bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Synthesis of Anti-Tuberculous Glycolipid Immunoglobulin G (IgG) and IgA with Cavity Formation in Patients with Pulmonary Tuberculosis
Authors: Mizusawa Masako , Kawamura Mizuoho , Takamori Mikio , Kashiyama Tetsuya , Fujita Akira , Usuzawa Motoki , Saitoh Hiroki , Ashino Yugo , Yano Ikuya , Hattori Toshio 
Published: January 2008

ABSTRACTTuberculous glycolipid (TBGL) antigen is a cell wall component ofMycobacterium tuberculosisand has been used for the serodiagnosis of tuberculosis. We investigated correlations between the levels of anti-TBGL antibodies and a variety of laboratory markers that are potentially influenced by tuberculous infection. Comparisons between patients with cavitary lesions and those without cavitary lesions were also made in order to determine the mechanism underlying the immune response to TBGL. Blood samples were obtained from 91 patients with both clinically and microbiologically confirmed active pulmonary tuberculosis (60 male and 31 female; mean age, 59 ± 22 years old). Fifty-nine patients had cavitary lesions on chest X-rays. Positive correlations were found between anti-TBGL immunoglobulin G (IgG) and C-reactive protein (CRP) (r= 0.361;P< 0.001), between anti-TBGL IgA and soluble CD40 ligand (sCD40L) (r= 0.404;P< 0.005), between anti-TBGL IgG and anti-TBGL IgA (r= 0.551;P< 0.0000005), and between anti-TBGL IgM and serum IgM (r= 0.603;P< 0.00000005). The patients with cavitary lesions showed significantly higher levels of anti-TBGL IgG (P< 0.005), anti-TBGL IgA (P< 0.05), white blood cells (P< 0.01), neutrophils (P< 0.005), basophils (P< 0.0005), natural killer cells (P< 0.05), CRP (P< 0.0005), KL-6 (sialylated carbohydrate antigen KL-6) (P< 0.0005), IgA (P< 0.05), and sCD40L (P< 0.01). The observed positive correlations between the anti-TBGL antibody levels and inflammatory markers indicate the involvement of inflammatory cytokines and NKT cells in the immunopathogenesis of pulmonary tuberculosis.
Local Immune Response to Upper Urinary Tract Infections in Children
Authors: Kantele Anu , Palkola Nina , Arvilommi Heikki , Honkinen Olli , Jahnukainen Timo , Mertsola Jussi , Kantele Jussi M. 
Published: January 2008

ABSTRACT

Vaccines are needed against urinary tract infections (UTIs) in children, as episodes of pyelonephritis (PN) may cause renal scarring. Local immune mechanisms are regarded to confer protection, yet they have been poorly characterized for children. This study explores the local immune response in children by looking for newly activated pathogen-specific antibody-secreting cells (ASC), expected to appear transiently in the circulation as a response to UTI. Urinary tract-originating ASC specific to each patient's own pathogen or P fimbria were studied in 37 children with PN. The children were examined for recidivism and renal scarring in a 6-month follow-up study. Pathogen-specific ASC were found in 33/37 children, with the magnitude increasing with age. In contrast to the case for adults, with immunoglobulin A (IgA) dominance, in 18/33 cases IgM dominated the response, and this occurred more frequently in infants (63%) than in older children (30%). The most vigorous response was found to whole
Escherichia coli
bacteria (geometric mean, 63 ± 2,135 ASC/10
6
peripheral blood mononuclear cells [PBMC]), yet responses were found to P fimbriae (13 ± 33 ASC/10
6
PBMC), too. The response peaked at 1 to 2 weeks and was low/negligible 3 to 7 weeks after the beginning of symptoms. Recidivism was seen in seven patients, and renal scarring was seen in nine patients. In conclusion, a response of circulating ASC was found in children with UTIs, with the magnitude increasing with age. Since IgM is not present in urine, the IgM dominance of the response suggests that systemic immune mechanisms are more important in the immune defense in children than in adults. In 81% of patients, no recidivism was seen, suggesting a successful immune defense.
Peripheral Blood Gamma Interferon Release Assays Predict Lung Responses andMycobacterium tuberculosisDisease Outcome in Mice
Authors: Beamer Gillian L. , Flaherty David K. , Vesosky Bridget , Turner Joanne 
Published: January 2008

