections through the acquisition of genetic changes. Thus, understanding the evolution of the viruses in humans is important for the surveillance and the selection of vaccine strains. A total of 30 influenza A/H3N2 viruses and 35 influenza A/H1N1 viruses that were collected in Vietnam from 2001 to 2006 were used to analyze the evolution of the hemagglutinin (HA), neuraminidase (NA), and matrix protein (M) genes. Phylogenetic analysis of individual gene segments revealed that the HA and the NA genes of the influenza A viruses evolved in a sequential way. However, the evolutionary pattern of the M gene proved to be nonlinear and was not linked with that of the HA and NA genes. Genetic drift in HA1 segments, especially in the antigenic sites of A/H3N2 viruses, occurred more frequently in A/H3N2 viruses than it did in A/H1N1 viruses. Two reassortants, one influenza A/H3N2 strain and one A/H1N1 strain, were found on the basis of the phylogenetic analysis of the three genes. While both genetic mutation and reassortment contributed to their evolution, the frequency of genetic changes and reassortment events differs between the two subtypes. As influenza viruses circulate throughout the year, we emphasize the importance of surveillance in tropical and subtropical zones, where the emergence of new strains may be detected earlier than it is in temperate zones.
Microevolution of
Helicobacter pylori
Type IV Secretion Systems in an Ulcer Disease Patient over a Ten-Year Period
Authors: Alvi Ayesha , Devi S. Manjulata , Ahmed Irshad , Hussain M. Abid , Rizwan Mohammed , Lamouliatte Hérve , Mégraud Francis , Ahmed Niyaz
Published: October 2007

Helicobacter pylori cagA
and
vacA
genotypes have been used for almost a decade as stable entities to link the severity of gastritis and ulcer disease. We describe here microevolution of the two genomic islands,
cag
pathogenicity island (
cag
PAI; 40 kb) and
tfs3
(16 kb) from isolates obtained at inclusion (one subclone) and after a 10-year period (two subclones) from a duodenal ulcer patient. Our results indicate microevolution in
cagA
,
cagE
, and
cag7
genes of the
cag
PAI and open reading frames G, P, and L in
tfs3
, which possibly leads to inactivation or pseudogenization of these genes. Interestingly, no significant reduction in the severity of gastroduodenal pathology was found. These results point to an obvious difficulty in correlating the continuously evolving virulence factors such as the
cag
PAI genes with disease characteristics that appear to remain stable.
Comparison of Three Commercial Test Systems for Biotyping
Haemophilus influenzae
and
Haemophilus parainfluenzae
Authors: Munson Erik L. , Doern Gary V.
Published: October 2007

The biotypes of
Haemophilus influenzae
and
Haemophilus parainfluenzae
isolates were determined with three commercially available biochemical test kits: the IDS RapID NH system, the
Neisseria-Haemophilus
identification test (NHI card), and the API NH strip. The API NH strip performed best, correctly classifying the biotypes of 371 of 380 (97.6%) different challenge strains.