bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the Bactericidal Response to an Experimental Neisseria meningitidis Vesicle Vaccine
Authors: Moran Elizabeth E. , Burden Robert , Labrie Joseph E. , Wen Zhiyun , Wang Xin-Min , Zollinger Wendell D. , Zhang Lan , Pinto Valerian B. 
Published: March 2012

ABSTRACTRabbit immunogenicity studies on an experimental trivalent native outer membrane vesicle vaccine derived from three serogroup B strains were conducted to evaluate the effectiveness of this vaccine at inducing an antibody response with serum bactericidal activity against meningococcal strains of other serogroups in addition to serogroup B strains. The results showed that the vaccine was capable of inducing an effective broad-based bactericidal antibody response in rabbits against a small sample ofNeisseria meningitidisstrains of serogroups C, W135, and X and, to a lesser extent, serogroups A and Y. Analysis of antibody specificity using a bactericidal depletion assay revealed that antibodies to lipooligosaccharide (LOS), PorA, and NadA induced in rabbits by the experimental trivalent outer membrane vesicle vaccine were responsible for most of the bactericidal activity against strains of the otherN. meningitidisserogroups. In the case of serogroup AN. meningitidisstrains, the outer membrane antigen NadA was primarily responsible for protection. The outer membrane antigens fHbp and OpcA were also effective in removing some bactericidal activity from the sera.
Added Value of Use of a Purified Protein Derivative-Based Enzyme-Linked Immunosorbent Spot Assay for Patients with Mycobacterium bovis BCG Infection after Intravesical BCG Instillations
Authors: Heemstra Karen A. , Bossink Ailko W. J. , Spermon Roan , Bouwman John J. M. , van der Kieft Robert , Thijsen Steven F. T. 
Published: March 2012

ABSTRACT

In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic)
Mycobacterium bovis
BCG infections after intravesical BCG instillations for bladder carcinoma.
Ion Torrent Personal Genome Machine Sequencing for Genomic Typing of Neisseria meningitidis for Rapid Determination of Multiple Layers of Typing Information
Authors: Vogel Ulrich , Szczepanowski Rafael , Claus Heike , Jünemann Sebastian , Prior Karola , Harmsen Dag 
Published: March 2012

ABSTRACT

Neisseria meningitidis
causes invasive meningococcal disease in infants, toddlers, and adolescents worldwide. DNA sequence-based typing, including multilocus sequence typing, analysis of genetic determinants of antibiotic resistance, and sequence typing of vaccine antigens, has become the standard for molecular epidemiology of the organism. However, PCR of multiple targets and consecutive Sanger sequencing provide logistic constraints to reference laboratories. Taking advantage of the recent development of benchtop next-generation sequencers (NGSs) and of BIGSdb, a database accommodating and analyzing genome sequence data, we therefore explored the feasibility and accuracy of Ion Torrent Personal Genome Machine (PGM) sequencing for genomic typing of meningococci. Three strains from a previous meningococcus serogroup B community outbreak were selected to compare conventional typing results with data generated by semiconductor chip-based sequencing. In addition, sequencing of the meningococcal type strain MC58 provided information about the general performance of the technology. The PGM technology generated sequence information for all target genes addressed. The results were 100% concordant with conventional typing results, with no further editing being necessary. In addition, the amount of typing information, i.e., nucleotides and target genes analyzed, could be substantially increased by the combined use of genome sequencing and BIGSdb compared to conventional methods. In the near future, affordable and fast benchtop NGS machines like the PGM might enable reference laboratories to switch to genomic typing on a routine basis. This will reduce workloads and rapidly provide information for laboratory surveillance, outbreak investigation, assessment of vaccine preventability, and antibiotic resistance gene monitoring.
Wild-Type MIC Distributions and Epidemiological Cutoff Values for Amphotericin B, Flucytosine, and Itraconazole and Candida spp. as Determined by CLSI Broth Microdilution
Authors: Pfaller M. A. , Espinel-Ingroff A. , Canton E. , Castanheira M. , Cuenca-Estrella M. , Diekema D. J. , Fothergill A. , Fuller J. , Ghannoum M. , Jones R. N , Lockhart S. R. , Martin-Mazuelos E. , Melhem M. S. C. , Ostrosky-Zeichner L. , Pappas P. , Pelaez T. , Peman J. , Rex J. , Szeszs M. W. 
Published: March 2012

