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161.
Studies of the hyaluronan (HA) tetrasaccharides are important for
understanding hydrogen-bonding in the HA polymer, as they are probably the
smallest oligomers in which characteristics of the constituent
monosaccharides and the polymer are simultaneously exhibited. Here we
present extensive molecular dynamics simulations of the two
tetrasaccharides of HA in dilute aqueous solution. These simulations have
confirmed the existence of intramolecular hydrogen-bonds between the
neighboring sugar residues of HA in solution, as proposed by Scott (1989).
However, our simulations predict that these intramolecular hydrogen-bonds
are not static as previously proposed, but are in constant dynamic exchange
on the sub-nanosecond time-scale. This process results in discrete internal
motion of the HA tetrasaccharides where they rapidly move between low
energy conformations. Specific interactions between water and
intramolecular hydrogen-bonds involving the hydroxymethyl group were found
to result in differing conformations and dynamics for the two alternative
tetrasaccharides of HA. This new observation suggests that this residue may
play a key role in the entropy and stability of HA in solution, allowing it
to stay soluble up to high concentration. The vicinal coupling constants3 J
NHCH of the acetamido groups have been calculated from our aqueous
simulations of HA. We found that high values of 3J NHCH approximately 8 Hz,
as experimentally measured for HA, are consistent with mixtures of both
trans and cis conformations, and thus3 J NHCH cannot be used to imply a
purely trans conformation of the acetamido. The rapid exchange of
intramolecular hydrogen-bonds indicates that although the structure is at
any moment stabilized by these hydrogen-bonds, no one hydrogen-bond exists
for an extended period of time. This could explain why NMR often fails to
provide evidence for intramolecular hydrogen-bonds in HA and other aqueous
carbohydrate structures.
相似文献
162.
The host defense against intracellular pathogens depends largely on activation of phagocytes and is regulated by a complex network of cytokines. Modulation of this cytokine network might lead to new or additional therapies in the treatment of infections with intracellular pathogens. Therefore, insight in the role of various cytokines in the host defense against these pathogens is required. The present contribution summarizes the results of various studies on the role of different cytokines in the host defense against the intracellular bacteriaListeria monocytogenes andSalmonella typhimurium.Abbreviations ROI
reactive oxygen intermediates
- IFN
interferon
- TNF
tumor necrosis factors
- IL
interleukin
- CSF
colony-stimulating factor
- CF
cerebrospinal fluid 相似文献
163.
164.
Beatrijs L.P. Bloemers Chantal J.M. Broers Louis Bont Michel E. Weijerman Reinoud J.B.J. Gemke A. Marceline van Furth 《Microbes and infection / Institut Pasteur》2010,12(11):799-808
Down syndrome (DS) is the most common chromosomal abnormality among live-born infants. Respiratory tract infections are the most important cause of mortality in individuals with DS at all ages. In recent decades several studies have been performed to elucidate abnormalities of the immune system in DS. However, the influence of the immune system on the occurrence of respiratory tract infections in these children has never been reviewed. 相似文献
165.
Binding of bivalent cations by hyaluronate in aqueous solution 总被引:1,自引:0,他引:1
Furth G Knierim R Buss V Mayer C 《International journal of biological macromolecules》2008,42(1):33-40
The interaction between sodium hyaluronate and bivalent cations was investigated by conductometry, viscosimetry, circular dichroism and nuclear magnetic resonance spectroscopy. It is shown that the hyaluronate chains (Mn approximately 4.0 x 10(5)-1.7 x 10(6)g/mol) bind various bivalent cations (Ca2+, Mg2+, Mn2+, Fe2+, Cu2+, Zn2+, Cd2+ and Pb2+) at pH 6 in aqueous solutions. Hyaluronate deriving from Streptococcus equi was studied in comparison with dextran from Leuconostoc mesenteroides which was shown to develop no specific interactions with the bivalent cations. The molar relation between the bivalent cations and the disaccharide units of the resulting complex was determined with the result that one bivalent cation is bound by approximately five disaccharide units. Heavy metal ions (Cd2+, Pb2+) seem to bind stronger to the hyaluronate chain than their lighter counterparts (Ca2+, Mg2+). Circular dichroism spectra of the hyaluronate exhibit a cation-induced change in the n-pi* transition, indicating that the acetamide group of the aminoglucane unit is involved during the complexation. NMR spectra of hyaluronic acid in presence of paramagnetic manganese cations show strong interactions between the acetamide as well as the carboxylate groups and the cations. Based on these data, a structure of the binding complex is proposed which involves two disaccharide units. 相似文献
166.
