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81.
Cerebral vasospasm (CVS) is a life-threatening condition that occurs in a large proportion of those affected by subarachnoid haemorrhage and stroke. CVS manifests itself as the progressive narrowing of intracranial arteries. It is usually diagnosed using Doppler ultrasound, which quantifies blood velocity changes in the affected vessels, but has low sensitivity when CVS affects the peripheral vasculature. The aim of this study was to identify alternative biomarkers that could be used to diagnose CVS. We used a 1D modelling approach to describe the properties of pulse waves that propagate through the cardiovascular system, which allowed the effects of different types of vasospasm on waveforms to be characterised at several locations within a simulated cerebral network. A sensitivity analysis empowered by the use of a Gaussian process statistical emulator was used to identify waveform features that may have strong correlations with vasospasm. We showed that the minimum rate of velocity change can be much more effective than blood velocity for stratifying typical manifestations of vasospasm and its progression. The results and methodology of this study have the potential not only to improve the diagnosis and monitoring of vasospasm, but also to be used in the diagnosis of many other cardiovascular diseases where cardiovascular waves can be decoded to provide disease characterisation. 相似文献
82.
J. P. Adler-Moore W. Ernst H. Kim N. Ward S. M. Chiang T. Do 《Journal of liposome research》2017,27(3):210-220
AbstractGiven the interest in the ectodomain of the matrix 2 (M2e) channel protein as a target for development of a universal influenza vaccine, we examined the role of the antigen configuration of M2e in generating a protective immune response. A series of M2e mutations and a truncated M2e segment were prepared as a means of controlling the formation of monomer, dimer, and higher order multimeric forms of M2e. Each of these M2e peptides was incorporated into a liposome-based vaccine technology platform previously shown to stimulate a protective response to influenza A infection using M2e as a mixture of monomers, dimers and multimers (L-M2e1-HD/MPL). Our results using these modified forms of M2e produced 90–100% survival following lethal challenge with H1N1 (A/PR/8/34) in both inbred BALB/c and outbred Swiss Webster mice vaccinated with a truncated monomeric form of the M2 protein, M2e1–15 in liposomes. These observations show that a tetrameric configuration is not required to elicit significant protection when the M2e antigen is formulated in immunogenic liposomes and further, that the first 15 amino acids of M2e likely play a primary role in providing the protective immune response. 相似文献
83.
Tonometry-based devices are valuable method for vascular function assessment and for measurement of blood pressure. However current design and calibration methods rely on simple models, neglecting key geometrical features, and anthropometric and property variability among patients. Understanding impact of these influences on tonometer measurement is thus essential for improving outcomes of current devices, and for proposing improved design. Towards this goal, we present a realistic computational model for tissue-device interaction using complete wrist section with hyperelastic material and frictional contact. Three different tonometry geometries were considered including a new design, and patient-specific influences incorporated via anthropometric and age-dependent tissue stiffness variations. The results indicated that the new design showed stable surface contact stress with minimum influence of the parameters analyzed. The computational predictions were validated with experimental data from a prototype based on the new design. Finally, we showed that the underlying mechanics of vascular unloading in tonometry to be fundamentally different from that of oscillatory method. Due to directional loading in tonometry, pulse amplitude maxima was observed to occur at a significantly lower compression level (around 31%) than previously reported, which can impact blood pressure calibration approaches based on maximum pulse pressure recordings. 相似文献
84.
João Silva Rui Santos Carlos M. Duarte 《Journal of experimental marine biology and ecology》2005,317(1):87-95
The photosynthetic productivity of the intertidal communities dominated by the seagrass Zostera noltii and the cordgrass Spartina maritima was assessed in two contrasting situations during a tidal cycle, i.e., air exposure and water immersion. Two complementary methods were used: infra red gas analysis of CO2 flux measurements in whole communities and chlorophyll a fluorescence measurements of individual plants photosynthetic activity. Higher photosynthetic rates of Z. noltii in air were observed both at the individual plants response level determined by chlorophyll fluorescence and at the community level measured as gas exchange (CO2 uptake). S. maritima plants consistently showed low photosynthetic response when immersed. Gross community production (GCP) measured as carbon dioxide uptake was always higher in air than in water for both communities. When immersed, the GCP of both communities was similar. However, when exposed to the air, the GCP of the S. maritima community was higher than the one of Z. noltii's. The key factor in CO2 assimilation by air-exposed Z. noltii was the retention of water in sediment microdepressions. During low tide, depressions in the sediment retain a considerable amount of water, enough to maintain leaf hydration. In these conditions, rapid air-water CO2 diffusion occurs, making it readily available to plants. The community gas exchange measurements compared well with the fluorescence indications. Both Z. noltii and S. maritima were shown to be responsible for the overall pattern of photosynthetic carbon fixation within their respective communities, both during submersion and emersion periods. The short-term incubations method described in this report proved to be a valuable tool for field measurements of intertidal lagoon productivity. It provides fast and precise values of carbon dioxide fixation, both in submerged and air-exposed communities. 相似文献
85.
Hüttinger C Hirschberger J Jahnke A Köstlin R Brill T Plank C Küchenhoff H Krieger S Schillinger U 《The journal of gene medicine》2008,10(6):655-667
Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing. 相似文献
86.
87.
