bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventing Migraine: A Study of Precipitating Factors
Authors: Blau J.N. , Thavapalan M.
Published: June 2005

SYNOPSIS

Precipitants of individual migraine attacks were studied in 23 migraineurs. Patients were aware of 91 precipitants (average 4 per patient); by direct questioning we could add a further 127 (average 5.5 per patient) provoking factors for migraine episodes.

Avoiding these stimuli reduced attacks from 2 to 1g per month in 19 of the 23 patients without prophylactic drugs. Lessened severity or better analgesic control was noted by some. In 4 of the 23 patients the frequency of attacks remained unchanged.
Sublingual Administration of Flunarizine for Acute Migraine: Will Flunarizine Take the Place of Ergotamine?
Authors: Takeshima Takao , Nishikawa Seiho , Takahashi Kazuro
Published: June 2005

SYNOPSIS

Clinical effectiveness of 10 mg sublingual flunarizine during 89 headache attacks was observed in 68 chronic headache patients. The study population consisted of 36 patients with migraine, 12 with combined headache, 11 with muscle contraction headache (MCH) and nine with cluster headache. Improved cases, defined as cases showing more than moderate improvement, were 75.0% in the migraine group, 50.0% in the combined headache group, 18.2% in the MCH group and 33.3% in the cluster headache group. The migraine group showed a significantly higher percentage of improved cases than did the MCH group (p<0.002). The group in which subjects received flunarizine within 10 min. from the beginning of headache, showed significantly better improvement than did the group in which subjects were treated after 10 min. (p<0.01). No remarkable side effects were observed except for transient numbness of the tongue and a feeling of sleepiness. Four typical case histories utilizing flunarizine administration, and a case showing recovery from angiospasm after sublingual flunarizine administration during an angiographic examination, are reported. A possible favorable role of flunarizine during migraine attacks is discussed. Double blind studies based on the present observations are necessary.
Relaxation Therapy and Compliance in the Treatment of Adolescent Headache
Authors: Wisniewski Jack J. , Genshaft Judy L. , Mulick James A. , Mulick James A. , Mulick James A. , Coury Daniel L. , Coury Daniel L. , Hammer David
Published: June 2005

SYNOPSIS

Few controlled studies have examined the effectiveness of relaxation therapy for the treatment of adolescent headaches. In this study, ten chronic headache sufferers (migraine or muscle contraction), ranging in age from 12 to 17 years (M = 13.5 SD = 1.3), were sequentially assigned to either a relaxation therapy or waiting‐list control group. Following treatment, subjects in the treatment group demonstrated significantly lower Headache Index scores than subjects in the control group (U = 0, p £ .004). Group differences in Headache Free Days, Peak Headache Rating, and Medication Index scores were not significant; differences in Medication Index scores approached significance at U = 3, p £ .03. Objective compliance to treatment data indicated subjects overreported their actual practice time, on average, by 70%. Results and implications for future research are discussed.
Galleria mellonella
as a Model System To Study
Cryptococcus neoformans
Pathogenesis
Authors: Mylonakis Eleftherios , Moreno Roberto , El Khoury Joseph B. , Idnurm Alexander , Heitman Joseph , Calderwood Stephen B. , Ausubel Frederick M. , Diener Andrew
Published: June 2005

Evaluation of
Cryptococcus neoformans
virulence in a number of nonmammalian hosts suggests that
C. neoformans
is a nonspecific pathogen. We used the killing of
Galleria mellonella
(the greater wax moth) caterpillar by
C. neoformans
to develop an invertebrate host model system that can be used to study cryptococcal virulence, host immune responses to infection, and the effects of antifungal compounds. All varieties of
C. neoformans
killed
G. mellonella
. After injection into the insect hemocoel,
C. neoformans
proliferated and, despite successful phagocytosis by host hemocytes, killed caterpillars both at 37°C and 30°C. The rate and extent of killing depended on the cryptococcal strain and the number of fungal cells injected. The sequenced
C. neoformans
clinical strain H99 was the most virulent of the strains tested and killed caterpillars with inocula as low as 20 CFU/caterpillar. Several
C. neoformans
genes previously shown to be involved in mammalian virulence (
CAP59
,
GPA1
,
RAS1
, and
PKA1
) also played a role in
G. mellonella
killing. Combination antifungal therapy (amphotericin B plus flucytosine) administered before or after inoculation was more effective than monotherapy in prolonging survival and in decreasing the tissue burden of cryptococci in the hemocoel. The
G. mellonella
-
C. neoformans
pathogenicity model may be a substitute for mammalian models of infection with
C. neoformans
and may facilitate the in vivo study of fungal virulence and efficacy of antifungal therapies.
Arrangement of the Translocator of the Autotransporter Adhesin Involved in Diffuse Adherence on the Bacterial Surface
Authors: Müller Daniel , Benz Inga , Tapadar Damini , Buddenborg Christian , Greune Lilo , Schmidt M. Alexander
Published: June 2005

