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101.
IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12 总被引:15,自引:0,他引:15
Lieberman LA Cardillo F Owyang AM Rennick DM Cua DJ Kastelein RA Hunter CA 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(3):1887-1893
IL-23 and IL-12 are heterodimeric cytokines which share the p40 subunit, but which have unique second subunits, IL-23p19 and IL-12p35. Since p40 is required for the development of the Th1 type response necessary for resistance to Toxoplasma gondii, studies were performed to assess the role of IL-23 in resistance to this pathogen. Increased levels of IL-23 were detected in mice infected with T. gondii and in vitro stimulation of dendritic cells with this pathogen resulted in increased levels of mRNA for this cytokine. To address the role of IL-23 in resistance to T. gondii, mice lacking the p40 subunit (common to IL-12 and IL-23) and mice that lack IL-12 p35 (specific for IL-12) were infected and their responses were compared. These studies revealed that p40(-/-) mice rapidly succumbed to toxoplasmosis, while p35(-/-) mice displayed enhanced resistance though they eventually succumbed to this infection. In addition, the administration of IL-23 to p40(-/-) mice infected with T. gondii resulted in a decreased parasite burden and enhanced resistance. However, the enhanced resistance of p35(-/-) mice or p40(-/-) mice treated with IL-23 was not associated with increased production of IFN-gamma. When IL-23p19(-/-) mice were infected with T. gondii these mice developed normal T cell responses and controlled parasite replication to the same extent as wild-type mice. Together, these studies indicate that IL-12, not IL-23, plays a dominant role in resistance to toxoplasmosis but, in the absence of IL-12, IL-23 can provide a limited mechanism of resistance to this infection. 相似文献
102.
Cardillo I Spugnini EP Verdina A Galati R Citro G Baldi A 《Histology and histopathology》2005,20(4):1267-1274
Cyclooxygenases catalyze the rate limiting step in the production of prostanoids. Accumulating data demonstrate that overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Malignant mesothelioma is a lethal pleural, peritoneal and pericardial neoplasia that actually lacks valid therapies and in which cyclooxygenases-2 is recognized as an important adverse prognostic factor. Hence, there is an increasing interest in the development of new treatments based on cyclooxygenases-2 inhibitors, to prolong survival and even potentially cure this neoplasia. 相似文献
103.
Gianna Allegrone Massimo Barbeni Rosanna Cardillo Claudio Fuganti Piero Grasselli Anna Miele Antonella Pisciotta 《Biotechnology letters》1991,13(11):765-768
Summary (Z6)-gamma-dodecenolactone samples produced endogenously inFusarium
poae and biogenerated from (10R, S) 10-hydroxy-octadeca-(E8, Z12)-dienoic acid inCladosporium
suaveolens show (R) and (S) configurations, respectively. 相似文献
104.
Gentilucci L Cardillo G Squassabia F Tolomelli A Spampinato S Sparta A Baiula M 《Bioorganic & medicinal chemistry letters》2007,17(8):2329-2333
In this paper, we describe the synthesis of a selected library of heterochiral d-Pro-containing RGD-peptidomimetics (RpD) and we investigate the biological activity as inhibitors of fibronectin adhesion to SK-MEL-24 tumor cells. In particular, peptides 4 and 8 showed an IC(50) in the 10(-8)M range. Despite the linear structure, the peptides tend to adopt a folded conformation in a polar environment. 相似文献
105.
Amrita Pati Cecilia Vasquez-Robinet Lenwood S Heath Ruth Grene TM Murali 《BMC bioinformatics》2006,7(1):218-14
Background
Modeling of cis-elements or regulatory motifs in promoter (upstream) regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. 相似文献106.
