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排序方式: 共有3799条查询结果,搜索用时 15 毫秒
81.
Marianna Agudelo Martin Palus Jennifer R. Keeffe Filippo Bianchini Pavel Svoboda Jií Salt Avery Peace Anna Gazumyan Melissa Cipolla Tania Kapoor Francesca Guidetti Kai-Hui Yao Jana Elsterov Dana Teislerov Ale Chrdle Vclav Hnig Thiago Oliveira Anthony P. West Jr. Yu E. Lee Charles M. Rice Margaret R. MacDonald Pamela J. Bjorkman Daniel Rek Davide F. Robbiani Michel C. Nussenzweig 《The Journal of experimental medicine》2021,218(5)
Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV. 相似文献
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The expression of metalloproteinase MMP-1 was traced in frontal sections of the rat brain in normal conditions and 4 h after an intraperitoneal injection of kainate. In the olfactory lobe, immunoreactivity was normally detected in the lateral olfactory tract. Kainate treatment led to the appearance of additional immunoreactivity in the neuropilar tracts. In the hippocampal part of brain, immunoreactive neurons were found exclusively after the kainate treatment in several hypothalamic and amygdalar nuclei, and in the restricted cortex areas (clusters of neurons in layers 3–4 of cortex, and a stripe of cells in layer 6). In the area between the hippocampus and cerebellum, MMP-1-like immunoreactivity was normally present in the entorhinal cortex, in the lateral periaqueductal gray, and in the pontine nucleus. After kainate treatment, the immunoreactive neurons were also found in the medial entorhinal cortex and in the dorsal raphe nucleus. In the brain stem, the immunoreactive cells were normally found in six nuclei. After kainate treatment, additional immunoreactivity appeared in the inferior olive neurons and in tracts supplying the cerebellar cortex. Thus, MMP-1 is present in several brain areas in normal conditions at a detectable level, and its expression increases after kainate-induced seizures. 相似文献
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Christoph Stephan Valentin Bartha Eva Herrmann Nils von Hentig Pavel Khaykin Gaby Knecht Peter Gute Hans-Reinhard Brodt Martin Stürmer Annemarie Berger Markus Bickel 《Medical microbiology and immunology》2013,202(2):117-124
To explore CD4-cell and viral evolution in relation to different levels of HIV-1 replication, as observed during protease inhibitor (PI)-based antiretroviral therapy. Adult HIV-1 infected cohort patients, receiving historical salvage therapy with daily doses of saquinavir (2,000 mg), ritonavir (200 mg) and either lopinavir (800 mg) or atazanavir (300 mg) for >36 weeks were retrospectively analysed for highest detectable viral load up to week 96 and assigned to groups according to the viral load level: always <50 copies/ml (1), 50–199 copies/ml (2), 200–499 copies/ml (3) and ≥500 copies/ml (4). A total of 126 patients were evaluated; at baseline, median CD4-cell count was 204/mm3, HIV-1 RNA was 5.13 Log10-copies/ml and duration of prior HIV-1 infection was 11.7 years. Patients were assigned by 43, 30, 7 and 20 % to groups 1–4. Median observation time was 136 weeks (range: 38–304); at weeks 48/96, the CD4-cell gains for groups 1–4 were +88/+209, +209/+349, +67/+300 and +114.5/+ 128, respectively. After fitting data in a linear fixed effect model, ascending CD4 slopes were continuously increasing for group 1, similarly for 2 and clearly decreasing for 3–4 (p = 0.0006). Of 25 individuals from group 4, patient number with major IAS-USA protease mutations increased from 5 to 10 before and after failing PI therapy, whereas minor mutations remained stable (n = 18). On double-boosted PI therapy, CD4-cell increases through week 96 were similar for patients at always undetectable or with detection of low viral load. Viral detection >200 copies/ml was associated with decreasing CD4-cell slopes and emergence of major mutations, supporting this as benchmark for virological failure definition on PI therapy. 相似文献
85.