Autotransporters of gram-negative bacteria are single-peptide secretion systems that consist of a functional N-terminal α-domain (“passenger”) fused to a C-terminal β-domain (“translocator”). How passenger proteins are translocated through the outer membrane has not been resolved, and at present essentially three different models are discussed. In the widely accepted “hairpin model” the passenger proteins are translocated through a channel formed by the β-barrel of the translocator that is integrated in the outer membrane. This model has been challenged by a recent proposal for a general autotransporter model suggesting that there is a hexameric translocation pore that is generated by the oligomerization of six β-domains. A third model suggests that conserved Omp85 participates in autotransporter integration and passenger protein translocation. To examine these models, in this study we investigated the presence of putative oligomeric structures of the translocator of the autotransporter adhesin involved in diffuse adherence (AIDA) in vivo by cross-linking techniques. Furthermore, the capacity of isolated AIDA fusion proteins to form oligomers was studied in vitro by several complementary analytical techniques, such as analytical gel filtration, electron microscopy, immunogold labeling, and cross-linking of recombinant autotransporter proteins in which different passenger proteins were fused to the AIDA translocator. Our results show that the AIDA translocator is mostly present as a monomer. Only a fraction of the AIDA autotransporter was found to form dimers on the bacterial surface and in solution. Higher-order structures, such as hexamers, were not detected either in vivo or in vitro and can therefore be excluded as functional moieties for the AIDA autotransporter.
Listeriolysin O-Induced Membrane Permeation Mediates Persistent Interleukin-6 Production in Caco-2 Cells duringListeria monocytogenesInfection In Vitro
Authors: Tsuchiya Kohsuke , Kawamura Ikuo , Takahashi Akira , Nomura Takamasa , Kohda Chikara , Mitsuyama Masao
Published: June 2005

Listeriolysin O (LLO), a major virulence factor ofListeria monocytogenes, is a member of the cholesterol-dependent cytolysin family and plays important roles not only in survival of this bacterium in phagocytes but also in induction of various cellular responses, including cytokine production. In this work, we examined the involvement of LLO in induction of the cytokine response in intestinal epithelial cells, the front line of host defense against food-borne listeriosis. Infection of Caco-2 cells with wild-typeL. monocytogenesinduced persistent expression of interleukin-6 (IL-6) mRNA. In contrast, IL-6 expression was observed only transiently during infection with non-LLO-producing strains. A sublytic dose of recombinant LLO (rLLO) induced the expression of IL-6 via formation of membrane pores. Under conditions of LLO-induced pore formation without extensive cell lysis, Ca2+influx was observed, and the IL-6 expression induced by rLLO was inhibited by pretreatment with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), an intracellular Ca2+chelator. LLO secreted by cytoplasmicL. monocytogenesappeared to induce pore formation in the membrane and to enable the trafficking of intracellular and extracellular molecules. Pretreatment with BAPTA-AM inhibited persistent IL-6 expression in Caco-2 cells infected with wild-typeL. monocytogenes. These results suggest that LLO is involved in IL-6 production in the late phase of infection through the formation of Ca2+-permeable pores and subsequent Ca2+-dependent modulation of signaling and gene expression.
Intranasal Administration of RecombinantNeisseria gonorrhoeaeTransferrin Binding Proteins A and B Conjugated to the Cholera Toxin B Subunit Induces Systemic and Vaginal Antibodies in Mice
Authors: Price Gregory A. , Russell Michael W. , Cornelissen Cynthia Nau
Published: June 2005

The transferrin binding proteins (TbpA and TbpB) comprise the gonococcal transferrin receptor and are considered potential antigens for inclusion in a vaccine againstNeisseria gonorrhoeae. Intranasal (IN) immunization has shown promise in development of immunity against sexually transmitted disease pathogens, in part due to the induction of antigen-specific genital tract immunoglobulin A (IgA) and IgG. Conjugation of antigens to the highly immunogenic cholera toxin B subunit (Ctb) enhances antibody responses in the serum and mucosal secretions following IN vaccination. In the current study, we characterized the anti-Tbp immune responses following immunization of mice IN with recombinant transferrin binding proteins (rTbpA and rTbpB) conjugated to rCtb. We found that both rTbpA-Ctb and rTbpB-Ctb conjugates administered IN induced antibody responses in the serum and genital tract. IN immunization resulted in both IgA and IgG in the genital tract; however, subcutaneous immunization mainly generated IgG. Surprisingly, rTbpA alone was immunogenic and induced serum and mucosal antibody responses similar to those elicited against the rTbpA-Ctb conjugate. Overall, rTbpB was much more immunogenic than rTbpA, generating serum IgG levels that were greater than those elicited against rTbpA. Bactericidal assays conducted with sera collected from mice immunized IN with TbpA and/or TbpB indicated that both antigens generated antibodies with bactericidal activity. Anti-TbpA antibodies were cross-bactericidal against heterologous gonococcal strains, whereas TbpB-specific antibodies were less cross-reactive. By contrast, antibodies elicited via subcutaneous immunization were not cross-bactericidal against heterologous strains, indicating that IN vaccination could be the preferred route for elicitation of biologically functional antibodies.
Suppression of Bladder Epithelial Cytokine Responses by UropathogenicEscherichia coli
Authors: Hunstad David A. , Justice Sheryl S. , Hung Chia S. , Lauer Scott R. , Hultgren Scott J.
Published: June 2005

Urinary tract infections are most commonly caused by uropathogenic strains ofEscherichia coli(UPEC), which invade superficial bladder epithelial cells via a type 1 pilus-dependent mechanism. Inside these epithelial cells, UPEC organisms multiply to high numbers to form intracellular bacterial communities, allowing them to avoid immune detection. Bladder epithelial cells produce interleukin-6 (IL-6) and IL-8 in response to laboratory strains ofE. coliin vitro. We investigated the ability of UPEC to alter epithelial cytokine signaling by examining the in vitro responses of bladder epithelial cell lines to the cystitis strains UTI89 and NU14. The cystitis strains induced significantly less IL-6 than did the laboratoryE. colistrain MG1655 from 5637 and T24 bladder epithelial cells. The cystitis strains also suppressed epithelial cytokine responses to exogenous lipopolysaccharide (LPS) and to laboratoryE. coli. We found that insertional mutations in therfaandrfboperons and in thesurAgene all abolished the ability of UTI89 to suppress cytokine induction. Therfaandrfboperons encode LPS biosynthetic genes, whilesurAencodes a periplasmiccis-transprolyl isomerase important in the biogenesis of outer membrane proteins. We conclude that, in this in vitro model system, cystitis strains of UPEC have genes encoding factors that suppress proinflammatory cytokine production by bladder epithelial cells.
Oral Spore Vaccine Based on Live Attenuated Nontoxinogenic
Bacillus anthracis
Expressing Recombinant Mutant Protective Antigen
Authors: Aloni-Grinstein R. , Gat O. , Altboum Z. , Velan B. , Cohen S. , Shafferman A.
Published: June 2005

