bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐1 stimulates ceramide accumulation without inducing apoptosis in intestinal epithelial cells
Authors: Homaidan Fadia R. , El-Sabban Marwan E. , Chakroun Iman , El-Sibai Mirvat , Dbaibo Ghassan S. 
Published: November 2003

Background: In inflammatory bowel disease (IBD), cytokine levels (such as interleukin‐1 (IL‐1)) are elevated. We have shown previously that IL‐1 activates phospholipid signaling pathways in intestinal epithelial cells (IEC), leading to increased ceramide levels.Aim: To determine whether ceramide induces apoptosis in IEC.Methods: Apoptosis was evaluated by annexin‐Vbinding or Hoechst nuclear staining. Levels of bcl‐2, bcl‐x, bax, p53 and p21 were determined by Western blotting, and cell cycle analysis was determined by flow cytometry.Results: IL‐1 increased ceramide accumulation in a time‐dependent and concentration‐dependent manner with a peak response at 4 h, with [IL‐1] = 30 ng/ml. Neither IL‐1 nor ceramide induced apoptosis in IEC, but they increased bcl‐2 levels and decreased bax and p21 levels without affecting bcl‐x and p53 levels. They also caused a slight but significant increase in the G2/M phase. These data suggest a role for ceramide in IBD and suggest a possible mechanism for the enhanced tumorigenic activity in IBD patients.
High serum level of endostatin in multiple myeloma at diagnosis but not in the plateau phase after treatment
Authors: Urbańska-Ryś Halina , Robak Tadeusz 
Published: November 2003

We investigated the serum concentration of endostatin in 84 patients with multiple myeloma (MM) and in 13 healthy controls. The level of measured anti‐angiogenic agent was correlated with the phase and stage of the disease, and most importantly with clinical and laboratory parameters depicting the disease activity (haemoglobin, creatinine, albumins, calcium, M‐component, C‐reactive protein, β2‐microglobulin, lactate dehydrogenase, stage of bone disease) as well as serum levels of pro‐angiogenic cytokines such as vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor and transforming growth factor‐β. The median serum level of endostatin in MM patients was 58 ng/ml and was statistically significantly higher than in the control group (median, 40 ng/ml; P = 0.015). MM patients in phase I (at diagnosis) had higher levels of endostatin (median, 69 ng/ml) than those in phase II (plateau phase after treatment) (median, 49 pg/ml; P = 0.044). We did not find any statistical correlation between the level of endostatin and stage of MM according to the Durie and Salmon system. The serum concentration of endostatin in MM patients with a normal level of albumins was significantly higher than in others with hypoalbuminaemia (median, 62 ng/ml versus 39 ng/ml; P = 0.033). Also, patients with a normal value of lactate dehydrogenase had a higher concentration of endostatin than those with values >425 U/l (median, 70 ng/ml versus 39 ng/ml; P = 0.019). We did not show any statistical correlation between the concentration of endostatin and level of haemoglobin, creatinine, calcium, C‐reactive protein, β2‐microglobulin and stage of bone disease. We failed to find positive or negative correlations between the level of endostatin and vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor and transforming growth factor‐β. The concentration of endostatin did not influence the probability of survival in MM patients in our study.In conclusion, our data indicate that endostatin has a higher level in MM patients than in healthy controls. Highest values were stated in active phases of the disease (at presentation and in progression). Different clinical and laboratory parameters generally do not influence the concentration of endostatin (except albumins and lactate dehydrogenase).
FHA Domains as Phospho‐Threonine Binding Modules in Cell Signaling
Authors: Hammet Andrew , Pike Brietta , McNees Carolyn , Conlan Lindus , Tenis Nora , Heierhorst Jörg 
Published: November 2003

AbstractForkhead‐associated (FHA) domains are present in <200 diverse proteins in all phyla from bacteria to mammals and seem to be particularly prevalent in proteins with cell cycle control functions. Recent work from several laboratories has considerably improved our understanding of the structure and function of these domains that were virtually unknown a few years ago, and the first disease associations of FHA domains have now emerged. FHA domains form 11‐stranded beta‐sandwiches that contain some 100‐180 amino acid residues with a high degree of sequence diversity. FHA domains act as phosphorylation‐dependent protein‐protein interaction modules that preferentially bind to phospho‐threonine residues in their targets. Interestingly, point mutations in the human CHK2 gene that lead to single‐residue amino acid substitutions in the FHA domain of this cell cycle checkpoint kinase have been found to cause a subset of cases of the Li‐Fraumeni multi‐cancer syndrome. IUBMB Life, 55: 23‐27, 2003
Apoptosis in Yeasts
Authors: Weinberger Martin , Ramachandran Lakshmi , Burhans William 
Published: November 2003

