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61.
Cancer vaccines: single-epitope anti-idiotype vaccine versus multiple-epitope antigen vaccine 总被引:5,自引:0,他引:5
Maruyama H Zaloudik J Li W Sperlagh M Koido T Somasundaram R Scheck S Prewett M Herlyn D 《Cancer immunology, immunotherapy : CII》2000,49(3):123-132
In this study, we compared the immunogenicity and tumor-protective activity of anti-idiotypic antibodies mimicking a single
tumor-associated epitope and tumor-associated antigen expressing multiple potentially immunogenic epitopes. We focused our
study on the colorectal-carcinoma(CRC)-associated antigen GA733 (also known as CO17-1A/KS1-4/KSA/EpCAM). Monoclonal anti-idiotypic
antibody (Ab2) BR3E4 was produced against murine anti-CRC mAb CO17-1A (Ab1) in rats. Full-length native GA733 protein was
isolated from human tumor cells, and the extracellular domain protein (GA733-2E) was isolated from supernatants of recombinant
baculovirus-infected insect cells by immunoafffinity chromatography. The immunomodulatory activity of the Ab2 was compared
with that of the antigen, both in rabbits and in mice. Mice, like humans but not rabbits, express a GA733 antigen homologue
on some of their normal tissues. Thus, these in vivo models allow the comparison of the immunogenicity of Ab2 and antigen
in the presence (mice) and absence (rabbits) of normal tissue expression and immunological tolerance of the GA733 antigen
homologue. In rabbits, aluminum-hydroxide(alum)-precipitated native GA733 antigen was superior to alum-precipitated Ab2 in
inducing specific humoral immunity. In mice, alum-precipitated recombinant GA733-2E antigen, but not alum-precipitated Ab2,
induced specific humoral immunity. However, when the Ab2 was administered to mice in Freund's complete adjuvant, specific
humoral immune responses were elicited. Ab2 in complete Freund's adjuvant and GA733-2E in alum were compared for their capacity
to induce antigen-specific cellular immunity in mice. Whereas lymphoproliferative responses were obtained with the recombinant
antigen only, delayed-type hypersensitivity responses were obtained with both recombinant antigen and Ab2, although these
responses were lower than after antigen immunization. The recombinant antigen in alum did not protect mice against challenge
with antigen-positive syngeneic murine CRC cells. Similar studies with Ab2 BR3E4 mimicking the CO17-1A epitope were not possible
because the tumor cells do not express this epitope after transfection with the human GA733-2 cDNA. However, similar studies
with Ab2 mimicking the epitope defined by mAb GA733, which is expressed by the transfected tumor cells, indicated a lack of
tumor-protective activity of this Ab2. In contrast, the full-length antigen expressed by recombinant adenovirus inhibited
the growth of established tumors in mice. In conclusion, soluble antigen is a more potent modulator of humoral and cellular
immune responses than Ab2, both administered in adjuvant. However, for induction of protective immunity, the immunogenicity
of the antigen must be further enhanced, e.g., by expression of the antigen in a viral vector.
Received: 27 December 1999 / Accepted: 27 January 2000 相似文献
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Mami Yamamoto-Kihara† Tamako Hata† Michael Breuer Seiji Tanaka† 《Physiological Entomology》2004,29(1):73-77
Abstract. Certain types of antennal sensilla are known to be more abundant in solitarious individuals than in gregarious ones in the migratory locust, Locusta migratoria . We tested the hypothesis that injection of a neurohormone, [His7 ]-corazonin, into isolated-reared nymphs of this species mimics the effect of crowding on the frequencies of various types of antennal sensilla. One nmol of the hormone was injected into nymphs on two occasions, on the third days of the second and third stadia, respectively. Upon adult emergence, the numbers of different types of sensilla on the eighth antennal segment were compared with those of oil-injected controls. [His7 ]-corazonin did not influence the numbers of basiconic sensilla type A, basiconic sensilla type B and trichoid sensilla significantly compared to oil-injected controls. However, the number of coeloconic sensilla was reduced significantly by the hormone injections. Because the length of the antennal segment was not affected by the hormone injection, it appears that the hormone influenced the development of coeloconic sensilla. The results support the hypothesis tested and are consistent with the idea that [His7 ]-corazonin plays an important role in the control of phase polymorphism in L. migratoria . 相似文献
64.
Elizabeth Peacock Sarah A. Sonsthagen Martyn E. Obbard Andrei Boltunov Eric V. Regehr Nikita Ovsyanikov Jon Aars Stephen N. Atkinson George K. Sage Andrew G. Hope Eve Zeyl Lutz Bachmann Dorothee Ehrich Kim T. Scribner Steven C. Amstrup Stanislav Belikov Erik W. Born Andrew E. Derocher Ian Stirling Mitchell K. Taylor ?ystein Wiig David Paetkau Sandra L. Talbo 《PloS one》2015,10(8)
65.
