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31.
Induction of cyclooxygenase-2 (COX-2) with production of prostaglandins occurs in a wide spectrum of acute and chronic neurodegenerative diseases and is associated with neuronal death. Inhibition of the COX-2 pathway and downstream production of prostaglandins protect neurons in rodent models of cerebral ischemia and neurodegeneration. Recent studies investigating the functions of selected prostaglandin receptor pathways in mediating COX-2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of several receptors in models of excitotoxicity. In this study, we investigate the functions of additional prostaglandin receptors not previously characterized in organotypic models of glutamate excitotoxicity. We find that PGD2, PGI2, and PGF2α receptors protect motor neurons in an organotypic spinal cord model of amyotrophic lateral sclerosis (ALS). In addition, PGI2 and TXA2 receptors rescue CA1 neurons in an organotypic hippocampal model of N-methyl-d-aspartate excitotoxicity. However, in a model of inflammation induced by lipopolysaccharide, prostaglandin receptors previously found to be protective in excitotoxicity now cause CA1 neuronal death. Taken together, these studies identify novel eicosanoid receptor signaling pathways that mediate neuronal protection in excitotoxic paradigms; these data also support the emerging hypothesis that the toxic/protective effects of eicosanoid signaling on neuronal viability diverge significantly depending on whether excitotoxicity or inflammation predominates as the underlying toxic stimulus. 相似文献
32.
Primary antitumor immune response mediated by CD4+ T cells 总被引:7,自引:0,他引:7
Corthay A Skovseth DK Lundin KU Røsjø E Omholt H Hofgaard PO Haraldsen G Bogen B 《Immunity》2005,22(3):371-383
Gene-targeted mice have recently revealed a role for lymphocytes and interferon-gamma (IFNgamma) in conferring protection against cancer, but the mechanisms remain unclear. Here, we have characterized a successful primary antitumor immune response initiated by naive CD4+ T cells. Major histocompatibility complex class II (MHC-II)-negative myeloma cells injected subcutaneously into syngeneic mice were surrounded within 3 days by macrophages that captured tumor antigens. Within 6 days, naive myeloma-specific CD4+ T cells became activated in draining lymph nodes and subsequently migrated to the incipient tumor site. Upon recognition of tumor-derived antigenic peptides presented on MHC-II by macrophages, the myeloma-specific CD4+ T cells were reactivated and started to secrete cytokines. T cell-derived IFNgamma activated macrophages in close proximity to the tumor cells. Tumor cell growth was completely inhibited by such locally activated macrophages. These data indicate a mechanism for immunosurveillance of MHC-II-negative cancer cells by tumor-specific CD4+ T cells through collaboration with macrophages. 相似文献
33.
Transgenic rat model of Huntington's disease 总被引:12,自引:0,他引:12
von Hörsten S Schmitt I Nguyen HP Holzmann C Schmidt T Walther T Bader M Pabst R Kobbe P Krotova J Stiller D Kask A Vaarmann A Rathke-Hartlieb S Schulz JB Grasshoff U Bauer I Vieira-Saecker AM Paul M Jones L Lindenberg KS Landwehrmeyer B Bauer A Li XJ Riess O 《Human molecular genetics》2003,12(6):617-624
Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation. 相似文献
34.
We describe here a 3-year-old girl demonstrating combined cellular immunodeficiency of B- and T-cells, pancytopenia, multiple anomalies, and severe mental retardation. Cytogenetic analysis and fluorescent in situ hybridization (FISH) indicated an unbalanced translocation of chromosomes 8q and 11q, resulting in monosomy 11q23.3-qter and trisomy 8q24.3-qter. The association of cellular immunodeficiency and partial deletion 11q and/or partial trisomy 8q has not been described previously; however, the 11q deletion has been reported with humoral immunodeficiency or pancytopenia. Some one-third to one-half of patients with partial monosomy 11q were reported to have pancytopenia, which has been related to the absence of the 11q23-q24 region. Our case narrows down the critical interval for thrombo- or pancytopenia to 11q23.3-q24 and excludes both the ATM (which resides on 11q23.1) and the MLL genes as possible candidate genes. We are proposing that haploinsufficiency of the NFRKB gene on 11q24-q25 and/or the ETS-1 proto-oncogene on 11q24 may have caused or contributed to the immunodeficiency (decreased levels of B- and T-lymphocytes) in our patient. 相似文献
35.
Katrin Gaardbo Kuhn Anne Kathrine Hvass Annette Hartvig Christiansen Steen Ethelberg Susan Alice Cowan 《Emerging infectious diseases》2021,27(4):1133
Campylobacteriosis is a disease of worldwide importance, but aspects of its transmission dynamics, particularly risk factors, are still poorly understood. We used data from a matched case-control study of 4,269 men who have sex with men (MSM) and 26,215 controls, combined with national surveillance data on Campylobacter spp., Salmonella spp., and Shigella spp., to calculate matched odds ratios (mORs) for infection among MSM and controls. MSM had higher odds of Campylobacter (mOR 14, 95% CI 10–21) and Shigella (mOR 74, 95% CI 27–203) infections, but not Salmonella (mOR 0.2, 95% CI 0–13), and were less likely than controls to have acquired Campylobacter infection abroad (χ2 = 21; p<0.001). Our results confirm that sexual contact is a risk factor for campylobacteriosis and also suggest explanations for unique features of Campylobacter epidemiology. These findings provide a baseline for updating infection risk guidelines to the general population. 相似文献
36.
