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131.
A low molecular weight (LMW) antigen of Eimeria tenella, initially identified using a murine monoclonal antibody (mAb C34F1) raised against E. tenella sporozoites, was partially characterized using enzymatic degradation, solvent extraction, and immunization into various inbred
lines of mice. The LMW antigen could be isolated using Folch extraction (methanol/chloroform/water) and the epitope recognized
by mAb C34F1 was resistant to degradation by α-amylase, pronase, and proteinase K, but was sensitive to sodium m-periodate treatment or digestion using mixed glycosidases (from Turbo cornutus). These observations suggest that the antigenic epitope recognized by mAb C34F1 is carbohydrate-dependent and, based on our ability to isolate the LMW antigen by Folch extraction, the epitope probably
resides on a polar glycolipid. The inability of sporozoite-immunized nude mice to elicit a serum antibody response to this
molecule indicates that it acts as a T-dependent antigen. Furthermore, sporozoite-immunized male CBA/N mice (with an X-linked
immunodeficiency) also failed to elicit a serum antibody response to this molecule, which is consistent with a carbohydrate
antigenic epitope. We propose that this antigenic molecule be designated ET-GL1 to reflect its origin and probable structure
(E. tenella glycolipid 1).
Received: 30 June 1999 / Accepted: 2 December 1999 相似文献
132.
Prasad V. Jallepalli Grant W. Brown Marco Muzi-Falconi Deborah Tien Thomas J. Kelly 《Genes & development》1997,11(21):2767-2779
Cyclin-dependent kinases (CDKs) promote the initiation of DNA replication and prevent reinitiation before mitosis, presumably through phosphorylation of key substrates at origins of replication. In fission yeast, the p65cdc18 protein is required to initiate DNA replication and interacts with the origin recognition complex (ORC) and the p34cdc2 CDK. Here we report that p65cdc18 becomes highly phosphorylated as cells undergo the G1→S phase transition. This modification is dependent on p34cdc2 protein kinase activity, as well as six consensus CDK phosphorylation sites within the p65cdc18 polypeptide. Genetic interactions between cdc18+ and the S-phase cyclin cig2+ suggest that CDK-dependent phosphorylation antagonizes cdc18+ function in vivo. Using site-directed mutagenesis, we show that phosphorylation at CDK consensus sites directly targets p65cdc18 for rapid degradation and inhibits its replication activity, as strong expression of a constitutively hypophosphorylated mutant form of p65cdc18 results in large amounts of DNA over-replication in vivo. Furthermore, the over-replication phenotype produced by this mutant p65cdc18 is resistant to increased mitotic cyclin/CDK activity, a known inhibitor of over-replication. Therefore, p65cdc18 is the first example of a cellular initiation factor directly regulated in vivo by CDK-dependent phosphorylation and proteolysis. Regulation of p65cdc18 by CDK phosphorylation is likely to contribute to the CDK-driven “replication switch” that restricts initiation at eukaryotic origins to once per cell cycle. 相似文献
133.
van Strien RT Engel R Holst O Bufe A Eder W Waser M Braun-Fahrländer C Riedler J Nowak D von Mutius E;ALEX Study Team 《The Journal of allergy and clinical immunology》2004,113(5):860-867
BACKGROUND: Endotoxin exposure has been shown to be associated with a decreased prevalence of atopic sensitization and symptoms. Yet endotoxin represents only a part of the indoor microbial exposure. Muramic acid, a constituent of peptidoglycan, is present in gram-negative and gram-positive bacteria in the environment and may therefore serve as an additional marker of microbial exposure. OBJECTIVE: To study the factors determining the level of indoor exposure to muramic acid/peptidoglycan, as well as its potential association with respiratory health. METHODS: In 553 farm and nonfarm school children from Austria, Switzerland, and Germany, mattress dust muramic acid concentrations were determined, and health was assessed by using IgE measurements and questionnaire information. RESULTS: The muramic acid concentration was found to be significantly higher in dust from farm children's mattresses than in dust from nonfarm children's mattresses (157 vs 131 ng/mg). Children with higher mattress dust muramic acid concentrations had a significantly lower prevalence of wheezing (odds ratio of highest vs lowest tertile of muramic acid concentration, 0.3; 95% CI, 0.1-0.9), regardless of farming status and endotoxin exposure. The association for asthma was similar, and no association was found with atopic sensitization. CONCLUSION: Next to endotoxin, muramic acid provides us with an independent marker of microbial exposure. Unlike endotoxin, muramic acid was inversely associated with wheezing rather than with atopic sensitization. 相似文献
134.
