bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pro‐inflammatory cytokines in Turkish children with protein‐energy malnutrition
Authors: Dülger Haluk , Arik Mehmet , Şekeroğlu M. Ramazan , Tarakçioğlu Mehmet , Noyan Tevfik , Cesur Yaşar , Balahoroğlu Ragip 
Published: February 2003

Background: Protein‐energy malnutrition (PEM) results from food insufficiency as well as from poor social and economic conditions. Development of PEM is due to insufficient nutrition. Children with PEM lose their resistance to infections because of a disordered immune system. It has been reported that the changes occurring in mediators referred to as cytokines in the immune system may be indicators of the disorders associated with PEM.Aims: To determine the concentrations of pro‐inflammatory cytokines in children with PEM, and to find out whether there was an association with the clinical presentation of PEM.Methods: The levels of serum total protein, albumin, tumour necrosis factor‐α, and interleukin‐6 were measured in 25 patients with PEM and in 18 healthy children as a control group. PEM was divided into two groups as kwashiorkor and marasmus. The kwashiorkor group consisted of 15 children and the marasmus group consisted of 10 children.Results: Levels of serum total protein and albumin of the kwashiorkor group were significantly lower than both the marasmus group and controls
(p < 0.05).
In view of tumour necrosis factor‐α levels, there was no difference between groups
(p > 0.05).
While levels of interleukin‐6 in both the marasmus group and the kwashiorkor group were significantly higher compared with controls
(p < 0.05),
there was no significant difference between the groups of marasmus and kwashiorkor
(p > 0.05).Conclusions: It was observed that the inflammatory response had increased in children with malnutrition.
Regions of PspA/EF3296 Best Able To Elicit Protection against
Streptococcus pneumoniae
in a Murine Infection Model
Authors: Roche Hazeline , Håkansson Anders , Hollingshead Susan K. , Briles David E. 
Published: February 2003

ABSTRACT

Pneumococcal surface protein A (PspA) can elicit protection against
Streptococcus pneumoniae
in mouse infection models. PspA is classified by serology and amino acid sequence into two major families that are divided by sequence into five clades. The most variable portion of the molecule is the α-helical domain, which comprises the N-terminal half of PspA. Prior studies of a family 1 PspA protein observed that protective antibodies are reactive with epitopes in the α-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the α-helical region. In these studies, we have used six overlapping recombinant fragments of family 2, clade 3 PspA/EF3296 to map the protection-eliciting regions of its α-helical domain. The three fragments, which included the 104 most C-terminal amino acids of the α-helical domain (314 to 418), could each elicit protection against EF3296. A fragment comprising amino acids 75 to 305 failed to elicit significant protection. A fragment containing amino acids 1 to 115 elicited protection against EF3296 in BALB/c mice but not in CBA/N mice. All three fragments containing amino acids 314 to 418 were able to elicit cross-protection against pneumococci expressing PspA proteins of clades 2, 3, 4, and 5. Cross-protection elicited by these three fragments was easier to demonstrate in CBA/N mice than in BALB/c mice. The 1-to-115 fragment, however, elicited some cross-protection against clades 2 and 4 in BALB/c mice but not in CBA/N mice. These studies provide support for the importance of the C-terminal 104 and N-terminal 115 amino acids of the α-helical region of PspA in the elicitation of cross-protection.
Antibodies Raised against Bcvir15, an Extrachromosomal Double-Stranded RNA-Encoded Protein fromBabesia canis, Inhibit the In Vitro Growth of the Parasite
Authors: Drakulovski P. , Carcy B. , Moubri K. , Carret C. , Depoix D. , Schetters T. P. M. , Gorenflot A. 
Published: February 2003