ABSTRACT

Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been established for several
Candida
spp. and the newer triazoles and echinocandins but are not yet available for older antifungal agents, such as amphotericin B, flucytosine, or itraconazole. We determined species-specific ECVs for amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight
Candida
spp. (30,221 strains) using isolates from 16 different laboratories in Brazil, Canada, Europe, and the United States, all tested by the CLSI reference microdilution method. The calculated 24- and 48-h ECVs expressed in μg/ml (and the percentages of isolates that had MICs less than or equal to the ECV) for AMB, FC, and ITR, respectively, were 2 (99.8)/2 (99.2), 0.5 (94.2)/1 (91.4), and 0.12 (95.0)/0.12 (92.9) for
C. albicans
; 2 (99.6)/2 (98.7), 0.5 (98.0)/0.5 (97.5), and 2 (95.2)/4 (93.5) for
C. glabrata
; 2 (99.7)/2 (97.3), 0.5 (98.7)/0.5 (97.8), and 05. (99.7)/0.5 (98.5) for
C. parapsilosis
; 2 (99.8)/2 (99.2), 0.5 (93.0)/1 (90.5), and 0.5 (97.8)/0.5 (93.9) for
C. tropicalis
; 2 (99.3)/4 (100.0), 32 (99.4)/32 (99.3), and 1 (99.0)/2 (100.0) for
C. krusei
; 2 (100.0)/4 (100.0), 0.5 (95.3)/1 (92.9), and 0.5 (95.8)/0.5 (98.1) for
C. lusitaniae
; −/2 (100.0), 0.5 (98.8)/0.5 (97.7), and 0.25 (97.6)/0.25 (96.9) for
C. dubliniensis
; and 2 (100.0)/2 (100.0), 1 (92.7)/−, and 1 (100.0)/2 (100.0) for
C. guilliermondii
. In the absence of species-specific CBP values, these wild-type (WT) MIC distributions and ECVs will be useful for monitoring the emergence of reduced susceptibility to these well-established antifungal agents.
Is Hepatitis C Virus Core Antigen an Adequate Marker for Community Screening?
Authors: Kuo Yuan-Hung , Chang Kuo-Chin , Wang Jing-Houng , Tsai Pei-Shan , Hung Shu-Feng , Hung Chao-Hung , Chen Chien-Hung , Lu Sheng-Nan 
Published: March 2012

ABSTRACT

A new hepatitis C virus (HCV) core antigen (HCV Ag) assay was thought to have a good correlation with HCV RNA. The aim was to elucidate the usefulness of this HCV Ag assay in community screening. In a township where HCV is endemic, 405 residents aged 58 years or older responded to a follow-up community screening. All subjects were tested for anti-HCV (AxSYM, version 3.0; Abbott Diagnostics) and HCV Ag (Architect HCV Ag test; Abbott Diagnostics). For subjects with anti-HCV signal-to-cutoff ratios (S/CO) > 10 and/or HCV Ag > 3 fmol/liter, HCV RNA data (Taqman HCV RNA; Roche Diagnostics) were further checked. A total of 115 (28.4%) subjects had their serum HCV RNA levels measured, and 93 were HCV RNA positive. The other 290 subjects were supposed to be HCV RNA negative. HCV Ag was significantly correlated with HCV RNA according to the following equation: (log HCV RNA) = 2.08 + 1.03 (log HCV Ag) (
R
2
= 0.94;
P
< 0.001). As determined using a combination of the values for anti-HCV (S/CO > 40) and HCV Ag (>3 fmol/liter) as a cutoff to predict viremia, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.8%, 100%, 99.3%, 100%, and 99%, respectively. In conclusion, for a community study, HCV Ag showed good correlation with HCV RNA. In addition, anti-HCV or HCV Ag can predict HCV viremia well, while a combination of anti-HCV (>40 S/CO) and HCV Ag (>3 fmol/liter) can provide the best result validity.
Human Cytomegalovirus-Specific T-Cell Immune Reconstitution in Preemptively Treated Heart Transplant Recipients Identifies Subjects at Critical Risk for Infection
Authors: Abate Davide , Fiscon Marta , Saldan Alda , Cofano Simona , Mengoli Carlo , Sgarabotto Dino , d'Agostino Chiara , Barzon Luisa , Cusinato Riccardo , Toscano Giuseppe , Feltrin Giuseppe , Gambino Antonio , Gerosa Gino , Palù Giorgio 
Published: March 2012