CH Chang Y Wang P Trisal R Li DL Rossi A Nair P Gupta M Losman TM Cardillo EA Rossi DM Goldenberg 《PloS one》2012,7(8):e44235
A major mechanism of monoclonal antibodies that selectively target the insulin-like growth factor type 1 receptor (IGF-1R) to inhibit tumor growth is by downregulating the receptor, regardless whether they are capable (antagonistic) or incapable (agonistic) of blocking the binding of cognate ligands. We have developed and characterized a novel agonistic anti-IGF-1R humanized antibody, hR1, and used the Dock-and-Lock (DNL) method to construct Hex-hR1, the first multivalent antibody comprising 6 functional Fabs of hR1, with the aim of enhancing potency of hR1. Based on cross-blocking experiments, hR1 recognizes a region of cysteine-rich domain on the α-subunit, different from the epitopes mapped for existing anti-IGF-1R antibodies, yet hR1 is similar to other anti-IGF-1R antibodies in downregulating IGF-1R and inhibiting proliferation, colony formation, or invasion of selected cancer cell lines in vitro, as well as suppressing growth of the RH-30 rhabdomyosarcoma xenograft in nude mice when combined with the mTOR inhibitor, rapamycin. Hex-hR1 and hR1 are generally comparable in their bioactivities under the in-intro and in-vivo conditions investigated. Nevertheless, in selective experiments involving a direct comparison of potency, Hex-hR1 demonstrated a stronger effect on inhibiting cell proliferation stimulated by IGF-1 and could effectively downregulate IGF-1R at a concentration as low as 20 pM. 相似文献
107.
Isolated populations of drosophila pseudoobscura, separated from North
American populations by about 2,400 km, were found in Colombia in 1960. We
compared for sequences of the small ribosomal RNA (srRNA) gene on the
mitochondria between North American and Colombian D. pseudoobscura in order
to clarify the age of the Colombian isolates. The North American
populations were not genetically different from each other but were
genetically different from the Colombian populations. The Mexican strains
represent the area from which the Colombian founders might have come. The
estimated net nucleotide divergence between Mexican and Colombian D.
pseudoobscura indicates that the Colombian population is not an ancient
lineage. Phylogenies using both distance and parsimony methodologies
reinforced this conclusion. The Colombian samples group together with both
methods but, according to the bootstrap analysis, not significantly. It
appears that the populations have not been separated long enough for their
DNA sequences to show much divergence.
相似文献
108.
In vertebrates, large body size is often a key diagnostic feature of species threatened with extinction. However, in amphibians the link between body size and extinction risk is highly uncertain, with previous studies suggesting positive, negative, u-shaped, or no relationship. Part of the reason for this uncertainty is ‘researcher degrees of freedom’: the subjectivity and selectivity in choices associated with specifying and fitting models. Here, I clarify the size–threat association in amphibians using Specification Curve Analysis, an analytical approach from the social sciences that attempts to minimize this problem by complete mapping of model space. I find strong support for prevailing negative associations between body size and threat status, the opposite of patterns typical in other vertebrates. This pattern is largely explained by smaller species having smaller geographic ranges, but smaller amphibian species also appear to lack some of the life-history advantages (e.g. higher reproductive output) that are often assumed to ‘protect’ small species in other taxa. These results highlight the need for a renewed conservation focus on the smallest species of the world''s most threatened class of vertebrates, as aquatic habitats become increasingly degraded by human activity. 相似文献
109.
Entomopathogenic nematodes (EPN) are efficient biological pest control agents. Population genetics studies on EPN are seldom
known. Therefore, it is of interest to evaluate the significance of molecular sampling method (MSM) for accuracy, time needed, and
cost effectiveness over traditional sampling method (TSM). The study was conducted at the Mohican Hills golf course at the state
of Ohio where the EPN H. bacteriophora has been monitored for 18 years. The nematode population occupies an area of
approximately 3700 m2 with density range from 0.25-2 per gram soil. Genetic diversity of EPN was studied by molecular sampling
method (MSM) and traditional sampling method (TSM) using the mitochondrial gene pcox1. The MSM picked 88% in compared to
TSM with only 30% of sequenced cox 1 gene. All studied genetic polymorphism measures (sequence and haplotype) showed high
levels of genetic diversity of MSM over TSM. MSM minimizes the chance of mitochondrial genes amplification from non target
organisms (insect or other contaminating microorganisms). Moreover, it allows the sampling of more individuals with a reliable
and credible representative sample size. Thus, we show that MSM supersedes TSM in labour intensity, time consumption and
requirement of no special experience and efficiency. 相似文献
110.