An attenuated nontoxinogenic nonencapsulated
Bacillus anthracis
spore vaccine expressing high levels of recombinant mutant protective antigen (PA), which upon subcutaneous immunization provided protection against a lethal
B. anthracis
challenge, was found to have the potential to serve also as an oral vaccine. Guinea pigs immunized per os with the recombinant spore vaccine were primed to
B. anthracis
vegetative antigens as well as to PA, yet only a fraction of the animals (30% to 50%) mounted a humoral response to all of these antigens. Protective immunity provided by per os immunization correlated with a threshold level of PA neutralizing antibody titers and was long-lasting. Protection conferred by per os immunization was attained when the vaccine was administered in the sporogenic form, which, unlike the vegetative cells, survived passage through the gastrointestinal tract. A comparison of immunization of unirradiated spores with immunization of γ-irradiated spores demonstrated that germination and de novo synthesis of PA were prerequisites for mounting an immune protective response. Oral immunization of guinea pigs with attenuated
B. anthracis
spores resulted in a characteristic anti-PA immunoglobulin isotype profile (immunoglobulin [G1 IgG1] versus IgG2), as well as induction of specific anti-PA secretory IgA, indicating development of mucosal immunity.
Nontoxic Shiga Toxin Derivatives fromEscherichia coliPossess Adjuvant Activity for the Augmentation of Antigen-Specific Immune Responses via Dendritic Cell Activation
Authors: Ohmura Mari , Yamamoto Masafumi , Tomiyama-Miyaji Chikako , Yuki Yoshikazu , Takeda Yoshifumi , Kiyono Hiroshi
Published: June 2005

Shiga toxin (Stx) derivatives, such as the Stx1 B subunit (StxB1), which mediates toxin binding to the membrane, and mutant Stx1 (mStx1), which is a nontoxic doubly mutated Stx1 harboring amino acid substitutions in the A subunit, possess adjuvant activity via the activation of dendritic cells (DCs). Our results showed that StxB1 and mStx1, but not native Stx1 (nStx1), resulted in enhanced expression of CD86, CD40, and major histocompatibility complex (MHC) class II molecules and, to some extent, also enhanced the expression of CD80 on bone marrow-derived DCs. StxB1-treated DCs exhibited an increase in tumor necrosis factor alpha and interleukin-12 (IL-12) production, a stimulation of DO11.10 T-cell proliferation, and the production of both Th1 and Th2 cytokines, including gamma interferon (IFN-γ), IL-4, IL-5, IL-6, and IL-10. When mice were given StxB1 subcutaneously, the levels of CD80, CD86, and CD40, as well as MHC class II expression by splenic DCs, were enhanced. The subcutaneous immunization of mice with ovalbumin (OVA) plus mStx1 or StxB1 induced high titers of OVA-specific immunoglobulin M (IgM), IgG1, and IgG2a in serum. OVA-specific CD4+T cells isolated from mice immunized with OVA plus mStx1 or StxB1 produced IFN-γ, IL-4, IL-5, IL-6, and IL-10, indicating that mStx1 and StxB1 elicit both Th1- and Th2-type responses. Importantly, mice immunized subcutaneously with tetanus toxoid plus mStx1 or StxB1 were protected from a lethal challenge with tetanus toxin. These results suggest that nontoxic Stx derivatives, including both StxB1 and mStx1, could be effective adjuvants for the induction of mixed Th-type CD4+T-cell-mediated antigen-specific antibody responses via the activation of DCs.
Saturation of Immunoglobulin E (IgE) Binding Sites by Polyclonal IgE Does Not Explain the Protective Effect of Helminth Infections against Atopy
Authors: Mitre Edward , Norwood Stephanie , Nutman Thomas B.
Published: June 2005

One hypothesis for the decreased rates of atopy observed among helminth-infected individuals is that parasite-induced polyclonal immunoglobulin E (IgE) outcompetes allergen-specific IgE for FcεRI binding on basophils and mast cells. In experiments with fresh blood drawn from filaria-infected patients, we found no association between ratios of polyclonal toBrugia malayiantigen (BmAg)-specific IgE (range, 14:1 to 388:1) and basophil responses to BmAg as measured by histamine release. Using serum samples from a filaria-infected patient who also had dust mite (Dermatophagoides pteronyssinus)-specific IgE antibodies from time points with various ratios of polyclonal toD. pteronyssinus-specific IgE (16:1 to 86:1), we demonstrated that increased ratios of polyclonal toD. pteronyssinus-specific IgE did not attenuate basophil sensitization as measured byD. pteronyssinus-specific histamine release. Suppression of histamine release was likely not observed in either of these sets of experiments because polyclonal to antigen-specific IgE ratios were not sufficiently high, as concurrent passive sensitization of basophil experiments required ratios of polyclonal to antigen-specific IgE of greater than 500:1 to suppress basophil histamine release. Further, the intensity of IgE staining in basophil populations from 20 patients with active filaria infections correlated strongly with total serum IgE levels (rho = 0.698;P= 0.0024) with no plateau in intensity of IgE staining, even though some patients had total IgE levels of greater than 10,000 ng/ml. Our data therefore suggest that in helminth infections (and in filarial infections in particular), the ratios of polyclonal to allergen-specific IgE rarely reach those levels necessary to inhibit allergen-specific IgE-FcεRI binding and to suppress allergen-induced degranulation of mast cells and basophils.
Trichomonas vaginalis-Induced Epithelial Monolayer Disruption and Human Immunodeficiency Virus Type 1 (HIV-1) Replication: Implications for the Sexual Transmission of HIV-1
Authors: Guenthner Patricia C. , Secor W. Evan , Dezzutti Charlene S.
Published: June 2005