ABSTRACTAs part of a search for homologous members of thePlasmodium falciparumPf60 multigene family in the intraerythrocytic protozoan parasiteBabesia canis, we report here the characterization of a cDNA of 1,115 bp, which was designatedBcvirfor its potential viral origin. TheBcvircDNA contained two overlapping open reading frames (ORFs) (ORF1 from nucleotide [nt] 61 to 486 and ORF2 from nt 417 to 919), where Bcvir15, the deduced ORF1 peptide (M1to I141), is the main expressed product. TheBcvircDNA was derived from an extrachromosomal dsRNA element of 1.2 kbp that was always found associated with a double-stranded RNA (dsRNA) of 2.8 kbp by hybridization, and no copy of this cDNA sequence was found inB. canisgenomic DNA. Biochemical characterization of Bcvir15, by using polyclonal rabbit sera directed against recombinant proteins, indicated that it is a soluble protein which remained associated with the cytoplasm of theB. canismerozoite. Interestingly, purified immunoglobulins from the anti-glutathioneS-transferase-Bcvir15 (at a concentration of 160 μg/ml) induced 50% inhibition of the in vitro growth ofB. canis, and the inhibitory effect was associated with morphological damage of the parasite. Our data suggest that the extrachromosomal dsRNA-encoded Bcvir15 protein might interfere with the intracellular growth of the parasite rather than with the process of invasion of the host cell by the merozoite. Epitope mapping of Bcvir15 identified three epitopes that might be essential for the function of the protein.
Enteral Immunization with Attenuated RecombinantListeria monocytogenesas a Live Vaccine Vector: Organ-Dependent Dynamics of CD4 T Lymphocytes Reactive to aLeishmania majorTracer Epitope
Authors: Saklani-Jusforgues Hélène , Fontan Elisabeth , Soussi Neirouz , Milon Geneviève , Goossens Pierre L. 
Published: February 2003

ABSTRACTListeria monocytogenesis considered as a potential live bacterial vector, particularly for the induction of CD8 T cells. The CD4 T-cell immune response triggered after enteral immunization of mice has not yet been thoroughly characterized. The dynamics of gamma interferon (IFN-γ)- and interleukin-4 (IL-4)-secreting CD4 T cells were analyzed after priming through intragastric delivery of an attenuated ΔactArecombinantL. monocytogenesstrain expressing theLeishmania majorLACK protein; a peptide of this protein, LACK158-173peptide (pLACK), is a well-characterized CD4 T-cell target in BALB/c mice. Five compartments were monitored: Peyer's patches, mesenteric lymph nodes (MLN), spleen, liver, and blood. A single intragastric inoculation ofΔactA-LACK-LM in BALB/c mice led to colonization of the MLN and spleen at a significant level for at least 3 days. Efficient priming of IFN-γ-secreting pLACK-reactive CD4 T cells was observed in all tested compartments. Interestingly, IL-4-secreting pLACK-reactive CD4 T cells were detectable at day 6 or 7 only in blood and liver. The absence of translocation of viable bacteria through the intestinal epithelium after furtherΔactA-LACK-LM inoculations was concomitant with the absence of an increase in the level of IFN-γ secreted by the MLN, blood, and splenic pLACK-reactive Th1 T cells, although the levels remained significantly above the basal level. No change in this population size was detected in the spleen. However, an increase in the number of intragastric inoculations had a clinical beneficial effect inL. major-infected BALB/c mice.L. monocytogenesthus presents the potential of an efficient vector for induction of CD4 T cells when administered by the enteral route.
Identification of Genetic Loci Required for Capsular Expression in
Vibrio vulnificus
Authors: Smith Amy B. , Siebeling Ronald J. 
Published: February 2003

ABSTRACT

Transposon mutagenesis of an encapsulated, virulent strain of
Vibrio vulnificus
1003(O) led to the identification of four genetic regions that are essential to capsular polysaccharide (CPS) expression and virulence. Of the four regions, three are believed to be part of a capsule gene locus comprised of biosynthesis, polymerization, and transport genes clustered on a single chromosomal fragment. Genes indicating a Wzy-dependent system of polymerization and transmembrane export are present, suggesting that the CPS of
V. vulnificus
is lipid linked. The fourth region, while it contains a gene essential for CPS expression, is characteristic of an integron-gene cassette region, similar to the super integron of
V. cholerae.
It is not believed to be part of a CPS gene locus and is located in a region of the chromosome separate from the putative CPS loci. It is comprised of open reading frames (ORFs) carrying genes of unknown function surrounded by direct repeats. This region also contains IS
492
, an insertion sequence located numerous times throughout a region of the genome, demonstrating a restriction fragment length polymorphism among an encapsulated and nonencapsulated morphotype of
V. vulnificus.
Collectively, 22 ORFs were recognized: 13 capsule synthesis genes, 4 insertion sequences, 1 truncated biosynthesis gene, and 4 genes of unknown function. This study has led to the identification of previously unrecognized genetic loci that may help to increase the understanding of capsular genetics and antigenic diversity among
V. vulnificus
strains.
Position-Based Scanning for Comparative Genomics and Identification of Genetic Islands in
Haemophilus influenzae
Type b
Authors: Bergman Nicholas H. , Akerley Brian J. 
Published: February 2003

