bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of Basic Fibroblast Growth Factor and Interleukin 6 by Human Smooth Muscle Cells following Infection with
Chlamydia pneumoniae
Authors: Rödel Jürgen , Woytas Marcus , Groh Annemarie , Schmidt Karl-Hermann , Hartmann Matthias , Lehmann Marc , Straube Eberhard 
Published: July 2002

ABSTRACT

Chlamydia pneumoniae
infection has been associated with asthma and atherosclerosis. Smooth muscle cells represent host cells for chlamydiae during chronic infection. In this study we demonstrated that
C. pneumoniae
infection of human smooth muscle cells in vitro increased production of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) as shown by reverse transcription-PCR, immunoblotting, and enzyme-linked immunosorbent assay. In contrast, levels of platelet-derived growth factor A-chain mRNA were not affected after infection. The stimulation of bFGF and IL-6 production was most effective when viable chlamydiae were used as inoculum. Furthermore, inhibition of bacterial protein synthesis with chloramphenicol prevented up-regulation of IL-6 and bFGF in infected cells. Addition of IL-6 antibody to infected cultures diminished bFGF expression, indicating involvement of produced IL-6. These findings suggest that chlamydial infection of smooth muscle cells elicits a cytokine response that may contribute to structural remodeling of the airway wall in chronic asthma and to fibrous plaque formation in atherosclerosis.
Delayed Mortality and Attenuated Thrombocytopenia Associated with Severe Malaria in Urokinase- and Urokinase Receptor-Deficient Mice
Authors: Piguet Pierre Francois , Da Laperrousaz Chen , Vesin Christian , Tacchini-Cottier Fabienne , Senaldi Giorgio , Grau Georges Emile 
Published: July 2002

ABSTRACTWe explored the role of urokinase and tissue-type plasminogen activators (uPA and tPA), as well as the uPA receptor (uPAR; CD87) in mouse severe malaria (SM), using genetically deficient (−/−) mice. The mortality resulting fromPlasmodium bergheiANKA infection was delayed in uPA−/−and uPAR−/−mice but was similar to that of the wild type (+/+) in tPA−/−mice. Parasitemia levels were similar in uPA−/−, uPAR−/−, and +/+ mice. Production of tumor necrosis factor, as judged from the plasma level and the mRNA levels in brain and lung, was markedly increased by infection in both +/+ and uPAR−/−mice. Breakdown of the blood-brain barrier, as evidenced by the leakage of Evans Blue, was similar in +/+ and uPAR−/−mice. SM was associated with a profound thrombocytopenia, which was attenuated in uPA−/−and uPAR−/−mice. Administration of aprotinin, a plasmin antagonist, also delayed mortality and attenuated thrombocytopenia. Platelet trapping in cerebral venules or alveolar capillaries was evident in +/+ mice but absent in uPAR−/−mice. In contrast, macrophage sequestration in cerebral venules or alveolar capillaries was evident in both +/+ and uPAR−/−mice. Polymorphonuclear leukocyte sequestration in alveolar capillaries was similar in +/+ and uPAR−/−mice. These results demonstrate that the uPAR deficiency attenuates the severity of SM, probably by its important role in platelet kinetics and trapping. These results therefore suggest that platelet sequestration contributes to the pathogenesis of SM.
Anti-HSP70 Autoantibody Formation by B-1 Cells inToxoplasma gondii-Infected Mice
Authors: Chen Mei , Aosai Fumie , Mun Hye-Seong , Norose Kazumi , Hata Hidekazu , Yano Akihiko 
Published: July 2002

ABSTRACTFormation of anti-Toxoplasma gondiiHSP70 (TgHSP70) antibody cross-reactive to mouse HSP70 (mHSP70) was observed in the sera of BALB/c (a resistant strain) and C57BL/6 (B6; a susceptible strain) mice after peroral infection withT. gondiicysts of the Fukaya strain. The levels of anti-mHSP70 immunoglobulin G (IgG) autoantibody production in B6 mice were higher than those in BALB/c mice. The isotype and subclass of IgG of anti-TgHSP70 monoclonal antibodies cross-reactive to mHSP70 were μ and γ3. Anti-mHSP70 autoantibody inT. gondii-infected BALB/c and B6 mice was shown to be produced by the CD5+subset of B cells (B-1a cells) but not by conventional B cells (B-2 cells). The epitopes recognized by anti-mHSP70 autoantibody were located primarily in the C-terminal fragment of mHSP70.
Helicobacter hepaticusDoes Not Induce or Potentiate Colitis in Interleukin-10-Deficient Mice
Authors: Dieleman Levinus A. , Arends Annemarie , Tonkonogy Susan L. , Goerres Marije S. , Craft David W. , Grenther Wetonia , Sellon Rance K. , Balish Ed , Sartor R. Balfour 
Published: July 2002