The objective of this study was to evaluate potential mechanisms ofTrichomonas vaginalisinvolvement in human immunodeficiency virus type 1 (HIV-1) transmission. Polarized monolayer integrity of primary cervical and prostate epithelial cells or cell lines cultured withT. vaginaliswas measured by monitoring transepithelium resistance. The effect ofT. vaginalisisolates on HIV-1 passage through polarized epithelial cell monolayers was evaluated for HIV-1 p24gagin the basolateral supernatants. Coincubation withT. vaginalisisolates induced disruption of monolayer integrity and resulted in passage of virus to the basolateral side of the monolayer. Furthermore, there was isolate variability in which two isolates induced greater monolayer damage and increased HIV-1 passage than did the other two isolates. Coincubation ofT. vaginalisisolates with acutely HIV-1-infected peripheral blood mononuclear cells enhanced HIV-1 replication. This enhancement was associated with cellular proliferation and activation, as well as with tumor necrosis factor alpha production. In contrast to the monolayer disruption, the effect ofT. vaginalison HIV-1 replication was not isolate dependent. Thus, two mechanisms have been identified that could contribute to the epidemiologic association of trichomoniasis with the sexual transmission of HIV-1. (i)T. vaginalisdisruption of urogenital epithelial monolayers could facilitate passage of HIV-1 to underlying layers. (ii) Activation of local immune cells byT. vaginalisin the presence of infectious HIV-1 might lead to increased viral replication. Collectively, these data suggest the need for more vigilant efforts in the diagnosis and treatment ofT. vaginalisin women and men, especially in countries with a high prevalence of HIV-1.
Differential Regulation of β-Chemokines in Children with
Plasmodium falciparum
Malaria
Authors: Ochiel Daniel O. , Awandare Gordon A. , Keller Christopher C. , Hittner James B. , Kremsner Peter G. , Weinberg J. Brice , Perkins Douglas J.
Published: June 2005

Chemokines regulate the host immune response to a variety of infectious pathogens. Since the role of chemokines in regulating host immunity in children with
Plasmodium falciparum
malaria has not previously been reported, circulating levels of β-chemokines (MIP-1α, MIP-1β, and RANTES) and their respective transcriptional profiles in ex vivo peripheral blood mononuclear cells (PBMCs) were investigated. Peripheral blood MIP-1α and MIP-1β levels were significantly elevated in mild and severe malaria, while RANTES levels decreased with increasing disease severity. β-Chemokine gene expression profiles in blood mononuclear cells closely matched those of circulating β-chemokines, illustrating that PBMCs are a primary source for the observed pattern of β-chemokine production during acute malaria. Statistical modeling revealed that none of the chemokines was significantly associated with either parasitemia or anemia. Additional investigations in healthy children with a known history of malaria showed that children with prior severe malaria had significantly lower baseline RANTES production than children with a history of mild malaria, suggesting inherent differences in the ability to produce RANTES in these two groups. Baseline MIP-1α and MIP-1β did not significantly differ between children with prior severe malaria and those with mild malaria. Additional in vitro experiments in PBMCs from healthy, malaria-naïve donors revealed that
P. falciparum
-derived hemozoin (Hz; malarial pigment) and synthetic Hz (β-hematin) promote a similar pattern of β-chemokine gene expression. Taken together, the results presented here demonstrate that children with severe malaria have a distinct profile of β-chemokines characterized by increased circulating levels of MIP-1α and MIP-1β and decreased RANTES. Altered patterns of circulating β-chemokines result, at least in part, from Hz-induced changes in β-chemokine gene expression in blood mononuclear cells.
Roles of 3-Deoxy-
d
-
manno
-2-Octulosonic Acid Transferase from
Moraxella catarrhalis
in Lipooligosaccharide Biosynthesis and Virulence
Authors: Peng Daxin , Choudhury Biswa P. , Petralia Ronald S. , Carlson Russell W. , Gu Xin-Xing
Published: June 2005

Lipooligosaccharide (LOS), a major outer membrane component of
Moraxella catarrhalis
, is a possible virulence factor in the pathogenesis of human infections caused by the organism. However, information about the roles of the oligosaccharide chain from LOS in bacterial infection remains limited. Here, a
kdtA
gene encoding 3-deoxy-
d
-
manno
-2-octulosonic acid (Kdo) transferase, which is responsible for adding Kdo residues to the lipid A portion of the LOS, was identified by transposon mutagenesis and construction of an isogenic
kdtA
mutant in strain O35E. The resulting O35EkdtA mutant produced only lipid A without any core oligosaccharide, and it was viable. Physicochemical and biological analysis revealed that the mutant was susceptible to hydrophobic reagents and a hydrophilic glycopeptide and was sensitive to bactericidal activity of normal human serum. Importantly, the mutant showed decreased toxicity by the
Limulus
amebocyte lysate assay, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. These data suggest that the oligosaccharide moiety of the LOS is important for the biological activity of the LOS and the virulence capability of the bacteria in vitro and in vivo. This study may bring new insights into novel vaccines or therapeutic interventions against
M. catarrhalis
infections.
SepZ/EspZ Is Secreted and Translocated into HeLa Cells by the Enteropathogenic
Escherichia coli
Type III Secretion System
Authors: Kanack Kristen J. , Crawford J. Adam , Tatsuno Ichiro , Karmali Mohamed A. , Kaper James B.
Published: June 2005

