bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of Complement Source in Measuring Meningococcal Bactericidal Titers
Authors: Santos George F. , Deck R. Randall , Donnelly John , Blackwelder William , Granoff Dan M. 
Published: July 2002

ABSTRACTComplement-mediated bactericidal antibodies in serum confer protection against meningococcal disease. The minimum protective titer is estimated to be between 1:4 and 1:8 when measured by the Goldschneider assay performed with human complement, the assay used in the 1960s to establish the correlation between bactericidal antibodies and protection. A more recently described bactericidal assay standardized by an international consortium uses rabbit complement, which is known to augment bactericidal titers. To define a protective titer measured by the standardized assay, we compared bactericidal titers against serogroup C strains measured by this assay to titers measured by the assay described by Goldschneider et al. A titer of ≥1:128 measured by the standardized assay was needed to predict with ≥80% certainty a positive titer of ≥1:4 as measured by the Goldschneider assay. However, the majority of samples with titers of 1:4 measured by the Goldschneider assay had titers of <1:128 when measured by the standardized assay. Therefore, by the results of the standardized assay such persons would be falsely categorized as being susceptible to disease. In conclusion, high bactericidal titers measured with the standardized assay performed with rabbit complement are predictive of protection, but no threshold titer is both sensitive and specific for predicting a positive titer measured by the Goldschneider assay using human complement. Up to 10% of the U.S. adult population lacks intrinsic bactericidal activity against serogroup C strains in serum and can serve as complement donors. Therefore, use of the Goldschneider assay or an equivalent assay performed with human complement is preferred over assays that use rabbit complement.
Invasive Pneumococcal Infections in Denmark from 1995 to 1999: Epidemiology, Serotypes, and Resistance
Authors: Konradsen Helle Bossen , Kaltoft Margit Staum 
Published: July 2002

ABSTRACT
Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described. Annual overall incidence rates, serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored. Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed. The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively. Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%). These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy.
Characterization of the
Yersinia pestis
Yfu ABC Inorganic Iron Transport System
Authors: Gong Shimei , Bearden Scott W. , Geoffroy Valerie A. , Fetherston Jacqueline D. , Perry Robert D. 
Published: July 2002

ABSTRACT

In
Yersinia pestis
, the causative agent of plague, two inorganic iron transport systems have been partially characterized. The yersiniabactin (Ybt) system is a siderophore-dependent transport system required for full virulence. Yfe is an ABC transport system that accumulates both iron and manganese. We have identified and cloned a
Y. pestis yfuABC
operon. The YfuABC system is a member of the cluster of bacterial ABC iron transporters that include Sfu of
Serratia
, Hit of
Haemophilus
, and Yfu of
Yersinia enterocolitica
. The
Y. pestis
KIM6+ system is most homologous to that in
Y. enterocolitica
, showing identities of 84% for YfuA (periplasmic binding protein), 87% for YfuB (inner membrane permease), and 75% for YfuC (ATP hydrolase). We constructed a
yfuABC
promoter-
lacZ
fusion to examine regulation of transcription. This promoter contains a potential Fur binding sequence and is iron and Fur regulated. Significant expression from the
yfuABC
promoter occurred during iron-deficient growth conditions. In vitro transcription and translation of a recombinant plasmid encoding
yfuABC
indicates that YfuABC proteins are expressed.
Escherichia coli
1017 (an enterobactin-deficient mutant) carrying this plasmid was able to grow in an iron-restrictive complex medium. We constructed a deletion encompassing the
yfuABC
promoter and most of
yfuA
. This mutation was introduced into strains with mutations in Ybt, Yfe, or both systems to examine the role of Yfu in iron acquisition in
Y. pestis
. Growth of the
yfu
mutants in a deferrated, defined medium (PMH2) at 26 and 37°C failed to identify a growth or iron transport defect due to the
yfu
mutation. Fifty percent lethal dose studies in mice did not demonstrate a role for the Yfu system in mammalian virulence.
Human Lactoferrin and Peptides Derived from a Surface-Exposed Helical Region Reduce ExperimentalEscherichia coliUrinary Tract Infection in Mice
Authors: Håversen Liliana A. , Engberg Inga , Baltzer Lars , Dolphin Gunnar , Hanson Lars Å. , Mattsby-Baltzer Inger 
Published: July 2002