ABSTRACTCurrent diagnostic tests for tuberculosis (TB) are not able to distinguish active disease from latentMycobacterium tuberculosisinfection, nor are they able to quantify the risk of a latently infected person progressing to active TB. There is interest, however, in adapting antigen-specific gamma interferon (IFN-γ) release assays (IGRAs) to predict disease outcome. In this study, we used the differential susceptibilities of inbred mouse strains toM. tuberculosisinfection to evaluate the prognostic capabilities of IGRAs. Using lung and blood cultures, we determined that CBA/J, DBA/2, and C3H/HeJ mice (models of heightened risk of progression to active TB) produced less antigen-specific IFN-γ in response toM. tuberculosisculture filtrate proteins and early secreted antigenic target-6 than the relatively resistant C57BL/6 mouse strain. Additionally, reduced IFN-γ secretion in supernatants reflected a reduced frequency of IFN-γ-responding cells in the lung and blood and not a specific defect in IFN-γ secretion at the single-cell level. Importantly, detection of antigen-specific IFN-γ from blood cultures accurately reflected lung responses, indicating that blood can be an appropriate test tissue in humans. Furthermore, reduced antigen-specific IFN-γ production and low frequencies of IFN-γ-responding cells from peripheral blood predicted increased risk of TB disease progression across genetically diverse TB disease-susceptible mouse strains, suggesting that similar results may occur in humans. The development of efficacious predictive diagnostic tests for humans would lead to targeted therapy prior to progression to active TB, reducing transmission, incidence, and prevalence rates while maximizing the use of public health resources.
Passive Transfer of MaternalMycoplasma hyopneumoniae-Specific Cellular Immunity to Piglets
Authors: Bandrick Meggan , Pieters Maria , Pijoan Carlos , Molitor Thomas W. 
Published: January 2008

ABSTRACTImmunity in the neonatal animal is primarily maternally derived, either by lymphocytes that pass into the newborn across the placenta or following colostrum ingestion. However, the effect of this passively transferred cellular maternal immunity on the newborn's immune repertoire is not clearly understood. Various studies have shown that colostral lymphocytes are activated and possess functional abilities; however, no studies have shown the transfer of colostral antigen-specific T-cell-specific responses in a newborn. In this study we examined the transfer of vaccine-inducedMycoplasma hyopneumoniaecellular immunity from immune dams to newborn piglets. Newborn piglets from vaccinated and nonvaccinated dams were assessed in two ways for cellular immune responses specific toM. hyopneumoniae: (i) delayed-type hypersensitivity (DTH) testing and (ii) in vitro lymphocyte proliferation, assayed on piglet blood lymphocytes and sow colostral lymphocytes. DTH responses toM. hyopneumoniaewere detected only for offspring of vaccinated sows, whereas DTH responses to the nonspecific mitogen phytohemagglutinin were seen for all piglets.M. hyopneumoniae-specific proliferation was seen for colostral lymphocytes from vaccinated sows and for blood lymphocytes from neonatal piglets of vaccinated dams but not for blood lymphocytes from piglets of nonvaccinated sows. Functional antigen-specific T cells were transferred to offspring from vaccinated sows and participated in the neonatal immune response upon stimulation. These data have implications for defining disease intervention strategies.
Nasopharyngeal
Haemophilus influenzae
Carriage in Japanese Children Attending Day-Care Centers
Authors: Hashida Koichi , Shiomori Teruo , Hohchi Nobusuke , Muratani Tetsuro , Mori Takanori , Udaka Tsuyoshi , Suzuki Hideaki 
Published: January 2008