Enteropathogenic
Escherichia coli
(EPEC) is a major bacterial cause of infantile diarrhea in developing countries and is the prototype for a group of gastrointestinal pathogens causing characteristic attaching and effacing (A/E) histopathology on intestinal epithelia. A/E pathogens utilize a type III secretion system (TTSS), encoded by the locus of enterocyte effacement (LEE) pathogenicity island, to deliver effector proteins into host cells. Here, we investigate sequence divergence of the LEE-encoded SepZ protein and identify it as a TTSS-secreted and -translocated molecule. SepZ is hypervariable among A/E pathogens, with sequences sharing between 60 to 81% amino acid identity with SepZ of EPEC. A SepZ-CyaA fusion was secreted and translocated into HeLa cells in a TTSS-dependent manner. Additionally, we determined that the first 20 amino acids of SepZ were sufficient to direct its translocation. In contrast to previous studies suggesting a role in invasion and the structure and/or regulation of the TTSS, we found that SepZ does not mediate uptake of EPEC into host cells or affect translocation and tyrosine phosphorylation of the translocated intimin receptor. Immunohistochemistry reveals that, after an extended HeLa cell infection, accumulated SepZ can be detected beneath the site of bacterial attachment in a subset of pedestal regions. To indicate its newly identified status as a translocated effector protein, we propose to rename SepZ as EspZ.
Involvement ofListeria monocytogenesPhosphatidylinositol-Specific Phospholipase C and Host Protein Kinase C in Permeabilization of the Macrophage Phagosome
Authors: Poussin Mathilde A. , Goldfine Howard
Published: June 2005

We have previously shown that phosphatidylinositol-specific phospholipase C (PI-PLC) produced byListeria monocytogenesactivates a host protein kinase C (PKC) cascade which promotes escape of the bacterium from a macrophage-like cell phagosome. Here, we provide evidence linking bacterial PI-PLC and host PKC β to phagosome permeabilization, which precedes escape.
Cross-Recognition ofN-Formylmethionine Peptides Is a General Characteristic of H2-M3-Restricted CD8+T Cells
Authors: Ploss Alexander , Tran An , Menet Ewa , Leiner Ingrid , Pamer Eric G.
Published: June 2005

H2-M3-restricted CD8+T cells can exhibit cross-reactivity to different bacterially derivedN-formylmethionine peptides. The extent of this promiscuity is unclear. We deleted the nonredundant fMIVTLF epitope and found thatListeria monocytogenesstill primed fMIVTLF-specific T cells. Thus, cross-reactivity appears to be a more general characteristic of H2-M3-restricted T cells.
Campylobacter jejuni
Induces Secretion of Proinflammatory Chemokines from Human Intestinal Epithelial Cells
Authors: Hu Lan , Hickey Thomas E.
Published: June 2005

Campylobacter jejuni
is a common cause of diarrhea in humans. While the pathogenic mechanisms of
C. jejuni
are not completely understood, host inflammatory responses are thought to be contributing factors. In this report,
C. jejuni
81-176 is shown to up-regulate chemokines essential to inflammatory responses. Growth-related oncogene α (GROα), GROγ, macrophage inflammatory protein 1, monocyte chemoattractant protein 1 (MCP-1), and gamma interferon-inducible protein 10 (γIP-10) mRNA transcription in INT-407 cells was enhanced within 4 h of bacterial exposure. Infection with viable campylobacters was necessary for sustained chemokine transcription and was NF-κB dependent. GROα, γIP-10, and MCP-1 chemokine secretions were confirmed by immunological assays.
Genome Scale Identification ofTreponema pallidumAntigens
Authors: McKevitt Matthew , Brinkman Mary Beth , McLoughlin Melanie , Perez Carla , Howell Jerrilyn K. , Weinstock George M. , Norris Steven J. , Palzkill Timothy
Published: June 2005

Antibody responses for 882 of the 1,039 proteins in the proteome ofTreponema pallidumwere examined. Sera collected from infected rabbits were used to systematically identify 106 antigenic proteins, including 22 previously identified antigens and 84 novel antigens. Additionally, sera collected from rabbits throughout the course of infection demonstrated a progression in the breadth and intensity of humoral immunoreactivity against a representative panel ofT. pallidumantigens.
INTERPRETING GROUPS AND FIELDS IN SOME NONELEMENTARY CLASSES
Authors: HYTTINEN TAPANI , LESSMANN OLIVIER , SHELAH SAHARON
Published: June 2005

This paper is concerned with extensions of geometric stability theory to some nonelementary classes. We prove the following theorem:

Theorem. Let [Formula: see text] be a large homogeneous model of a stable diagram D. Let p, q ∈ SD(A), where p is quasiminimal and q unbounded. Let [Formula: see text] and [Formula: see text]. Suppose that there exists an integer n < ω such that [Formula: see text] for any independent a1, …, an∈ P and finite subset C ⊆ Q, but [Formula: see text] for some independent a1, …, an, an+1∈ P and some finite subset C ⊆ Q.

Then [Formula: see text] interprets a group G which acts on the geometry P′ obtained from P. Furthermore, either [Formula: see text] interprets a non-classical group, or n = 1,2,3 and

•If n = 1 then G is abelian and acts regularly on P′.

•If n = 2 the action of G on P′ is isomorphic to the affine action of K ⋊ K* on the algebraically closed field K.

•If n = 3 the action of G on P′ is isomorphic to the action of PGL2(K) on the projective line ℙ1(K) of the algebraically closed field K.