AbstractAlthough yeasts lack some elements of the complex apoptotic machinery of metazoan cells, recent studies show that many features of apoptosis, including a caspase‐like activity, can be induced in these organisms by DNA damage and other apoptotic triggers. These remarkable findings provide a compelling argument for increased efforts to bring the powerful genetic approaches available to yeast researchers more directly to bear on questions related to apoptosis and its induction or inhibition by drugs. Yeasts may provide a particularly useful model for understanding connections between DNA damage, cell cycle regulation and apoptosis. Here we summarize these recent findings and explore their implications, particularly for the development of more effective therapeutic strategies for treating cancer. IUBMB Life, 55: 467‐472, 2003
Genetic Basis for Biosynthesis of the(α1→4)-Linked
N
-Acetyl-
d
-Glucosamine 1-Phosphate Capsuleof
Neisseria meningitidis
SerogroupX
Authors: Tzeng Yih-Ling , Noble Corie , Stephens David S. 
Published: November 2003

ABSTRACT

The
genetic basis for biosynthesis of the (α1→4)-linked
N
-acetyl-
d
-glucosamine 1-phosphate capsule of
Neisseria meningitidis
serogroup X was defined. The
biosynthesis gene cassette was a ∼4.2-kb region located between
ctrA
of the capsule transport operon and
galE
, which
encodes the UDP-glucose-4-epimerase. This location was identical to the
locations of the biosynthesis cassettes in other meningococcal
serogroups. Three open reading frames unique to meningococcus serogroup
X were identified. Deletion-insertion mutation and colony
immunoblotting confirmed that these three genes were essential for
serogroup X capsule expression, and the genes were designated
xcbA
,
xcbB
, and
xcbC
(serogroup
X
c
apsule
b
iosynthesis). Reverse transcriptase PCR
indicated that the
xcbABC
genes form an operon and are
cotranscribed divergently from
ctrA
. XcbA exhibited 52%
amino acid similarity to SacB, the putative capsule polymerase of
meningococcus serogroup A, suggesting that it plays a role as the
serogroup X capsule polymerase. An IS
1016
element was found
within the intergenic region separating
ctrA
and
xcbA
in multiple strains, and this element did not interfere with capsule
expression.
Association of
Salmonella enterica
SerovarEnteritidis YafD with Resistance to Chicken EggAlbumen
Authors: Lu Sangwei , Killoran Patrick B. , Riley Lee W. 
Published: November 2003

ABSTRACT

Salmonella
enterica
serovar Enteritidis is a major cause of food-borne
diseases in industrialized countries. The incidence of
S.
enterica
serovar Enteritidis infections has increased
substantially in recent decades, and
S. enterica
serovar
Enteritidis is now one of the leading serovars of
Salmonella
in the United States. A unique epidemiological characteristic of
S.
enterica
serovar Enteritidis is its association with chicken shell
eggs, since approximately 80% of all human gastrointestinal
diseases can be traced to contaminated egg products. Eggs are
contaminated when bacteria from reproductive tissues of infected hens
are packaged into the eggs and persist inside the hostile egg albumen
environment. Therefore, resistance to egg albumen is an important
aspect in the transmission of
S. enterica
serovar Enteritidis.
We identified a gene,
yafD
from
S. enterica
serovar
Enteritidis, whose overexpression conferred upon
S. enterica
serovar Typhimurium enhanced resistance to egg albumen, while
disruption of this gene in
S. enterica
serovar Enteritidis
rendered the organism more susceptible to egg albumen. YafD is
homologous to members of an exonuclease-endonuclease-phosphatase
family, including some enzymes involved in DNA repair. Furthermore, we
discovered that egg albumen has nuclease activities and uses both
circular and linear DNA as substrates. We propose that YafD provides a
survival advantage to
S. enterica
serovar Enteritidis in eggs
by repairing DNA damage caused by egg albumen and that it may be one of
the biologic determinants that contribute to the epidemiological
association of
S. enterica
serovar Enteritidis with egg
products.
Lipopolysaccharide Binding Protein Is an Essential Component of the Innate Immune Response toEscherichia coliPeritonitis in Mice
Authors: Knapp Sylvia , de Vos Alex F. , Florquin Sandrine , Golenbock Douglas T. , van der Poll Tom 
Published: November 2003

