bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Protective Efficacy of a ProphylacticLeishmania donovaniDNA Vaccine against Visceral and Cutaneous Murine Leishmaniasis
Authors: Aguilar-Be Ingrid , da Silva Zardo Renata , Paraguai de Souza Edilma , Borja-Cabrera Gulnara Patrícia , Rosado-Vallado Miguel , Mut-Martin Mirza , del Rosario García-Miss Maria , Palatnik de Sousa Clarisa Beatriz , Dumonteil Eric
Published: January 2005

The fucose-mannose ligand (FML) complex ofLeishmania donovaniis a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36 (rNH36), and NH36 DNA vaccines against the agents of visceral (L. chagasi) and cutaneous (L. mexicana) leishmaniasis in BALB/c mice. Mice developed weak humoral response to the vaccines alone, except for those immunized with FML. However, all three vaccine groups presented elevated immunoglobulin G (IgG), IgG1, and IgG2a levels after infection withL. chagasi, whereas no differences were observed between vaccine and control groups after infection withL. mexicana. A strong intradermal reaction toL. donovaniandL. mexicanaantigens was observed in mice immunized with rNH36 or FML, whereas mice immunized with NH36 DNA only reacted againstL. donovaniantigens. Experimental infection of immunized mice demonstrated that FML and rNH36 induced significant protection againstL. chagasiinfection with reductions in parasite loads of 79%. FML also conferred partial protection againstL. mexicanainfection. The best protection was observed in mice immunized with the VR1012-NH36 DNA vaccine, which induced an 88% reduction inL. chagasiparasite load and a 65% reduction inL. mexicanalesion size. Fluorescence-activated cell sorting analysis indicated the DNA vaccine induced a two- to fivefold increase in gamma interferon-producing CD4+T cells, indicating a Th1-type immune response. Our results showed that the NH36 DNA vaccine induced a strong immunoprotection against visceral and cutaneous leishmaniasis, suggesting that this DNA vaccine represents a very good candidate for use against severalLeishmaniaspecies.
Mannoproteins fromCryptococcus neoformansPromote Dendritic Cell Maturation and Activation
Authors: Pietrella Donatella , Corbucci Cristina , Perito Stefano , Bistoni Giovanni , Vecchiarelli Anna
Published: January 2005

Our previous data show that mannoproteins (MPs) fromCryptococcus neoformansare able to induce protective responses against bothC. neoformansandCandida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IκBα phosphorylation, which is necessary for nuclear factor κB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.
CpG Oligodeoxynucleotides Adsorbed onto Polylactide-Co-Glycolide Microparticles Improve the Immunogenicity and Protective Activity of the Licensed Anthrax Vaccine
Authors: Xie Hang , Gursel Ihsan , Ivins Bruce E. , Singh Manmohan , O'Hagan Derek T. , Ulmer Jeffrey B. , Klinman Dennis M.
Published: January 2005

To reduce the biothreat posed by anthrax, efforts are under way to improve the protection afforded by vaccination. This work examines the ability of immunostimulatory CpG oligodeoxynucleotides (ODN) adsorbed onto cationic polylactide-co-glycolide (PLG) microparticles (CpG ODN-PLG) to accelerate and boost the protective immunity elicited by Anthrax Vaccine Adsorbed (AVA, the licensed human anthrax vaccine). The results indicate that coadministering CpG ODN-PLG with AVA induces a stronger and faster immunoglobulin G response against the protective antigen of anthrax than AVA alone. Immunized mice were protected from lethal anthrax challenge within 1 week of vaccination with CpG ODN-PLG plus AVA, with the level of protection correlating with serum immunoglobulin G anti-protective antigen titers.
Invariant Vα14 Chain NKT Cells PromotePlasmodium bergheiCircumsporozoite Protein-Specific Gamma Interferon- and Tumor Necrosis Factor Alpha-Producing CD8+T Cells in the Liver after Poxvirus Vaccination of Mice
Authors: Korten Simone , Anderson Richard J. , Hannan Carolyn M. , Sheu Eric G. , Sinden Robert , Gadola Stephan , Taniguchi Masaru , Hill Adrian V. S.
Published: January 2005

Understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. Most studies in mice have focused on splenic and peripheral blood T cells and identified gamma interferon (IFN-γ)-producing CD8+T cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. Invariant natural killer T (Vα14iNKT) cells can also protect against liver stage malaria, when activated, and are abundant in the liver. Since poxviruses have nonspecific immunomodulating effects, which are incompletely understood, we investigated whether recombinant poxviruses affect the protective properties of hepatic Vα14iNKT cells and thus vaccine efficacy. We show that intradermal vaccination with recombinant poxviruses activated Vα14iNKT cells and NK cells in the livers of BALB/c mice while inducing IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing pre-erythrocytic stage antigen-specific CD8+T cells. Greater numbers of hepatic Vα14iNKT cells secreted interleukin-4 than IFN-γ. Vaccinated Vα14iNKT-cell-deficient mice had lower, but still protective levels of hepatic and splenic IFN-γ+and TNF-α+CD8+T cells and better protection rates later after challenge withPlasmodium bergheisporozoites. Therefore, vaccine-activated hepatic Vα14iNKT cells help in generating specific T cells but are not required for protection induced by recombinant poxviruses. Furthermore, double-positive INF-γ+/TNF-α+CD8+T cells were enriched in protected livers, suggesting that cells expressing both of these cytokines may be most relevant for protection.
The M Protein Is Dispensable for Maturation of Streptococcal Cysteine Protease SpeB
Authors: Zimmerlein Björn , Park Hae-Sun , Li Shaoying , Podbielski Andreas , Cleary P. Patrick
Published: January 2005