We prove a similar result for excellent classes.
Concerted and Birth-and-Death Evolution of Multigene Families
Authors: Nei Masatoshi , Rooney Alejandro P.
Published: June 2005

Until around 1990, most multigene families were thought to be subject to concerted evolution, in which all member genes of a family evolve as a unit in concert. However, phylogenetic analysis of MHC and other immune system genes showed a quite different evolutionary pattern, and a new model called birth-and-death evolution was proposed. In this model, new genes are created by gene duplication and some duplicate genes stay in the genome for a long time, whereas others are inactivated or deleted from the genome. Later investigations have shown that most non-rRNA genes including highly conserved histone or ubiquitin genes are subject to this type of evolution. However, the controversy over the two models is still continuing because the distinction between the two models becomes difficult when sequence differences are small. Unlike concerted evolution, the model of birth-and-death evolution can give some insights into the origins of new genetic systems or new phenotypic characters.
RANK ligand and TNF-α mediate acid-induced bone calcium efflux in vitro
Authors: Frick Kevin K. , LaPlante Kelly , Bushinsky David A.
Published: June 2005

Chronic metabolic acidosis stimulates net calcium efflux from bone due to increased osteoclastic bone resorption and decreased osteoblastic collagen synthesis. Previously, we determined that incubation of neonatal mouse calvariae in medium simulating physiological metabolic acidosis leads to a significant, cyclooxygenase-dependent, increase in RNA for bone cell receptor activator of NF-κB ligand (RANKL) compared with incubation in neutral pH medium. In this study, we tested the hypothesis that the acid-mediated increase in RANKL expression is a primary mechanism for the stimulated osteoclastic resorption. Acid medium increased the medium concentration of sRANKL without altering the concentration of the decoy receptor osteoprotegerin (OPG). Inhibition of the RANKL pathway with concentrations of OPG up to 25 ng/ml, far greater than physiological, did not significantly decrease the robust acid-induced Ca efflux from bone nor did incubation of the calvariae with a different inhibitor, RANK/Fc (up to 50 ng/ml). Thus acid-induced net Ca efflux appears to involve mechanisms in addition to the RANK/RANKL pathway. Osteoblasts also produce TNF-α, another cytokine that stimulates the maturation and activity of osteoclasts. Incubation of calvariae in acid medium caused a significant increase in TNF-α levels. Incubation of calvariae with anti-TNF (up to 250 ng/ml) did not significantly decrease acid-induced net Ca efflux. However, the combination of RANK/Fc plus anti-TNF caused a significant but subtotal reduction in acid-induced Ca efflux, whereas the combination of RANK/Fc plus an isotype-matched control for the anti-TNF had no effect on Ca release. Thus simultaneous inhibition of RANKL and TNF-α is necessary to reduce acid-induced, cell-mediated net Ca efflux from bone; however, additional osteoblast-produced factors must also be involved in acid-induced, cell-mediated bone resorption.
BOLD indirect vs. ASL direct measurement of muscle perfusion
Authors: Leroy-Willig A.
Published: June 2005

The following is the abstract of the article discussed in the subsequent letter:

Although skeletal muscle perfusion is fundamental to proper muscle function, in vivo measurements are typically limited to those of limb or arterial blood flow, rather than flow within the muscle bed itself. We present a noninvasive functional MRI (fMRI) technique for measuring perfusion-related signal intensity (SI) changes in human skeletal muscle during and after contractions and demonstrate its application to the question of occlusion during a range of contraction intensities. Eight healthy men (aged 20–31 yr) performed a series of isometric ankle dorsiflexor contractions from 10 to 100% maximal voluntary contraction. Axial gradient-echo echo-planar images (repetition time = 500 ms, echo time = 18.6 ms) were acquired continuously before, during, and following each 10-s contraction, with 4.5-min rest between contractions. Average SI in the dorsiflexor muscles was calculated for all 240 images in each contraction series. Postcontraction hyperemia for each force level was determined as peak change in SI after contraction, which was then scaled to that obtained following a 5-min cuff occlusion of the thigh (i.e., maximal hyperemia). A subset of subjects ( n = 4) performed parallel studies using venous occlusion plethysmography to measure limb blood flow. Hyperemia measured by fMRI and plethysmography demonstrated good agreement. Postcontraction hyperemia measured by fMRI scaled with contraction intensity up to 60% maximal voluntary contraction. fMRI provides a noninvasive means of quantifying perfusion-related changes during and following skeletal muscle contractions in humans. Temporal changes in perfusion can be observed, as can the heterogeneity of perfusion across the muscle bed.
Similarity of Direction Tuning Among Responses to Stimulation of Different Whiskers in Neurons of Rat Barrel Cortex
Authors: Kida Hiroyuki , Shimegi Satoshi , Sato Hiromichi
Published: June 2005

Cells in the rat barrel cortex exhibit stimulus-specific response properties. To understand the network mechanism of direction selectivity in response to facial whisker deflection, we examined direction selectivity of neuronal responses to single- and multiwhisker stimulations. In the case of regular-spiking units, i.e., putative excitatory cells, direction preferences were quite similar between responses to single-whisker stimulation of the principal and adjacent whiskers. In multiwhisker stimulation at short (≤5 ms) interstimulus intervals (ISIs), response facilitation was evoked only when the whiskers were deflected to the preferred direction of the response to the single whisker stimulation. These results suggest that there are neuronal networks among cells with different whisker preferences but with a common direction preference that could be the neuronal basis of the direction-selective facilitation of the response to multiwhisker stimulation. In contrast, multiwhisker stimulation at long (≥6 ms) ISIs caused non–direction-selective suppression of the response to the second stimulus. In the case of fast-spiking units, i.e., putative inhibitory cells, poor direction selectivity was exhibited. Thus stimulus direction is represented as the direction-selective responses to the single- and multiwhisker stimulations of putative excitatory cells rather than those of putative inhibitory cells.
A note on asymptotic stability conditions for delay difference equations
Authors: Kaewong T. , Lenbury Y. , Niamsup P.
Published: June 2005