ABSTRACT

Bacteria exhibit extensive genetic heterogeneity within species. In many cases, these differences account for virulence properties unique to specific strains. Several such loci have been discovered in the genome of the type b serotype of
Haemophilus influenzae
, a human pathogen able to cause meningitis, pneumonia, and septicemia. Here we report application of a PCR-based scanning procedure to compare the genome of a virulent type b (Hib) strain with that of the laboratory-passaged Rd KW20 strain for which a complete genome sequence is available. We have identified seven DNA segments or
H. influenzae
genetic islands (HiGIs) present in the type b genome and absent from the Rd genome. These segments vary in size and content and show signs of horizontal gene transfer in that their percent G+C content differs from that of the rest of the
H. influenzae
genome, they contain genes similar to those found on phages or other mobile elements, or they are flanked by DNA repeats. Several of these loci represent potential pathogenicity islands, because they contain genes likely to mediate interactions with the host. These newly identified genetic islands provide areas of investigation into both the evolution and pathogenesis of
H. influenzae
. In addition, the genome scanning approach developed to identify these islands provides a rapid means to compare the genomes of phenotypically diverse bacterial strains once the genome sequence of one representative strain has been determined.
Enteric Salmonella Infection Inhibits Paneth Cell Antimicrobial Peptide Expression
Authors: Salzman Nita H. , Chou Margaret M. , de Jong Hendrik , Liu Lide , Porter Edith M. , Paterson Yvonne 
Published: February 2003

ABSTRACTPaneth cells, highly secretory epithelial cells found at the bases of small intestinal crypts, release a variety of microbicidal molecules, including α-defensins and lysozyme. The secretion of antimicrobials by Paneth cells is thought to be important in mucosal host defense against invasion by enteric pathogens. We explored whether enteric pathogens can interfere with this arm of defense. We found that oral inoculation of mice with wild-typeSalmonella entericaserovar Typhimurium decreases the expression of α-defensins (called cryptdins in mice) and lysozyme. Oral inoculation withSalmonellaserovar Typhimurium strains that are heat killed, lack the PhoP regulon, and lack the SPI1 type III secretion system or withListeria monocytogenesdoes not have this effect.Salmonellamay gain a specific survival advantage in the intestinal lumen by decreasing the expression of microbicidal peptides in Paneth cells through direct interactions betweenSalmonellaand the small intestinal epithelium.
Allelic Variation inTLR4Is Linked to Susceptibility toSalmonella entericaSerovar Typhimurium Infection in Chickens
Authors: Leveque Gary , Forgetta Vincenzo , Morroll Shaun , Smith Adrian L. , Bumstead Nat , Barrow Paul , Loredo-Osti J. C. , Morgan Kenneth , Malo Danielle 
Published: February 2003