135.
Paul S. Miller Marco Beato Robert J. Harvey Trevor G. Smart 《The Journal of physiology》2005,566(3):657-670
Glycine receptors exhibit a biphasic sensitivity profile in response to Zn2+ -mediated modulation, with low Zn2+ concentrations potentiating (< 10 μ m ), and higher Zn2+ concentrations inhibiting submaximal responses to glycine. Here, a substantial 30-fold increase in sensitivity to Zn2+ -mediated inhibition was apparent for the homomeric glycine receptor (GlyR) α1 subunit compared to either GlyR α2 or α3 subtypes. Swapping the divergent histidine (H107) residue in GlyR α1, which together with the conserved H109 forms part of an intersubunit Zn2+ -binding site, for the equivalent asparagine residue present in GlyR α2 and α3, reversed this phenotype. Co-expression of heteromeric GlyR α1 or α2 with the ancillary β subunit yielded receptors that maintained their distinctive sensitivities to Zn2+ inhibition. However, GlyR α2β heteromers were consistently 2-fold more sensitive to inhibition compared to the GlyR α2 homomer. Comparative studies to elucidate the specific residue in the β subunit responsible for this differential sensitivity revealed instead threonine 133 in the α1 subunit as a new vital component for Zn2+ -mediated inhibition. Further studies on heteromeric receptors demonstrated that a mutated β subunit could indeed affect Zn2+ -mediated inhibition but only from one side of the intersubunit Zn2+ -binding site, equivalent to the GlyR α1 H107 face. This strongly suggests that the α subunit is responsible for Zn2+ -mediated inhibition and that this is effectively transduced, asymmetrically, from the side of the Zn2+ -binding site where H109 and T133 are located. 相似文献
136.
Ultrasonographic assessment of human skeletal muscle size 总被引:7,自引:0,他引:7
The measurement of human muscle size is essential when assessing the effects of training, disuse and ageing. The considered gold standard for cross-sectional area measurements of muscle size is magnetic resonance imaging (MRI). However, MRI is costly and often inaccessible. The aim of the present study was to test the reproducibility and validity of a more accessible alternative method using ultrasonography (ULT). We examined the cross-sectional areas in the vastus lateralis muscle of six individuals. Axial-plane ULT scans were taken at given levels along the entire muscle length. The ULT scanning was repeated on different days (reliability) and validated against MRI-based measurements. Mean intraclass correlation coefficients were 0.998 for the reliability of ULT and 0.999 for the validity of ULT against MRI. The coefficient of variation values for cross-sectional area measurements assessed by six different experimenters were 2.1% and 0.8% for images obtained with ULT and MRI, respectively. The ULT method is a valid and reliable alternative tool for assessing cross-sectional areas of large individual human muscles. The present findings justify the application of the ULT method for the detection of changes throughout large muscles in response to training, disuse or as a consequence of sarcopenia. 相似文献
137.
Ghiorzo P Villaggio B Sementa AR Hansson J Platz A Nicoló G Spina B Canepa M Palmer JM Hayward NK Bianchi-Scarrà G 《Human pathology》2004,35(1):25-33
Little is known about the correlation between the loss of p16 expression and tumor progression in familial melanoma; no systematic study has been conducted on p16 expression in melanocytic tumors from patients carrying germline CDKN2A mutations. We analyzed 98 early primary lesions from familial patients, previously tested for germline CDKN2A status, by quantitative immunohistochemistry using 3 p16 antibodies. We found that p16 expression was inversely correlated with tumor progression and was significantly lower in melanomas, including in situ lesions, than in nevi. Of other features analyzed, tumor thickness showed the most significant correlation with p16 levels. Lesions from mutation-negative patients displayed combined nuclear and cytoplasmic staining. However, some mutation-positive lesions (ie, G101W, 113insR, M53I, R24P, and 33ins24), including benign nevi, showed nuclear mislocalization, confirming previous studies suggesting that subcellular distribution indicates functional impairment of p16. 相似文献
138.