We obtain necessary and sufficient conditions for
the asymptotic stability of the linear delay difference equation
, where n = 0, 1, 2, …, is a real number, and k, l, and N are positive integers
such that k > (N − 1)l.
Mesh‐based interpolation on 2‐manifolds
Authors: Scully Kevin
Published: June 2005

This paper presents a global L1‐estimate for the convergence of
mesh‐based interpolants on 2‐manifolds defined over multiple
coordinate systems and analyzes the convergence of an integral on
a triangulated approximate manifold to the desired integral on the
manifold being approximated. To place this estimate in context,
previous convergence estimates for interpolation techniques on
manifolds are presented. Finally, numerical results demonstrating
the value of the L1‐estimate are presented.
Generalized (ℱ, b, ϕ, ρ, θ)‐univex n‐setfunctions and semiparametric duality models in multiobjective fractional subset programming
Authors: Zalmai G. J.
Published: June 2005

We construct a number of semiparametric duality models and
establish appropriate duality results under various generalized
(ℱ, b, ϕ, ρ, θ)‐univexity assumptions for a multiobjective fractional subset programming problem.
Witt group of Hermitian forms over a noncommutativediscrete valuation ring
Authors: Oukhtite L.
Published: June 2005

We investigate Hermitian forms on finitely generated
torsion modules over a noncommutative discrete valuation ring.
We also give some results for lattices, which still are satisfied
even if the base ring is not commutative. Moreover, for a
noncommutative discrete-valued division algebraD with
valuation ring R and residual division algebra , we prove
that where WT(R) denotes the Witt group
of regular Hermitian forms on finitely generated torsion R‐modules.
Application of an integral formula to CR‐submanifolds of complex hyperbolic space
Authors: Pak Jin Suk , Kim Hyang Sook
Published: June 2005

The purpose of this paper is to study n‐dimensional compact CR‐submanifolds of complex hyperbolic space CH(n+p)/2, and especially to characterize
geodesic hypersphere in CH(n+1)/2 by an integral formula.
Existence and stability of periodic solutions for a classof generalized nonautonomous neural networks with distributed delays
Authors: Li Yongkun , Zhu Lifei , Liu Wenxiang
Published: June 2005

By using the continuation theorem of coincidence degree theory and
Lyapunov functions, we study the existence and global stability of
periodic solutions for a class of generalized nonautonomous neural
networks with distributed delays.
Inefficacy of Piracetam in the Prevention of Painful Crises in Children and Adolescents with Sickle Cell Disease
Authors: Alvim R.C. , Viana M.B. , Pires M.A.S. , Franklin H.M.O.H. , Paula M.J. , Brito A.C. , Oliveira T.F. , Rezende P.V.
Published: June 2005

Analgesia and hydration remain the only safe treatment for painful crises of sickle cell disease; hydroxyurea is effective, but the toxicity is still a problem. Piracetam is a nootropic drug that has reportedly been effective and non-toxic in sickle cell patients, but most studies were not placebo-controlled and included a small number of patients. The present study evaluated the drug in a double-blind crossed placebo-controlled clinical trial in 73 children and adolescents suffering from moderate to severe painful crises for 13 months. Information regarding frequency and severity of pain was acquired through monthly clinical evaluation, visits and house calls, and 4,300 weekly questionnaires filled out by the patients in their domiciles. A monthly pain score was calculated for each patient. Pain was the most frequent adverse manifestation of the disease stressing its significant bio-psycho-social impact. Although nearly all patients and relatives reported a better clinical course throughout the whole study, the drug was ineffective in the prevention of painful crises. This placebo effect may be ascribed to an unplanned and unsystematic ‘cognitive-behavioural’ management of the children. The pain score in the second semester of the study – both in the experimental and in the control groups – was significantly smaller than that in the first semester. In conclusion, piracetam was found to be ineffective in the prevention of painful crises; a powerful placebo effect due to adequate patient care was demonstrated.
Fatal Splenic Rupture Caused by Infiltration of Adult T Cell Leukemia Cells
Authors: Arimura Kosei , Arima Naomichi , Kukita Toshimasa , Inoue Hirosaka , Arai Akihiko , Matsushita Kakushi , Taguchi Shuuhei , Yoshida Hiroki , Ozaki Atsuo , Kawada Hideaki , Akimoto Masaki , Tei Chuwa
Published: June 2005

The spleen is an immunological organ commonly involved in both hematological and nonhematological diseases. Pathological rupture of the spleen has been described in a variety of diseases affecting the spleen. Infections have been cited in most cases involving splenic rupture, but are rare in hematological malignancies despite frequent involvement of the spleen. The present report describes a fatal case of splenic rupture caused by infiltration of adult T cell leukemia cells and reports the mechanism of splenic rupture. The importance of rapid diagnosis and surgery is emphasized.
The Selective Glucocorticoid Receptor Antagonist ORG 34116 Decreases Immobility Time in the Forced Swim Test and Affects cAMP-Responsive Element-Binding Protein Phosphorylation in Rat Brain
Authors: Bachmann Cornelius G. , Bilang-Bleuel Alicia , de Carli Sonja , Linthorst Astrid C.E. , Reul Johannes M.H.M.
Published: June 2005