ABSTRACTLactoferrin (LF) is a multifunctional immunoregulatory protein that has been associated with host defense at mucosal surfaces through its antibacterial properties. The antibacterial and anti-inflammatory properties of LF were further explored with an animal model of experimental urinary tract infection. Bovine LF (bLF), human LF (hLF), and synthetic peptide sequences based on the antibacterial region of hLF (amino acid residues 16 to 40 [HLD1] and 18 to 40 [HLD2]) were given orally to female mice 30 min after the instillation of 108Escherichia colibacteria into the urinary bladder. The control groups received phosphate-buffered saline or water. C3H/Tif mice were treated with hLF or bLF, and C3H/HeN mice were treated with bLF only. The numbers of bacteria in the kidneys and bladder of C3H/Tif and C3H/HeN mice were significantly reduced 24 h later by the LF treatments compared to the findings for the control group. The hLF-treated group showed the strongest reduction compared with the vehicle-treated-group (Pvalues were 0.009 and 0.0001 for the kidneys and bladder, respectively). The urinary leukocyte response was diminished in the hLF-treated group. The hLF treatment also significantly reduced the urinary interleukin-6 (IL-6) levels at 2 h and the systemic IL-6 levels at 24 h after infection (Pvalues were 0.04 and < 0.002, respectively). In the bLF-treated animals, no such strong anti-inflammatory effects were obtained. In another series of experiments, C3H/Tif mice perorally treated with HLD1 or HLD2 also showed reduced numbers of bacteria in the kidneys compared with the vehicle-treated mice, although the results were significantly different only for HLD2 (P< 0.01). Analysis of urine from hLF-fed C3H/Tif mice showed that hLF was excreted into the urinary tract at 2 h after feeding. Testing of the in vitro bactericidal activity of LF (1 mg/ml) or the peptides (0.1 mg/ml) in mouse urine against theE. colibacteria revealed moderate killing only by HLD2. In conclusion, these results demonstrate for the first time that oral administration of hLF or peptides thereof is effective in reducing infection and inflammation at a remote site, the urinary tract, possibly through transfer of hLF or its peptides to the site of infection via renal secretion. The antibacterial mechanism is suggested to involve bactericidal capacities of LF, fragments thereof, or its peptides.
Mechanisms of Intracellular Killing ofRickettsia conoriiin Infected Human Endothelial Cells, Hepatocytes, and Macrophages
Authors: Feng Hui-Min , Walker David H. 
Published: July 2002

ABSTRACTThe mechanism of killing of obligately intracellularRickettsia conoriiwithin human target cells, mainly endothelium and, to a lesser extent, macrophages and hepatocytes, has not been determined. It has been a controversial issue as to whether or not human cells produce nitric oxide. AKN-1 cells (human hepatocytes) stimulated by gamma interferon, tumor necrosis factor alpha, interleukin 1β, and RANTES (regulated by activation, normal T-cell-expressed and -secreted chemokine) killed intracellular rickettsiae by a nitric oxide-dependent mechanism. Human umbilical vein endothelial cells (HUVECs), when stimulated with the same concentrations of cytokines and RANTES, differed in their capacity to kill rickettsiae by a nitric oxide-dependent mechanism and in the quantity of nitric oxide synthesized. Hydrogen peroxide-dependent intracellular killing ofR. conoriiwas demonstrated in HUVECs, THP-1 cells (human macrophages), and human peripheral blood monocytes activated with the cytokines. Rickettsial killing in the human macrophage cell line was also mediated by a limitation of the availability of tryptophan in association with the expression of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase. The rates of survival of all of the cell types investigated under the conditions of activation and infection in these experiments indicated that death of the host cells was not the explanation for the control of rickettsial infection. This finding represents the first demonstration that activated human hepatocytes and, in some cases, endothelium can kill intracellular pathogens via nitric oxide and that RANTES plays a role in immunity to rickettsiae. Human cells are capable of controlling rickettsial infections intracellularly, the most relevant location in these infections, by one or a combination of three mechanisms involving nitric oxide synthesis, hydrogen peroxide production, and tryptophan degradation.
Effects of Reproductive Hormones on Experimental Vaginal Candidiasis
Authors: Fidel Paul L. , Cutright Jessica , Steele Chad 
Published: July 2002