ABSTRACTHelicobacter hepaticushas been reported to induce colitis, hepatitis, and hepatocellular carcinoma in several different murine models. The aim of this study was to determine ifH. hepaticuswill cause colitis in monoassociated mice lacking the interleukin-10 gene (IL-10−/−mice) and potentiate colitis in specific-pathogen-free (SPF) IL-10−/−mice. Germfree IL-10−/−mice on either a mixed (C57BL/6 × 129/Ola) or inbred (129/SvEv) genetic background were monoassociated withH. hepaticusATCC 51448 by oral feeding and rectal enemas. In a second experiment, germfree IL-10−/−mice were colonized with stool from SPF mice that harbored or did not harbor endogenousH. hepaticus. After 7 to 9 weeks of colonization, weight loss and mortality were assessed, the colon was isolated for histology and IL-12 secretion, and mesenteric lymph node cells were assessed for T-cell activation markers. It was found that IL-10−/−mice monoassociated withH. hepaticusfor up to 16 weeks showed almost no histologic colitis or increased IL-12 production. SPF IL-10-knockout mice had no significant difference in weight loss, mortality rate, histologic scores, colonic IL-12 secretion, or T-cell activation with or withoutH. hepaticus. We conclude thatH. hepaticusdoes not induce or potentiate disease in our IL-10−/−mice and therefore is not required to induce colitis in genetically susceptible hosts.
Mycobacterium tuberculosisandLegionella pneumophilaPhagosomes Exhibit Arrested Maturation despite Acquisition of Rab7
Authors: Clemens Daniel L. , Lee Bai-Yu , Horwitz Marcus A. 
Published: July 2002

ABSTRACTRab7 is a small GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. Phagosomes containing inert particles have also been shown to transiently acquire Rab7 as they mature. Disruption in the pathway prior to the acquisition of Rab7 has been suggested as playing a role in the altered maturation ofMycobacterium bovisBCG phagosomes. As a first step to determine whether disruption in the delivery or function of Rab7 could play a role in the altered maturation ofLegionella pneumophilaandM. tuberculosisphagosomes, we have examined the distribution of wild-type Rab7 and the GTPase-deficient, constitutively active mutant form of Rab7 in HeLa cells infected withL. pneumophilaorM. tuberculosis. We have found that the majority ofL. pneumophilaandM. tuberculosisphagosomes acquire relatively abundant staining for Rab7 and for the constitutively active mutant Rab7 in HeLa cells that overexpress these proteins. Nevertheless, despite acquisition of wild-type or constitutively active Rab7, both theL. pneumophilaand theM. tuberculosisphagosomes continue to exhibit altered maturation as manifested by a failure to acquire lysosome-associated membrane glycoprotein 1. These results demonstrate thatL. pneumophilaandM. tuberculosisphagosomes have receptors for Rab7 and that the altered maturation of these phagosomes is not due to a failure to acquire Rab7.
Immunopathology of Cerebral Malaria: Morphological Evidence of Parasite Sequestration in Murine Brain Microvasculature
Authors: Hearn Jocelyn , Rayment Neil , Landon David N. , Katz David R. , de Souza J. Brian 
Published: July 2002

ABSTRACTA murine model that closely resembles human cerebral malaria is presented, in which characteristic features of parasite sequestration and inflammation in the brain are clearly demonstrable. “Young” (BALB/c × C57BL/6)F1mice infected withPlasmodium berghei(ANKA) developed typical neurological symptoms 7 to 8 days later and then died, although their parasitemias were below 20%. Older animals were less susceptible. Immunohistopathology and ultrastructure demonstrated that neurological symptoms were associated with sequestration of both parasitized erythrocytes and leukocytes and with clogging and rupture of vessels in both cerebral and cerebellar regions. Increases in tumor necrosis factor alpha and CD54 expression were also present. Similar phenomena were absent or substantially reduced in older infected but asymptomatic animals. These findings suggest that this murine model is suitable both for determining precise pathogenetic features of the cerebral form of the disease and for evaluating circumventive interventions.
Serotype AD Strains of
Cryptococcus neoformans
Are Diploid or Aneuploid and Are Heterozygous at the Mating-Type Locus
Authors: Lengeler Klaus B. , Cox Gary M. , Heitman Joseph 
Published: July 2002

