bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant Contraction of Antigen-Specific CD4 T Cells after Infection in the Absence of Gamma Interferon or Its Receptor
Authors: Haring Jodie S. , Harty John T. 
Published: October 2006

ABSTRACT

Several lines of evidence from different model systems suggest that gamma interferon (IFN-γ) is an important regulator of T-cell contraction after antigen (Ag)-driven expansion. To specifically investigate the role of IFN-γ in regulating the contraction of Ag-specific CD4 T cells, we infected IFN-γ
−/−
and IFN-γR1
−/−
mice with attenuated
Listeria monocytogenes
and monitored the numbers of Ag-specific CD4 T cells during the expansion, contraction, and memory phases of the immune response to infection. In the absence of IFN-γ or the ligand-binding portion of its receptor, Ag-specific CD4 T cells exhibited normal expansion in numbers, but in both strains of deficient mice there was very little decrease in the number of Ag-specific CD4 T cells even at time points later than day 90 after infection. This significant delay in contraction was not due to prolonged infection, since mice treated with antibiotics to conclusively eliminate infection exhibited the same defect in contraction. In addition to altering the number of Ag-specific CD4 T cells, the absence of IFN-γ signaling also changed the phenotype of cells generated after infection. IFN-γR1
−/−
Ag-specific CD4 T cells reacquired expression of CD127 more quickly than wild-type cells, and more IFN-γR1
−/−
CD4 T cells were capable of producing both IFN-γ and interleukin 2 following Ag stimulation. From these data we conclude that IFN-γ regulates the contraction, phenotype, and function of Ag-specific CD4 T cells generated after infection.
Hierarchy of Iron Uptake Systems: Yfu and Yiu Are Functional in
Yersinia pestis
Authors: Kirillina Olga , Bobrov Alexander G. , Fetherston Jacqueline D. , Perry Robert D. 
Published: October 2006

ABSTRACT

In addition to the yersiniabactin (Ybt) siderophore-dependent system, two inorganic iron ABC transport systems of
Yersinia pestis
, Yfe and Yfu, have been characterized. Here we show that the Yfu system functions in
Y. pestis
: a Ybt
−
Yfe
−
Yfu
−
mutant exhibited a greater growth defect under iron-deficient conditions than its Ybt
−
Yfe
−
parental strain. We also demonstrate that another putative
Y. pestis
iron uptake system, Yiu, which potentially encodes an outer membrane receptor, YiuR, and an ABC iron transport cassette, YiuABC, is functional. The cloned
yiuABC
operon restored growth of an enterobactin-deficient mutant
Escherichia coli
strain, 1017, under iron-chelated conditions. Iron uptake by the Yiu system in
Y. pestis
was demonstrated only when the Ybt, Yfe, and Yfu systems were mutated. Using a
yiuA
::
lacZ
fusion, we show that the
yiuABC
promoter is repressed by iron through Fur. A mouse model of bubonic plague failed to show a significant role for the Yiu system in the disease process. These results demonstrate that two additional iron transporters are functional in
Y. pestis
and indicate that there is a hierarchy of iron transporters, with Ybt being most effective and Yiu being the least effective of those systems which have been characterized.
Role of Inducible Nitric Oxide Synthase and NADPH Oxidase in Early Control ofBurkholderia pseudomalleiInfection in Mice
Authors: Breitbach Katrin , Klocke Sonja , Tschernig Thomas , van Rooijen Nico , Baumann Ulrich , Steinmetz Ivo 
Published: October 2006