Voelkl S Moore TV Rehli M Nishimura MI Mackensen A Fischer K 《Cancer immunology, immunotherapy : CII》2009,58(5):709-718
The immune attack against malignant tumors require the concerted action of CD8+ cytotoxic T lymphocytes (CTL) as well as CD4+ T helper cells. The contribution of T cell receptor (TCR) αβ+ CD4− CD8− double-negative (DN) T cells to anti-tumor immune responses is widely unknown. In previous studies, we have demonstrated
that DN T cells with a broad TCR repertoire are present in humans in the peripheral blood and the lymph nodes of healthy individuals.
Here, we characterize a human DN T cell clone (T4H2) recognizing an HLA-A2-restricted melanoma-associated antigenic gp100-peptide
isolated from the peripheral blood of a melanoma patient. Antigen recognition by the T4H2 DN clone resulted in specific secretion
of IFN-γ and TNF. Although lacking the CD8 molecule the gp100-specifc DN T cell clone was able to confer antigen-specific
cytotoxicity against gp100-loaded target cells as well as HLA-A2+ gp100 expressing melanoma cells. The cytotoxic capacity was found to be perforin/granzymeB-dependent. Together, these data
indicate that functionally active antigen-specific DN T cells recognizing MHC class I-restricted tumor-associated antigen
(TAA) may contribute to anti-tumor immunity in vivo.
A. Mackensen and K. Fischer contributed equally to this work and should be considered joint senior authors. This work was
supported by the Deutsche Forschungsgemeinschaft (MA 1351/5-1, KFO 146) and NIH grants CA90873, CA102280, 104947 (MIN).
Companion paper: “Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition”
by Tamson V. Moore et al. doi: . 相似文献
88.
Jon Amund Kyte Sissel Trachsel Bente Risberg Per thor Straten Kari Lislerud Gustav Gaudernack 《Cancer immunology, immunotherapy : CII》2009,58(10):1609-1626
Cancer vaccine trials frequently report on immunological responses, without any clinical benefit. This paradox may reflect
the challenge of discriminating between effective and pointless immune responses and sparse knowledge on their long-term development.
Here, we have analyzed T cell responses in long-term survivors after peptide vaccination. There were three main study aims:
(1) to characterize the immune response in patients with a possible clinical benefit. (2) To analyze the long-term development
of responses and effects of booster vaccination. (3) To investigate whether the Th1/Th2-delineation applies to cancer vaccine
responses. T cell clones were generated from all nine patients studied. We find that surviving patients harbor durable tumor-specific
responses against vaccine antigens from telomerase, RAS or TGFβ receptor II. Analyses of consecutive samples suggest that
booster vaccination is required to induce robust T cell memory. The responses exhibit several features of possible clinical
advantage, including combined T-helper and cytotoxic functionality, recognition of naturally processed antigens and diverse
HLA-restriction and fine-specificity. CD4−CD8− T cell clones display unconventional cytotoxicity and specifically kill tumor cells expressing mutated TGFβ receptor II.
Cytokine profiling on the long-term survivors demonstrates high IFNγ/IL10-ratios, favoring immunity over tolerance, and secretion
of multiple chemokines likely to mobilize the innate and adaptive immune system. Interestingly, these pro-inflammatory cytokine
profiles do not follow a Th1/Th2-delineation. Most IFNγhigh/IL4low/IL10low cultures include high concentrations of hallmark Th2-cytokines IL-5 and IL-13. This does not reflect a mixture of Th1- and
Th2-clones, but applies to 19/20 T cell clones confirmed to be monoclonal through TCR clonotype mapping. The present study
identifies several factors that may promote clinical efficacy and suggests that cytokine profiling should not rely on the
Th1/Th2-paradigm, but assess the overall inflammatory milieu and the balance between key cytokines.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
89.
Chun Xia Hu Zi Rong Xu Wei Fen Li Niu Dong Ping Lu Ling Lin Fu 《Biotechnology letters》2009,31(7):991-997
K88 (F4) fimbrial adhesin, FaeG, was expressed extracellularly in Lactococcus lactis using a nisin-controlled gene expression system. The antibody response and protective efficacy of the recombinant bacteria
(L. lactis [spNZ8048-faeG]) against live enterotoxigenic E. coli (ETEC) C83549 challenge were evaluated in ICR mice. Mice vaccinated with L. lactis [spNZ8048-faeG] had a significantly increased antigen-specific IgG level in the serum and decreased mortality rate (P < 0.05) compared with the control. This indicates that oral immunization of L. lactis [spNZ8048-faeG] can induce an immune-response protection upon challenge with live ETEC in ICR mice.
An erratum to this article can be found at 相似文献
90.
Diego La Mendola Serena Caminati Salvatore S. Emmi Giuseppe Maccarrone Adriana Pietropaolo 《Journal of inorganic biochemistry》2009,103(2):195-204
Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies were carried out on copper(II) complexes with chicken prion protein N-terminal fragments, Ac-(PHNPGY)4-NH2, and the mutated residue, Ac-(PHNPGF)4-NH2, to assess the role of tyrosine in the copper coordination. Both thermodynamic and spectroscopic results indicate that chicken prion fragments are not able to bind more than two copper ions and only with the involvement of side chain tyrosine groups. The prevailing complex shows one copper ion bound to four imidazole nitrogen atoms in the 1:1 metal to ligand ratio systems. The superoxide dismutase (SOD)-like activity of copper(II) complexes with the avian peptides and mammal analogue, Ac-(PHGGGWGQ)4-NH2, was also investigated by means of Pulse radiolysis. The copper(II) complexes with avian peptides do not display SOD-like activity, while very low activity has been detected for the copper(II) complexes with mammalian tetraoctarepeat. 相似文献