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1.
Prion colonization of secondary lymphoid organs (SLOs) is a critical step preceding neuroinvasion in prion pathogenesis. Follicular dendritic cells (FDCs), which depend on both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance, are thought to be the primary sites of prion accumulation in SLOs. However, prion titers in RML-infected TNFR1−/− lymph nodes and rates of neuroinvasion in TNFR1−/− mice remain high despite the absence of mature FDCs. Recently, we discovered that TNFR1-independent prion accumulation in lymph nodes relies on LTβR signaling. Loss of LTβR signaling in TNFR1−/− lymph nodes coincided with the de-differentiation of high endothelial venules (HEVs)—the primary sites of lymphocyte entry into lymph nodes. These findings suggest that HEVs are the sites through which prions initially invade lymph nodes from the bloodstream. Identification of HEVs as entry portals for prions clarifies a number of previous observations concerning peripheral prion pathogenesis. However, a number of questions still remain: What is the mechanism by which prions are taken up by HEVs? Which cells are responsible for delivering prions to lymph nodes? Are HEVs the main entry site for prions into lymph nodes or do alternative routes also exist? These questions and others are considered in this article. 相似文献
2.
The design of single-stranded nucleic acid knots 总被引:1,自引:0,他引:1
Nadrian C. Seeman 《Molecular Engineering》1992,2(3):297-307
A general strategy is described for the synthesis of single-stranded nucleic acid knots. Control of nucleic acid sequence is used to direct the formation of secondary structures that produce the target topology. The key feature of the strategy is the equation of a half-turn of double helical DNA or RNA with a node in a knot. By forming nodes from complementary DNA sequences, it appears possible to direct the assembly of any simple knot. Stabilization of individual nodes may be achieved by constructing them from long regions containing both B-DNA and Z-DNA. Control over the braiding of DNA that acts as a link between node-forming domains can be realized by condensing the nodes into well-defined DNA structures, such as extended domains of linear duplex, branched junctions, antijunctions or mesojunctions. Further topological control may be derived from the pairing of linker regions to complementary single-stranded molecules, thereby preventing them from braiding in an undesirable fashion. 相似文献
3.
Keith K.T. Lim Matt J. Kessler Kenneth P.H. Pritzker Jean E. Turnquist Paul A. Dieppe 《Journal of medical primatology》1996,25(4):301-308
Abstract: We describe the relative prevalence and pattern of distribution of osteoarthritis (OA) in the hands of elderly (>15 years) rhesus macaques using clinical, radiographic, and skeletal examinations. In the clinical study the prevalence of nodes was 72% and 16% in the distal inter-phalangeal joints (DIPJ) and proximal inter-phalangeal joints (PIPJ), respectively, 31% of all monkeys had polyarticular nodes. Radiographic OA was present in 55%, 9.1%, and 0% of the DIPJs, PIPJs, and thumb bases, respectively. Skeletal OA as defined by joint surface eburnation for the DIPJ, PIPJ, and thumb base were 16%, 8%, and 2%, respectively. A similar pattern of hand OA with humans is described except for the thumb base OA. This may be due to the relatively rudimentary manipulative role of the macaque thumb. The finding of polyarticular nodal OA raises the possibility of a common pathogenensis for IPJ OA amongst primates. 相似文献
4.
The aim of this study was to evaluate the diagnostic value of fine needle aspiration cytology (FNAC) in the assessment of palpable supraclavicular lymph nodes. The material was analysed in 218 cases with enlarged supraclavicular lymph nodes in which FNAC was performed by the conventional method. In all cases cytological examination was performed on-site after staining the smears by the Papanicolaou method. In addition, air-dried smears, fixed smears, filter preparations from needle washings and cell blocks were studied. The FNAC diagnosis was supported by examining cell blocks which added the reliability of histological architecture; further support was obtained by tissue biopsy and/or comparison with the primary tumour in some of the cases. Eleven cases were diagnosed as inflammatory lesions and 41 cases were unsatisfactory because of scanty/acellular samples (despite two to three repeat samplings). However, in five of these, malignant tumours were later found on biopsy, which was done for persistent enlargement of the supraclavicular lymph node(s). Fifty-three cases were diagnosed as negative for malignancy (normal cellular elements, n=15; reactive elements, n=38) and 12 cases were suspicious of malignancy. In 11 cases a diagnosis of lymphoma was made on histology and in 90 cases metastatic tumours were diagnosed. The overall sensitivity was 92.7%, specificity 98.5%, positive predictive value 97.3% and the negative predictive value was 94.8%. Based on our study we feel that FNAC of palpable supraclavicular lymph nodes as a first line of investigation is a cost-effective procedure and is not only useful in the diagnosis of various lesions but can also help in deciding on appropriate management. Furthermore, the histological architecture from cell blocks can be correlated with cytology, and such material can be used for appropriate histochemical and immunomarker studies, which can be useful in enhancing the diagnosis. 相似文献
5.