The streptococcal pyrogenic exotoxin B (SpeB) is an important virulence factor of group A streptococci (GAS) with cysteine protease activity. Maturation of SpeB to a proteolytically active form was suggested to be dependent on cell-wall-anchored M1 protein, the major surface protein of GAS (M. Collin and A. Olsén, Mol. Microbiol.36:1306-1318, 2000). Collin and Olsén showed that mutant GAS strains expressing truncated M protein secrete a conformationally different form of unprocessed SpeB with no proteolytic activity. Alternatively, we hypothesized that a truncated M protein may interfere with processing of this secreted protease, and therefore we tested cysteine protease activity in genetically defined mutant strains that express either no M protein or membrane-anchored M protein with an in-frame deletion of the AB repeat region. Measurements of SpeB activity by cleavage of a substraten-benzoyl-Pro-Phe-Arg-p-nitroanilide hydrochloride showed that the proteolytic activities in culture supernatants of both mutants were similar to those from the wild-type strain. In addition, Western blot analysis of culture supernatants showed that SpeB expression and processing to a mature form was unaffected by either deletion mutation. Therefore, we conclude that M protein is not required for maturation of the streptococcal cysteine protease SpeB.
Solubility and Bioactivity of the
Pseudomonas
Quinolone Signal Are Increased by a
Pseudomonas aeruginosa
-Produced Surfactant
Authors: Calfee M. Worth , Shelton John G. , McCubrey James A. , Pesci Everett C.
Published: January 2005

Pseudomonas aeruginosa
is a gram-negative bacterium that causes serious infections in immunocompromised individuals and cystic fibrosis patients. This opportunistic pathogen controls many of its virulence factors and cellular functions through the activity of three cell-to-cell signals,
N
-(3-oxododecanoyl)-
l
-homoserine lactone,
N
-butyryl-
l
-homoserine lactone, and the
Pseudomonas
quinolone signal (PQS). The activity of these signals is dependent upon their ability to dissolve in and freely diffuse through the aqueous solution in which
P. aeruginosa
happens to reside. Despite this, our data indicated that PQS was relatively insoluble in aqueous solutions, which led us to postulate that
P. aeruginosa
could be producing a PQS-solubilizing factor. In this report, we show that the
P. aeruginosa
-produced biosurfactant rhamnolipid greatly enhances the solubility of PQS in aqueous solutions. The enhanced solubility of PQS led to an increase in PQS bioactivity, as measured by both a gene induction assay and an apoptosis assay. This is the first demonstration of the importance of a bacterial surfactant in the solubilization and bioactivity of a cell-to-cell signal.
A Functional Virulence Complex Composed of Gingipains, Adhesins, and Lipopolysaccharide Shows High Affinity to Host Cells and Matrix Proteins and Escapes Recognition by Host Immune Systems
Authors: Takii Ryosuke , Kadowaki Tomoko , Baba Atsuyo , Tsukuba Takayuki , Yamamoto Kenji
Published: January 2005

Arg-gingipain (Rgp) and Lys-gingipain (Kgp) arePorphyromonas gingivaliscysteine proteinases implicated as major virulence factors in pathologies of periodontitis. We purified a 660-kDa cell-associated gingipain complex existing as a homodimer of two catalytically active monomers which comprises their catalytic and adhesin domains. Electron microscopy revealed that the complex was composed of a globular particle with a 10-nm external diameter possessing one or two electron-dense hole-like structures. Two-dimensional gel electrophoresis and immunoblot analyses revealed the association of lipopolysaccharide (LPS) with the catalytic domains and a hemagglutinin domain, Hgp44, of Rgp and Kgp in the complex. The complex significantly degraded human type I collagen and elastin and strongly disrupted viability of human gingival fibroblasts and umbilical vein endotherial cells with an efficiency which was higher than that of the monomeric gingipains. The native complex produced only a small amount of nitrogen dioxide, tumor necrosis factor alpha, and interleukin-6 by macrophages, whereas the heat-denatured complex resulted in increased production. Inhibition of the proteolytic activities of the gingipain complex did not up-regulate the cytokine production, indicating that the functional domains in LPS are structurally masked by the complex proteins. These results indicate the importance of the complex in evasion of host defense mechanisms as well as in host tissue breakdown.
Contribution of Three Bile-Associated Loci,bsh,pva, andbtlB, to Gastrointestinal Persistence and Bile Tolerance ofListeria monocytogenes
Authors: Begley Máire , Sleator Roy D. , Gahan Cormac G. M. , Hill Colin
Published: January 2005