Weiss YG Bellin L Kim PK Andrejko KM Haaxma CA Raj N Furth EE Deutschman CS 《American journal of physiology. Gastrointestinal and liver physiology》2001,280(5):G968-G973
Sepsis is the leading cause of death in surgical intensive care units. Although both mild sepsis secondary to cecal ligation and single puncture (CLP) and fulminant, double puncture CLP (2CLP) may provoke hepatocyte death, we hypothesize that regeneration compensates for cell death after CLP but not 2CLP. In male Sprague-Dawley rats, hepatic necrosis, as determined by serum alpha-glutathione S-transferase (alpha-GST) levels, was significantly but equally elevated over time after both CLP and 2CLP. Apoptosis, evaluated using both terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and morphological examination, was minimal after both CLP and 2CLP. Regeneration, assayed by staining tissue for incorporation of exogenously administered bromodeoxyuridine, was present after CLP but not after 2CLP. To further substantiate impaired regeneration, steady-state levels of mRNAs encoding JunB, LRF-1, and cyclin D1 were determined. After 2CLP, the absence of JunB, LRF-1, and cyclin D1 mRNAs confirmed failed activation of the mitogen-activated protein kinase-linked proliferative pathway and progression through the cell cycle. Therefore, failed hepatocyte regeneration may be a manifestation of hepatic dysfunction in fulminant sepsis. 相似文献
167.
Genetic variation in innate immune response genes contributes to inter-individual differences in disease manifestation and degree of complications upon infection. We recently described an association of single nucleotide polymorphisms (SNPs) in TLR9 with susceptibility to meningococcal meningitis (MM). In this study, we investigate the association of SNPs in multiple pathogen recognition and immune response genes with clinical features that determine severity and outcome (especially hearing loss) of childhood MM and pneumococcal meningitis (PM). Eleven SNPs in seven genes (TLR2, TLR4, TLR9, NOD1, NOD2, CASP1, and TRAIL) were genotyped in 393 survivors of childhood bacterial meningitis (BM) (327 MM patients and 66 PM patients). Genotype distributions of single SNPs and combination of SNPs were compared between thirteen clinical characteristics associated with severity of BM. After correction for multiple testing, TLR4+896 mutant alleles were highly associated with post-meningitis hearing loss, especially MM (p=?0.001, OR 4.0 for BM, p=?0.0004, OR 6.2 for MM). In a multigene analysis, combined carriership of the TLR2+2477 wild type (WT) with TLR4+896 mutant alleles increases the risk of hearing loss (p<0.0001, OR 5.7 in BM and p=?0.0001, OR 7.6 in MM). Carriage of one or both mutant alleles in TLR4+896 and TLR9 -1237 increases the risk for hearing loss (p?=?0.0006, OR 4.1 in BM). SNPs in immune response genes contribute to differences in clinical severity and outcome of BM. The TLR system seems to play an important role in the immune response to BM and subsequent neuronal damage as well as in cochlear inflammation. Genetic markers may be used for identification of high-risk patients by creating prediction rules for post-meningitis hearing loss and other sequelae, and provide more insight in the complex immune response in the CNS possibly resulting in new therapeutic interventions. 相似文献
168.
169.
Furth EE Li J Purev E Solomon AC Rogler G Mick R Putt M Zhang T Somasundaram R Swoboda R Herlyn D 《Cancer immunology, immunotherapy : CII》2006,55(5):528-537
Purpose: The gastrointestinal carcinoma-associated antigen epithelial cell adhesion molecule (EpCAM) has been a target for passive and active immunotherapy of gastrointestinal carcinoma patients. The antigen is expressed by both tumor and normal tissues. The immunogenicity of EpCAM in colorectal cancer patients has been described previously. The purpose of this study was to evaluate humoral and cellular immune responses of healthy individuals and ulcerative colitis patients to EpCAM and to relate immune responses to colonic tissue expression of EpCAM. Methods: An inhibition radioimmunoassay was used to detect anti-EpCAM serum antibodies. Anti-EpCAM antibodies of a healthy donor were expressed by phages and sequenced. 3H-thymidine incorporation assay was used for detection of lymphoproliferative responses to stimulation with EpCAM. EpCAM tissue expression was determined by immunohistochemistry. Results: We detected anti-EpCAM serum antibodies in 4 of 10, and EpCAM-specific lymphoproliferation responses in 1 of 10 healthy volunteers. The majority of anti-EpCAM antibodies derived from a healthy donor were germline-encoded. In contrast, none of the 23 patients with ulcerative colitis showed serum antibodies to EpCAM (P=0.005). Antigen expression was greatly reduced and altered in ulcerative colitis patients, whereas colon from healthy individuals and uninvolved colon of colorectal cancer patients expressed high levels of EpCAM. Conclusion: The results of these studies suggest an association between EpCAM antibody production and colonic EpCAM expression in healthy individuals and patients with ulcerative colitis. Decreased and altered colonic EpCAM expression in ulcerative colitis patients may be related to the disease induction, based on the previously demonstrated adhesion function of this molecule. Healthy individuals with anti-EpCAM immune responses and high risk for developing colorectal carcinoma are prime candidates for prophylactic immunization against EpCAM.Emma E. Furth and Jian Li contributed equally 相似文献
170.
The present results challenge the view that macrophage activation leads to a general, non-specific increase of microbicidal activity of these cells. Instead, it was found that the interactions between activated macrophages and micro-organisms are dependent on the kind of activation and the type of target micro-organism. 相似文献