bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemolysis of Erythrocytes by Granulysin-Derived Peptides but Not by Granulysin
Authors: Li Qing , Dong Chen , Deng Anmei , Katsumata Masao , Nakadai Ari , Kawada Tomoyuki , Okada Satoshi , Clayberger Carol , Krensky Alan M. 
Published: December 2004

ABSTRACTGranulysin, a 9-kDa protein localized in human cytolytic T lymphoctyes and natural killer cell granules, is cytolytic against tumors and microbes but not against red blood cells. Synthetic peptides corresponding to the central region of granulysin recapitulate the lytic activity of the intact molecule, and some peptides cause hemolysis of red blood cells. Peptides in which cysteine residues were replaced by serine maintain their activity against microbes but lose activity against human cells, suggesting their potential as antibiotics. Studies were undertaken to determine the mechanism of resistance of red blood cells to granulysin and sensitivity to a subset of granulysin-derived peptides. Granulysin lyses immature reticulocytes, which have mitochondria, but not red blood cells. Granulysin lyses U937 cells but not U937 cells lacking mitochondrial DNA and a functional respiratory chain (U937ρ° cells), further demonstrating the requirement of intact mitochondria for granulysin-mediated death. Peptide G8, which corresponds to helix 2/loop 2/helix 3, lyses red blood cells, while peptide G9, which is identical except that the cysteine residues were replaced by serine, does not lyse red blood cells. Granulysin peptide-induced hemolysis is markedly inhibited by an anion transporter inhibitor and by Na+, K+, and Ca2+channel blockers but not by Na+/K+pump, cotransport, or Cl−channel blockers. Although recombinant granulysin and G9 peptide do not induce hemolysis, they both competitively inhibit G8-induced hemolysis. The finding that some derivatives of granulysin are hemolytic may have important implications for the design of granulysin-based antimicrobial therapeutics.
Glycine-Amide Is an Active Metabolite of the Antiretroviral Tripeptide Glycyl-Prolyl-Glycine-Amide
Authors: Andersson Elin , Horal Peter , Jejcic Alenka , Höglund Stefan , Balzarini Jan , Vahlne Anders , Svennerholm Bo 
Published: December 2004

ABSTRACT

The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH
2
) inhibits replication of human immunodeficiency virus (HIV) type 1 (HIV-1) in vitro, probably by interfering with capsid formation. The aim of the present study was to determine whether the metabolites glycyl-proline (GP-OH), glycine (G-OH), prolyl-glycine-amide (PG-NH
2
), proline (P-OH), and glycine-amide (G-NH
2
) from proteolytic cleavage may inhibit the replication of HIV-1 in vitro. PG-NH
2
has previously been shown to have a modest effect on HIV-1 replication. In the present study we show that G-NH
2
exhibits a pronounced inhibitory effect on HIV-1. This effect was not due to a decrease in cell proliferation or viability and could not be shown for herpes simplex virus type 1. The G-NH
2
concentration that inhibited virus replication by 50% (IC
50
) was equimolar to that of GPG-NH
2
and ranged from 3 to 41 μM. Transmission electron microscopy revealed that the effect of G-NH
2
on HIV-1 morphology was equivalent to that of GPG-NH
2
and showed disarranged capsid structures, indicating interference with capsid formation. Serial passage of HIV-infected cells with G-NH
2
for more than 20 subcultivations did not decrease the susceptibility to the compound. The results from this study suggest that GPG-NH
2
might act as a prodrug and that G-NH
2
is an active antiretroviral metabolite.
Comparative In Vitro Activities of XRP 2868, Pristinamycin, Quinupristin-Dalfopristin, Vancomycin, Daptomycin, Linezolid, Clarithromycin, Telithromycin, Clindamycin, and Ampicillin against Anaerobic Gram-Positive Species, Actinomycetes, and Lactobacilli
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi A. , Tyrrell Kerin L. , Fernandez Helen T. , Bryskier Andre 
Published: December 2004

ABSTRACT

A comparative study of the in vitro activities of XRP 2868, a new oral streptogramin, against 266 anaerobic gram-positive clinical isolates using the agar dilution method showed that the XRP 2868 MICs for 95% (254 of 266) of isolates were ≤0.5 μg/ml. XRP 2868 MICs for only two strains, one being
Clostridium clostridioforme
(MIC, 16 μg/ml) and the other being
Clostridium difficile
(MIC, 32 μg/ml), were >2 μg/ml. Depending on its pharmacokinetics and pharmacodynamics, XRP 2868 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.
Comparison of Tn
1546
-Like Elements in Vancomycin-Resistant
Staphylococcus aureus
Isolates from Michigan and Pennsylvania
Authors: Clark Nancye C. , Weigel Linda M. , Patel Jean B. , Tenover Fred C. 
Published: December 2004