ABSTRACT

Cryptococcus neoformans
is a pathogenic basidiomycete with a defined sexual cycle involving mating between haploid yeast cells with a transient diploid state.
C. neoformans
occurs in four predominant serotypes (A, B, C, and D), which represent different varieties or species. Rare clinical and environmental isolates with an unusual AD serotype have been reported and suggested to be diploid. We found by fluorescence-activated cell sorter analysis that serotype AD strains are aneuploid or diploid. PCR analysis with primers specific for serotype A or D alleles of the
CNA1
,
CLA4
, and
GPA1
genes revealed that both alleles are often present in serotype AD strains. PCR analysis with primers specific for genes in the
MAT
a or
MAT
α mating-type loci revealed that serotype AD strains are heterozygous for the mating-type locus. Interestingly, in several serotype AD strains, the
MAT
α locus was derived from the serotype D parent and the
MAT
a locus was inherited from a serotype A parent that has been thought to be extinct. Basidiospores from a self-fertile serotype AD strain bearing the putative serotype A
MAT
a locus showed a very low viability (∼5%), and no fertile serotype A
MAT
a strain could be recovered. Serotype AD strains were virulent in a murine model. Hybrid AD strains could readily be isolated following a laboratory cross between a serotype A strain and a serotype D strain. In summary, serotype AD strains of
C. neoformans
are unusual aneuploid or diploid strains that result from matings between serotype A and D strains. Self-fertile isolates fail to undergo normal meiosis because of genetic divergence. Our findings further suggest that serotype A
MAT
a strains may exist in nature.
Natural Antibody Affects Survival of the SpirocheteBorrelia burgdorferiwithin Feeding Ticks
Authors: Belperron Alexia A. , Bockenstedt Linda K. 
Published: July 2002

ABSTRACTNatural antibodies are those immunoglobulin molecules found in mammalian serum that arise in the absence of exposure to environmental pathogens and may comprise an early host defense against invading pathogens. The spirocheteBorrelia burgdorferifirst encounters natural antibodies when its arthropod vector,Ixodes scapularis, begins feeding on a mammalian host. Natural antibodies may therefore have an impact on pathogens within blood-sucking vectors, prior to pathogen transmission to the mammal. In this study, we investigated whether natural antibodies influenced the number and/or phenotype ofB. burgdorferiorganisms within feedingI. scapularisnymphs. Using a competitive PCR, we found that ticks ingesting a blood meal from B-cell-deficient mice, which lack all immunoglobulins, contained fivefold more spirochete DNA than ticks feeding on control mice. Spirochete DNA levels could be reduced to that of controls with passive transfer of normal mouse serum or polyclonal immunoglobulin M (IgM), but not IgG, into B-cell-deficient mice prior to placement of infected ticks. At 48 h of tick feeding, 90% of spirochetes within salivary glands of ticks removed from B-cell-deficient mice were found by confocal immunofluorescence microscopy to express outer surface protein A (OspA), compared to only 5% of salivary gland spirochetes from ticks detached from control mice. Taken together, these results show that ingestion of natural antibodies limits the spirochete burden within feeding ticks. Because OspA is normally downregulated when spirochetes moved from the tick midgut to the salivary gland, our findings suggest that OspA-expressing midgut spirochetes may be particularly susceptible to the borrelicidal effects of these molecules.
Intranasal Immunization with RecombinantAscaris suum14-Kilodalton Antigen Coupled with Cholera Toxin B Subunit Induces Protective Immunity toA. suumInfection in Mice
Authors: Tsuji Naotoshi , Suzuki Kayo , Kasuga-Aoki Harue , Matsumoto Yasunobu , Arakawa Takeshi , Ishiwata Kenji , Isobe Takashi 
Published: July 2002

ABSTRACTAnimals can be rendered immune toAscarisparasites by immunization with infectious-stage larvae. The specific parasite gene products that mediate protective responses in ascariasis are unknown. We have identified a cDNA encodingAscaris suum14-kDa antigen (As14) and evaluated the vaccinal effect of theEscherichia coli-expressed recombinant protein (rAs14). GenBank analysis showed that As14 has low similarity at the amino acid level to aCaenorhabditis elegansgene product and to antigens of the filarial nematodes but not to other known proteins. In addition, As14 homologues were found to be expressed in human and dog roundworms. In mice that received intranasal administration of rAs14 coupled with cholera toxin B subunit (rAs14-CTB), there was a 64% reduction of recovery of larvae compared with that in the nontreated group. The vaccinated mice showed a significant increase in the total serum immunoglobulin G (IgG) levels and the mucosal IgA responses. Elevation of the rAs14-specific IgE response was also seen. Measurement of the IgG subclasses showed a higher level of IgG1 and a lower level of IgG2a antibody response in the sera of the immunized mice, suggesting that protection was associated with a type II immune response. As14 is the first protective antigen againstA. suuminfection to be identified. Our immunization trial results in laboratory animals suggest the possibility of developing a mucosal vaccine for parasitic diseases caused by ascarid nematodes.
Search for Correlates of Protective Immunity Conferred by Anthrax Vaccine
Authors: Reuveny Shaul , White Moshe D. , Adar Yaakov Y. , Kafri Yaron , Altboum Zeev , Gozes Yehusha , Kobiler David , Shafferman Avigdor , Velan Baruch 
Published: July 2002