ABSTRACT

Vulvovaginal candidiasis (VVC) is an opportunistic mucosal infection caused by
Candida albicans
that affects large numbers of otherwise healthy women of childbearing age. Acute episodes of VVC often occur during pregnancy and during the luteal phase of the menstrual cycle, when levels of progesterone and estrogen are elevated. Although estrogen-dependent experimental rodent models of
C. albicans
vaginal infection are used for many applications, the role of reproductive hormones and/or their limits in the acquisition of vaginal candidiasis remain unclear. This study examined the effects of estrogen and progesterone on several aspects of an experimental infection together with relative cell-mediated immune responses. Results showed that while decreasing estrogen concentrations eventually influenced infection-induced vaginal titers of
C. albicans
and rates of infection in inoculated animals, the experimental infection could not be achieved in mice treated with various concentrations of progesterone alone. Furthermore, progesterone had no effect on (i) the induction and persistence of the infection in the presence of estrogen, (ii) delayed-type hypersensitivity in primary-infected mice, or (iii) the partial protection from a secondary vaginal infection under pseudoestrus conditions. Other results with estrogen showed that a persistent infection could be established with a wide range of
C. albicans
inocula under supraphysiologic and near-physiologic (at estrus) concentrations of estrogen and that vaginal fungus titers or rates of infection were similar if pseudoestrus was initiated several days before or after inoculation. However, the pseudoestrus state had to be maintained for the infection to persist. Finally, estrogen was found to reduce the ability of vaginal epithelial cells to inhibit the growth of
C. albicans
. These results suggest that estrogen, but not progesterone, is an important factor in hormone-associated susceptibility to
C. albicans
vaginitis.
Functional Conservation of the Polysaccharide Biosynthetic Protein WbpM and Its Homologues in
Pseudomonas aeruginosa
and Other Medically Significant Bacteria
Authors: Burrows Lori L. , Urbanic Robert V. , Lam Joseph S. 
Published: July 2002

ABSTRACT

WbpM is a highly conserved protein involved in synthesis of the O antigens of
Pseudomonas aeruginosa
. Homologues of this protein have been identified in a large number of bacteria, and they can be divided into two subfamilies: subfamily 1, including WbpM, contains large proteins (∼600 amino acids), while subfamily 2, typified by HP0840 (FlaA1) of
Helicobacter pylori
, contains smaller proteins (∼350 amino acids) homologous to the C termini of proteins in subfamily 1. Analysis of knockout mutants of
wbpM
in
P. aeruginosa
serotypes O3, O10, O15, and O17 showed that although all 20 serotypes of
P. aeruginosa
possess
wbpM
, it is not universally required for O-antigen biosynthesis. Homologous genes from
Bordetella pertussis
(
wlbL
),
Staphylococcus aureus
(
cap8D
), and
H. pylori
(
flaA1
) complemented a
P. aeruginosa
O5
wbpM
mutant to various degrees. These conserved proteins may represent interesting targets for the design of inhibitors of bacterial exopolysaccharide biosynthesis.
Subunit Vaccination of Mice against New World Cutaneous Leishmaniasis: Comparison of Three Proteins Expressed in Amastigotes and Six Adjuvants
Authors: Aebischer Toni , Wolfram Markus , Patzer Silke I. , Ilg Thomas , Wiese Martin , Overath Peter 
Published: July 2002