ABSTRACT

Human cytomegalovirus (CMV) infection represents a major threat for heart transplant recipients (HTXs). CMV-specific T cells effectively control virus infection, and thus, assessment of antiviral immune recovery may have clinical utility in identifying HTXs at risk of infection. In this study, 10 CMV-seropositive (R
+
) pretransplant patients and 48 preemptively treated R
+
HTXs were examined before and after 100 days posttransplant. Preemptive treatment is supposed to favor the immune recovery. CMV DNAemia and gamma interferon enzyme-linked immunosorbent spot (ELISPOT) assay were employed to assess the viremia and immune reconstitution. HTXs could be categorized into three groups characterized by high (>100), medium (50 to 100), and low (<50) spot levels. Early-identified high responders efficiently controlled the infection and also maintained high immunity levels after 100 days after transplant. No episodes of grade ≥2R rejection occurred in the high responders. Midresponders were identified as a group with heterogeneous trends of immune reconstitution. Low responders were 41% and 21% of HTXs before and after 100 days posttransplant, respectively. Low responders were associated with a higher incidence of infection. The effect of viremia on immune recovery was investigated: a statistically significant inverse correlation between magnitude of viremia and immune recovery emerged; in particular, each 10-fold increase in viremia (>4 log
10
DNAemia/ml) was associated with a 36% decrease of the ELISPOT assay spot levels. All episodes of high viremia (>4 log
10
DNAemia/ml) occurred from 1 to 60 days after transplant. Thus, the concomitant evaluation of viremia and CMV immune reconstitution has clinical utility in identifying HTXs at risk of infection and may represent a helpful guide in making therapeutic choices.
Detection of First- and Second-Line Drug Resistance in Mycobacterium tuberculosis Clinical Isolates by Pyrosequencing
Authors: Engström Anna , Morcillo Nora , Imperiale Belen , Hoffner Sven E. , Juréen Pontus 
Published: March 2012

ABSTRACT

Conventional phenotypic drug susceptibility testing (DST) methods for
Mycobacterium tuberculosis
are laborious and very time-consuming. Early detection of drug-resistant tuberculosis (TB) is essential for prevention and control of TB transmission. We have developed a pyrosequencing method for simultaneous detection of mutations associated with resistance to rifampin, isoniazid, ethambutol, amikacin, kanamycin, capreomycin, and ofloxacin. Seven pyrosequencing assays were optimized for following loci:
rpoB
,
katG
,
embB
,
rrs
,
gyrA
, and the promoter regions of
inhA
and
eis
. The molecular method was evaluated on a panel of 290 clinical isolates of
M. tuberculosis
. In comparison to phenotypic DST, the pyrosequencing method demonstrated high specificity (100%) and sensitivity (94.6%) for detection of multidrug-resistant
M. tuberculosis
as well as high specificity (99.3%) and sensitivity (86.9%) for detection of extensively drug-resistant
M. tuberculosis
. The short turnaround time combined with multilocus sequencing of several isolates in parallel makes pyrosequencing an attractive method for drug resistance screening in
M. tuberculosis
.
Comparative Evaluation of a Prototype Chromogenic Medium (ChromID CARBA) for Detecting Carbapenemase-Producing Enterobacteriaceae in Surveillance Rectal Swabs
Authors: Vrioni Georgia , Daniil Ioannis , Voulgari Evangelia , Ranellou Kyriaki , Koumaki Vasiliki , Ghirardi Sandrine , Kimouli Maria , Zambardi Gilles , Tsakris Athanassios 
Published: March 2012

ABSTRACT

Carbapenemase-producing
Enterobacteriaceae
(CPE) are an increasing problem worldwide, and rectal swab surveillance is recommended as a component of infection control programs. The performance of a prototype chromogenic medium (chromID CARBA) was evaluated and compared with media tested by four other screening methods: (i) overnight selective enrichment in 5 ml tryptic soy broth with a 10-μg ertapenem disk followed by plating onto MacConkey agar (CDC-TS), (ii) short selective enrichment in 9 ml brain heart infusion broth with a 10-μg ertapenem disk followed by plating onto chromID ESBL medium (ESBL-BH), (iii) direct plating onto chromID ESBL, and (iv) direct plating onto MacConkey agar supplemented with meropenem (1 μg/ml) (MCM). The screening methods were applied to detect CPE in 200 rectal swab specimens taken from different hospitalized patients. Identification and antimicrobial susceptibility were performed by the Vitek 2 system. Carbapenem MICs were checked by Etest. Carbapenemase production was confirmed using the modified Hodge test, combined-disk tests, and PCR assays. In total, 133 presumptive CPE strains were detected. Phenotypic and genotypic assays confirmed 92 strains to be CPE (56 KPC-positive
Klebsiella pneumoniae
, 29 VIM-positive
K. pneumoniae
, and 7 KPC-positive
Enterobacter aerogenes
strains) recovered from 73 patients, while the remaining 41 strains were confirmed to be CPE negative (19 ESBL producers and 22 nonfermenters). chromID CARBA, ESBL-BH, and chromID ESBL exhibited the highest sensitivity (92.4%), followed by CDC-TS and MCM (89.1%) (
P
= 0.631). The specificity was greater for chromID CARBA (96.9%) and ESBL-BH (93.2%) than for CDC-TS (86.4%), MCM (85.2%), and chromID ESBL (84.7%) (
P
= 0.014). In conclusion, chromID CARBA was found to be a rapid and accurate culture screening method for active CPE surveillance.
Electroacupuncture Reduces the Dose of Midazolam Monitored by the Bispectral Index in Critically Ill Patients with Mechanical Ventilation: An Exploratory Study
Authors: Zheng Xia , Meng Jian-biao , Fang Qiang 
Published: March 2012