Listeria monocytogenesmust resist the deleterious actions of bile in order to infect and subsequently colonize the human gastrointestinal tract. The molecular mechanisms used by the bacterium to resist bile and the influence of bile on pathogenesis are as yet largely unexplored. This study describes the analysis of three genes—bsh,pva, andbtlB—previously annotated as bile-associated loci in the sequencedL. monocytogenesEGDe genome (lmo2067, lmo0446, and lmo0754, respectively). Analysis of deletion mutants revealed a role for all three genes in resisting the acute toxicity of bile and bile salts, particularly glycoconjugated bile salts at low pH. Mutants were unaffected in the other stress responses examined (acid, salt, and detergents). Bile hydrolysis assays demonstrate thatL. monocytogenespossesses only one bile salt hydrolase gene, namely,bsh. Transcriptional analyses and activity assays revealed that, although it is regulated by both PrfA and σB, the latter appears to play the greater role in modulatingbshexpression. In addition to being incapable of bile hydrolysis, asigBmutant was shown to be exquisitely sensitive to bile salts. Furthermore, increased expression ofsigBwas detected under anaerobic conditions and during murine infection. A gene previously annotated as a possible penicillin V amidase (pva) or bile salt hydrolase was shown to be required for resistance to penicillin V but not penicillin G but did not demonstrate a role in bile hydrolysis. Finally, animal (murine) studies revealed an important role for bothbshandbtlBin the intestinal persistence ofL. monocytogenes.
TheSalmonella entericaSerovar Typhimurium-Encoded Type III Secretion Systems Can TranslocateChlamydia trachomatisProteins into the Cytosol of Host Cells
Authors: Ho Theresa D. , Starnbach Michael N.
Published: January 2005

Chlamydia trachomatisis an obligate, intracellular pathogen that is a major cause of preventable blindness and infertility worldwide. Although the published genome sequence suggests thatC. trachomatisencodes a type III secretion system, the lack of genetic tools for studyingChlamydiahas hindered the examination of this potentially important class of virulence genes. We have developed a technique to identifyChlamydiaproteins that can be translocated into the host cell cytoplasm by a type III secretion system. We have selected severalChlamydiaproteins and tagged them with a multiple peptide motif element called F8M4. Epitopes contained in the F8M4 tag allow us to use tools corresponding to different arms of the adaptive immune system to detect the expression and translocation of these proteins bySalmonella entericaserovar Typhimurium. In particular, CD8+-T-cell reactivity can be used to detect the translocation of F8M4-tagged proteins into the cytoplasm of host cells. We have found that CD8+-T-cell activity assays are sensitive enough to detect translocation of even a small amount of F8M4-tagged protein. We have used CD8+-T-cell activity to show that CopN, aChlamydiaprotein previously shown to be translocated byYersiniatype III secretion, can be translocated by theSalmonellapathogenicity island 1 (SPI-1) type III secretion system. Additionally, we demonstrate that CopD and Pkn5, twoChlamydiaproteins hypothesized to be substrates of a type III secretion system, are translocated via the SPI-2 type III secretion system of serovar Typhimurium. The epitope tag system described here can be used more generally to examine the expression and subcellular compartmentalization of bacterial proteins deployed during the interaction of pathogens with mammalian cells.
ProbioticLactobacillusspp. DiminishHelicobacter hepaticus-Induced Inflammatory Bowel Disease in Interleukin-10-Deficient Mice
Authors: Peña Jeremy A. , Rogers Arlin B. , Ge Zhongming , Ng Vivian , Li Sandra Y. , Fox James G. , Versalovic James
Published: January 2005

Clinical and experimental evidence has demonstrated the potential role of probiotics in the prevention or treatment of inflammatory bowel disease. Probiotic clones with direct immunomodulatory activity may have anti-inflammatory effects in the intestine. We investigated the roles of tumor necrosis factor alpha (TNF-α)-inhibitoryLactobacillusclones with a pathogen-induced murine colitis model. Murine-derived probiotic lactobacilli were selected in vitro for their ability to inhibit TNF-α secretion byHelicobacter hepaticus-stimulated macrophages. Interleukin-10 (IL-10)-deficient mice were treated with probioticLactobacillus reuteriin combination withLactobacillus paracaseiand then challenged withH. hepaticus. Ten weeks postinoculation, the severity of typhlocolitis was assessed by histologic examination of the cecocolic region. Intestinal proinflammatory cytokine responses were evaluated by real-time quantitative reverse transcriptase PCR and immunoassays, and the quantities of intestinalH. hepaticuswere evaluated by real-time PCR. Intestinal colonization by TNF-α-inhibitory lactobacilli reduced intestinal inflammation inH. hepaticus-challenged IL-10-deficient mice despite similar quantities ofH. hepaticusin cocolonized animals. Proinflammatory colonic cytokine (TNF-α and IL-12) levels were lowered inLactobacillus-treated animals. In thisH. hepaticus-challenged IL-10-deficient murine colitis model, lactobacilli demonstrated probiotic effects by direct modulation of mucosal inflammatory responses.
Cytokine Profiling of Macrophages Exposed toPorphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein
Authors: Zhou Qingde , Desta Tesfahun , Fenton Matthew , Graves Dana T. , Amar Salomon
Published: January 2005