ABSTRACT

We conducted a prospective bacteriological survey to investigate antibiotic resistance-related genetic characteristics and the turnover of nasopharyngeal
Haemophilus influenzae
carriage in healthy children in day-care centers (DCCs). A total of 363 nasopharyngeal mucus samples were collected from children aged 0 to 6 years attending two DCCs in the summer of 2004 (
n
= 184) and the following winter (
n
= 179). We obtained 172
H. influenzae
isolates and analyzed them by antimicrobial susceptibility testing, PCR for
bla
TEM-1
and the penicillin-binding protein (PBP) gene, and pulsed-field gel electrophoresis (PFGE). The overall carriage rate was 47.4% (172/363), and 37.2% of the isolates (64/172) were ampicillin (AMP) resistant. All the resistant isolates had a PBP mutation(s), while only three isolates had TEM-1. The carriage rate was significantly higher in the winter than in the summer (56.4% and 38.6%, respectively), owing to the increase in the numbers of AMP-susceptible
H. influenzae
isolates in the winter. Children aged ≤3 years showed a higher rate of carriage of
H. influenzae
isolates with an AMP resistance gene(s) than those aged ≥4 years (21.9% and 12.6%, respectively). Forty-two strains with different PFGE patterns were obtained from among the 172 isolates. Only five strains were observed in both seasons. None of the strains isolated in the summer was isolated from the same carrier in the winter. Twenty-seven strains (64.3%) were isolated from two or more children, and 25 of these were each isolated from children belonging to the same DCC. These results indicate the spread of
H. influenzae
, particularly those with a PBP mutation(s), and the highly vigorous genetic turnover and substantial horizontal transmission of this pathogen in healthy children attending DCCs in Japan.
Dissemination of CTX-M-15 β-Lactamase Genes Carried on Inc FI and FII Plasmids among Clinical Isolates of
Escherichia coli
in a University Hospital in Istanbul, Turkey
Authors: Gonullu Nevriye , Aktas Zerrin , Kayacan Cigdem Bal , Salcioglu Melek , Carattoli Alessandra , Yong Dong Eun , Walsh Timothy R. 
Published: January 2008

ABSTRACT

The CTX-M-1 group was found in 86.8% of the
Escherichia coli
isolates from Istanbul. A subset study revealed all isolates carrying
bla
CTX-M-15
genes flanked by the insertion element IS
Ecp1
. Plasmid typing of transconjugates carrying
bla
CTX-M-15
showed that most isolates belonged to the Inc/rep FII group but that one isolate also belonged to the FI group.
Differential Requirements for T Cells in Viruslike Particle- and Rotavirus-Induced Protective Immunity
Authors: Blutt Sarah E. , Warfield Kelly L. , Estes Mary K. , Conner Margaret E. 
Published: January 2008

ABSTRACTCorrelates of protection from rotavirus infection are controversial. We compared the roles of B and T lymphocytes in protective immunity induced either by intranasally administered nonreplicating viruslike particles or inactivated virus or by orally administered murine rotavirus. We found that protection induced by nonreplicating vaccines requires CD4+T cells and CD40/CD40L. In contrast, T cells were not required for short-term protective immunity induced by infection, but both T-cell-dependent and -independent mechanisms contributed to long-term maintenance of protection. Our findings indicate that more than one marker of protective immunity exists and that these markers depend on the vaccine that is administered.
Egress of Light Particles among Filopodia on the Surface of Varicella-Zoster Virus-Infected Cells
Authors: Carpenter John E. , Hutchinson Jennifer A. , Jackson Wallen , Grose Charles 
Published: January 2008

ABSTRACT
Varicella-zoster virus (VZV) is renowned for its very low titer when grown in cultured cells. There remains no single explanation for the low infectivity. In this study, viral particles on the surfaces of infected cells were examined by several imaging technologies. Few surface particles were detected at 48 h postinfection (hpi), but numerous particles were observed at 72 and 96 hpi. At 72 hpi, 75% of the particles resembled light (L) particles, i.e., envelopes without capsids. By 96 hpi, 85% of all particles resembled L particles. Subsequently, the envelopes of complete virions and L particles were investigated to determine their glycoprotein constituents. Glycoproteins gE, gI, and gB were detected in the envelopes of both types of particles in similar numbers; i.e., there appeared to be no difference in the glycoprotein content of the L particles. The viral particles emerged onto the cell surface amid actin-based filopodia, which were present in abundance within viral highways. Viral particles were easily detected at the base of and along the exterior surfaces of the filopodia. VZV particles were not detected within filopodia. In short, these results demonstrate that VZV infection of cultured cells produces a larger proportion of aberrant coreless particles than has been seen with any other previously examined alphaherpesvirus. Further, these results suggested a major disassociation between capsid formation and envelopment as an explanation for the invariably low VZV titer in cultured cells.
Envelope Protein Palmitoylations Are Crucial for Murine Coronavirus Assembly
Authors: Boscarino Joseph A. , Logan Hillary L. , Lacny Jason J. , Gallagher Thomas M. 
Published: January 2008

