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71.
Vladimir Turzhitsky Yang Liu Nahla Hasabou Michael Goldberg Hemant K. Roy Vadim Backman Randall Brand 《Disease markers》2008,25(6):313-321
Pancreatic cancer screening has been hampered by the high rate of complications associated with interrogating the pancreas. The closest non-invasively accessible mucosa available for pancreatic cancer screening is the periampullary duodenal tissue. Our earlier report has shown the potential of using optical markers to interrogate this tissue for the presence of pancreatic cancer. In this study, we report a larger data set of low-coherence enhanced backscattering (LEBS) and elastic light scattering fingerprinting (ELF) optical markers from the periampullary duodenal mucosa. Optical measurements from biopsy samples were acquired from a total of 203 patients with varying clinical classification including healthy controls, a family history of pancreatic cancer, pancreatitis, mucinous cystic precursor lesions, pancreatic cancer, and other pancreatic malignancies. Evaluation of the performance of an independent testing set for discriminating healthy control patients from pancreatic cancer patients showed a 95% sensitivity, 71% specificity, and 85% area under the receiver operator characteristic (AUROC) curve. Importantly, this performance was uncompromised for detecting potentially curable stages of the disease. Additionally, optical markers in higher risk populations such as family history and pancreatitis had values between those of healthy control and pancreatic cancer patients, thus allowing for future investigations of screening from these high risk groups. 相似文献
72.
Two methods of whole-genome amplification enable accurate genotyping across a 2320-SNP linkage panel 总被引:6,自引:0,他引:6
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Barker DL Hansen MS Faruqi AF Giannola D Irsula OR Lasken RS Latterich M Makarov V Oliphant A Pinter JH Shen R Sleptsova I Ziehler W Lai E 《Genome research》2004,14(5):901-907
Comprehensive genome scans involving many thousands of SNP assays will require significant amounts of genomic DNA from each sample. We report two successful methods for amplifying whole-genomic DNA prior to SNP analysis, multiple displacement amplification, and OmniPlex technology. We determined the coverage of amplification by analyzing a SNP linkage marker set that contained 2320 SNP markers spread across the genome at an average distance of 2.5 cM. We observed a concordance of >99.8% in genotyping results from genomic DNA and amplified DNA, strongly indicating the ability of both methods used to amplify genomic DNA in a highly representative manner. Furthermore, we were able to achieve a SNP call rate of >98% in both genomic and amplified DNA. The combination of whole-genome amplification and comprehensive SNP linkage analysis offers new opportunities for genetic analysis in clinical trials, disease association studies, and archiving of DNA samples. 相似文献
73.
Kovalenko P Fujinaka H Yoshida Y Kawamura H Qu Z El-Shemi AG Li H Matsuki A Bilim V Yaoita E Abo T Uchiyama M Yamamoto T 《International immunology》2004,16(5):625-634
Anti-glomerular basement membrane (GBM) glomerulonephritis induced in WKY rats is characterized by glomerular accumulation of CD8(+) T cells and monocytes/macrophages, followed by crescent formation. The mechanism of leukocyte accumulation after antibody binding to GBM is still unclear. To unveil an involvement of Fcgamma receptors (FcgammaR) in leukocytes recruitment we examined the expression of FcgammaR in glomeruli and the effects of the administration of F(ab')(2) fragment of anti-GBM antibody or FcgammaR blocking on the initiation and progression of this model. A gradual increase of FcgammaR mRNA expression in glomeruli during the time course of disease suggested their significance in the development of glomerulonephritis. Glomerular lesions and proteinuria were induced only in rats injected with intact IgG of anti-GBM antibody, but not with the F(ab')(2) fragment. In vivo blocking of FcgammaR by administering heat-aggregated IgG led to the decrease of mRNA expression for all types of FcgammaR (types 1, 2 and 3) and a significant amelioration of glomerulonephritis manifestations. By flow cytometry and immunohistochemistry FcgammaR2-expressing cells in glomeruli were identified as macrophages, but not CD8(+) T cells. The expression of FcgammaR1 and 3 was significantly decreased, and that of FcgammaR2 became undetectable in CD8(+) T cell-depleted rats. Thus, CD8(+) T cells may stimulate FcgammaR expression on macrophages, contributing to their glomerular accumulation and injury. These studies provide direct evidence for a crucial involvement of IgG Fc-FcgammaR interaction in glomerular recruitment of macrophages and following induction of anti-GBM glomerulonephritis in WKY rats. 相似文献
74.