To characterize the roles ofPorphyromonas gingivalisand its components in the disease processes, we investigated the cytokine profile induced by liveP. gingivalis, its lipopolysaccharides (LPS), and its major fimbrial protein, fimbrillin (FimA). Using cytokine antibody arrays, we found thatP. gingivalisLPS and FimA induced a similar profile of cytokine expression when exposed to mouse peritoneal macrophages but that this profile differed significantly in response to liveP. gingivalis. In vitro, mouse peritoneal macrophages were stimulated to produce interleukin-6 (IL-6), granulocyte colony-stimulating factor, and lymphotactin by liveP. gingivalis, but not byP. gingivalisLPS or FimA, while RANTES, gamma interferon, IL-17, vascular cell adhesion molecule 1 (VCAM-1), and vascular endothelial growth factor were induced byP. gingivalisLPS or FimA, but not by liveP. gingivalis. In vivo, IL-6 mRNA was strongly induced only by liveP. gingivaliswhile monocyte chemoattractant protein 1 mRNA was strongly induced only byP. gingivalisLPS and FimA in mouse calvarial scalp, further confirming the differences of cytokine profile induced in vitro. Cytokine antibody arrays using toll-like receptor 2 (TLR2)- and TLR4-deficient macrophages revealed that most of the cytokines induced byP. gingivalisLPS or FimA signal through TLR2, while most of cytokines induced by liveP. gingivalissignal through both TLR2 and TLR4. Interestingly, the activation of TLR2 by liveP. gingivalisinhibited the release of RANTES, VCAM-1, and IL-1α from mouse peritoneal macrophages. A tumor necrosis factor alpha enzyme-linked immunosorbent assay further confirmed thatP. gingivalisLPS and FimA activate mouse peritoneal macrophages via TLR2. These results indicate that host immune cells sense liveP. gingivalisand its components differently, which translates into the expression of different inflammatory cytokine profiles.
The IrgA Homologue Adhesin Iha Is an
Escherichia coli
Virulence Factor in Murine Urinary Tract Infection
Authors: Johnson James R. , Jelacic Srdjan , Schoening Laura M. , Clabots Connie , Shaikh Nurmohammad , Mobley Harry L. T. , Tarr Phillip I.
Published: January 2005

The role of the
Escherichia coli
iron-regulated gene homologue adhesin (Iha) in the pathogenesis of urinary tract infections (UTIs) is unknown. We performed a series of complementary analyses to confirm or refute the hypothesis that Iha is a virulence factor in uropathogenic
E. coli
. Fecal
E. coli
isolates exhibited significantly lower prevalences of
iha
(range, 14 to 22%) than did clinical isolates from cases of pediatric cystitis or pyelonephritis, adult pyelonephritis or urosepsis, or bacteremia (range, 38 to 74%). Recombinant Iha from
E. coli
pyelonephritis isolate CFT073 conferred upon nonadherent
E. coli
ORN172 the ability to adhere to cultured T-24 human uroepithelial cells. In a well-established mouse model of ascending UTI, CFT073 and its derivative UPEC76 (a
pap
[P fimbriae] mutant version of strain CFT073) each significantly outcompeted their respective
iha
deletion mutants in CBA/J mice 48 h after bladder challenge (
P
< 0.03 for urine, both kidneys, and bladders of both constructs, except for bladders of mice challenged with UPEC76 and its deletion mutant, where
P
= 0.11). These data suggest that Iha
CFT073
is a virulence factor and might be a target for anti-UTI interventions.
PppA, a Surface-Exposed Protein ofStreptococcus pneumoniae, Elicits Cross-Reactive Antibodies That Reduce Colonization in a Murine Intranasal Immunization and Challenge Model
Authors: Green Bruce A. , Zhang Ying , Masi Amy W. , Barniak Vicki , Wetherell Michael , Smith Robert P. , Reddy Molakala S. , Zhu Duzhang
Published: January 2005

The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the present conjugate vaccine may still cause pneumococcal disease. To address these serotypes, and the remaining otitis media due toStreptococcus pneumoniae, efforts have been devoted to identifying protective protein antigens. Immunity to conserved surface proteins important for adhesion, nutrient acquisition, or other functions could result in a reduction of colonization and a lower disease potential. We have been searching for conserved surface-exposed proteins fromS. pneumoniaethat may be involved in pathogenesis to test as vaccine candidates. Here, an ∼20-kDa protein that has significant homology to a nonheme iron-containing ferritin protein fromListeria innocuaand other bactoferritins was identified as pneumococcal protective protein A (PppA). We expressed and purified recombinant PppA (rPppA) and evaluated its potential as a vaccine candidate. The antibodies elicited by purified rPppA were cross-reactive with PppA from multiple strains ofS. pneumoniaeand were directed against surface-exposed epitopes. Intranasal immunization of BALB/c mice with PppA protein and either a synthetic monophosphoryl lipid A analog, RC529AF, or a cholera toxin mutant, CT-E29H, used as an adjuvant reduced nasopharyngeal colonization in mice following intranasal challenge with a heterologous pneumococcal strain. PppA-specific systemic and local immunoglobulin G (IgG) and IgA antibody responses were induced. The antisera reacted with whole cells of a heterologousS. pneumoniaetype 3 strain. These observations indicate that PppA may be a promising candidate for inclusion in a vaccine against pneumococcal otitis media.
Molecular Basis of LFER. Simple Model for the Estimation of Brønsted Exponent in Acid-Base Catalysis
Authors: Ponec Robert
Published: January 2005

A simple model was proposed allowing to estimate the Brønsted exponents in acid-base catalysis on the basis of the pKvalues of the species participating in the proton transfer process. The approach was tested using the experimental data on the basically catalyzed halogenation of carbonyl compounds and on the proton removal from nitroalkanes. It has been shown that the model is able to reproduce the Brønsted exponents not only in the case of "ordinary" Brønsted plots with the slope within the expected range 0-1 but also for unusual plots with negative slopes. In addition, the proposed model opens the possibility of calculation of the activation energies of a given proton transfer reaction and also provides straightforward theoretical justification for the validity of the Hammond postulate in these reactions.
Protic Acidity of Some Aliphatic and Alicyclic Hydrocarbons in the Gas Phase and in Solution. An Empirical and Computational Link
Authors: Quintanilla Esther , Dávalos Juan Z. , Herrero Rebeca , Jiménez Pilar , Alkorta Ibon , Abboud José-Luis M.
Published: January 2005