ABSTRACT

Vaccination by anthrax protective antigen (PA)-based vaccines requires multiple immunization, underlying the need to develop more efficacious vaccines or alternative vaccination regimens. In spite of the vast use of PA-based vaccines, the definition of a marker for protective immunity is still lacking. Here we describe studies designed to help define such markers. To this end we have immunized guinea pigs by different methods and monitored the immune response and the corresponding extent of protection against a lethal challenge with anthrax spores. Active immunization was performed by a single injection using one of two methods: (i) vaccination with decreasing amounts of PA and (ii) vaccination with constant amounts of PA that had been thermally inactivated for increasing periods. In both studies a direct correlation between survival and neutralizing-antibody titer was found (
r
2
= 0.92 and 0.95, respectively). Most significantly, in the two protocols a similar neutralizing-antibody titer range provided 50% protection. Furthermore, in a complementary study involving passive transfer of PA hyperimmune sera to naive animals, a similar correlation between neutralizing-antibody titers and protection was found. In all three immunization studies, neutralization titers of at least 300 were sufficient to confer protection against a dose of 40 50% lethal doses (LD
50
) of virulent anthrax spores of the Vollum strain. Such consistency in the correlation of protective immunity with anti-PA antibody titers was not observed for antibody titers determined by an enzyme-linked immunosorbent assay. Taken together, these results clearly demonstrate that neutralizing antibodies to PA constitute a major component of the protective immunity against anthrax and suggest that this parameter could be used as a surrogate marker for protection.
Multistage Multiantigen Heterologous Prime Boost Vaccine forPlasmodium knowlesiMalaria Provides Partial Protection in Rhesus Macaques
Authors: Rogers William O. , Baird J. Kevin , Kumar Anita , Tine John A. , Weiss Walter , Aguiar João C. , Gowda Kalpana , Gwadz Robert , Kumar Sanjai , Gold Mark , Hoffman Stephen L. 
Published: July 2002

ABSTRACTA nonhuman primate model for malaria vaccine development allowing reliable, stringent sporozoite challenge and evaluation of both cellular and antibody responses is needed. We therefore constructed a multicomponent, multistage DNA vaccine for the simian malaria speciesPlasmodium knowlesiincluding two preerythrocytic-stage antigens, the circumsporozoite protein (PkCSP) and sporozoite surface protein 2 (PkSSP2), and two blood stage antigens, apical merozoite antigen 1 (PkAMA1) and merozoite surface protein 1 (PkMSP1p42), as well as recombinant canarypox viruses encoding the four antigens (ALVAC-4). The DNA vaccine plasmids expressed the corresponding antigens in vitro and induced antiparasite antibodies in mice. Groups of four rhesus monkeys received three doses of a mixture of the four DNA vaccine plasmids and a plasmid encoding rhesus granulocyte-monocyte colony-stimulating factor, followed by boosting with a single dose of ALVAC-4. Three groups received the priming DNA doses by different routes, either by intramuscular needle injection, by intramuscular injection with a needleless injection device, the Biojector, or by a combination of intramuscular and intradermal routes by Biojector. Animals immunized by any route developed antibody responses against sporozoites and infected erythrocytes and against a recombinant PkCSP protein, as well as gamma interferon-secreting T-cell responses against peptides from PkCSP. Following challenge with 100P. knowlesisporozoites, 1 of 12 experimental monkeys was completely protected and the mean parasitemia in the remaining monkeys was significantly lower than that in 4 control monkeys. This model will be important in preclinical vaccine development.
Identification and Characterization of
hsa
, the Gene Encoding the Sialic Acid-Binding Adhesin of
Streptococcus gordonii
DL1
Authors: Takahashi Yukihiro , Konishi Kiyoshi , Cisar John O. , Yoshikawa Masanosuke 
Published: July 2002