The T-cell deficiency of nude mice is due to an abnormal differentiation of the thymus epithelium; it can be persistently corrected by grafting a neonatal thymus. However, grafted adult thymuses or epithelial thymuses are not repopulated by large numbers of host-derived lymphocytes, as is the case when a whole neonatal thymus is grafted. Furthermore, the repopulation of the spleen and lymph nodes by T cells is less pronounced than after whole neonatal thymus transplantation, and the restoration of the reactivity to T-cell mitogens is irregular. Therefore, the integrity and the age of the thymus graft are important for a good restoration of the T-lymphoid system of congenitally athymic animals. 相似文献
6.
Infections with the nematode Trichinella spiralis induce unresponsiveness in mice. A study was made to determine whether suppression could be due to a deficiency in the cells responsible for the immunological response. Mice were given low or moderate infections and were killed 7, 14, 28, or 56 days after inoculation; spleen macrophages and leucocytes, θ cells, and Con A- and LPS-sensitive cells were determined in the thymus, spleen, and the mesenteric and axillary lymph nodes. Spleen macrophages are diminished throughout the course of the infection, reaching significantly low levels on the 14th day. The thymus loses, whereas the spleen and the axillary node gain, cells bearing the θ antigen. In spite of the increase in leucocytes and θ cells in the secondary lymphoid tissue, the cells of these organs are insensitive to the blastogenic action of Con A in the heavier infections. In lower infections, however, spleen cells show an enhanced response to Con A and LPS; mesenteric cells, on the other hand, show an early enhanced susceptibility to LPS and a reduced susceptibility to Con A and, in the later phases of parasitism, an enhanced Con A and a reduced LPS susceptibility. It is suggested that these phenomena contribute to the immunosuppression phenomena which are characteristic of T. spiralis infections. 相似文献
7.
Malyukova A. V. Loginov W. I. Hodyrev D. S. Kadyrova E. L. Pronina I. V. Ivanova T. A. Kisseljov F. L. Zabarovsky E. R. Kisseljova N. P. Braga E. A. 《Molecular Biology》2004,38(6):857-864
Methylation-sensitive restriction endonuclease analysis (MSRA) followed by polymerase chain reaction (PCR) have been used to estimate the methylation level of 13 CpG dinucleotides in the promoter region of the putative suppressor gene RASSF1A (3p21.31) in squamous cell carcinomas of the uterine cervix (SCCs) carrying human papillomavirus (HPV) types 16, 18, and related types. Methylation of 3 to 13 CpG pairs has been found in 64% (25 out of 39) tumor DNA samples, 22% (2 out of 9) DNA samples from morphologically normal tissues adjacent to the tumor (P = 0.0306), and two out of three DNA samples from peripheral blood leukocytes of carcinoma patients. These CpG pairs are not methylated in the DNA of leukocytes of healthy donors (0 out of 10). The methylation level of the RASSF1A promoter region studied in tumors of the patients with regional lymph node metastases is significantly higher than in tumors of the patient that have no metastases (P = 8.5 × 10–12). The methylation frequency of gene RASSF1A is two times higher than the frequency of hemi- and homozygous deletions in the chromosome 3 region where the gene is located. The data obtained indicate that methylation is one of the main mechanisms of the RASSF1A gene inactivation in HPV-positive human cervical tumors. The methylation of this gene may be an early event in the genesis of cervical tumors, the methylation level increasing with tumor progression. 相似文献
8.
本研究选用两个籼稻杂交品种西农优1号和冈优725,采用人工去蘖形成分蘖初期的早发、中发、迟发三个处理,在群体条件下研究分蘖和生产力的补偿能力。本研究发现,迟发处理高节位群的分蘖补偿能力最明显,但绝对补偿量小。迟发处理高节位群的生长势、有效分蘖倍数增加,抽穗期单茎叶面积有增加的趋势,但抽穗期有效穗数、叶面积系数降低;迟发处理冠层光分布增加,叶绿素、蛋白质含量提高,叶片细胞内保护酶类(Superoxide dismutase, SOD、catalase,CAT)活性下降慢,叶片衰老慢,但是漏光率增加,截光率下降;迟发处理净光合生产率(Net assimulation rate, NAR)增加,同化物分配合理,经济系数有增加的趋势,但物质积累速度(Crop growth rate ,CGR)和干物质生产量减少。在本实验条件下,早发与中发处理的经济产量差异不显著,但早发与迟发处理的经济产量差异达极显著。本研究结果表明大苗秧对生物、非生物因素胁迫,如本田前期一定程度的人工去蘖,具有一定的分蘖补偿能力。 相似文献
9.
10.