ABSTRACT
The coronavirus assembly process encloses a ribonucleoprotein genome into vesicles containing the lipid-embedded proteins S (spike), E (envelope), and M (membrane). This process depends on interactions with membranes that may involve palmitoylation, a common posttranslational lipidation of cysteine residues. To determine whether specific palmitoylations influence coronavirus assembly, we introduced plasmid DNAs encoding mouse hepatitis coronavirus (MHV) S, E, M, and N (nucleocapsid) into 293T cells and found that virus-like particles (VLPs) were robustly assembled and secreted into culture medium. Palmitate adducts predicted on cysteines 40, 44, and 47 of the 83-residue E protein were then evaluated by constructing mutant cDNAs with alanine or glycine codon substitutions at one or more of these positions. Triple-substituted proteins (E.Ts) lacked palmitate adducts. Both native E and E.T proteins localized at identical perinuclear locations, and both copurified with M proteins, but E.T was entirely incompetent for VLP production. In the presence of the E.T proteins, the M protein subunits accumulated into detergent-insoluble complexes that failed to secrete from cells, while native E proteins mobilized M into detergent-soluble secreted forms. Many of these observations were corroborated in the context of natural MHV infections, with native E, but not E.T, complementing debilitated recombinant MHVs lacking E. Our findings suggest that palmitoylations are essential for E to act as a vesicle morphogenetic protein and further argue that palmitoylated E proteins operate by allowing the primary coronavirus assembly subunits to assume configurations that can mobilize into secreted lipid vesicles and virions.
Importance of Conserved Cysteine Residues in the Coronavirus Envelope Protein
Authors: Lopez Lisa A. , Riffle Ambere J. , Pike Steven L. , Gardner Douglas , Hogue Brenda G. 
Published: January 2008

ABSTRACT
Coronavirus envelope (E) proteins play an important, not fully understood role(s) in the virus life cycle. All E proteins have conserved cysteine residues located on the carboxy side of the long hydrophobic domain, suggesting functional significance. In this study, we confirmed that mouse hepatitis coronavirus A59 E protein is palmitoylated. To understand the role of the conserved residues and the necessity of palmitoylation, three cysteines at positions 40, 44, and 47 were changed singly and in various combinations to alanine. Double- and triple-mutant E proteins resulted in decreased virus-like particle output when coexpressed with the membrane (M) protein. Mutant E proteins were also studied in the context of a full-length infectious clone. Single-substitution viruses exhibited growth characteristics virtually identical to those of the wild-type virus, while the double-substitution mutations gave rise to viruses with less robust growth phenotypes indicated by smaller plaques and decreased virus yields. In contrast, replacement of all three cysteines resulted in crippled virus with significantly reduced yields. Triple-mutant viruses did not exhibit impairment in entry. Mutant E proteins localized properly in infected cells. A comparison of intracellular and extracellular virus yields suggested that release is only slightly impaired. E protein lacking all three cysteines exhibited an increased rate of degradation compared to that of the wild-type protein, suggesting that palmitoylation is important for the stability of the protein. Altogether, the results indicate that the conserved cysteines and presumably palmitoylation are functionally important for virus production.
Differential CD4+versus CD8+T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates
Authors: Mooij Petra , Balla-Jhagjhoorsingh Sunita S. , Koopman Gerrit , Beenhakker Niels , van Haaften Patricia , Baak Ilona , Nieuwenhuis Ivonne G. , Kondova Ivanela , Wagner Ralf , Wolf Hans , Gómez Carmen E. , Nájera José L. , Jiménez Victoria , Esteban Mariano , Heeney Jonathan L. 
Published: January 2008

ABSTRACTPoxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeficiency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modified vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-specific systemic immune responses, we undertook a head-to-head vaccine immunogenicity and efficacy study in the pathogenic HIV type 1 (HIV-1) model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzyme-linked immunospot assays, but differences were distinguished by multiparameter fluorescence-activated cell sorter analysis, revealing a difference between the number of animals with both CD4+and CD8+T-cell responses to vaccine inserts (MVA) and those that elicit a dominant CD4+T-cell response (NYVAC). Remarkably, vector-induced differences in CD4+/CD8+T-cell immune responses persisted for more than a year after challenge and even accompanied antigenic modulation throughout the control of chronic infection. Importantly, strong preexposure HIV-1/simian immunodeficiency virus-specific CD4+T-cell responses did not prove deleterious with respect to accelerated disease progression. In contrast, in this setting, animals with strong vaccine-induced polyfunctional CD4+T-cell responses showed efficacies similar to those with stronger CD8+T-cell responses.
Clonogenic Assay of Type A Influenza Viruses Reveals Noninfectious Cell-Killing (Apoptosis-Inducing) Particles
Authors: Ngunjiri John M. , Sekellick Margaret J. , Marcus Philip I. 
Published: January 2008