ABSTRACTInfection with the soil bacteriumBurkholderia pseudomalleican result in a variety of clinical outcomes, including asymptomatic infection. The initial immune defense mechanisms which might contribute to the various outcomes after environmental contact withB. pseudomalleiare largely unknown. We have previously shown that relatively resistant C57BL/6 mice can restrict bacterialB. pseudomalleigrowth more efficiently within 1 day after infection than highly susceptible BALB/c mice. By using this model, our study aimed to investigate the role of macrophage-mediated effector mechanisms during earlyB. pseudomalleiinfection. Depletion of macrophages revealed an essential role of these cells in the early control of infection in BALB/c and C57BL/6 mice. Strikingly, the comparison of the anti-B. pseudomalleiactivity of bone marrow-derived macrophages (BMM) from C57BL/6 and BALB/c mice revealed an enhanced bactericidal activity of C57BL/6 BMM, particularly after gamma interferon (IFN-γ) stimulation. In vitro experiments with C57BL/6gp91phox−/−BMM showed an impaired intracellular killing ofB. pseudomalleicompared to experiments with wild-type cells, although C57BL/6gp91phox−/−cells still exhibited substantial killing activity. The anti-B. pseudomalleiactivity of C57BL/6iNOS−/−BMM was not impaired. C57BL/6gp91phox−/−mice lacking a functional NADPH oxidase were more susceptible to infection, whereas C57BL/6 mice lacking inducible nitric oxide synthase (iNOS) did not show increased susceptibility but were slightly more resistant during the early phase of infection. Thus, our data suggest that IFN-γ-mediated but iNOS-independent anti-B. pseudomalleimechanisms of macrophages might contribute to the enhanced resistance of C57BL/6 mice compared to that of BALB/c mice in the early phase of infection.
Cryptococcus neoformans
Cells in Biofilms Are Less Susceptible than Planktonic Cells to Antimicrobial Molecules Produced by the Innate Immune System
Authors: Martinez Luis R. , Casadevall Arturo 
Published: October 2006

ABSTRACT

The human pathogenic fungus
Cryptococcus neoformans
can form biofilms on polystyrene plates and medical devices in a process that requires capsular polysaccharide release. Although biofilms are known to be less susceptible to antimicrobial drugs, little is known about their susceptibility to antimicrobial molecules produced by the innate immune system. In this study, we investigated the susceptibility of
C. neoformans
cells in biofilm and planktonic states to oxidative and nonoxidative antimicrobial molecules produced by phagocytic cells. The effects of various immune effector molecules on the fungal mass, metabolic activity, and architecture of
C. neoformans
biofilms were measured by colony counts, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide reduction, and confocal microscopy, respectively. Biofilms were more resistant than planktonic cells to oxidative stress but remained vulnerable to cationic antimicrobial peptides. However, melanized biofilms were significantly less susceptible to antimicrobial peptides than nonmelanized biofilms. These results suggest that the biofilm phenotype increases resistance against host immune mechanisms, a phenomenon that could contribute to the ability of biofilm-forming microbes to establish persistent infections.
Role for Matrix Metalloproteinase 9 in Granuloma Formation during PulmonaryMycobacterium tuberculosisInfection
Authors: Taylor Jennifer L. , Hattle Jessica M. , Dreitz Steven A. , Troudt JoLynn M. , Izzo Linda S. , Basaraba Randall J. , Orme Ian M. , Matrisian Lynn M. , Izzo Angelo A. 
Published: October 2006

ABSTRACTRecent studies have shown that matrix metalloproteinases (MMPs) are induced byMycobacterium tuberculosisduring pulmonary infection. Here, expression of MMP-9 during pulmonaryM. tuberculosisinfection was characterized to determine whether its production correlated with disease resistance in vivo and to determine what role, if any, MMP-9 might have in granuloma formation. Following aerosol infection withM. tuberculosis, dissemination of bacilli occurred earlier in the C57BL/6 resistant mouse strain than in the susceptible CBA/J strain, as was evident from an increased number of bacteria in the blood, spleen, and liver at day 14 after infection. In addition, early dissemination of the bacilli was associated with early induction of protective immunity as assessed from gamma interferon levels. Nonspecific blocking of MMPs in C57BL/6 mice early during infection reduced hematogenous spread of the bacilli, suggesting that MMPs indeed play a role in facilitating dissemination, likely via extracellular matrix degradation. The concentration of active MMP-9, specifically, was greater in the lungs of C57BL/6 mice than in those of the CBA/J mice at day 28, thereby suggesting that MMP-9 is not one of the MMPs directly involved in promoting early dissemination ofM. tuberculosis. Instead, however, histological lung sections and flow cytometric analysis of lung cells from MMP-9-knockout mice showed that MMP-9 is involved in macrophage recruitment and granuloma development. These combined data support the idea that early MMP activity is an essential component of resistance to pulmonary mycobacterial infection and that MMP-9, specifically, is required for recruitment of macrophages and tissue remodeling to allow for the formation of tight, well-organized granulomas.
Comparison of two indices of exposure to polycyclic aromatic hydrocarbons in a retrospective aluminium smelter cohort
Authors: Friesen Melissa C , Demers Paul A , Spinelli John J , Lorenzi Maria F , Le Nhu D 
Published: October 2006