Maria Nazarova Pavel Novikov Ekaterina Ivanina Ksenia Kozlova Larisa Dobrynina Vadim V. Nikulin 《Human brain mapping》2021,42(8):2508
The spatial accuracy of transcranial magnetic stimulation (TMS) may be as small as a few millimeters. Despite such great potential, navigated TMS (nTMS) mapping is still underused for the assessment of motor plasticity, particularly in clinical settings. Here, we investigate the within‐limb somatotopy gradient as well as absolute and relative reliability of three hand muscle cortical representations (MCRs) using a comprehensive grid‐based sulcus‐informed nTMS motor mapping. We enrolled 22 young healthy male volunteers. Two nTMS mapping sessions were separated by 5–10 days. Motor evoked potentials were obtained from abductor pollicis brevis (APB), abductor digiti minimi, and extensor digitorum communis. In addition to individual MRI‐based analysis, we studied normalized MNI MCRs. For the reliability assessment, we calculated intraclass correlation and the smallest detectable change. Our results revealed a somatotopy gradient reflected by APB MCR having the most lateral location. Reliability analysis showed that the commonly used metrics of MCRs, such as areas, volumes, centers of gravity (COGs), and hotspots had a high relative and low absolute reliability for all three muscles. For within‐limb TMS somatotopy, the most common metrics such as the shifts between MCR COGs and hotspots had poor relative reliability. However, overlaps between different muscle MCRs were highly reliable. We, thus, provide novel evidence that inter‐muscle MCR interaction can be reliably traced using MCR overlaps while shifts between the COGs and hotspots of different MCRs are not suitable for this purpose. Our results have implications for the interpretation of nTMS motor mapping results in healthy subjects and patients with neurological conditions. 相似文献
86.
Katrin Mueller Yoshiaki Sunami Michael Stuetzle Nurdan Guldiken Ozlem Kucukoglu Sebastian Mueller Hasan Kulaksiz Peggy Schwarz Pavel Strnad 《The Journal of pathology》2013,231(4):532-542
The liver is the central regulator of iron metabolism and accordingly, chronic liver diseases often lead to systemic iron overload due to diminished expression of the iron‐regulatory hormone hepcidin. To study the largely unknown regulation of iron metabolism in the context of hepatic disease, we used two established models of chronic liver injury, ie repeated carbon tetrachloride (CCl4) or thioacetamide (TAA) injections. To determine the impact of CCAAT/enhancer‐binding protein (C/EBP)‐homologous protein (CHOP) on hepcidin production, the effect of a single TAA injection was determined in wild‐type and CHOP knockout mice. Furthermore, CHOP and hepcidin expression was assessed in control subjects and patients with alcoholic liver disease. Both chronic injury models developed a distinct iron overload in macrophages. TAA‐, but not CCl4‐ injected mice displayed additional iron accumulation in hepatocytes, resulting in a significant hepatic and systemic iron overload which was due to suppressed hepcidin levels. C/EBPα signalling, a known hepcidin inducer, was markedly inhibited in TAA mice, due to lower C/EBPα levels and overexpression of CHOP, a C/EBPα inhibitor. A single TAA injection resulted in a long‐lasting (> 6 days) suppression of hepcidin levels and CHOP knockouts (compared to wild‐types) displayed significantly attenuated hepcidin down‐regulation in response to acute TAA administration. CHOP mRNA levels increased 5‐fold in alcoholic liver disease patients versus controls (p < 0.005) and negatively correlated with hepcidin expression. Our results establish CHOP as an important regulator of hepatic hepcidin expression in chronic liver disease. The differences in iron metabolism between the two widely used fibrosis models likely reflect the differential regulation of hepcidin expression in human liver disease. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
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Molecular characteristic of acute leukemias with t(16;21)/<Emphasis Type="Italic">FUS-ERG</Emphasis>