Here we report the results of the study of a set of thirteen hydrocarbons R-H not leading to extensively charge-delocalized anions R- upon ionization, R-H → R- + H+. It essentially involves the following: (i) The computation at the G2 level of the changes in thermodynamic state functions for this process in the gas phase. The reliability of the computational method was further assessed by comparison with CCSD(T)/Aug-cc-pVTZ results. (ii) A direct comparison of the experimentally available thermodynamic (gas phase) and kinetic (solution) data pertaining to this reaction. (iii) A careful re-examination of the experimental data sets and the Brønsted-type relationships derived therefrom by using the computed thermodynamic data. This treatment suggests the existence of mechanistic features affecting the experimental data and indicates the need for further experimental and computational work.
Hydrogen Bonding Contribution to Lipophilicity Parameters. Hydrogen Acceptor and Hydrogen Acceptor Donor Parameters
Authors: Charton Marvin , Charton Barbara I.
Published: January 2005

In our analysis of the composition of lipophilicity parameters by the intermolecular force (IMF) model we have made use of nH, the number of OH and/or NH bonds, as a measure of the hydrogen donor capacity of a substituent; and nn, the number of lone pairs on O and/or N atoms in the substituent, as a measure of the hydrogen acceptor capacity of the substituent. The basis of this method is the reasonable assumption that in 55.6 molar water hydrogen bonding is maximized. The method does not account however for differences in the energy of different types of hydrogen bonds, but further assumes that these differences are to a first approximation negligible. In order to improve the model we have defined a scale of group hydrogen bonding acceptor parameters, ηXHA, and overall hydrogen bond parameters ηXHAD from the water/1-octanol partition coefficients of AkX where Ak is alkyl. These parameters should account for both the extent of hydrogen bonding in water and for the difference in hydrogen bond energies of the various types of hydrogen bonds encountered. Correlations of log P values for Ph(CH2)nX, X1(CH2)X2, and substituted amino acids Xaa with the IMF equation using the ηXHA and ηXHAD parameters demonstrated their use. Correlation of log P values for PhX suggested that for many groups separate sets of ηXHA and ηXHAD values are required when they are bonded to sp2 hybridized carbon rather than sp3 hybridized carbon.
Kinetics and Mechanism of the Aminolysis of S-Aryl O-Ethyl Dithiocarbonates in Acetonitrile
Authors: Oh Hyuck Keun , Oh Ji Young , Sung Dae Dong , Lee Ikchoon
Published: January 2005

The aminolysis of S-aryl O-ethyl dithiocarbonates with benzylamines are studied in acetonitrile at -25.0 °C. The βX (βnuc) values are in the range 0.67-0.77 with a negative cross-interaction constant, ρXZ = -0.24, which are interpreted to indicate a concerted mechanism. The kinetic isotope effects involving deuterated benzylamine nucleophiles (XC6H4CH2ND2) are large, kH/kD = 1.41-1.97, suggesting that the N-H(D) bond is partially broken in the transition state by forming a hydrogen-bonded four-center cyclic structure. The concerted mechanism is enforced by the strong push provided by the EtO group which enhances the nucleofugalities of both benzylamine and arenethiolate from the putative zwitterionic tetrahedral intermediate.
Substituent Effects on the Acidity of Weak Acids. 4. Anilinium Ions
Authors: Wiberg Kenneth B.
Published: January 2005

The gas phase acidity of anilinium ions has been calculated at a number of theoretical levels from B3LYP/6-311++G** to MP2 and CCSD/6-311++G(2dp,2pd). The highest level calculations find anilinium ion and p-protonated aniline to have essentially the same energy, in agreement with experimental studies. They also give a proton affinity for aniline that is in very good agreement with the experimental value. The B3LYP and MP2 calculations are less successful, with B3LYP favoring p-protonation and MP2 favoring N-protonation for aniline. Despite this difficulty, the calculated effect of substituents on the proton affinities of p-substituted anilines that undergo N-protonation agreed well with the experimental data. The effect of substituents on the anilinium ions and on the anilines were examined separately using a series of group transfer reaction.
Synthetic Studies Toward Chiral Aromatic Triynes as Key Substrates for the Asymmetric Synthesis of Helicene-Like Molecules
Authors: Alexandrová Zuzana , Stará Irena G. , Sehnal Petr , Teplý Filip , Starý Ivo , Šaman David , Fiedler Pavel
Published: January 2005

We have developed the synthesis of model nonracemic aromatic triynes (-)-(S)-1-4 containing the 1-{[2-(but-3-yn-1-yl)-1-naphthyl]ethynyl}-2-{[((S)-1-methylprop-2-yn-1-yl)oxy]- methyl}naphthalene unit. The common 1,2-di(2-substituted-1-naphthyl)acetylene part was constructed via Sonogashira coupling of appropriate 1-iodonaphthalenes with 1-ethynylnaphthalenes both bearing tethered acetylene units in positions 2. The chirality of triynes (-)-(S)-1-4 was introduced by incorporating commercially available (-)-(S)-but-3-yn-2-ol (10) into tethered acetylene units. The nonracemic triynes are intended to be used as substrates in stereoselective [2+2+2] triyne cycloisomerization catalyzed by transition metal complexes.
Kinetics and Mechanism of Desulfurization Reaction of 1-Methyl-2-phenylquinazoline-4(1H)-thiones
Authors: Hanusek Jiří , Sedlák Miloš , Keder Roman , Štěrba Vojeslav
Published: January 2005