Background:The association between coal tar-derived substances, a complex mixture of polycyclic aromatic hydrocarbons, and cancer is well established. However, the specific aetiological agents are unknown.Objective:To compare the dose–response relationships for two common measures of coal tar-derived substances, benzene-soluble material (BSM) and benzo(a)pyrene (BaP), and to evaluate which among these is more strongly related to the health outcomes.Methods:The study population consisted of 6423 men with ⩾3 years of work experience at an aluminium smelter (1954–97). Three health outcomes identified from national mortality and cancer databases were evaluated: incidence of bladder cancer (n = 90), incidence of lung cancer (n = 147) and mortality due to acute myocardial infarction (AMI, n = 184). The shape, magnitude and precision of the dose–response relationships and cumulative exposure levels for BSM and BaP were evaluated. Two model structures were assessed, where 1n(relative risk) increased with cumulative exposure (log-linear model) or with log-transformed cumulative exposure (log–log model).Results:The BaP and BSM cumulative exposure metrics were highly correlated (r = 0.94). The increase in model precision using BaP over BSM was 14% for bladder cancer and 5% for lung cancer; no difference was observed for AMI. The log-linear BaP model provided the best fit for bladder cancer. The log–log dose–response models, where risk of disease plateaus at high exposure levels, were the best-fitting models for lung cancer and AMI.Conclusion:BaP and BSM were both strongly associated with bladder and lung cancer and modestly associated with AMI. Similar conclusions regarding the associations could be made regardless of the exposure metric.
PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase
Authors: Chan Rebecca J. , Feng Gen-Sheng 
Published: October 2006

AbstractElucidation of the molecular mechanisms underlying carcinogenesis has benefited tremendously from the identification and characterization of oncogenes and tumor suppressor genes. One new advance in this field is the identification of PTPN11 as the first proto-oncogene that encodes a cytoplasmic tyrosine phosphatase with 2 Src-homology 2 (SH2) domains (Shp2). This tyrosine phosphatase was previously shown to play an essential role in normal hematopoiesis. More recently, somatic missense PTPN11 gain-of-function mutations have been detected in leukemias and rarely in solid tumors, and have been found to induce aberrant hyperactivation of the Ras-Erk pathway. This progress represents another milestone in the leukemia/cancer research field and provides a fresh view on the molecular mechanisms underlying cell transformation.
Correlation between antiphospholipid antibodies that recognize domain I of β2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5
Authors: de Laat Bas , Wu Xiao-Xuan , van Lummel Menno , Derksen Ronald H. W. M. , de Groot Philip G. , Rand Jacob H. 
Published: October 2006

AbstractThe paradoxical correlation between thrombosis and the lupus anticoagulant (LAC) effect is an enigmatic feature of the antiphospholipid (aPL) syndrome. The Dutch authors previously reported that thrombosis-related anti–β2-glycoprotein I (β2GPI) antibodies recognize domain I and cause LAC. The American authors reported that aPLs disrupt an anticoagulant annexin A5 (AnxA5) crystal shield. We investigated whether antidomain I antibodies correlate with disruption of AnxA5-anticoagulant activity. We studied a well-characterized group of 33 patients including subgroups with β2GPI-dependent LAC that recognize domain I (n = 11), with β2GPI-independent LAC (n = 12), and lacking LAC (n = 10). The effects on AnxA5-anticoagulant activity were determined with an AnxA5 resistance assay that measures coagulation times with and without AnxA5. Patients with β2GPI-dependent LAC (group A, all with thrombosis) had significantly lower AnxA5-anticoagulant ratios than those with β2GPI-independent LAC (group B, thrombosis n = 4; 157.8% versus 235.6%, P < .001) and those without LAC (group C, thrombosis n = 2; 157.8% versus 232.5%, P < .001). There was no difference in the ratios between groups B and C (P = .92). Plasmas with β2GPI-dependent LAC that recognize domain I displayed significantly increased AnxA5 resistance, suggesting that specifically anti-β2GPI antibodies compete with AnxA5 for anionic phospholipids. These results are consistent with a model in which aPL antibodies may promote thrombosis by interfering with the anticoagulant activity of AnxA5.
Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial
Authors: Antunes Héliton Spíndola , de Azevedo Alexandre Mello , da Silva Bouzas Luiz Fernando , Adão Carlos Alberto Esteves , Pinheiro Claudia Tereza , Mayhe Renato , Pinheiro Lucia Helena , Azevedo Renato , D'Aiuto de Matos Valkiria , Rodrigues Pedro Carvalho , Small Isabele Avila , Zangaro Renato Amaro , Ferreira Carlos Gil 
Published: October 2006