ABSTRACTToll-like receptor 4 (TLR4) is part of a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens and in the innate defense against infection. We describe here the cloning and characterization of the avian orthologue of mammalianTLR4. ChickenTLR4encodes a 843-amino-acid protein that contains a leucine-rich repeat extracellular domain, a short transmembrane domain typical of type I transmembrane proteins, and a Toll-interleukin-1R signaling domain characteristic of all TLR proteins. The chicken TLR4 protein shows 46% identity (64% similarity) to human TLR4 and 41% similarity to other TLR family members. Northern blot analysis reveals thatTLR4is expressed at approximately the same level in all tissues tested, including brain, thymus, kidney, intestine, muscle, liver, lung, bursa of Fabricius, heart, and spleen. The probe detected only one transcript of ca. 4.4 kb in length for all tissues except muscle where the size ofTLR4mRNA was ca. 9.6 kb. We have mappedTLR4to microchromosome E41W17 in a region harboring the gene for tenascin C and known to be well conserved between the chicken and mammalian genomes. This region of the chicken genome was shown previously to harbor aSalmonellasusceptibility locus. By using linkage analysis,TLR4was shown to be linked to resistance to infection withSalmonella entericaserovar Typhimurium in chickens (likelihood ratio test of 10.2,P= 0.00138), suggesting a role of TLR4 in the host response of chickens toSalmonellainfection.
Microarray Analysis of mRNA Levels from RAW264.7 Macrophages Infected withBrucella abortus
Authors: Eskra Linda , Mathison Angela , Splitter Gary 
Published: February 2003

ABSTRACTIdentification of host responses at the gene transcription level provides a molecular profile of the events that occur following infection.Brucella abortusis a facultative intracellular pathogen of macrophages that induces chronic infection in humans and domestic animals. Using microarray technology, the response of macrophages 4 h followingB. abortusinfection was analyzed to identify early intracellular infection events that occur in macrophages. Of the >6,000 genes, we identified over 140 genes that were reproducibly differentially transcribed. First, an increase in the transcription of a number of proinflammatory cytokines and chemokines, such as tumor necrosis factor alpha, interleukin-1β (IL-1β), IL-1α, and members of the SCY family of proteins, that may constitute a general host recruitment of antibacterial defenses was evident. Alternatively,Brucellamay subvert newly arriving macrophages for additional intracellular infection. Second, transcription of receptors and cytokines associated with antigen presentation, e.g., major histocompatibility complex class II and IL-12p40, were not evident at this 4-h period of infection. Third,Brucellainhibited transcription of various host genes involved in apoptosis, cell cycling, and intracellular vesicular trafficking. Identification of macrophage genes whose transcription was inhibited suggests thatBrucellautilizes specific mechanisms to target certain cell pathways. In conclusion, these data suggest thatB. abortuscan alter macrophage pathways to recruit additional macrophages for future infection while simultaneously inhibiting apoptosis and innate immune mechanisms within the macrophage, permitting intracellular survival of the bacterium. These results provide insights into the pathogenic strategies used byBrucellafor long-term survival within a hostile environment.
Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease Is Due to a Th1-Specific Immune Response
Authors: Gomes J. A. S. , Bahia-Oliveira L. M. G. , Rocha M. O. C. , Martins-Filho O. A. , Gazzinelli G. , Correa-Oliveira R. 
Published: February 2003

ABSTRACTThe role of interleukin 10 (IL-10) and gamma interferon (IFN-γ) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-γ, were identified based on the levels of secretion of this cytokine in the supernatant of peripheral blood mononuclear cell (PBMC) cultures. Eighty-three percent of the patients presenting with cardiac disease (CARD) of different degrees and 59% of the patients with the indeterminate form of disease (IND) were identified as high IFN-γ producers. PBMC from IND patients classified as low IFN-γ producers secreted significantly higher amounts of IL-10 than did those from other groups. Flow cytometry analysis demonstrated that in PBMC from the IND group, the majority of the IL-10-producing cells were monocytes (CD14High+cells), whereas in the CARD group, the major sources of IFN-γ were T lymphocytes (CD3+CD4+cells). These results suggest an association between the production of IFN-γ by CD3+CD4+cells and morbidity in Chagas' disease, whereas the production of IL-10 by macrophages/monocytes leads to regulation of the immune response in IND patients. We hypothesize that an exacerbated production of IFN-γ againstTrypanosoma cruziantigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.
Trypanosoma cruziInfection Modulates In Vivo Expression of Major Histocompatibility Complex Class II Molecules on Antigen-Presenting Cells and T-Cell Stimulatory Activity of Dendritic Cells in a Strain-Dependent Manner
Authors: Alba Soto Catalina D. , Mirkin Gerardo A. , Solana Maria E. , González Cappa Stella M. 
Published: February 2003