Kinetics and mechanism of desulfurization reaction of 1-methyl-2-(substituted phenyl)-quinazoline-4(1H)-thiones in sodium methoxide solutions have been studied, giving the corresponding 1-methyl-2-(substituted phenyl)quinazolin-4(1H)-ones. The reaction proceeds in two steps. The first step involves splitting off of sulfur in the form of SH- and is much faster than the second step, whose rate is almost independent of the concentration of water in methanol. At lowest concentrations of methoxide, the rate of the first step increases linearly, but at higher concentrations a gradual decrease in the rate takes place. The rate of the second step, i.e. the transformation of the intermediate formed In into 1-methyl-2-(substituted phenyl)quinazolin-4(1H)-one (2a-2e), is independent of the methoxide concentration but increases with increasing concentration of water in methanol. On the basis of the kinetic dependences, the mechanism for both steps of desulfurization and the structure of intermediate In were proposed.
Reparametrization and/or Determination of Hammett, Inductive, Mesomeric and AISE Substituent Constants for Five Substituents: N+(CH3)3, CH2N+(CH3)3, CH2Py+, CH2SO2CH3 and PO(OCH3)2
Authors: Pícha Jan , Cibulka Radek , Liška František , Pařík Patrik , Pytela Oldřich
Published: January 2005

Ten meta- and para-substituted benzoic acids with substituents N+(CH3)3, CH2N+(CH3)3, CH2Py+, CH2SO2CH3 and PO(OCH3)2 were synthesized. Dissociation constants of these acids were determined in five solvents (water, ethanol, methanol, N,N-dimethylformamide, dimethyl sulfoxide) at 25 °C. Dissociation constants of benzoic acid derivatives with other substituents H, CH3, NHCOCH3, OCH3, F, Cl, Br, I, COCH3, CN, NO2, SO2CH3 were taken from the literature (calibration set). Substituent constants σm, σp, σI, σR, and σi for substituents N+(CH3)3, CH2N+(CH3)3, CH2Py+, CH2SO2CH3, and PO(OCH3)2 were calculated by nonlinear and PLS (partial least-square method with latent variables) calibration in three correlation models using the calibration set. Nonlinear regression appears more suitable and more universal than PLS calibration. The advantage of nonlinear regression is its independence on possibly missing data in the given solvent, evaluation of precision (standard deviation), the accessibility of necessary software, and easy calculation. However, in contrast to PLS calibration, this procedure fails in calculation of substituent constants with description of properties of substituents (substituent constants σI, σR). The obtained values of substituent constants are in good agreement with those published in the literature.
Chlorination of N-Phenylbenzenesulfonamides with NCP in Aqueous Acetic Acid. Using the para/meta Ratio of Substituent Effects for Mechanism Elucidation
Authors: Reis João Carlos R. , Segurado Manuel A. P. , Gomes de Oliveira Jaime D. , Kabilan Senthamaraikannan , Suganya Krishnasamy
Published: January 2005

Rate constants were measured for the oxidative chlorination reaction of N-phenylbenzenesulfonamide 2 and twelve ortho-, nine meta- and twelve para-substituted derivatives in the aniline moiety, using 1-chloro-3-methyl-2,6-diphenylpiperidin-4-one (1) as chlorinating agent. The kinetics was run in 50% (v/v) aqueous acetic acid acidified with perchloric acid under pseudo-first-order conditions with respect to 1 at five different temperatures between 298 and 318 K. The dependence of rate constants on temperature was analysed in terms of the isokinetic relationship (IKR). The resulting isokinetic temperature was estimated to be 513 K. Using the Linert's theory of the IKR, the experimental isokinetic temperature was interpreted as evidence for the preferential involvement of water molecules in the formation of activated complexes. The dependence of the rate constants on the substituents was analysed using the tetralinear extension of the Yukawa-Tsuno equation for the effects of meta and para substituents. A positively charged transition state was suggested by an experimental value r+ = 0.39 for the resonance demand, which was found to be insensitive to temperature variation. The parameter λ for the para/meta ratio of substituent effects was estimated to be 0.952. The electrostatic modelling of λ values was re-examined in the light of the recent calculations of the energies of interaction between charged and/or dipolar groups by Exner and Böhm. Based on energy ratios, the electrostatic method was shown to remain valid for the purpose of modelling λ values. The experimental λ value for the reaction indicates the formation of an activated complex possessing an electric charge in the vicinity of the nitrogen atom of the substrate. The electrophilic attack on the substrate nitrogen atom by the protonated chlorinating reagent has been proposed as the rate-determining step, with the last step being the fast rearrangement of the intermediate N-chloro-N-phenylbenzenesulfonamidium cation into the products.
σI Values for Arylureido Groups
Authors: Blagoeva Iva B. , Koedjikov Asen H. , Pojarlieff Ivan G. , Stanchev Stefan P.
Published: January 2005