ABSTRACTLipopolysaccharide (LPS) binding protein (LBP) is an acute-phase protein that enhances the responsiveness of immune cells to LPS by virtue of its capacity to transfer LPS to CD14. To determine the role of LBP in the innate immune response to peritonitis, LBP gene-deficient (LBP−/−) and normal wild-type mice were intraperitoneally infected withEscherichia coli, the most common causative pathogen of this disease. LBP was detected at low concentrations in peritoneal fluid of healthy wild-type mice, and the local LBP levels increased rapidly upon induction of peritonitis. LBP−/−mice were highly susceptible toE. coliperitonitis, as indicated by accelerated mortality, earlier bacterial dissemination to the blood, impaired bacterial clearance in the peritoneal cavity, and more severe remote organ damage. LBP−/−mice displayed diminished early tumor necrosis factor alpha, interleukin-6, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein 2 production and attenuated recruitment of polymorphonuclear leukocytes to the site of infection, indicating that acute inflammation was promoted by LBP. Locally produced LBP is an essential component of an effective innate immune response toE. coliperitonitis.
Characterization and Development of T-Cell Immune Responses in B-Cell-Deficient (Igh-6−/−) Mice withSalmonella entericaSerovar TyphimuriumInfection
Authors: Ugrinovic Sanja , Ménager Nathalie , Goh Natalie , Mastroeni Pietro 
Published: November 2003

ABSTRACTInfection of mice withSalmonella entericaserovar Typhimurium induces strong Th1 T-cell responses that are central to the control of the infection. In the present study, we examined the role of B cells in the development of Th1 T-cell responses toSalmonellaby using gene-targeted B-cell-deficient mice (Igh-6−/−mice). The development of Th1 T-cell responses inIgh-6−/−mice was impaired in the early stage of a primary infection. This impairment persisted throughout the course of the disease. The ability of T cells to produce the Th1 cytokine gamma interferon and the frequency at which they did so were lower inIgh-6−/−mice than in control mice. We also observed a transient switch toward Th2 cytokine production inIgh-6−/−mice. Thus, B cells are important for the induction of protective Th1 T-cell responses in the early phase of aSalmonellainfection. Activated B cells express high levels of major histocompatibility complex and costimulatory molecules and are nearly as effective as dendritic cells in their antigen-presenting cell (APC) activity. However, their importance as APCs in infection and their role in initiating and/or maintaining T-cell responses are unknown. Here, we show that B cells upregulate costimulatory molecules upon in vitro stimulation withS. entericaserovar Typhimurium and that they can presentSalmonellaantigens toSalmonella-specific CD4+T cells. Our results show that B cells are important for the development of T-cell responses in the early stage of aSalmonellainfection and that this property may be due to their ability to present antigens to T cells.
Resistance and Susceptibility to Filarial InfectionwithLitomosoides sigmodontisAre Associated with EarlyDifferences in Parasite Development and in Localized ImmuneReactions
Authors: Babayan Simon , Ungeheuer Marie-Noëlle , Martin Coralie , Attout Tarik , Belnoue Elodie , Snounou Georges , Rénia Laurent , Korenaga Masataka , Bain Odile 
Published: November 2003

ABSTRACTIn order to understand natural resistance to filariasis, we comparedLitomosoides sigmodontisprimary infection of C57BL/6 mice, which eliminate the worms before patency, and BALB/c mice, in which worms complete their development and produce microfilariae. Our analysis over the first month of infection monitoredmigration of the infective larvae from the lymph nodes to the pleural cavity, where the worms settle. Although immune responses from the mouse strains differed from the outset, the duration of lymphatic migration (4 days) and filarial recovery rates were similar, thus confirming that the proportion of larvae that develop in the host species upon infection is not influenced by host genetic variability. The majority of worms reached the adult stage in both mouse strains; however, worm growth and molting were retarded in resistant C57BL/6 mice. Surprisingly, the only immune responses detected at 60 h postinfection occurred in the susceptible mice and only upon stimulation of cells from lymph nodes draining the inoculation site with infective larva extract: massive production of interleukin-6 (IL-6) and IL-5 (the latter cytokine was previously suspected to have an effect onL. sigmodontisgrowth). However, between days 10 and 30 postinfection, extraordinarily high levels of type 1 and type 2 cytokines and expansion of pleural leukocyte infiltration were seen in the resistant C57BL/6 mice, explaining the destruction of worms later. Our results suggest that events early in the infection determine susceptibility or resistance to subsequent microfilarial production and a parasite strategy to use specific immune responses to its own benefit.
The Site ofLeishmania majorInfection Determines Disease Severity andImmuneResponses
Authors: Baldwin Tracey M. , Elso Colleen , Curtis Joan , Buckingham Lynn , Handman Emanuela 
Published: November 2003