Objective Electroacupuncture, a modern variation on a traditional Chinese treatment, might be useful for sedation and analgesia. This study aims to investigate whether electroacupuncture can modify the dose of midazolam monitored by the bispectral index (BIS) in critically ill patients with mechanical ventilation. Methods Orotracheally intubated patients undergoing mechanical ventilation were randomly assigned into three groups (groups A, B and C). All patients were given an intravenous infusion of midazolam. Patients in group A received no additional treatment. Patients in group B were given acupuncture without electrical stimulation at acupuncture points GV24 and EX–HN3 ( Yintang) for 6 h simultaneously, and patients in group C were given electroacupuncture to the same points as in group B. Results Maintaining the BIS between 60 and 80, the hourly mean one dose of midazolam within the first 6 h after sedation in group C was 0.05 (±0.02 mg/kg per hour), which was significantly lower than both group A (0.08±0.03 mg/kg per hour, p<0.001) and group B (0.07±0.01 mg/kg per hour, p<0.021). The doses in groups A and B showed no significant difference. Between-group comparison analysis of hepatic and renal function and severe adverse reactions all showed no significant difference between the three groups. Conclusions Electroacupuncture appears to reduce markedly the dose of sedative drug required in critically ill patients with mechanical ventilation monitored by BIS, without any obvious severe adverse action, and larger studies to confirm the effect are justified.
Quality control by tissue microarray in immunohistochemistry: Figure 1
Authors: Tripodi Sergio Antonio , Rocca Bruno Jim , Hako Lizart , Barbagli Letizia , Bartolommei Sabrina , Ambrosio Maria Raffaella 
Published: March 2012

AimsAn external positive control section is included in each immunohistochemical analysis as a well recognised and validated technique for standardising results. The method is time-consuming and expensive. On the contrary, internal controls are warranted and inexpensive, but their use is only feasible in selected diagnoses. The aim of this work is to show how the method of the authors allows improving the interpretation and cuts costs in the immunohistochemical analysis of bone marrow specimens.MethodsA paraffin-embedded tonsil tissue cylinder was sampled from a donor block using an automated sampler and included as an ‘internal control’ together with a bone marrow biopsy in a recipient block, avoiding the use of external tonsil tissue control. To validate this technique, the authors compared the quality of immunohistochemistry, the workload and costs with routine external control in 50 consecutive bone marrow biopsies.ResultsProcessing simultaneously the sample and the tissue control in the same block, 60 external positive control tests were spared. Only a few minutes were taken for the preparation of the recipient blocks, and no particular technical skill was required. Considering that the volume of antibodies used for the analysis of each sample was not increased, a considerable amount of the disposable material was saved. The workload of technicians was decreased and some potential technical bias was avoided. The time required for pathologists to interpret the slides was also reduced.ConclusionsIn conclusion, this seems to be a feasible, cost-cutting and quality-improving technique, not limited to haematopathology but potentially extensible to other fields of pathology.
Differential expression of TRPM7 in rat hepatoma and embryonic and adult hepatocytes
Authors: Lam D. Hung , Grant Caroline E. , Hill Ceredwyn E. 
Published: March 2012