ABSTRACTA striking feature of Chagas' disease is the diversity of clinical presentations. Such variability may be due to the heterogeneity amongTrypanosoma cruziisolates or to the host immune response. Employing two strains which differ in their virulence, we investigated the effect of in vivo infection on professional antigen-presenting cells (APC). Acute infection with the virulent RA strain downregulated the expression of major histocompatibility complex (MHC) class II on splenic dendritic cells (DC) and inhibited its induction on peritoneal macrophages and splenic B cells. It also impaired the ability of DC to prime allogeneic T cells and to form homotypic clusters, suggesting a low maturation state of these cells. In contrast, the low-virulence K98 strain maintained the expression of MHC class II on DC or stimulated it on peritoneal macrophages and B cells and preserved DC's T-cell priming capacity and homotypic clustering. DC from RA-infected mice elicited a lower activation ofT. cruzi-specific T-cell proliferation than those from K98-infected mice. APC from RA-infected mice that reached the chronic phase of infection restored MHC class II levels to those found in K98-infected mice and upregulated costimulatory molecules expression, suggesting that the immunosuppression caused by this strain is only transient. Taken together, the results indicate that in vivo infection withT. cruzimodulates APC functionality and that this is accomplished in a strain-dependent manner.
Activation of Natural Killer T Cells by α-Galactosylceramide Impairs DNA Vaccine-Induced Protective Immunity againstTrypanosoma cruzi
Authors: Miyahira Yasushi , Katae Masaharu , Takeda Kazuyoshi , Yagita Hideo , Okumura Ko , Kobayashi Seiki , Takeuchi Tsutomu , Kamiyama Tsuneo , Fukuchi Yoshinosuke , Aoki Takashi 
Published: February 2003

ABSTRACTInnate immunity as a first defense is indispensable for host survival against infectious agents. We examined the roles of natural killer (NK) T cells in defense againstTrypanosoma cruziinfection. TheT. cruziparasitemia and survival of CD1d-deficient mice exhibited no differences compared to wild-type littermates. NK T-cell activation induced by administering α-galactosylceramide (α-GalCer) toT. cruzi-infected mice significantly changed the parasitemia only in the late phase of infection and slightly improved survival when mice were infected intraperitoneally. The combined usage of α-GalCer and benznidazole, a commercially available drug for Chagas' disease, did not enhance the therapeutic efficacy of benznidazole. These results suggest that NK T cells do not play a pivotal role in resistance toT. cruziinfection. In addition, we found that the coadministration of α-GalCer with DNA vaccine impaired the induction of epitope-specific CD8+T cells and undermined the DNA vaccine-induced protective immunity againstT. cruzi. Our results, in contrast to previous reports demonstrating the protective roles of NK T cells against other infectious agents, suggest that these cells might even exhibit adverse effects on vaccine-mediated protective immunity.
Congenital Exposure toPlasmodium falciparumAntigens: Prevalence and Antigenic Specificity of In Utero-Produced Antimalarial Immunoglobulin M Antibodies
Authors: Xi Guoling , Leke Rose G. F. , Thuita Lucy W. , Zhou Ainong , Leke Robert J. I. , Mbu Robinson , Taylor Diane Wallace 
Published: February 2003

ABSTRACTCongenitalPlasmodium falciparummalaria in newborns is uncommon in sub-Saharan Africa. A significant number of infants, however, become infected or exposed to malarial antigens either in utero or at delivery and have the potential to produce antimalarial antibodies and memory cells before their first natural infection. In Yaounde, Cameroon, parasite-specific immunoglobulin M (IgM) was detected in 14% of cord blood samples. The IgM antibodies reacted with a wide range of asexual-stage antigens, with each newborn having its own unique pattern of IgM reactivity. PCR-based detection and genotyping of cord blood parasites found that the prevalence, total number of parasite genotypes, and complexity of infection were higher in newborns who had produced antimalarial IgM than those who had not. Maternal placental malaria and anemia were associated with the production ofP. falciparum-specific IgM by the fetus. The effect of early immune priming on acquisition of immunity by infants is unknown and merits further investigation, since a significant proportion of Cameroonian newborns developed a humoral response to malaria before birth.