The choice for specific parameter estimation methods is often more dependent on its availability than its performance. We developed SPOTPY (Statistical Parameter Optimization Tool), an open source python package containing a comprehensive set of methods typically used to calibrate, analyze and optimize parameters for a wide range of ecological models. SPOTPY currently contains eight widely used algorithms, 11 objective functions, and can sample from eight parameter distributions. SPOTPY has a model-independent structure and can be run in parallel from the workstation to large computation clusters using the Message Passing Interface (MPI). We tested SPOTPY in five different case studies to parameterize the Rosenbrock, Griewank and Ackley functions, a one-dimensional physically based soil moisture routine, where we searched for parameters of the van Genuchten-Mualem function and a calibration of a biogeochemistry model with different objective functions. The case studies reveal that the implemented SPOTPY methods can be used for any model with just a minimal amount of code for maximal power of parameter optimization. They further show the benefit of having one package at hand that includes number of well performing parameter search methods, since not every case study can be solved sufficiently with every algorithm or every objective function. 相似文献
66.
Corinna Schroeter Johannes C. Ehrenthal Martina Giulini Eva Neubauer Simone Gantz Dorothee Amelung Doreen Balke Marcus Schiltenwolf 《PloS one》2015,10(3)
Background
Attachment insecurity relates to the onset and course of chronic pain via dysfunctional reactions to pain. However, few studies have investigated the proportion of insecure attachment styles in different pain conditions, and results regarding associations between attachment, pain severity, and disability in chronic pain are inconsistent. This study aims to clarify the relationships between insecure attachment and occurrence or severity of chronic pain with and without clearly defined organic cause. To detect potential differences in the importance of global and romantic attachment representations, we included both concepts in our study.Methods
85 patients with medically unexplained musculoskeletal pain (UMP) and 89 patients with joint pain from osteoarthritis (OA) completed self-report measures of global and romantic attachment, pain intensity, physical functioning, and depression.Results
Patients reporting global insecure attachment representations were more likely to suffer from medically unexplained musculoskeletal pain (OR 3.4), compared to securely attached patients. Romantic attachment did not differ between pain conditions. Pain intensity was associated with romantic attachment anxiety, and this relationship was more pronounced in the OA group compared to the UMP group. Both global and romantic attachment anxiety predicted depression, accounting for 15% and 17% of the variance, respectively. Disability was independent from attachment patterns.Conclusions
Our results indicate that global insecure attachment is associated with the experience of medically unexplained musculoskeletal pain, but not with osteoarthritis. In contrast, insecure attachment patterns seem to be linked to pain intensity and pain-related depression in unexplained musculoskeletal pain and in osteoarthritis. These findings suggest that relationship-informed focused treatment strategies may alleviate pain severity and psychological distress in chronic pain independent of underlying pathology. 相似文献67.
Verena Leder Martina Lummer Kathrin Tegeler Fabian Humpert Martin Lewinski Mark Schüttpelz Dorothee Staiger 《Biochemical and biophysical research communications》2014
Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased Kd value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R49 that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding. 相似文献
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70.
Juliane Mittasch Sabine Mikolajewski Frank Breuer Dieter Strack Carsten Milkowski 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(8):1485-1500
In oilseed rape (Brassica napus), the glucosyltransferase UGT84A9 catalyzes the formation of 1-O-sinapoyl-β-glucose, which feeds as acyl donor into a broad range of accumulating sinapate esters, including the major antinutritive
seed component sinapoylcholine (sinapine). Since down-regulation of UGT84A9 was highly efficient in decreasing the sinapate
ester content, the genes encoding this enzyme were considered as potential targets for molecular breeding of low sinapine
oilseed rape. B. napus harbors two distinguishable sequence types of the UGT84A9 gene designated as UGT84A9-1 and UGT84A9-2. UGT84A9-1 is the predominantly expressed variant, which is significantly up-regulated during the seed filling phase, when sinapate
ester biosynthesis exhibits strongest activity. In the allotetraploid genome of B. napus, UGT84A9-1 is represented by two loci, one derived from the Brassica C-genome (UGT84A9a) and one from the Brassica A-genome (UGT84A9b). Likewise, for UGT84A9-2 two loci were identified in B. napus originating from both diploid ancestor genomes (UGT84A9c, Brassica C-genome; UGT84A9d, Brassica A-genome). The distinct UGT84A9 loci were genetically mapped to linkage groups N15 (UGT84A9a), N05 (UGT84A9b), N11 (UGT84A9c) and N01 (UGT84A9d). All four UGT84A9 genomic loci from B. napus display a remarkably low micro-collinearity with the homologous genomic region of Arabidopsis thaliana chromosome III, but exhibit a high density of transposon-derived sequence elements. Expression patterns indicate that the
orthologous genes UGT84A9a and UGT84A9b should be considered for mutagenesis inactivation to introduce the low sinapine trait into oilseed rape. 相似文献