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81.
Raymond G. Goodwin Wenie S. Din Terri Davis-Smith Dirk M. Anderson Steven D. Gimpel Timothy A. Sato Charles R. Maliszewski Camilynn I. Brannan Neal G. Copeland Nancy A. Jenkins Terry Farrah Richard J. Armitage William C. Fanslow Craig A. Smith 《European journal of immunology》1993,23(10):2631-2641
4-1BB is an inducible T cell antigen that shows sequence homology to members of an emerging family of cytokine receptors, including those for tumor necrosis factor and nerve growth factor. To aid in the analysis of the function of 4-1BB we have utilized a soluble form of the molecule as a probe to identify and clone the gene which encodes its ligand. The ligand for 4-1BB is a type II membrane glycoprotein that has homology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this superfamily. The gene for 4-IBB is on mouse chromosome 4 and maps close to the p80 form of the tumor necrosis factor receptor as well as the gene for CD30. The gene for 4-IBB ligand maps to mouse chromosome 17, but considerably distal to the tumor necrosis factor and lymphotoxin genes. Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4-1BB. 相似文献
82.
Gilissen LJ Bolhaar ST Matos CI Rouwendal GJ Boone MJ Krens FA Zuidmeer L Van Leeuwen A Akkerdaas J Hoffmann-Sommergruber K Knulst AC Bosch D Van de Weg WE Van Ree R 《The Journal of allergy and clinical immunology》2005,115(2):364-369
BACKGROUND: Apple allergy is dominated by IgE antibodies against Mal d 1 in areas where birch pollen is endemic. Apples with significantly decreased levels of Mal d 1 would allow most patients in these areas to eat apples without allergic reactions. OBJECTIVE: The aim of this study was to inhibit the expression of Mal d 1 in apple plants by RNA interference. METHODS: In vitro -grown apple plantlets were transformed with a construct coding for an intron-spliced hairpin RNA containing a Mal d 1-specific inverted repeat sequence separated by a Mal d 1-specific intron sequence. The presence of the construct in transformants was checked by PCR. Expression of Mal d 1 in leaves was monitored by prick-to-prick skin testing in 3 patients allergic to apples and by immunoblotting with a Mal d 1-reactive mAb and with IgE antibodies against Mal d 1. RESULTS: After transformation, plantlets were selected on the basis of having a normal phenotype and growth rate. With PCR, in 6 of 9 selected plantlets, the presence of the gene-silencing construct was demonstrated. By skin prick test it was shown that a wild-type plantlet had significantly ( P < .05) higher allergenicity than 5 of the transformants. Reduction of expression of Mal d 1 was confirmed by immunoblotting. In wild-type and unsuccessful transformants, a strong band was detected with Mal d 1-reactive mAb 5H8 at the expected apparent M r of 17 kDa. This band was virtually absent in the transformants that carried the gene-silencing construct. With human IgE antibodies, the same observations were made. CONCLUSIONS: Mal d 1 expression was successfully reduced by RNA interference. This translated into significantly reduced in vivo allergenicity. These observations support the feasibility of the production by gene silencing of apples hypoallergenic for Mal d 1. 相似文献
83.
Kasper HU Longerich T Stippel DL Kern MA Drebber U Schirmacher P 《Archives of pathology & laboratory medicine》2005,129(2):234-237
We report a case in an elderly adult of a highly malignant liver tumor with blastoid features that resembled hepatoblastoma. A liver tumor with a diameter of 23 cm was removed in a 78-year-old woman. The tumor showed highly differentiated epithelial hepatocellular and poorly differentiated epithelial and mesenchymal components. The blastoid nature and pluripotent differentiation potential were supported by immunohistologic analysis and suggest an origin of a poorly differentiated pluripotent hepatic cell with the potential to mature. We believe that this case of a mixed hepatoblastoma in an adult should be added to the growing number of presumed hepatic precursor cell neoplasms in adults. 相似文献
84.
Dirk Pette 《Journal of molecular medicine (Berlin, Germany)》1958,36(16):775-777
Zusammenfassung Die Frage der quantitativen und elektiven Erfassung des Liquor--Globulins mit der vonRoboz u. Mitarb. beschriebenen Zinksulfatfällung wurde an Modellversuchen mit reinem -Globulin und Albumin und an der elektrophoretischen Auftrennung des mit Zinksulfat aus Liquor präzipitierten Proteins untersucht. Aus reinen -Globulinlösungen wurden in Abhängigkeit zu der in Ansatz gebrachten -Globulinmenge nur 18–46% gefällt. Das Elektrophoresediagramm der mit Zinksulfat gefällten Liquorproteine zeigte, daß neben einer Anreicherung des -Globulins eine Fällung sämtlicher Liquorproteine zustande kam. Die elektrophoretische Auftrennung der im Überstand der Fällung verbliebenen Eiweißkörper ließ neben den übrigen Fraktionen noch eine deutliche -Globulinbande erkennen. Eine elektive und quantitative Fällung des Liquor--Globulins mit der Zinksulfatmethode konnte demnach nicht nachgewiesen werden.Herrn Dozent Dr.H. Bauer danke ich für die Anregung und Unterstützung bei Durchführung dieser Untersuchungen. 相似文献
85.