ABSTRACTInbred strains of mice infected withLeishmania majorhave been classified as genetically resistant or susceptible on the basis of their ability to cure their lesions, the parasite burden in the draining lymph nodes, and their type of T helper cell immune responses to the parasite. Using the intradermal infection at the base of the tail and the ear pinna, we compared for the first time the above-mentioned parameters in six strains of mice infected with metacyclic promastigotes, and we show that the severity of disease depends greatly on the site of infection. Although the well-documented pattern of disease susceptibility of BALB/c and C57BL/6 mice described for the footpad and base-of-the-tail models of leishmaniasis were confirmed, C3H/HeN and DBA/2 mice, which are intermediate and susceptible, respectively, in the tail and other models, were resistant to ear infection. Moreover, in the CBA/H, C3H/HeN, C57BL/6J, and DBA/2 mouse strains, there was little correlation between the pattern of cytokines produced and the disease phenotype observed at the ear and tail sites. We conclude that the definition of susceptibility and the immune mechanisms leading to susceptibility or resistance to infection may differ substantially depending on the route of infection.
ConformationalEpitopes Recognized by Protective Anti-Neisserial Surface Protein AAntibodies
Authors: Hou Victor C. , Moe Gregory R. , Raad Zyde , Wuorimaa Tomi , Granoff Dan M. 
Published: November 2003

ABSTRACT

NspA
is a conserved membrane protein that elicits protective antibody
responses in mice against
Neisseria meningitidis
. A recent
crystallographic study showed that NspA adopts an eight-strandedβ
-barrel structure when reconstituted in detergent. In order to
define the segments of NspA-containing epitopes recognized by
protective murine anti-NspA antibodies, we studied the binding of two
bactericidal and protective anti-NspA monoclonal antibodies (MAbs),
AL12 and 14C7. Neither MAb binds to overlapping synthetic peptides
(10-mers, 12-mers, and cyclic 12-mers) corresponding to the entire
mature sequence of NspA, or to denatured recombinant NspA (rNspA),
although binding to the protein can be restored by refolding in
liposomes. Based on the ability of the two MAbs to bind to
Escherichia coli
microvesicles prepared from a set of rNspA
variants created by site-specific mutagenesis, the most important
contacts between the MAbs and NspA appear to be located within the LGG
segment of loop 3. The conformation of loop 2 also appears to be an
important determinant, as particular combinations of residues in this
segment resulted in loss of antibody binding. Thus, the two anti-NspA
MAbs recognize discontinuous conformational epitopes that result from
the close proximity of loops 2 and 3 in the three-dimensional structure
of NspA. The data suggest that optimally immunogenic vaccines using
rNspA will require formulations that permit proper folding of the
protein.
TheMycobacterium tuberculosisComplex-Restricted Genecfp32Encodes an Expressed Protein That Is Detectable inTuberculosis Patients and Is Positively Correlated with PulmonaryInterleukin-10
Authors: Huard Richard C. , Chitale Sadhana , Leung Mary , Lazzarini Luiz Claudio Oliveira , Zhu Hongxia , Shashkina Elena , Laal Suman , Conde Marcus B. , Kritski AfrÂnio L. , Belisle John T. , Kreiswirth Barry N. , Lapa e Silva José Roberto , Ho John L. 
Published: November 2003