ABSTRACT

Clonogenic (single-cell plating) assays were used to define and quantify subpopulations of two genetically closely related variants of influenza virus A/TK/OR/71 that differed primarily in the size of the NS1 gene product; they expressed a full-size (amino acids [aa] 1 to 230) or truncated (aa 1 to 124) NS1 protein. Monolayers of Vero cells were infected with different amounts of virus, monodispersed, and plated. Cell survival curves were generated from the fraction of cells that produced visible colonies as a function of virus multiplicity. The exponential loss of colony-forming capacity at low multiplicities demonstrated that a single virus particle sufficed to kill a cell. The ratios of cell-killing particles (CKP) to plaque-forming particles (PFP) were 1:1 and 7:1 in populations of variants NS1
1-124
and NS1
1-230
, respectively. This study revealed a new class of particles in influenza virus populations—noninfectious CKP. Both infectious and noninfectious CKP were 6.3 times more resistant to UV radiation than PFP activity. Based on UV target theory, a functional polymerase subunit was implicated in a rate-limiting step in cell killing. Since influenza viruses kill cells by apoptosis (programmed cell death), CKP are functionally apoptosis-inducing particles. Noninfectious CKP are present in excess of PFP in virus populations with full-size NS1 and induce apoptosis that is temporally delayed and morphologically different than that initiated by infectious CKP present in the virus population expressing truncated NS1. The identification and quantification of both infectious and noninfectious CKP defines new phenotypes in influenza virus populations and presents a challenge to determine their role in regulating infectivity, pathogenesis, and vaccine efficacy.
Increased Cytotoxic T-Lymphocyte Epitope Variant Cross-Recognition and Functional Avidity Are Associated with Hepatitis C Virus Clearance
Authors: Yerly Daniel , Heckerman David , Allen Todd M. , Chisholm John V. , Faircloth Kellie , Linde Caitlyn H. , Frahm Nicole , Timm Joerg , Pichler Werner J. , Cerny Andreas , Brander Christian 
Published: January 2008

ABSTRACT
Hepatitis C virus (HCV) clearance has been associated with reduced viral evolution in targeted cytotoxic T-lymphocyte (CTL) epitopes, suggesting that HCV clearers may mount CTL responses with a superior ability to recognize epitope variants and prevent viral immune escape. Here, 40 HCV-infected subjects were tested with 406 10-mer peptides covering the vast majority of the sequence diversity spanning a 197-residue region of the NS3 protein. HCV clearers mounted significantly broader CTL responses of higher functional avidity and with wider variant cross-recognition capacity than nonclearers. These observations have important implications for vaccine approaches that may need to induce high-avidity responses in vivo.
Control of mRNA Export by Adenovirus E4orf6 and E1B55K Proteins during Productive Infection Requires E4orf6 Ubiquitin Ligase Activity
Authors: Blanchette Paola , Kindsmüller Kathrin , Groitl Peter , Dallaire Frédéric , Speiseder Thomas , Branton Philip E. , Dobner Thomas 
Published: January 2008

ABSTRACT

During the adenovirus infectious cycle, the early proteins E4orf6 and E1B55K are known to perform several functions. These include nuclear export of late viral mRNAs, a block of nuclear export of the bulk of cellular mRNAs, and the ubiquitin-mediated degradation of selected proteins, including p53 and Mre11. Degradation of these proteins occurs via a cellular E3 ubiquitin ligase complex that is assembled through interactions between elongins B and C and BC boxes present in E4orf6 to form a cullin 5-based ligase complex. E1B55K, which has been known for some time to associate with the E4orf6 protein, is thought to bind to specific substrate proteins to bring them to the complex for ubiquitination. Earlier studies with E4orf6 mutants indicated that the interaction between the E4orf6 and E1B55K proteins is optimal only when E4orf6 is able to form the ligase complex. These and other observations suggested that most if not all of the functions ascribed to E4orf6 and E1B55K during infection, including the control of mRNA export, are achieved through the degradation of specific substrates by the E4orf6 ubiquitin ligase activity. We have tested this hypothesis through the generation of a virus mutant in which the E4orf6 product is unable to form a ligase complex and indeed have found that this mutant behaves identically to an E4orf6
−
virus in production of late viral proteins, growth, and export of the late viral L5 mRNA.