ABSTRACT

In 2002, the first two clinical isolates of vancomycin-resistant
Staphylococcus aureus
(VRSA) containing
vanA
were recovered in Michigan and Pennsylvania. Tn
1546
, a mobile genetic element that encodes high-level vancomycin resistance in enterococci, was present in both isolates. With PCR and DNA sequence analysis, we compared the Tn
1546
elements from each isolate to the prototype Tn
1546
element. The Michigan VRSA element was identical to the prototype Tn
1546
element. The Pennsylvania VRSA element showed three distinct modifications: a deletion of nucleotides 1 to 3098 at the 5′ end, which eliminated the
orf1
region; an 809-bp IS
1216V
-like element inserted before nucleotide 3099 of Tn
1546
; and an inverted 1,499-bp IS
1251
-like element inserted into the
vanSH
intergenic region. These differences in the Tn
1546
-like elements indicate that the first two VRSA isolates were the result of independent genetic events.
Antifungal Activities of R-135853, a Sordarin Derivative, in Experimental Candidiasis in Mice
Authors: Kamai Yasuki , Kakuta Masayo , Shibayama Takahiro , Fukuoka Takashi , Kuwahara Shogo 
Published: December 2004

ABSTRACT

The activities of R-135853, a novel sordarin derivative that possesses a 1,4-oxazepane ring moiety, were evaluated in vitro and in vivo. R-135853 exhibited potent in vitro activities against
Candida albicans
(fluconazole-susceptible strains),
Candida glabrata
,
Candida tropicalis
, and
Cryptococcus neoformans
, with MICs at which 90% of isolates were inhibited of 0.03, 1, 0.5, and 0.5 μg/ml, respectively. R-135853 also exhibited potent activities against fluconazole-susceptible dose-dependent and fluconazole-resistant strains of
C. albicans
, with MICs ranging from 0.03 to 0.06 μg/ml. However, R-135853 exhibited weak or no activity against
Candida parapsilosis
,
Candida krusei
, and
Aspergillus
spp. R-135853 exhibited dose-dependent efficacy against experimental murine hematogenous candidiasis induced by
C. albicans
when it was administered by both the subcutaneous and the oral routes and reduced viable cell counts in the kidneys significantly when it was administered at 50 mg/kg of body weight/dose (administration three times a day). In this model, R-135853 also exhibited dose-dependent efficacy by single oral administration. Subcutaneous administration of R-135853 exhibited dose-dependent efficacy against experimental murine esophageal candidiasis induced by fluconazole-resistant
C. albicans
, against which fluconazole at 50 mg/kg/dose was ineffective, and reduced viable cell counts in the esophagus significantly when it was administered at 10 and 50 mg/kg/dose. R-135853 eradicated
C. albicans
from the esophagi of one and four of five mice when it was administered at 10 and 50 mg/kg/dose, respectively. These results suggest that R-135853 is promising for the treatment of disseminated or mucosal candidiasis, including fluconazole-refractory infections.
Induction of Host Matrix Metalloproteinases byBorrelia burgdorferiDiffers in Human and Murine Lyme Arthritis
Authors: Behera Aruna K. , Hildebrand Ethan , Scagliotti Joanna , Steere Allen C. , Hu Linden T. 
Published: December 2004

ABSTRACTMatrix metalloproteinases (MMPs) are induced from host tissues in response toBorrelia burgdorferi. Upregulation of MMPs may play a role in the dissemination of the organism through extracellular matrix tissues, but it can also result in destructive pathology. Although mice are a well-accepted model for Lyme arthritis, there are significant differences compared to human disease. We sought to determine whether MMP expression could account for some of these differences. MMP expression patterns followingB. burgdorferiinfection were analyzed in primary human chondrocytes, synovial fluid samples from patients with Lyme arthritis, and cartilage tissue from Lyme arthritis-susceptible and -resistant mice by using a gene array, real-time PCR, an enzyme-linked immunosorbent assay, and immunohistochemistry.B. burgdorferiinfection significantly induced transcription of MMP-1, -3, -13, and -19 from primary human chondrocyte cells. Transcription of MMP-10 and tissue inhibitor of metalloprotease 1 was increased withB. burgdorferiinfection, but protein expression was only minimally increased. The synovial fluid levels of MMPs from patients with high and low spirochete burdens were consistent with results seen in the in vitro studies.B. burgdorferi-susceptible C3H/HeN mice infected withB. burgdorferishowed induction of MMP-3 and MMP-19 but no other MMP or tissue inhibitor of metalloprotease. As determined by immunohistochemistry, MMP-3 expression was increased only in chondrocytes near the articular surface. The levels of MMPs were significantly lower in the more Lyme arthritis-resistant BALB/c and C57BL/6 mice. Differences between human and murine Lyme arthritis may be related to the lack of induction of collagenases, such MMP-1 and MMP-13, in mouse joints.
SipA, SopA, SopB, SopD, and SopE2 Contribute toSalmonella entericaSerotype Typhimurium Invasion of Epithelial Cells
Authors: Raffatellu Manuela , Wilson R. Paul , Chessa Daniela , Andrews-Polymenis Helene , Tran Quynh T. , Lawhon Sara , Khare Sangeeta , Adams L. Garry , Bäumler Andreas J. 
Published: December 2004