ABSTRACT

Oral colonization by
Streptococcus gordonii
, an important cause of subacute bacterial endocarditis, involves bacterial recognition of sialic acid-containing host receptors. The sialic acid-binding activity of this microorganism was previously detected by bacterium-mediated hemagglutination and associated with a streptococcal surface component identified as the Hs antigen. The gene for this antigen (
hsa
) has now been cloned in
Escherichia coli
, and its expression has been detected by colony immunoblotting with anti-Hs serum. Mutants of
S. gordonii
containing
hsa
inactivated by the insertion of an erythromycin resistance gene or deletion from the chromosome were negative for Hs-immunoreactivity, bacterium-mediated hemagglutinating activity, and adhesion to α2-3-linked sialoglycoconjugates. The deletion in the latter mutants was complemented by plasmid-borne
hsa
, resulting in Hs antigen production and the restoration of cell surface sialic acid-binding activity. The
hsa
gene encodes a 203-kDa protein with two serine-rich repetitive regions in its 2,178-amino-acid sequence. The first serine-rich region occurs within the amino-terminal region of the molecule, between different nonrepetitive sequences that may be associated with sialic acid binding. The second serine-rich region, which is much longer than the first, is highly repetitive, containing 113 dodecapeptide repeats with a consensus sequence of SASTSASVSASE. This long repetitive region is followed by a typical gram-positive cell wall anchoring region at the carboxyl-terminal end. Thus, the predicted properties of Hsa, which suggest an amino-terminal receptor-binding domain attached to the cell surface by a molecular stalk, are consistent with the identification of this protein as the sialic acid-binding adhesin of
S. gordonii
DL1.
A Recombinant Carboxy-Terminal Domain of the Protective Antigen of
Bacillus anthracis
Protects Mice against Anthrax Infection
Authors: Flick-Smith Helen C. , Walker Nicola J. , Gibson Paula , Bullifent Helen , Hayward Sarah , Miller Julie , Titball Richard W. , Williamson E. Diane 
Published: July 2002

ABSTRACT

The immunogenicity and protective efficacy of overlapping regions of the protective antigen (PA) polypeptide, cloned and expressed as glutathione
S
-transferase fusion proteins, have been assessed. Results show that protection can be attributed to individual domains and imply that it is domain 4 which contains the dominant protective epitopes of PA.
Passive Immunization with Bovine Milk Containing Antibodies to a Cell Surface Protein Antigen-Glucosyltransferase Fusion Protein Protects Rats against Dental Caries
Authors: Mitoma Morihide , Oho Takahiko , Michibata Naoko , Okano Kaoru , Nakano Yutaka , Fukuyama Masataka , Koga Toshihiko 
Published: July 2002

ABSTRACT

Cell surface protein antigen (PAc) and glucosyltransferases (GTF) of
Streptococcus mutans
are major colonization factors of the organism. We prepared bovine milk containing antibodies against a fusion of the saliva-binding alanine-rich region of PAc with the glucan-binding domain of GTF-I. This study examined the effect of the immune milk on the cariogenicity of
S. mutans
in a rat model. Concentrated immune milk was fed to rats once a day for 55 days. The group that received immune milk had significantly less caries development than controls.
Regulation of the Overlapping
pic/set
Locus in
Shigella flexneri
and Enteroaggregative
Escherichia coli
Authors: Behrens Martin , Sheikh Jalaluddin , Nataro James P. 
Published: July 2002

ABSTRACT

Most strains of
Shigella flexneri
2a and enteroaggregative
Escherichia coli
carry a highly conserved chromosomal locus which encodes a 109-kDa secreted mucinase (called Pic) and, on the opposite strand in overlapping fashion, an oligomeric enterotoxin called ShET1, encoded by the
setA
and
setB
genes. Here, we characterize the genetic regulation of these overlapping genes. Our data suggest that
pic
and the
setBA
loci are transcribed as complementary 4-kb mRNA species. The major
pic
promoter is maximally activated at 37°C in exponential growth phase. Our data suggest that the
setB
gene is transcribed from a promoter which lies more than 1.5 kb upstream of the
setB
structural gene;
setA
may be transcribed via readthrough of the
setB
transcript and possibly by its own promoter. The long leader of the
setB
gene provides a strong silencing effect on
setB
transcription. The signals which provide relief from
setB
silencing are not clear, but significant induction is observed in a continuous anaerobic culture of human fecal bacteria, suggesting that some complex characteristics of the human intestine act to lift repression of
setB
expression. Our studies provide the first insights into the mechanisms affecting expression of this unusual virulence locus.