Like other complex behaviors, the cyclical, rhythmic consummatory feeding behaviors of Aplysia-biting, swallowing, and rejection of unsuitable food-are produced by a complex neuromuscular system: the animal's buccal mass, with numerous pairs of antagonistic muscles, controlled by the firing of numerous motor neurons, all driven by the motor programs of a central pattern generator (CPG) in the buccal ganglia. In such a complex neuromuscular system, it has always been assumed that the activities of the various components must necessarily be tightly coupled and coordinated if successful functional behavior is to be produced. However, we have recently found that the CPG generates extremely variable motor programs from one cycle to the next, and so very variable motor neuron firing patterns and contractions of individual muscles. Here we show that this variability extends even to higher-level parameters of the operation of the neuromuscular system such as the coordination between entire antagonistic subsystems within the buccal neuromusculature. In motor programs elicited by stimulation of the esophageal nerve, we have studied the relationship between the contractions of the accessory radula closer (ARC) muscle, and the firing patterns of its motor neurons B15 and B16, with those of its antagonist, the radula opener (I7) muscle, and its motor neuron B48. There are two separate B15/B16-ARC subsystems, one on each side of the animal, and these are indeed very tightly coupled. Tight coupling can, therefore, be achieved in this neuromuscular system where required. Yet there is essentially no coupling at all between the contractions of the ARC muscles and those of the antagonistic radula opener muscle. We interpret this result in terms of a hypothesis that ascribes a higher-order benefit to such loose coupling in the neuromusculature. The variability, emerging in the successive feeding movements made by the animal, diversifies the range of movements and thereby implements a trial-and-error search through the space of movements that might be successful, an optimal strategy for the animal in an unknown, rapidly changing feeding environment. 相似文献
75.
A single-chain antibody fragments (scFv) was developed directed against transmembrane envelope glycoprotein gp46 of the virus maedi-visna, by the application of the antibody phage display library. To get specific scFv binders, the library was panned against the biotinylated peptide of 20 amino acids corresponding to the principal immunodominant domain of gp46 protein. The number of positively binding scFvs was evaluated by scFv-phage ELISA, BstN1 fingerprinting and DNA sequencing. The scFvs were expressed in soluble form and purified by immobilized metal affinity chromatography (IMAC) with a yield of 2-2.5 mg/l. Two scFvs have shown to recognize gp46 and gp150 proteins in Western blot analysis. The scFvs also recognized the virus in infected cells as shown by immunofluorescence assay. The affinity of the obtained antibody fragments to gp46 peptide was measured by surface plasmon resonance, and the resulting K(A) was in the 10(6)-10(7)lmol(-1) range. The application of characterized scFvs for expression as intrabodies in intracellular immunization against virus maedi-visna infection and for the diagnosis of this virus is discussed. 相似文献
76.
Victor A. Sorokin Vladimir F. Fedorov Victor S. Leontiev Yuri P. Blagoi Vladimir L. Galkin 《Macromolecular chemistry and physics.》1987,188(10):2301-2309
The helix-coil transition in Phage T2 DNA in the presence of 6,4 · 10?3 mol/l Mn2+ is studied using light scattering and UV spectroscopy. The transition range is about 0,5°C. Near the temperature of the end of melting Tf the molecular weight Mw and the radius of gyration Rz of the complex are observed to decrease to about one half. At a temperature 0,1–0,25°C higher than Tf, Mw and Rz pass through a minimum, which implies that aggregation is preceded by unwinding of DNA strands. Thus, rise in temperature rather than Mn2+ -induced aggregation causes DNA + Mn2+ melting. 相似文献
77.
Ioulia?Kobliakova Olga?Zatsepina Vera?Stefanova Vladimir?Polyakov Igor?KireevEmail author 《Chromosome research》2005,13(2):169-181
In this study we used a novel technique to reveal both longitudinal and transverse differentiation within mammalian mitotic
chromosomes. Structural changes in chromosomes that we term ‘differential decondensation’ were produced in cells that were
first incubated in hypotonic medium (15% Hanks’ solution), then adapted to normotonic conditions and thereafter exposed to
a second short hypotonic shock. Such a double hypotonic treatment (DHT) is not critical for cell viability, but considerably
elongates the G2 phase of the cell cycle. Giemsa staining of differentially decondensed chromosomes corresponds to standard
G-banding, but does not need the standard post-fixation treatment. Using ‘dynamic’ BrdU banding, we show that such ‘differential’
staining is a result of differential resistance of the R- and G-bands to DHT. Thus, early-replicating foci, markers of R-bands,
are localized in the peripheral chromatin halo, whereas late-replicating foci, corresponding to G-bands, remain associated
with the axial regions of chromatids. Remarkably, despite these major changes in the structure of the chromosomal bands, the
replication foci still preserve their discrete structure. 相似文献
78.