TRPM7 channels are implicated in cellular survival, proliferation, and differentiation. However, a profile of TRPM7 activity in a specific cell type has not been determined from embryonic to terminally differentiated state. Here, we characterized TRPM7 expression in a spectrum of rat liver cells at different developmental stages. Using the whole-cell patch clamp technique, TRPM7-like Na+ currents were identified in RLC-18 cells, a differentiated, proliferating hepatocellular line derived from day 17 embryonic rat liver. Currents were outwardly rectifying, enhanced in divalent-free solutions, and inhibited by intracellular Mg2+. Reverse transcription – polymerase chain reaction (RT–PCR) revealed that RLC-18 cells express both TRPM6 and TRPM7. However, mean currents were reduced almost 80% by 1 mmol/L 2-aminoethoxyphenylborate (2-APB) and were abolished in RLC-18 cells heterologously expressing a dominant negative TRPM7 construct, suggesting that TRPM7 is the major current carrier in these cells. Functional comparison showed that relative to terminally differentiated adult rat hepatocytes, currents were 1.8 and 3.9 times higher in, respectively, RLC-18 and WIF-B cells, a rat hepatoma – human fibroblast cross. Our results demonstrate that plasma membrane TRPM7 channels are more highly expressed in proliferating cells as compared with terminally differentiated and nondividing rat hepatocytes and suggest that downregulation of this channel is associated with hepatocellular differentiation.
Phosphoproteomics Identifies Driver Tyrosine Kinases in Sarcoma Cell Lines and Tumors
Authors: Bai Yun , Li Jiannong , Fang Bin , Edwards Arthur , Zhang Guolin , Bui Marilyn , Eschrich Steven , Altiok Soner , Koomen John , Haura Eric B. 
Published: March 2012

Abstract
Driver tyrosine kinase mutations are rare in sarcomas, and patterns of tyrosine phosphorylation are poorly understood. To better understand the signaling pathways active in sarcoma, we examined global tyrosine phosphorylation in sarcoma cell lines and human tumor samples. Anti-phosphotyrosine antibodies were used to purify tyrosine phosphorylated peptides, which were then identified by liquid chromatography and tandem mass spectrometry. The findings were validated with RNA interference, rescue, and small-molecule tyrosine kinase inhibitors. We identified 1,936 unique tyrosine phosphorylated peptides, corresponding to 844 unique phosphotyrosine proteins. In sarcoma cells alone, peptides corresponding to 39 tyrosine kinases were found. Four of 10 cell lines showed dependence on tyrosine kinases for growth and/or survival, including platelet-derived growth factor receptor (PDGFR)α, MET, insulin receptor/insulin-like growth factor receptor signaling, and SRC family kinase signaling. Rhabdomyosarcoma samples showed overexpression of PDGFRα in 13% of examined cases, and sarcomas showed abundant tyrosine phosphorylation and expression of a number of tyrosine phosphorylated tyrosine kinases, including DDR2, EphB4, TYR2, AXL, SRC, LYN, and FAK. Together, our findings suggest that integrating global phosphoproteomics with functional analyses with kinase inhibitors can identify drivers of sarcoma growth and survival. Cancer Res; 72(10); 2501–11. ©2012 AACR.
HER3 Is Required for HER2-Induced Preneoplastic Changes to the Breast Epithelium and Tumor Formation
Authors: Vaught David B. , Stanford Jamie C. , Young Christian , Hicks Donna J. , Wheeler Frank , Rinehart Cammie , Sánchez Violeta , Koland John , Muller William J. , Arteaga Carlos L. , Cook Rebecca S. 
Published: March 2012

Abstract
Increasing evidence suggests that HER2-amplified breast cancer cells use HER3/ErbB3 to drive therapeutic resistance to HER2 inhibitors. However, the role of ErbB3 in the earliest events of breast epithelial transformation remains unknown. Using mouse mammary specific models of Cre-mediated ErbB3 ablation, we show that ErbB3 loss prevents the progressive transformation of HER2-overexpressing mammary epithelium. Decreased proliferation and increased apoptosis were seen in MMTV-HER2 and MMTV-Neu mammary glands lacking ErbB3, thus inhibiting premalignant HER2-induced hyperplasia. Using a transgenic model in which HER2 and Cre are expressed from a single polycistronic transcript, we showed that palpable tumor penetrance decreased from 93.3% to 6.7% upon ErbB3 ablation. Penetrance of ductal carcinomas in situ was also decreased. In addition, loss of ErbB3 impaired Akt and p44/42 phosphorylation in preneoplastic HER2-overexpressing mammary glands and in tumors, decreased growth of preexisting HER2-overexpressing tumors, and improved tumor response to the HER2 tyrosine kinase inhibitor lapatinib. These events were rescued by reexpression of ErbB3, but were only partially rescued by ErbB36F, an ErbB3 mutant harboring six tyrosine-to-phenylalanine mutations that block its interaction with phosphatidyl inositol 3-kinase. Taken together, our findings suggest that ErbB3 promotes HER2-induced changes in the breast epithelium before, during, and after tumor formation. These results may have important translational implications for the treatment and prevention of HER2-amplified breast tumors through ErbB3 inhibition. Cancer Res; 72(10); 2672–82. ©2012 AACR.