AbstractWe investigated the clinical effects of low-power laser therapy (LPLT) on prevention and reduction of severity of conditioning-induced oral mucositis (OM) for hematopoietic stem cell transplantation (HSCT). We randomized 38 patients who underwent autologous (AT) or allogeneic (AL) HSCT. A diode InGaAlP was used, emitting light at 660 nm, 50 mW, and 4 J/cm2, measured at the fiberoptic end with 0.196 cm2 of section area. The evaluation of OM was done using the Oral Mucositis Assessment Scale (OMAS) and the World Health Organization (WHO) scale. In the LPLT group, 94.7% of patients had an OM grade (WHO) lower than or equal to grade 2, including 63.2% with grade 0 and 1, whereas in the controls group, 31.5% of patients had an OM grade lower than or equal to grade 2 (P < .001). Remarkably, the hazard ratio (HR) for grades 2, 3, and 4 OM was 0.41 (range, 0.22-0.75; P = .002) and for grades 3 and 4 it was 0.07 (range, 0.11-0.53; P < .001). Using OMAS by the calculation of ulcerous area, 5.3% of the laser group presented with ulcers of 9.1 cm2 to 18 cm2, whereas 73.6% of the control group presented with ulcers from 9.1 cm2 to 18 cm2 (P = .003). Our results indicate that the use of upfront LPLT in patients who have undergone HSCT is a powerful instrument in reducing the incidence of OM and is now standard in our center.
Neutrophil elastase in cyclic and severe congenital neutropenia
Authors: Horwitz Marshall S. , Duan Zhijun , Korkmaz Brice , Lee Hu-Hui , Mealiffe Matthew E. , Salipante Stephen J. 
Published: October 2006

AbstractMutations in ELA2 encoding the neutrophil granule protease, neutrophil elastase (NE), are the major cause of the 2 main forms of hereditary neutropenia, cyclic neutropenia and severe congenital neutropenia (SCN). Genetic evaluation of other forms of neutropenia in humans and model organisms has helped to illuminate the role of NE. A canine form of cyclic neutropenia corresponds to human Hermansky-Pudlak syndrome type 2 (HPS2) and results from mutations in AP3B1 encoding a subunit of a complex involved in the subcellular trafficking of vesicular cargo proteins (among which NE appears to be one). Rare cases of SCN are attributable to mutations in the transcriptional repressor Gfi1 (among whose regulatory targets also include ELA2). The ultimate biochemical consequences of the mutations are not yet known, however. Gene targeting of ELA2 has thus far failed to recapitulate neutropenia in mice. The cycling phenomenon and origins of leukemic transformation in SCN remain puzzling. Nevertheless, mutations in all 3 genes are capable of causing the mislocalization of NE and may also induce the unfolded protein response, suggesting that there might a convergent pathogenic mechanism focusing on NE.
Chest CT screening of asbestos-exposed workers: lung lesions and incidental findings
Authors: Vierikko T. , Järvenpää R. , Autti T. , Oksa P. , Huuskonen M. , Kaleva S. , Laurikka J. , Kajander S. , Paakkola K. , Saarelainen S. , Salomaa E-R. , Tossavainen A. , Tukiainen P. , Uitti J. , Vehmas T. 
Published: October 2006

The objective of the present study is to determine the feasibility of chest computed tomography (CT) in screening for lung cancer among asbestos-exposed workers.In total, 633 workers were included in the present study and were examined with chest radiography and high-resolution CT (HRCT). A total of 180 current and ex-smokers (cessation within the previous 10 yrs) were also screened with spiral CT. Noncalcified lung nodules were considered positive findings. The incidental CT findings not related to asbestos exposure were registered and further examined when needed.Noncalcified lung nodules were detected in 86 workers. Five histologically confirmed lung cancers were found. Only one of the five cancers was also detected by plain chest radiography and three were from the group of patients with a pre-estimated lower cancer probability. Two lung cancers were stage Ia and were radically operated. In total, 277 individuals presented 343 incidental findings of which 46 required further examination. Four of these were regarded as clinically important.In conclusion, computed tomography and high-resolution computed tomography proved to be superior to plain radiography in detecting lung cancer in asbestos-exposed workers with many confounding chest findings. The numerous incidental findings are a major concern for future screenings, which should be considered for asbestos-exposed ex-smokers and current smokers.
Novel design and controls for focused DNA microarrays: applications in quality assurance/control and normalization for the Health Canada ToxArray™
Authors: Yauk Carole L , Williams Andrew , Boucher Sherri , Berndt Lynn M , Zhou Gu , Zheng Jenny L , Rowan-Carroll Andrea , Dong Hongyan , Lambert Iain B , Douglas George R , Parfett Craig L 
Published: October 2006

Abstract

Background
Microarray normalizations typically apply methods that assume absence of global transcript shifts, or absence of changes in internal control features such as housekeeping genes. These normalization approaches are not appropriate for focused arrays with small sets of genes where a large portion may be expected to change. Furthermore, many microarrays lack control features that can be used for quality assurance (QA). Here, we describe a novel external control series integrated with a design feature that addresses the above issues.