ABSTRACTHuman tuberculosis (TB) is caused by the bacillusMycobacteriumtuberculosis, a subspecies of theM.tuberculosiscomplex (MTC) of mycobacteria. Postgenomic dissection of theM. tuberculosisproteome is ongoing and critical to furthering our understanding of factors mediatingM. tuberculosispathobiology. Towards this end, a 32-kDa putative glyoxalase in the culture filtrate (CF) of growingM. tuberculosis(originally annotated as Rv0577 and hereafter designated CFP32) was identified, cloned, and characterized. Thecfp32gene is MTC restricted, and the gene product is expressed ex vivo as determined by the respective Southern and Western blot testing of an assortment of mycobacteria. Moreover, thecfp32gene sequence is conserved within the MTC, as no polymorphisms were found in the testedcfp32PCR products upon sequence analysis. Western blotting ofM.tuberculosissubcellular fractions localized CFP32 predominantly to the CF and cytosolic compartments. Data to support the in vivo expression of CFP32 were provided by the serum recognition of recombinant CFP32 in 32% of TB patients by enzyme-linked immunosorbent assay (ELISA) as well as the direct detection of CFP32 by ELISA in the induced sputum samples from 56% of pulmonary TB patients. Of greatest interest was the observation that, per sample, sputum CFP32 levels (a potential indicator of increasing bacterial burden) correlated with levels of expression in sputum of interleukin-10 (an immunosuppressive cytokine and a putative contributing factor to disease progression) but not levels of gamma interferon (a key cytokine in the protective immune response in TB), as measured by ELISA. Combined, these data suggest that CFP32 serves a necessary biological function(s) in tubercle bacilli and may contribute to theM. tuberculosispathogenic mechanism. Overall, CFP32 is an attractive target for drug and vaccine design as well as new diagnostic strategies.
Identification and Characterization ofpptA: a Gene Involved in the Phase-Variable Expression ofPhosphorylcholine on Pili ofNeisseriameningitidis
Authors: Warren Matthew J. , Jennings Michael P. 
Published: November 2003

ABSTRACTPili of pathogenicNeisseriaare major virulence factors associated with adhesion, cytotoxicity, twitching motility, autoaggregation, and DNA transformation. Pili are modified posttranslationally by the addition of phosphorylcholine. However, no genes involved in either the biosynthesis or the transfer of phosphorylcholine inNeisseria meningitidishave been identified. In this study, we identified five candidate open reading frames (ORFs) potentially involved in the biosynthesis or transfer of phosphorylcholine to pilin inN. meningitidis. Insertional mutants were constructed for each ORF inN.meningitidisstrain C311#3 to determine their effect on phosphorylcholine expression. The effect of the mutant ORFs on the modification by phosphorylcholine was analyzed by Western analysis with phosphorylcholine-specific monoclonal antibody TEPC-15. Analysis of the mutants showed that ORF NMB0415, now defined aspptA(pilin phosphorylcholine transferase A), is involved in the addition of phosphorylcholine to pilin inN. meningitidis. Additionally, the phase variation (high frequency on-off switching of expression) of phosphorylcholine on pilin is due to changes in a homopolymeric guanosine tract inpptA.
Heterologous Priming-Boosting Immunization of Cattle withMycobacterium tuberculosis85A Induces Antigen-Specific T-Cell Responses
Authors: Taracha Evans L. N. , Bishop Richard , Musoke Antony J. , Hill Adrian V. S. , Gilbert Sarah C. 
Published: November 2003

ABSTRACTHeterologous priming-boosting vaccination regimens involving priming with plasmid DNA antigen constructs and inoculating (boosting) with the same recombinant antigen expressed in replication-attenuated poxviruses have recently been demonstrated to induce immunity, based on CD4+- and CD8+-T-cell responses, against several diseases in both rodents and primates. We show that similar priming-boosting vaccination strategies using the 85A antigen ofMycobacterium tuberculosisare effective in inducing antigen-specific gamma interferon-secreting CD4+and CD8+T cells, detected by a bovine enzyme-linked immunospot assay, inBos indicuscattle. T-cell responses induced by priming with either plasmid DNA or fowlpox virus 85A constructs were enhanced by boosting with modified vaccinia virus Ankara expressing the same antigen administered intradermally. On the basis of the data, it appears that intradermal priming was more effective than intramuscular delivery of the priming dose for boosting with the modified vaccinia virus Ankara strain in cattle. Using either fowlpox virus or DNA priming, there was a significant bias toward induction of CD4+- rather than CD8+-T-cell responses. These data illustrate the general applicability of priming-boosting vaccination strategies for induction of antigen-specific T-cell responses and suggest that the method may be useful for development of veterinary vaccines.