ABSTRACTThe centisome 63 type III secretion system (T3SS-1) encoded bySalmonellapathogenicity island 1 (SPI1) mediates invasion of epithelial cells bySalmonella entericaserotype Typhimurium. Characterization of mutants lacking individual genes has revealed that T3SS-1 secreted proteins (effectors) SopE2 and SopB are required for invasion while the SipA protein accelerates entry into cells. Here we have revisited the question of which T3SS-1 effectors contribute to the invasion of epithelial cells by complementing a strain lacking all of the effector genes that are required to cause diarrhea in a calf (asipA sopABDE2mutant). Introduction of either the clonedsipA, the clonedsopB, or the clonedsopE2gene increased the invasiveness of thesipA sopABDE2mutant for nonpolarized HT-29 cells. However, a contribution ofsopAorsopDto invasion was not apparent when invasion assays were performed with the nonpolarized colon carcinoma cell lines T84 and HT-29. In contrast, introduction of either thesopA, thesopB, thesopD, or thesopE2gene increased the invasiveness of thesipA sopABDE2mutant for polarized T84 cells. Furthermore, introduction of a plasmid carryingsipAandsopBincreased the invasiveness of thesipA sopABDE2mutant for polarized T84 cells significantly compared to the introduction of plasmids carrying onlysipAorsopB. We conclude that SipA, SopA, SopB, SopD, and SopE2 contribute toS. entericaserotype Typhimurium invasion of epithelial cells in vitro.
SalmonellaPathogenicity Island 2-Mediated Overexpression of Chimeric SspH2 Proteins for Simultaneous Induction of Antigen-Specific CD4 and CD8 T Cells
Authors: Panthel Klaus , Meinel Katrin M. , Domènech Victòria E. Sevil , Retzbach Heike , Igwe Emeka I. , Hardt Wolf-Dietrich , Rüssmann Holger 
Published: December 2004

ABSTRACTSalmonella entericaserovar Typhimurium employs two different type III secretion systems (TTSS) encoded withinSalmonellapathogenicity islands 1 and 2 (SPI1 and SPI2) for targeting of effector proteins into the cytosol of eukaryotic cells during different stages of the infection cycle. The SPI1 TTSS translocates virulence factors across the plasma membrane when the bacterium initially contacts the host cell. In contrast, the SPI2 TTSS functions to translocate proteins across the membrane of theSalmonella-containing vacuole and promotes intracellular survival and replication. The aim of the present study was to directly compare the potentials of SPI1 and SPI2 type III effector proteins to act as carrier molecules for a heterologous antigen. The p60 protein ofListeria monocytogeneswas used as a model antigen to construct chimeric SopE2 (SPI1), SifA (SPI2), and SspH2 (SPI2) proteins. SPI1- and SPI2-dependent up- and down-regulation of hybrid gene expression led to sequential translocation of p60 fusion proteins into the cytosol ofSalmonella-infected macrophages. Mice orally immunized with recombinantSalmonellastrains expressing these hybrid proteins revealed comparable numbers of p60-specific CD8 T cells. However, only overexpression of translocated SspH2/p60 from a medium-copy-number vector induced simultaneous antigen-specific CD4 and CD8 T-cell responses, suggesting that SspH2 is an attractive carrier molecule for foreign-protein delivery.
Chitinase and Fizz Family Members Are a Generalized Feature of Nematode Infection with Selective Upregulation of Ym1 and Fizz1 by Antigen-Presenting Cells
Authors: Nair Meera G. , Gallagher Iain J. , Taylor Matthew D. , Loke P'ng , Coulson Patricia S. , Wilson R. A. , Maizels Rick M. , Allen Judith E. 
Published: December 2004