Results
An EC dilution series that involves spike-in of a single concentration of the A. thaliana chlorophyll synthase gene to hybridize against spotted dilutions (0.000015 to 100 μM) of a single complimentary oligonucleotide representing the gene was developed. The EC series is printed in duplicate within each subgrid of the microarray and covers the full range of signal intensities from background to saturation. The design and placement of the series allows for QA examination of frequently encountered problems in hybridization (e.g., uneven hybridizations) and printing (e.g., cross-spot contamination). Additionally, we demonstrate that the series can be integrated with a LOWESS normalization to improve the detection of differential gene expression (improved sensitivity and predictivity) over LOWESS normalization on its own.

Conclusion
The quality of microarray experiments and the normalization methods used affect the ability to measure accurate changes in gene expression. Novel methods are required for normalization of small focused microarrays, and for incorporating measures of performance and quality. We demonstrate that dilution of oligonucleotides on the microarray itself provides an innovative approach allowing the full dynamic range of the scanner to be covered with a single gene spike-in. The dilution series can be used in a composite normalization to improve detection of differential gene expression and to provide quality control measures.
Continued evolution of HIV-1 circulating in blood monocytes with antiretroviral therapy: genetic analysis of HIV-1 in monocytes and CD4+ T cells of patients with discontinued therapy
Authors: Llewellyn Nick , Zioni Rafael , Zhu Haiying , Andrus Thomas , Xu Younong , Corey Lawrence , Zhu Tuofu 
Published: October 2006

Abstract
The role of blood monocytes in HIV-1 infection is a relatively new field of interest. What happens to HIV-1 in monocytes and their relationship to CD4+ T cells before, during, and after suppressive antiretroviral therapy (ART) is largely unstudied. Here, considering that diversity is a good indicator of continued replication over time, we evaluated the effect of ART on HIV-1 in blood monocytes and CD4+ T cells by examining the diversity of HIV-1 from 4 infected patients who underwent and stopped therapy. We determined diversity and compartmentalization of HIV-1 between blood monocytes and CD4+ T cells in each patient in relationship to their ART regimens. Our data indicate that the rate of HIV-1 diversity increase in monocytes during therapy was significantly higher than in CD4+ T cells (P&lt;0.05), suggesting that HIV-1 present in monocytes diversify more during therapy than in CD4+ T cells. Increased rates of HIV-1 compartmentalization between monocytes and CD4+ T cells while on therapy were also observed. These results suggest that ART inhibits HIV-1 replication in CD4+ T cells more than in blood monocytes and that better treatments to combat HIV-1 in monocytes/macrophages may be needed for a more complete suppression of HIV replication.
Atelectatic tympanic membrane reversal by nitrous oxide supplemented general anesthesia and polyethylene ventilation tube insertion. A preliminary report
Authors: Graham Malcolm D. , Knight Paul R. 
Published: October 2006

AbstractIn certain instances an adherent atelectatic tympanic membrane (Sade Stage IV) may be successfully elevated off the promontory and ossicles by the use of nitrous oxide anesthesia and restored to a normal position and configuration by polyethylene ventilation tube insertion. Criteria of reversibility and long term follow‐up of the tympanic membranes so restored remain to be elucidated.
The loose wire syndrome
Authors: Mcgee T. Manford 
Published: October 2006

AbstractThe loose wire syndrome occurs in patients who have had stapedectomy surgery and insertion of a prosthesis which attaches to the long process of the incus by means of a crimped wire. The syndrome consists of a triad of one or more symptoms which improve temporarily with middle ear inflation. These include improvement in auditory acuity, in distortion of sound, and in speech discrimination. Forty‐three patients were studied for age, sex, and symptom distribution, and for results of corrective surgery. In all cases, a loose wire at its attachment to the incus was found and corrective survery (tightening of the wire) was performed. Objectively and subjectively all but two patients were relieved of their symptoms.