37.
Tobias Veit Dieter Munker Jürgen Barton Katrin Milger Teresa Kauke Bruno Meiser Sebastian Michel Michael Zoller Hans Nitschko Oliver T. Keppler Jürgen Behr Nikolaus Kneidinger 《American journal of transplantation》2021,21(10):3449-3455
Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log10) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account. 相似文献
38.
Wilms M Eickhoff SB Specht K Amunts K Shah NJ Malikovic A Fink GR 《Anatomy and embryology》2005,210(5-6):485-495
To date, the delineation of the human visual “motion area” still relies on functional paradigms originally devised to identify
monkey area MT. Using fMRI, we have identified putative human area V5/MT+ in normals by modelling the BOLD responses to alternating radially moving and stationary dot patterns. Functional activations
were compared with cytoarchitectonic probability maps of its putative correlate area hOc5, which was calculated based upon data from histological sections of ten human post-mortem brains. Bilateral visual cortex
activations were seen in the single subject dynamic versus stationary contrasts and in the group random-effects analysis. Comparison of group data with area hOc5 revealed that 19.0%/39.5% of the right/left functional activation was assigned to the right/left hOc5. Conversely, 83.2%/53.5% of the right/left hOc5 was functionally activated. Comparison of functional probability maps (fPM) with area hOc5 showed that 28.6%/18.1% of the fPM was assigned to hOc5. In turn, 84.9%/41.5% of the area hOc5 was covered by the respective fPM. Thus, random-effects data and fPMs yielded similar results. The present study shows for
the first time the correspondence between the functionally defined human V5/MT+ and the post-mortem cytoarchitectonic area hOc5. 相似文献
39.
Endothelial cell transplantation and growth behavior of the human corneal endothelium 总被引:1,自引:0,他引:1
Katrin Engelmann Jürgen Bednarz Matthias Böhnke 《Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft》1999,96(9):555-562
Background: The human corneal endothelium has a limited proliferative capacity in vivo. Until now it has only been possible to replace
damaged endothelium by transplantation of a donor cornea. After establishing methods for the isolation and in vitro cultivation
of human corneal endothelial cells, transplantation of these cells my be an alternative therapeutic option.
Materials and methods: In this review methods for the in vitro cultivation of human corneal endothelial cells and their transplantation on the Descemet
membrane of donor corneas are described.
Results: In vitro proliferation of human adult corneal endothelial cells was achieved by the development of defined cell culture conditions,
including supplementation of culture medium with specified growth factors and substances. Dependent on the culture conditions,
as well as independent of them, in vitro cultured endothelial cells showed phenotypic changes and different proliferative
behavior. Thus, molecular biological examinations revealed a different expression pattern of growth factor receptors in fibroblast-like
endothelial cells (dedifferentiated) compared to typical endothelial cells (differentiated). Moreover, the proliferative capacity
of the cells differed, dependent on their corneal location. Cells isolated from the peripheral part of donor corneas have
a higher proliferative capacity than cells obtained from the central part. The propagation of corneal endothelial cells in
vitro offered the possibility of their transplantation on donor corneas in an in vitro model. After transplantation, these
cells formed a monolayer whose morphology and cell density depended on the differentiation of the cells. DNA synthesis was
predominantly detectable in cells of the corneal periphery.
Conclusions: Our findings are the basis of the following hypothesis: the periphery of the cornea represents a regenerative zone of the
corneal endothelium. The fact that early after transplantation corneal endothelial cells form a monolayer on the natural extracellular
matrix (ECM), which shows contact inhibition, suggests that inhibitory factors are released by the Descemet membrane that
influence the proliferation of the cells. Further studies on the regulation of the proliferation and differentiation of human
corneal endothelial cells in vitro and after transplantation might offer the possibility to establish a selective procedure
for the treatment of corneal endothelial cell loss in the near future.
相似文献
40.
Philippe Béhé Katrin Sandmeier Hans Meves 《Pflügers Archiv : European journal of physiology》1992,422(2):120-128
The M current, I
M, a voltage-dependent non-inactivating K+ current, was recorded in NG108-15 neuroblastoma × glioma hybrid cells, using the whole-cell mode of the patch-clamp technique. We studied the effect of arachidonic acid, other fatty acids and inhibitors of the arachidonic acid metabolism. In relatively high concentrations (25–50 M) arachidonic acid first increased and later decreased the current, I
h, which holds the membrane potential at –30 mV and mainly flows through open M channels. It shifted the midpoint potential, V
o, of the relation between M conductance, g
M, and membrane potential, V, to more negative values and decreased the maximum conductance ¯g
M and the time constant
M. In smaller concentrations (5–10 M) arachidonic acid merely decreased I
h and ¯g
M with little effect on V
o and
M. Eicosatetraynoic acid and docosa-hexaenoic acid acted similarly to arachidonic acid whereas stearic acid had no effect. Of the three enzyme inhibitors studied, nordihydroguaiaretic acid acted similarly to arachidonic acid. i. e. caused a biphasic change in I
h. Indomethacin and quinacrine caused, respectively, a pure increase and a pure decrease of I
h and ¯g
M. Possible explanations are build-up of internally produced arachidonic acid, depletion of eicosanoid products or an inhibitory effect unrelated to arachidonic acid metabolism. 相似文献