ABSTRACTYm1 and Fizz1 are secreted proteins that have been identified in a variety of Th2-mediated inflammatory settings. We originally found Ym1 and Fizz1 as highly expressed macrophage genes in aBrugia malayiinfection model. Here, we show that their expression is a generalized feature of nematode infection and that they are induced at the site of infection with both the tissue nematodeLitomosoides sigmodontisand the gastrointestinal nematodeNippostrongylus brasiliensis. At the sites of infection withN. brasiliensis, we also observed induction of other chitinase and Fizz family members (ChaFFs): acidic mammalian chitinase (AMCase) and Fizz2. The high expression of both Ym1 and AMCase in the lungs of infected mice suggests that abundant chitinase production is an important feature of Th2 immune responses in the lung. In addition to expression of ChaFFs in the tissues, Ym1 and Fizz1 expression was observed in the lymph nodes. Expression both in vitro and in vivo was restricted to antigen-presenting cells, with the highest expression in B cells and macrophages. ChaFFs may therefore be important effector or wound-repair molecules at the site of nematode infection, with potential regulatory roles for Ym1 and Fizz1 in the draining lymph nodes.
Interaction and Cellular Localization of the Human Host Defense Peptide LL-37 with Lung Epithelial Cells
Authors: Lau Y. Elaine , Rozek Annett , Scott Monisha G. , Goosney Danika L. , Davidson Donald J. , Hancock Robert E. W. 
Published: December 2004

ABSTRACTLL-37 is a human cationic host defense peptide that is an essential component of innate immunity. In addition to its modest antimicrobial activity, LL-37 affects the gene expression and behavior of effector cells involved in the innate immune response, although its mode of interaction with eukaryotic cells remains unclear. The interaction of LL-37 with epithelial cells was characterized in tissue culture by using biotinylated LL-37 and confocal microscopy. It was demonstrated that LL-37 was actively taken up into A549 epithelial cells and eventually localized to the perinuclear region. Specific inhibitors were used to demonstrate that the uptake process was not mediated by actin but required elements normally involved in endocytosis and that trafficking to the perinuclear region was dependent on microtubules. By using nonlinear regression analysis, it was revealed that A549 epithelial cells have two receptors for LL-37B, with high and low affinity for LL-37, respectively. These results indicate the mode of interaction of LL-37 with epithelial cells and further our understanding of its role in modulating the innate immune response.
Shiga-Toxigenic
Escherichia coli
-Inoculated Neonatal Piglets Develop Kidney Lesions That Are Comparable to Those in Humans with Hemolytic-Uremic Syndrome
Authors: Pohlenz J. F. , Winter K. R. , Dean-Nystrom E. A. 
Published: December 2004

ABSTRACT

Kidney lesions similar to those in humans with hemolytic-uremic syndrome were observed histologically in 82 of 122 piglets inoculated intragastrically with Shiga-toxigenic
Escherichia coli
but not in 29 controls. The locations of lesions matched locations where Stx-2 binding and Gb3 (globotriasylceramide receptors for Stx) were identified immunohistochemically.
Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important for Generation of an Optimal Polymorphonuclear Response againstToxoplasma gondiiInfection
Authors: Kelly Michelle N. , Kolls Jay K. , Happel Kyle , Schwartzman Joseph D. , Schwarzenberger Paul , Combe Crescent , Moretto Magali , Khan Imtiaz A. 
Published: December 2004

ABSTRACTWe investigated the role of interleukin-17 (IL-17)/IL-17 receptor (IL-17R)-mediated signaling in the protective immunity againstToxoplasma gondii. IL-17R−/−mice developed a normal adaptive immunity against the parasite. However, increased mortality in the knockout animals can be attributed to a defect in the migration of polymorphonuclear leukocytes to infected sites during early infection.
An Immunoreactive 38-Kilodalton Protein of
Ehrlichia canis
Shares Structural Homology and Iron-Binding Capacity with the Ferric Ion-Binding Protein Family
Authors: Doyle C. Kuyler , Zhang Xiaofeng , Popov Vsevolod L. , McBride Jere W. 
Published: December 2004