Three (1-arylureido)acetic acids were prepared by means of controlled alkaline hydrolysis of the respective 1-arylimidazolidin-2,4-diones. Their pKa values and that of (3-phenylureido)- acetic acid were determined potentiometrically by titration in 0.01 M solutions at 25.0 °C. Four new σI constants were calculated from the acidity constants.
The Solvent Effects on Kinetics and Mechanism of Zinc or Cadmium Halide Catalyzed Reactions of Hydrosilanes with Hydroxylic Reagents
Authors: Chruściel Jerzy J.
Published: January 2005

The effect of solvent composition on reaction rates was studied by a kinetic method for reactions of Et3SiH with Ph2Si(OH)2 in the presence of ZnCl2 in a mixture of DMF and THF or Et3SiH with PhCOOH and cadmium bromide CdBr2 in DMF-1,4-dioxane and DMF-THF. A decrease in reaction rates with decreasing polarity of the medium (and its dielectric constant) has been observed. The kinetic order of dehydrocoupling reaction with respect to DMF was determined from kinetic studies. The constants of nucleophilic catalysis with DMF (λ) were found. The role of DMF in the mechanism of dehydrocoupling of hydrosilanes with hydroxylic reagents in the presence of ZnX2 and CdX2 halides (X = Cl, Br, I) is discussed.
Analysis of Substituent Effects in Naphthalene Skeleton
Authors: Pařík Patrik , Ludwig Miroslav
Published: January 2005

The dissociation constants of 45 substituted 1- and 2-naphthoic acids in six organic solvents (methanol, ethanol, acetonitrile, dimethylformamide, dimethyl sulfoxide, pyridine) have been used to evaluate the substituent effects in the naphthalene skeleton. The dissociation constants data have been treated traditionally by using Dewar-Grisdale equation and the Taft DSP equation, and the alternative interpretation of substituent effects (AISE) method. Quantitative comparison of substituent effects and their transmission from different positions, combination of inductive and resonance effects from various positions, and effects of solvents are discussed. Best results are predominantly provided by the AISE. Substituent effects are stronger in the case of substituents affecting from ring of the naphthalene skeleton bearing carboxylic group than from ring not bearing carboxylic group, and there are no substantial differences between the individual positions of this ring. The contribution of resonance effects at 4α and 8β positions distinctly changes with the medium. Special quality of substituent H was found in comparison with other substituents presumably due their bulkier character. The principal component analysis (PCA) has been also applied to treat the mean dissociation constants using the single substituent property approach. The dissociation together with reactivity data for other naphthalene derivatives have been tested for comprehensive evaluation using PCA. There was found a large similarity of naphthalene reactivity data tested from the point of view of substituent effects.
Ocular complications of boxing
Authors: Bianco M , Vaiano A S , Colella F , Coccimiglio F , Moscetti M , Palmieri V , Focosi F , Zeppilli P
Published: January 2005

Objectives:To investigate the prevalence of ocular injuries in a large population of boxers over a period of 16 years, in particular, the most severe lesions that may be vision threatening.

Methods:Clinical records of the medical archive of the Italian Boxing Federation were analysed. A total of 1032 boxers were examined from February 1982 to October 1998. A complete ophthalmological history was available for 956, who formed the study population (a total of 10 697 examinations). The following data were collected: age when started boxing; duration of competitive boxing career (from the date of the first bout); weight category; a thorough ocular history. The following investigations were carried out: measurement of visual acuity and visual fields, anterior segment inspection, applanation tonometry, gonioscopy, and examination of ocular fundus. Eighty age matched healthy subjects, who had never boxed, formed the control group.

Results:Of the 956 boxers examined, 428 were amateur (44.8%) and 528 professional (55.2%). The median age at first examination was 23.1 (4.3) years (range 15–36). The prevalence of conjunctival, corneal, lenticular, vitreal, ocular papilla, and retinal alterations in the study population was 40.9% compared with 3.1% in the control group (p⩽0.0001). The prevalence of serious ocular findings (angle, lens, macula, and peripheral retina alterations) was 5.6% in boxers and 3.1% in controls (NS).

Conclusions:Boxing does not result in a higher prevalence of severe ocular lesions than in the general population. However, the prevalence of milder lesions (in particular with regard to the conjunctiva and cornea) is noteworthy, justifying the need for adequate ophthalmological surveillance.
A nomogram for assessment of breathing patterns during treadmill exercise
Authors: Naranjo J , Centeno R A , Galiano D , Beaus M
Published: January 2005

Objective:To assess the breathing patterns of trained athletes under different conditions. The hypothesis is that the breathing pattern during a progressive treadmill exercise is independent of the protocol, at least in healthy people, and can be assessed using a nomogram.

Methods:A total of 43 male and 21 female athletes from different sports were studied. They performed one of two different protocols (steps or ramp) on a treadmill. The two protocols started at the same speed and had the same rate of increase in work. During the test, the expired air was analysed for CO2and O2. Ventilation (VE) was continuously recorded, and tidal volume (Vt) and breathing frequency (BF) at the same intensity were analysed for both protocols, as well as Vt/Tiand Ti/Ttot.

Results:No significant differences were observed in Vt and BF between the two protocols in either the men or women at any level (confidence intervals up to 0.958 in all the groups). Ti/Ttotremained constant, and all increases in VE were strongly related to the respective increases in Vt/Ti. Plots of data for men and women showed a curvilinear relation between Vt and BF which could be fitted with an exponential function with a strong correlation (R2 =  0.98 for men and 0.97 for women).