Dissecting natural killer cell activation pathways through analysis of genetic mutations in human and mouse 总被引:2,自引:1,他引:2
Summary: Natural killer (NK) cell cytotoxicity is mediated by multiple germ line-encoded activating receptors that recognize specific ligands expressed by tumor cells and virally infected cells. These activating receptors are opposed by NK inhibitory receptors, which recognize major histocompatibility complex class I molecules on potential targets, raising the threshold for NK cell activation. Once an abnormal cell has been detected, NK cells are the sentinel source of cytolytic mediators, such as granzymes and perforins, as well as interferon-γ, which can polarize the immune response to a T-helper 1 cell type. Activation signals are transmitted by adhesion-dependent pathways, immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathways, DAP10 ITAM-independent pathways, and by signaling through immunoreceptor tyrosine-based switch motifs. These pathways activate downstream signaling partners to trigger NK cell cytotoxicity. Some of these downstream molecules are unique to the various pathways, and some of these molecules are shared. Because of the complexity of signals involved in NK cell–target cell interaction, the generation of mice with targeted mutations in signaling molecules involved in adhesion, activation, or inhibition is essential for a precise dissection of the mechanisms regulating NK cell effector functions. Here we review recent advances in the genetic analysis of the signaling pathways that mediate NK cell killing. 相似文献
139.
Noninvasive measurement of human forearm oxygen consumption by near infrared spectroscopy 总被引:5,自引:0,他引:5
Roberto A. De Blasi Mark Cope Clare Elwell Fauzia Safoue Marco Ferrari 《European journal of applied physiology》1993,67(1):20-25
Summary This study reported on the application of near infrared spectroscopy (NIRS) to noninvasive measurements of forearm brachio-radial muscle oxygen consumption (
O2) and recovery time (t
r) in untrained volunteers. Seven healthy subjects were submitted to four consecutive protocols involving measurements made at rest, the induction of an ischaemia, and during a maximal increase of metabolic demand achieved with and without vascular occlusion. Two isometric maximal voluntary contractions (MVC) of 30-s duration were executed with and without vascular occlusion and a 50% MVC lasting 125 s was also performed. The protocols were repeated on 2 different days. The results showed that, during vascular occlusion at rest, the time to 95% of the final haemoglobin (Hb) + myoglobin (Mb) desaturation value was independent of
O2. The MVC, performed during vascular occlusion, caused complete Hb + Mb desaturation in 15–20 s, which was not followed by any further desaturation when the second contraction was performed. No difference was found between
O2during MVC with and without vascular occlusion. A consistent difference was seen between
O2measured during occlusion at rest and
O2measured during MVC with and without occlusion. During prolonged exercise (125 s) Hb + Mb desaturation was maintained for the whole contraction period. The results of this study show that
O2can be measured noninvasively by NIRS. The
O2during MVC was very similar both in the presence and absence of blood flow limitation in most of the subjects tested. This would suggest that muscle
O2might be accurately evaluated dynamically without cuff occlusion. 相似文献
140.
Adriana C. Gittenberger‐De Groot Edris A.F. Mahtab Nathan D. Hahurij Lambertus J. Wisse Marco C. Deruiter Maurits C.E.F. Wijffels Robert E. Poelmann 《Anatomical record (Hoboken, N.J. : 2007)》2007,290(1):115-122
Recent advances in the study of cardiac development have shown the relevance of addition of myocardium to the primary myocardial heart tube. In wild‐type mouse embryos (E9.5–15.5), we have studied the myocardium at the venous pole of the heart using immunohistochemistry and 3D reconstructions of expression patterns of MLC‐2a, Nkx2.5, and podoplanin, a novel coelomic and myocardial marker. Podoplanin‐positive coelomic epithelium was continuous with adjacent podoplanin‐ and MLC‐2a‐positive myocardium that formed a conspicuous band along the left cardinal vein extending through the base of the atrial septum to the posterior myocardium of the atrioventricular canal, the atrioventricular nodal region, and the His‐Purkinje system. Later on, podoplanin expression was also found in the myocardium surrounding the pulmonary vein. On the right side, podoplanin‐positive cells were seen along the right cardinal vein, which during development persisted in the sinoatrial node and part of the venous valves. In the MLC‐2a‐ and podoplanin‐positive myocardium, Nkx2.5 expression was absent in the sinoatrial node and the wall of the cardinal veins. There was a mosaic positivity in the wall of the common pulmonary vein and the atrioventricular conduction system as opposed to the overall Nkx2.5 expression seen in the chamber myocardium. We conclude that we have found podoplanin as a marker that links a novel Nkx2.5‐negative sinus venosus myocardial area, which we refer to as the posterior heart field, with the cardiac conduction system. Anat Rec, 290:115–122, 2007. © 2006 Wiley‐Liss, Inc. 相似文献