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61.
62.
Accelerated prion disease pathogenesis in Toll-like receptor 4 signaling-mutant mice 总被引:1,自引:0,他引:1
Spinner DS Cho IS Park SY Kim JI Meeker HC Ye X Lafauci G Kerr DJ Flory MJ Kim BS Kascsak RB Wisniewski T Levis WR Schuller-Levis GB Carp RI Park E Kascsak RJ 《Journal of virology》2008,82(21):10701-10708
Prion diseases such as scrapie involve the accumulation of disease-specific prion protein, PrP(Sc), in the brain. Toll-like receptors (TLRs) are a family of proteins that recognize microbial constituents and are central players in host innate immune responses. The TLR9 agonist unmethylated CpG DNA was shown to prolong the scrapie incubation period in mice, suggesting that innate immune activation interferes with prion disease progression. Thus, it was predicted that ablation of TLR signaling would result in accelerated pathogenesis. C3H/HeJ (Tlr4(Lps-d)) mice, which possess a mutation in the TLR4 intracellular domain preventing TLR4 signaling, and strain-matched wild-type control (C3H/HeOuJ) mice were infected intracerebrally or intraperitoneally with various doses of scrapie inoculum. Incubation periods were significantly shortened in C3H/HeJ compared with C3H/HeOuJ mice, regardless of the route of infection or dose administered. At the clinical phase of disease, brain PrP(Sc) levels in the two strains of mice showed no significant differences by Western blotting. In addition, compared with macrophages from C3H/HeOuJ mice, those from C3H/HeJ mice were unresponsive to fibrillogenic PrP peptides (PrP residues 106 to 126 [PrP(106-126)] and PrP(118-135)) and the TLR4 agonist lipopolysaccharide but not to the TLR2 agonist zymosan, as measured by cytokine production. These data confirm that innate immune activation via TLR signaling interferes with scrapie infection. Furthermore, the results also suggest that the scrapie pathogen, or a component(s) thereof, is capable of stimulating an innate immune response that is active in the central nervous system, since C3H/HeJ mice, which lack the response, exhibit shortened incubation periods following both intraperitoneal and intracerebral infections. 相似文献
63.
Chattopadhyay MB Mukherjee S Kulkarni I Vijayan V Doloi M Kanjilal N Chatterjee M 《Cancer cell international》2005,5(1):16
Combined effect of vanadium and beta-carotene on rat liver DNA-chain break and Proton induced X-ray emission (PIXE) analysis
was studied during a necrogenic dose (200 mg/kg of body weight) of Diethyl Nitrosamine (DENA) induced rat liver carcinogenesis.
Morphological and histopathological changes were observed as an end point biomarker. Supplementation of vanadium (0.5 ppm
ad libitum) in drinking water and beta-carotene in the basal diet (120 mg/Kg of body weight) were performed four weeks before DENA treatment
and continued till the end of the experiment (16 weeks). PIXE analysis revealed the restoration of near normal value of zinc,
copper, and iron, which were substantially altered when compared to carcinogen treated groups. Supplementation of both vanadium
and beta-carotene four weeks before DENA injection was found to offer significant (64.73%, P < 0.001) protection against generation
of single-strand breaks when compared with the carcinogen control counter parts. A significant stabilization of hepatic architecture
of the cells was observed as compared to carcinogen control in vanadium plus beta-carotene treated group. This study thus
suggests that vanadium, a prooxidant but potential therapeutic agent yield safe and effective pharmacological formulation
with beta-carotene, an antioxidant, in the inhibition of experimental rat hepatocarcinogenesis. 相似文献
64.
Simian T-lymphotropic virus type 1 (STLV-1) is a C-type retrovirus of nonhuman primates that is genetically and antigenically related to human T-lymphotropic virus type 1 (HTLV-1). Infection with STLV-1 has been reported in many species of Old World monkeys and apes, including rhesus macaques (Macaca mulatta). Similar to HTLV infection in humans, STLV infection has been associated with T-cell lymphoproliferative disease or lymphoma in a small proportion of infected animals, predominantly African species. There are conflicting reports of T-cell subset alterations in healthy HTLV-1 carriers. To the authors' knowledge, analysis of T-cell subsets in healthy STLV-1 carrier rhesus macaques has not been reported. Subsets of T cells in peripheral blood from healthy, STLV-1-seropositive rhesus macaques (n = 17) and seronegative controls matched for age and sex (n = 17) were determined by use of fluorescence-activated cell sorter analysis. Parameters measured included CD3, CD4, CD8, CD25, CD28, CD38, and HLA-DR cell sets. Significant differences in T-cell subsets or hematologic parameters were not observed between healthy STLV-seropositive and seronegative groups. 相似文献
65.