Conclusions:Graphic expression of VtvBF is a useful nomogram for the routine assessment of ventilatory response during exercise in healthy trained subjects.
Propagation of stress fracture of the patella
Authors: Crowther M A A , Mandal A , Sarangi P P
Published: January 2005

Anterior knee pain in athletes is common and usually self limited. There should be a high index of suspicion and low threshold for special imaging in cases with acute onset and specific tenderness. The risk of propagation of stress fracture of the patella in athletes is highlighted. The case report presented illustrates the potential sequence of events.
From catastrophe to complexity: a novel model of integrative central neural regulation of effort and fatigue during exercise in humans: summary and conclusions
Authors: Noakes T D , St Clair Gibson A , Lambert E V
Published: January 2005

It is hypothesised that physical activity is controlled by a central governor in the brain and that the human body functions as a complex system during exercise. Using feed forward control in response to afferent feedback from different physiological systems, the extent of skeletal muscle recruitment is controlled as part of a continuously altering pacing strategy, with the sensation of fatigue being the conscious interpretation of these homoeostatic, central governor control mechanisms.
Eccentric decline squat protocol offers superior results at 12 months compared with traditional eccentric protocol for patellar tendinopathy in volleyball players
Authors: Young M A , Cook J L , Purdam C R , Kiss Z S , Alfredson H
Published: January 2005

Background:Conservative treatment of patellar tendinopathy has been minimally investigated. Effective validated treatment protocols are required.

Objectives:To investigate the immediate (12 weeks) and long term (12 months) efficacy of two eccentric exercise programmes for the treatment of patellar tendinopathy.

Methods:This was a prospective randomised controlled trial of 17 elite volleyball players with clinically diagnosed and imaging confirmed patellar tendinopathy. Participants were randomly assigned to one of two treatment groups: a decline group and a step group. The decline group were required to perform single leg squats on a 25° decline board, exercising into tendon pain and progressing their exercises with load. The step group performed single leg squats on a 10 cm step, exercising without tendon pain and progressing their exercises with speed then load. All participants completed a 12 week intervention programme during their preseason. Outcome measures used were the Victorian Institute of Sport Assessment (VISA) score for knee function and 100 mm visual analogue scale (VAS) for tendon pain with activity. Measures were taken throughout the intervention period and at 12 months.

Results:Both groups had improved significantly from baseline at 12 weeks and 12 months. Analysis of the likelihood of a 20 point improvement in VISA score at 12 months revealed a greater likelihood of clinical improvements in the decline group than the step group. VAS scores at 12 months did not differ between the groups.

Conclusions:Both exercise protocols improved pain and sporting function in volleyball players over 12 months. This study indicates that the decline squat protocol offers greater clinical gains during a rehabilitation programme for patellar tendinopathy in athletes who continue to train and play with pain.
An economic evaluation of a proprioceptive balance board training programme for the prevention of ankle sprains in volleyball
Authors: Verhagen E A L M , van Tulder M , van der Beek A J , Bouter L M , van Mechelen W
Published: January 2005

Objectives:To evaluate the cost effectiveness of a proprioceptive balance board training programme for the prevention of ankle sprains in volleyball.

Methods:A total of 116 volleyball teams participated in this study which was carried out during the 2001–2002 volleyball season. Teams were randomly allotted to an intervention group (66 teams, 628 players) or a control group (52 teams, 494 players). Intervention teams followed a prescribed balance board training programme as part of their warm up. Control teams followed their normal training routine. An ankle sprain was recorded if it occurred as a result of volleyball and caused the subject to stop volleyball activity. The injured player completed a cost diary for the duration of the ankle sprain. Analyses were performed according to the intention to treat principle. Mean direct, indirect, and total costs were calculated and were compared between the two groups.

Results:The total costs per player (including the intervention material) were significantly higher in the intervention group (€36.99 (93.87)) than in the control group (€18.94 (147.09)). The cost of preventing one ankle sprain was approximately €444.03. Sensitivity analysis showed that a proprioceptive balance board training programme aimed only at players with previous ankle sprains could be cost effective over a longer period of time.

Conclusions:Positive effects of the balance board programme could only be achieved at certain costs. However, if broadly implemented, costs associated with the balance board programme would probably be lower.
Kleine-Levin syndrome: a unique cause of fatigue in an athlete
Authors: Conklin C M J , Taunton J E
Published: January 2005

Kleine-Levin syndrome (KLS) is a rare disorder characterised, most notably, by periodic episodes of hypersomnolence and hyperphagia. Associated features of the disorder include a lack of concentration, mood changes, and anxiety. Laboratory tests may show slight changes in the electroencephalogram. However, clinical presentation and laboratory tests are normal during asymptomatic intervals. KLS most often presents in adolescent males, with complete recovery by the 3rd to 4th decade of life. Possible precipitating factors include excessive workload, febrile illness, and respiratory infections. Presented is a classical case of KLS in an adolescent male athlete. The patient’s history, complete laboratory results, and symptoms are discussed. Possible treatments for this disorder are also mentioned, along with diagnostic criteria.
False aneurysm of the common femoral vein in a footballer: Figure 1
Authors: Karahan M , Isbir S , Baltacýoglu F , Caglar M M
Published: January 2005

Traumatic false aneurysm of the femoral vein has never been reported in the English literature. The case is here reported of a footballer with a traumatic false aneurysm of the common femoral vein which was initially misdiagnosed as an arterial pseudoaneurysm. This is a very rare clinical condition, but this diagnosis should be among those considered for post-traumatic unexplained thigh pain after trauma.