Glucocorticoid receptor (GR) antagonists can block the retention of the immobility response in the forced swimming test. Recently, we showed that forced swimming evokes a distinct spatiotemporal pattern of cAMP-responsive element-binding protein (CREB) phosphorylation in the dentate gyrus (DG) and neocortex. In the present study, we found that chronic treatment of rats with the selective GR antagonist ORG 34116 decreased the immobility time in the forced swim test, increased baseline levels of phosphorylated CREB (P-CREB) in the DG and neocortex and affected the forced swimming-induced changes in P-CREB levels in a time- and site-specific manner. Overall, we observed that, in control rats, forced swimming evoked increases in P-CREB levels in the DG and neocortex, whereas in ORG 34116-treated animals a major dephosphorylation of P-CREB was observed. These observations underscore an important role of GRs in the control of the phosphorylation state of CREB which seems to be of significance for the immobility response in the forced swim test and extend the molecular mechanism of action of GRs in the brain.
HLA-DRB1 and Anti-Cyclic Citrullinated Peptide Antibody Production in Rheumatoid Arthritis
Authors: Senkpiehl Ilka , Marget Matthias , Wedler Martina , Jenisch Stefan , Georgi Joachim , Kabelitz Dietrich , Steinmann Jörg
Published: June 2005

Anti-cyclic citrullinated peptide antibodies (anti-CCP) are a new diagnostic marker for rheumatoid arthritis (RA), which shows a specificity of 97% and a sensitivity of 81% in the second generation assay. About 61% of RA patients express HLA-DRB1*0401. In a cohort of patients with RA we investigated whether the expression of anti-CCP correlates with the carriage of certain genes on the HLA-DRB1 locus. Our data reveal a highly significant association between anti-CCP and HLA-DR4, and a weaker but still significant association with HLA-DR1. HLA-DRB1*0401 is not a prerequisite for anti-CCP production, but if HLA-DRB1*0401 was present, 90% of our RA patients were anti-CCP positive.
Much Atopy about the Skin: Genome-Wide Molecular Analysis of Atopic Eczema
Authors: Saito Hirohisa
Published: June 2005

Background: Atopic eczema (AE) is a chronic inflammatory skin disorder with an increasing prevalence in industrialized countries. Methods: Genox Research Incorporation was founded in 1996 to identify new genes involved in allergic diseases in collaboration with the National Children’s Hospital in Tokyo. In the AE project, they have discovered several hundred new genes and partial DNA sequences by mainly using microarrays. Here, I review the results obtained using transcriptome analysis, performed by Genox and other investigators. Results:Transcriptome analysis using skin lesion, CD4+ T cells, monocytes and eosinophils derived from AE patients identified some differentially expressed genes which became biologically relevant in the following studies. Missing linkages between these genes have been found due to the recent development of genomics. Conclusion:Many AE-related genes found in the genome-wide studies still remain to be determined regarding their functions and to be systemically organized. After the comprehensive characterization of these genes by further studies, we will identify the precise molecular mechanisms involved in AE and other diseases.
Role of the Adventitia in the Cyclic GMP-Mediated Relaxant Effect of Nω-Hydroxy-L-Arginine in Rat Aorta
Authors: Beranova Petra , Schott Christa , Chalupsky Karel , Kleschyov Andrei L. , Stoclet Jean-Claude , Muller Bernard
Published: June 2005

Nω-hydroxy-L-arginine (L-NOHA), the stable intermediate of the nitric oxide synthase (NOS)-catalyzed reaction, can induce NO/cyclic GMP-dependent relaxation in the rat aorta, in an endothelium- and NOS-independent manner. In this study, the role of the adventitia in the endothelium-independent effect of L-NOHA was investigated. Despite a decrease in norepinephrine (NE)-induced precontraction, adventitia removal in the rat aorta did not markedly alter the relaxant effect of forskolin, S-nitroso-N-acetylpenicillamine or glyceryl trinitrate. In contrast, both inhibition of NE-induced contraction and relaxation of NE-precontracted rings produced by L-NOHA were diminished in the absence of adventitia. Moreover, exposure to L-NOHA significantly enhanced the cyclic GMP level in the media of the aorta with, but not without adventitia. These findings demonstrate the role of the adventitia in the L-NOHA-induced decrease in tone and increase in cyclic GMP in the endothelium-denuded rat aorta. They suggest that NO or an NO-related compound formed from L-NOHA in the adventitia may produce paracrine effects.
A Family Support Organiser for Stroke Patients and Their Carers: A Randomised Controlled Trial
Authors: Tilling Kate , Coshall Catherine , McKevitt Christopher , Daneski Katharine , Wolfe Charles
Published: June 2005

Background: Previous trials of interventions to support stroke survivors and their families in the community have had contradictory and inconclusive results. Using the MRC Framework for Complex Interventions we developed a family support organiser (FSO) service and refined outcome measures for evaluation. We tested the effects of the intervention in a randomised controlled trial. Methods: From 1 March 1999 to 1 April 2001 all first-in-a-lifetime strokes (n = 513) were identified and 340 (96%) of eligible strokes randomised to receive FSO or usual care. Patients and their carers were followed up at 3 months and 1 year post-stroke. Outcomes included satisfaction (main outcome) with hospital staff and outpatient services, use of social services, reintegration to normal living (RNLI) and feelings about life after the stroke. Results: The mean number of contacts with the FSO was 15 (SD = 9.8) per patient. More intervention than control patients received some social services and had increased patient and carer satisfaction in most aspects, particularly with information about recovery and feeling that someone had listened. There was little evidence at 3 or 12 months of differences in RNLI. Conclusions: A meta-analysis of trials in this area is now needed along with further trials of interventions in subgroups of the stroke population to fully identify any benefits of the FSO role.