66.
Hunter NB Moseley 《BMC bioinformatics》2010,11(1):139
Background
Stable isotope tracing with ultra-high resolution Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS) can provide simultaneous determination of hundreds to thousands of metabolite isotopologue species without the need for chromatographic separation. Therefore, this experimental metabolomics methodology may allow the tracing of metabolic pathways starting from stable-isotope-enriched precursors, which can improve our mechanistic understanding of cellular metabolism. However, contributions to the observed intensities arising from the stable isotope's natural abundance must be subtracted (deisotoped) from the raw isotopologue peaks before interpretation. Previously posed deisotoping problems are sidestepped due to the isotopic resolution and identification of individual isotopologue peaks. This peak resolution and identification come from the very high mass resolution and accuracy of FT-ICR-MS and present an analytically solvable deisotoping problem, even in the context of stable-isotope enrichment. 相似文献67.
Protein disulfide isomerase appears necessary to maintain the catalytically active structure of the microsomal triglyceride transfer protein 总被引:16,自引:0,他引:16
Protein disulfide isomerase (PDI) is a component of the microsomal triglyceride transfer protein (MTP) complex. This study was initiated to help elucidate the role of PDI in MTP. The 88-kDa polypeptide of MTP (88K) was dissociated from PDI by using chaotropic agents (NaClO4 and KSCN), low concentrations of a denaturant (guanidine hydrochloride) or a nondenaturing detergent (octyl glucoside). As assessed by fluorescence and circular dichroism spectroscopy, these three different approaches appeared to dissociate the components of MTP under mild, nondenaturing conditions. The dissociating agents were diluted or removed by dialysis, and the free PDI and 88K were further characterized. In all cases, the dissociation coincided with the loss of triglyceride transfer activity. The free 88-kDa polypeptide readily aggregated, suggesting that it is a hydrophobic peptide. Even in the presence of chaotropic agents, when 88K was not aggregated, transfer activity was not expressed. These results suggest that the association of PDI with 88K is necessary to maintain the catalytically active form of the triglyceride transfer protein and prevent the aggregation of 88K. 相似文献
68.
69.
Dario Bongiovanni Melissa Klug Olga Lazareva Simon Weidlich Marina Biasi Simona Ursu Sarah Warth Christian Buske Marina Lukas Christoph D. Spinner Moritz von Scheidt Gianluigi Condorelli Jan Baumbach Karl-Ludwig Laugwitz Markus List Isabell Bernlochner 《Cell death & disease》2021,12(1)
Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet–leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.Subject terms: Mechanisms of disease, Viral infection 相似文献
70.
Joan E. Pellegrino Rhonda E. Schnur Leslie Boghosian-Sell Gordon Strathdee Joan Overhauser Nancy B. Spinner Tammy Stump Kimberly Grace Elaine H. Zackai 《Human genetics》1996,97(4):532-536
The ablepharon-macrostomia (AMS) and Barber-Say syndromes (BSS) are rare disorders characterized by absence of the eyelids
or ectropion, macrostomia, ambiguous genitalia, abnormal ears, rudimentary nipples, and dry, redundant skin. Patients with
Barber-Say syndrome also have hypertrichosis. We present a patient with a phenotype similar to AMS who has a complex rearrangement
of chromosome 18, involving both an inversion and interstitial deletion. Our patient lacks the typical features of the 18q
deletion syndrome. We review AMS and BSS as compared with our patient, and recognize cutis laxa as a feature shared by all.
We propose that the gene(s) for this phenotype may lie on chromosome 18 in the region of the deletion or inversion breakpoints.
Received: 1 March 1995 / Revised: 20 May 1995 相似文献