Gennadii D. Bukatov Sergei H. Shepelev Vladimir A. Zakharov Sergei A. Sergeev Yurii I. Yermakov 《Macromolecular chemistry and physics.》1982,183(11):2657-2665
By use of the quenching technique with 14CO and 14CO2 the number of active centers and the propagation rate constants (kp) were determined for the propylene polymerization on different titanium-magnesium catalysts in the presence and absence of an organoaluminium cocatalyst. The kp values at 70°C were found to be 500–1000 1·mol?1·s?1, which were confirmed by independent data of molecular mass measurements of the isotatic polymer after a short polymerization time (5 s). Similar isotactic and atactic kpvalues were found. The maximum number of active centers for supported titanium-magnesium catalysts can reach about 10% of the titanium content in the catalyst. The kp values of ethylene polymerization on catalysts active without an organoaluminium cocatalyst were also determined (≈ 104 l·mol?1·s?1 at 70°C). 相似文献
79.
Burova L Thern A Pigarevsky P Gladilina M Seliverstova V Gavrilova E Nagornev V Schalén C Totolian A 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(10):955-962
Our previous studies have indicated that the IgG-binding M-family proteins (IgGBP) of group A streptococci may be involved in eliciting experimental acute poststreptococcal glomerulonephritis (APSGN) in the rabbit. These surface proteins were also found to trigger production of anti-IgG, which might conceivably act to enhance renal deposition of immune complexes (IC). In the present study, a clinical isolate of serotype M22 (strain AL168), an isogenic double mutant deficient for both the IgGBPs Mrp and Emm, as well as mutants deficient in only one of the proteins were tested for capacity to induce glomerulonephritis. Streptococci to be used for injecting rabbits were heat-killed. Surface-bound IgG was removed by 1 M KSCN and cells were then repeatedly washed in PBS before use. Rabbits were injected intravenously with 109 cells three times a week for 8 weeks and, following one month of rest, for another 6 weeks. Deposits of IgG and C3 as well as induced chemokines TNF-alpha, IL-1beta and IL-6 were traced in cryostat sections using specific antibodies and appropriate peroxidase-labelled anti-antibodies. In four rabbits immunized with the double mutant strain, no deposits were found, and as examined by TEM, only subtle and transient renal changes were observed. In contrast, the original strain AL168 induced pronounced inflammatory and degenerative glomerular changes in all four rabbits injected, and deposits of TNF-alpha, IL-1beta and IL-6 were found in mesangial and endothelial cells. Similar deposits and glomerular changes were seen in all eight rabbits injected with the mrp-emm+ mutant and in four out of seven animals receiving the mrp+emm- mutant. There was a highly significant correlation between high levels of circulating anti-IgG and development of APSGN. These results confirm an important role of streptococcal IgGBP in triggering experimental APSGN as earlier proposed by our group. 相似文献
80.
Smooth muscle myosin filament assembly under control of a kinase-related protein (KRP) and caldesmon
Kudryashov DS Vorotnikov AV Dudnakova TV Stepanova OV Lukas TJ Sellers JR Watterson DM Shirinsky VP 《Journal of muscle research and cell motility》2002,23(4):341-351
Kinase-related protein (KRP) and caldesmon are abundant myosin-binding proteins of smooth muscle. KRP induces the assembly
of unphosphorylated smooth muscle myosin filaments in the presence of ATP by promoting the unfolded state of myosin. Based
upon electron microscopy data, it was suggested that caldesmon also possessed a KRP-like activity (Katayama et al., 1995, J Biol Chem 270: 3919–3925). However, the nature of its activity remains obscure since caldesmon does not affect the equilibrium between
the folded and unfolded state of myosin. Therefore, to gain some insight into this problem we compared the effects of KRP
and caldesmon, separately, and together on myosin filaments using turbidity measurements, protein sedimentation and electron
microscopy. Turbidity assays demonstrated that KRP reduced myosin filament aggregation, while caldesmon had no effect. Additionally,
neither caldesmon nor its N-terminal myosin binding domain (N152) induced myosin polymerization at subthreshold Mg2+ concentrations in the presence of ATP, whereas the filament promoting action of KRP was enhanced by Mg2+. Moreover, the amino-terminal myosin binding fragment of caldesmon, like the whole protein, antagonizes Mg2+-induced myosin filament formation. In electron microscopy experiments, caldesmon shortened myosin filaments in the presence
of Mg2+ and KRP, but N152 failed to change their appearance from control. Therefore, the primary distinction between caldesmon and
KRP appears to be that caldesmon interacts with myosin to limit filament extension, while KRP induces filament propagation
into defined polymers. Transfection of tagged-KRP into fibroblasts and overlay of fibroblast cytoskeletons with Cy3KRP demonstrated
that KRP colocalizes with myosin structures in vivo. We propose a new model that through their independent binding to myosin and differential effects on myosin dynamics, caldesmon
and KRP can, in concert, control the length and polymerization state of myosin filaments.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献