ABSTRACTA mixture of well-defined recombinant antigens together with an adjuvant that preferentially stimulates specific gamma interferon (IFN-γ)-secreting helper type 1 CD4+T cells (Th1 cells) presents a rational option for a vaccine against leishmaniasis. The potential of this approach was investigated in murine infections withLeishmania mexicana, which are characterized by the absence of a parasite-specific Th1 response and uncontrolled parasite proliferation. A mixture of three antigens (glycoprotein 63, cysteine proteinases, and a membrane-bound acid phosphatase), which are all expressed in amastigotes, the mammalian stage of the parasite, were used for the immunization of C57BL/6 mice in combination with six adjuvants (interleukin 12 [IL-12], Detox, 4′-monophosphoryl lipid A, QS-21,Mycobacterium bovisBCG, andCorynebacterium parvum). All six vaccine formulations containing the mixture of recombinant antigens were protective against challenge infections with promastigotes, the insect stage of the parasite, in that mice controlled and healed infections but developed transient and, in certain cases, accentuated disease. The most effective adjuvants were IL-12 followed by Detox. Further studies using these two adjuvants showed that a similar protective effect was observed with a mixture of the corresponding native proteins, and mice which had controlled the infection showed a preponderance of IFN-γ-secreting CD4+T cells in the lymph nodes draining the lesion. Using the recombinant proteins individually, it is shown that the relatively abundant cysteine proteinases and glycoprotein 63, but not the acid phosphatase, are able to elicit a protective response. The results are discussed in comparison to previous studies with subunit vaccines and with respect to cell biological aspects of antigen presentation inLeishmania-infected macrophages.
Linkage of Exogenous T-cell Epitopes to the 19-Kilodalton Region ofPlasmodium yoeliiMerozoite Surface Protein 1 (MSP119) Can Enhance Protective Immunity against Malaria and Modulate the Immunoglobulin Subclass Response to MSP119
Authors: Ahlborg Niklas , Ling Irene T. , Holder Anthony A. , Riley Eleanor M. 
Published: July 2002

ABSTRACTThe degree of protection againstPlasmodium yoeliiasexual blood stages induced by immunization of mice with the 19-kDa region of merozoite surface protein 1 (MSP119) is H-2 dependent. As a strategy to improve the protection, mouse strains with disparate H-2 haplotypes were immunized with glutathioneS-transferase (GST)–MSP119proteins including either a universal T-cell epitope from tetanus toxin (P2) or an I-Ak-restricted T-cell epitope (P8) fromPlasmodium falciparumPf332. In H-2kmice which are poorly protected following immunization with GST-MSP119, GST-P2-MSP119significantly improved the protection. In mice partially (H-2k/b) or well protected by GST-MSP119(H-2dand H-2b), P2 did not further increase the protection. However, the protection of H-2k/bmice and to some extent H-2kmice was improved by immunization with GST-P8-MSP119. The magnitudes of immunoglobulin G1 (IgG1) and IgG2a responses in mice immunized with the GST-MSP119variants correlated with low peak parasitemia, indicating a protective capacity of these IgG subclasses. In H-2kmice immunized with GST-P2-MSP119, both IgG1 and IgG2a responses were significantly enhanced. The epitope P2 appeared to have a general ability to modulate the IgG subclass response since all four mouse strains displayed elevated IgG2a and/or IgG2b levels after immunization with GST-P2-MSP119. In contrast, GST-P8-MSP119induced a slight enhancement of IgG responses in H-2k/band H-2kmice without any major shift in IgG subclass patterns. The ability to improve the protective immunity elicited byP. yoeliiMSP119may have implications for improvement of human vaccines based onP. falciparumMSP119.
Detection of
Chlamydia pneumoniae
DNA and Antigen in the Circulating Mononuclear Cell Fractions of Humans and Koalas
Authors: Bodetti Tracey J. , Timms Peter 
Published: July 2002

ABSTRACT

Chlamydia pneumoniae
is a common respiratory pathogen of humans which, in addition to causing disease at the respiratory site, has recently been linked to disease at other body sites. If
C. pneumoniae
does contribute to disease at nonrespiratory sites, then it must have a mechanism by which it reaches these sites. We analyzed the peripheral blood mononuclear cell (PBMC) fractions from 60 healthy human blood donors for the presence of
C. pneumoniae
DNA (by
ompA
PCR) and chlamydial antigens (by genus- and species-specific monoclonal antibody staining). Ten of the sixty (16.7%) blood donors were
C. pneumoniae
positive by PCR, and all 10 of these PCR-positive individuals' samples demonstrated specific staining with anti-
C. pneumoniae
monoclonal antibodies. The only other host naturally infected with
C. pneumoniae
is the koala, in which the bacterium also causes respiratory infections. We demonstrated the presence of
C. pneumoniae
DNA and antigens in the PBMC fractions of 30% of 20 koalas tested. Our finding of
C. pneumoniae
-infected PBMCs in koalas as well as humans suggests that the ability to infect PBMCs and to disseminate from the respiratory site is not restricted to the human biovar of
C. pneumoniae
but is a general characteristic of this chlamydial species.
Role of Eosinophils in the Pathogenesis of
Mycobacterium bovis
BCG Infection in Gamma Interferon Receptor-Deficient Mice
Authors: Kirman Joanna , Zakaria Zamsyari , McCoy Kathy , Delahunt Brett , Le Gros Graham 
Published: July 2002