Neurons have ion channels that are directly gated by voltage, ligands and temperature but not by light. Using structure-based design, we have developed a new chemical gate that confers light sensitivity to an ion channel. The gate includes a functional group for selective conjugation to an engineered K(+) channel, a pore blocker and a photoisomerizable azobenzene. Long-wavelength light drives the azobenzene moiety into its extended trans configuration, allowing the blocker to reach the pore. Short-wavelength light generates the shorter cis configuration, retracting the blocker and allowing conduction. Exogenous expression of these channels in rat hippocampal neurons, followed by chemical modification with the photoswitchable gate, enables different wavelengths of light to switch action potential firing on and off. These synthetic photoisomerizable azobenzene-regulated K(+) (SPARK) channels allow rapid, precise and reversible control over neuronal firing, with potential applications for dissecting neural circuits and controlling activity downstream from sites of neural damage or degeneration. 相似文献
86.
The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote 总被引:35,自引:2,他引:35
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87.
88.
Specific cytotoxic T lymphocytes in gene therapy 总被引:1,自引:0,他引:1
U. Altenschmidt Dirk Moritz B. Groner 《Journal of molecular medicine (Berlin, Germany)》1997,75(4):259-266
Cytotoxic T lymphocytes possess the capacity to lyse target cells which express antigens on their surface recognized by the
T cell receptor. These cells are crucial in the body’s defense against foreign antigens. It has long been a goal of tumor
biology to utilize T cells, specialized in the elimination of unwanted cells, for the treatment of cancer. The killing activity
of T lymphocytes is restricted to specific antigen-presenting cells. For this reason the use of cytotoxic T cells in the elimination
of cancer cells is limited to cancer cells which present neoantigens on their surface. To circumvent this limitation we describe
a procedure in which the ζ component of the T cell receptor is genetically manipulated and equipped with an extracellular
recognition domain. Introduction of a chimeric gene, consisting of the ζ chain of the T cell receptor and a single-chain antibody
domain, into cytotoxic T lymphocytes results in T cells with a predetermined recognition specificity for particular tumor
cells. The MHC restriction of target cell recognition can be avoided and tumor cells recognized by the single chain antibody
domain can be recognized and lysed. Retroviral-mediated gene transduction was used to introduce chimeric ζ chain constructs
into primary T cells of mice. The cocultivation of retrovirus producing helper cells with in vitro activated T lymphocytes
led to a high gene transduction efficiency into primary T cells. These primary T cells assumed a predetermined specificity
for target cell recognition and lysis. The production and provision of tumor cell specific T lymphocytes might not be sufficient
to eradicate large tumors in vivo. Using a Schwannoma cell line, we showed that transplanted tumors secrete transforming growth
factor β and thereby stifle the action of lymphocytes. We suggest that a coordinated strategy including the suppression of
tumor cells specific antilymphocyte action and the provision of tumor cell specific T cells might be required to successfully
eliminate tumor cells in vivo.
Received: 13 September 1996 / Accepted: 30 October 1996 相似文献
89.
It has been questioned whether the interaction of H2-antagonists with cytochrome P-450 that is observedin vitro is also relevant for thein vivo situation. Until now the possibility that cytochrome P-450 may function with different modes of action has been neglected in this respect. We studied the effect of cimetidine, ranitidine and famotidine on the monoxygenase, the oxidase and the peroxidase action of cytochrome P-450. Biotransformation catalyzed by the monoxygenase and oxidase action of cytochrome P-450 was affected by cimetidine (probably via its ligand interaction with cytochrome P-450), whereas metabolism by the peroxidase mode of action of cytochrome P-450 was hardly influenced. Ranitidine and famotidine (both pharmacodynamically more potent than cimetidine) only slightly affected cytochrome P-450 activities. 相似文献
90.
Steffen Dietzel Anna Jauch Dirk Kienle Guoquiong Qu Heidi Holtgreve-Grez Roland Eils Christian Munkel Michael Bittner Paul S. Meltzer Jeffrey M. Trent Thomas Cremer 《Chromosome research》1998,6(1):25-33
Fluorescence in situ hybridization (FISH) with microdissection probes from human chromosomes 3 and 6 was applied to visualize arm and subregional band domains in human amniotic fluid cell nuclei. Confocal laser scanning microscopy and quantitative three-dimensional image analysis showed a pronounced variability of p- and q-arm domain arrangements and shapes. Apparent intermingling of neighbouring arm domains was limited to the domain surface. Three-dimensional distance measurements with pter and qter probes supported a high variability of chromosome territory folding. 相似文献