ABSTRACT

Ehrlichiae are tick-transmitted, gram-negative, obligately intracellular bacteria that live and replicate in cytoplasmic vacuoles, but little is known about iron acquisition mechanisms necessary for their survival. In this study, a genus-conserved immunoreactive ferric ion-binding protein (Fbp) of
Ehrlichia canis
was identified and its iron-binding capability was investigated.
E. canis
Fbp was homologous to a family of periplasmic Fbp's involved in iron acquisition and transport in gram-negative bacteria.
E. canis
Fbp had a molecular mass (38 kDa) consistent with those of Fbp's in other bacteria and exhibited substantial immunoreactivity in its native conformation. The predicted three-dimensional structure of
E. canis
Fbp demonstrated conservation of important Fbp family structural motifs: two domains linked with a polypeptide “hinge” region. Under iron-binding conditions, the recombinant Fbp exhibited an intense red color and an absorbance spectrum indicative of iron binding, and it bound Fe(III) but not Fe(II). Fbp was observed primarily in the cytoplasm of the reticulate forms of
E. canis
and
Ehrlichia chaffeensis
but was notably found on extracellular morula fibers in morulae containing dense-cored organisms. Although expression of Fbp is regulated through an operon of three functionally linked genes in other gram-negative bacteria, the absence of an intact
fbp
operon in
Ehrlichia
spp. suggests that genes involved in ehrlichial iron acquisition have been subject to reductive evolution.
Intercellular Adhesion Molecule 1-Dependent Activation of Interleukin 8 Expression inCandida albicans-Infected Human Gingival Epithelial Cells
Authors: Egusa Hiroshi , Nikawa Hiroki , Makihira Seicho , Jewett Anahid , Yatani Hirofumi , Hamada Taizo 
Published: December 2004

ABSTRACTIncreased induction of interleukin 8 (IL-8) and intercellular adhesion molecule 1 (ICAM-1) by oral epithelial cells may play a role in the host defense mechanism in oropharyngeal candidiasis; however, little is known about the expression feature of these molecules on human gingival epithelial cells (HGECs) duringCandida albicansinfection. In this report we present evidence that neutralization with antibody against ICAM-1 inhibited both the adherence ofC. albicansto HGECs and theCandida-induced production of IL-8, suggesting a role for ICAM-1 in recognition and signaling in HGECs to express IL-8 upon infection withC. albicans.
Chlamydia pneumoniaeEnhances Cytokine-Stimulated Human Monocyte Matrix Metalloproteinases through a Prostaglandin E2-Dependent Mechanism
Authors: Kim Min P. , Gaydos Charlotte A. , Wood Billie Jo , Hardick Justin P. , Zhang Yahong , Wahl Larry M. 
Published: December 2004

ABSTRACTExposure of human monocytes toChlamydia pneumoniaeresulted in a significant enhancement of matrix metalloproteinase (MMP) 1 and 9 production following stimulation with tumor necrosis factor alpha and granulocyte monocyte-colony stimulating factor. The effect ofC. pneumoniaeon monocyte MMPs was mediated through the induction of prostaglandin E2. These findings may have implications for atherosclerotic plaque rupture.
Atypical
cpb2
Genes, Encoding Beta2-Toxin in
Clostridium perfringens
Isolates of Nonporcine Origin
Authors: Jost B. Helen , Billington Stephen J. , Trinh Hien T. , Bueschel Dawn M. , Songer J. Glenn 
Published: December 2004

ABSTRACT

Beta2-toxin, encoded by
cpb2
, is implicated in the pathogenesis of
Clostridium perfringens
enteritis. However,
cpb2
genes from nonporcine
C. perfringens
isolates were not always expressed, at least in vitro. Nucleotide sequencing identified atypical
cpb2
genes with 70.2 to 70.7% DNA identity to previously identified (consensus)
cpb2
. Atypical beta2-toxin displayed 62.3% identity and 80.4% similarity to consensus beta2-toxin. No porcine type C isolates (
n
= 16) and only 3.3% of porcine type A isolates (
n
= 60) carried atypical
cpb2
genes. However, 88.5% of nonporcine isolates carried atypical
cpb2
(
n
= 78), but beta2-toxin was not expressed. Almost half of the nonporcine consensus
cpb2
genes (44.4%) carried a frameshift mutation (
n
= 9), resulting in an absence of beta2-toxin expression. These findings strengthen the role of beta2-toxin in the pathogenesis of enteritis in neonatal pigs. However, the identification of apparently nonexpressed, atypical
cpb2
genes raises the question of whether this protein plays the same role in enteritis in other animal species.
Relative Contributions of Innate and Acquired Host Responses to Bacterial Control and Arthritis Development in Lyme Disease
Authors: Wang Xiaohui , Ma Ying , Weis John H. , Zachary James F. , Kirschning Carsten J. , Weis Janis J. 
Published: December 2004

ABSTRACTTLR2−/−/sciddouble-mutant mice were infected withB. burgdorferito assess the relative importance of acquired and innate host defenses. Although spirochete levels at 4 weeks were lower in TLR2−/−mice than in TLR2−/−/scidmice, the increased arthritis severity of TLR2 (Toll-like receptor 2)-deficient mice was reduced by the presence of thescidmutation.