ABSTRACT

A profound eosinophil infiltration of granulomas is observed in the lungs of
Mycobacterium bovis
bacillus Calmette Guérin-infected gamma interferon receptor-deficient mice. Blockade of eosinophil proliferation and recruitment into the lung by treatment with anti-interleukin-5 monoclonal antibody marginally reduced mycobacterial growth within the lung but did not affect dissemination of the infection to other tissues.
Salmonella enterica
Serovar Typhi Uses Type IVB Pili To Enter Human Intestinal Epithelial Cells
Authors: Zhang Xiao-Lian , Tsui Inez S. M. , Yip Cecilia M. C. , Fung Ada W. Y. , Wong Danny K.-H. , Dai Xiaoyun , Yang Yanhua , Hackett Jim , Morris Christina 
Published: July 2002

ABSTRACT

DNA sequencing upstream of the
Salmonella enterica
serovar Typhi
pilV
and
rci
genes previously identified in the ca. 118-kb major pathogenicity island (X.-L. Zhang, C. Morris, and J. Hackett, Gene 202:139–146, 1997) identified a further 10
pil
genes apparently forming a
pil
operon. The product of the
pilS
gene, prePilS protein (a putative type IVB structural prepilin) was purified, and an anti-prePilS antiserum was raised in mice. Mutants of serovar Typhi either lacking the whole
pil
operon or with an insertion mutation in the
pilS
gene were constructed, as was a strain in which the
pilN
to
pilV
genes were driven by the
tac
promoter. The
pil
+
strains synthesized type IVB pili, as judged by (i) visualization in the electron microscope of thin pili in culture supernatants of one such strain and (ii) the presence of PilS protein (smaller than the prePilS protein by removal of the leader peptide) on immunoblotting of material pelleted by high-speed centrifugation of either the culture supernatant or sonicates of
pil
+
strains. Control
pil
mutants did not express the PilS protein. A
pilS
mutant of serovar Typhi entered human intestinal INT407 cells in culture to levels only 5 to 25% of those of the wild-type strain, and serovar Typhi entry was strongly inhibited by soluble prePilS protein (50% inhibition of entry at 1.4 μM prePilS).
Innate Immune Responses in Children and Adults with Shigellosis
Authors: Raqib Rubhana , Mia S. M. Shahjahan , Qadri Firdausi , Alam Tanfis I. , Alam Nur H. , Chowdhury Ashish K. , Mathan Minnie M. , Andersson Jan 
Published: July 2002

ABSTRACTAn array of pro- and anti-inflammatory mediators of the innate immune system was analyzed in stool, urine, and rectal mucosa samples from adults and children with shigellosis to better understand their role in recovery from and in the immunopathogenesis of the disease. Increased concentrations of lactoferrin (Lf), myeloperoxidase (MPO), prostaglandin E2, and leukotriene B4(LTB4) in stool during acute shigellosis in both children and adults indicated that activated cells of the innate defense system at the mucosal site were secreting the mediators. Increased concentration of MPO and 8-iso-prostaglandin F2αand lower levels of superoxide dismutase (SOD) activity in stool during acuteShigellainfection suggested increased formation of reactive oxygen species, free radical-catalyzed peroxidation of membrane lipids, and decreased scavenging of the reactive oxygen radicals. In children, lower expression of SOD in tissue with severe inflammation and lower levels of SOD activity in stool for longer periods compared to adults may further worsen the tissue damage and predispose the children to a lowered defense. Both adult and pediatric patients had significantly higher expression of inducible nitric oxide synthase (iNOS) in the rectum with severe inflammation, compared to that seen with mild inflammation, accompanied by persistently up-regulated iNOS mRNA, reflecting increased production of nitric oxide at the local site. However, in contrast to adults, reduced urinary nitrate levels in pediatric patients during acute shigellosis suggested lower production of nitric oxide in the renal compartment. Persistent production of Lf in pediatric patients may contribute to chronic inflammation in the rectum. In addition, increased production of proinflammatory mediators in the rectum of patients with severe histology suggested contribution of these molecules to the immunopathogenesis of severe colitis caused by shigellae.