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11.
Negative selection by endogenous antigen and superantigen occurs at multiple thymic sites 总被引:1,自引:0,他引:1
Douek Daniel C.; Corley Kevin T. T.; Zal Tomasz; Mellor Andrew; Dyson P. Julian; Altmann Daniel M. 《International immunology》1996,8(9):1413-1420
The site of negative selection in the thymus has been inferredfrom a range of different experiments. Analysis of thymic deletionof Vß5+, Vß11+ or Vß17a+ cellsH-2E transgenic mice led to the theory that negative selectionoccurs predominantly in the medulla (specifically, through presentationby medullary dendritic cells). Other experiments investigatedwhether transgenic TCR are deleted at the double-positive (DP)or single-positive stage following encounter with peptide ligand:by flow cytometric analysis deletion is generally found to occurat the DP thymocyte stage and as these cells are found predominantlyin the cortex, it has been inferred that this is the key siteof negative selection. The visualization of apoptotic thymocytesin situ has recently been reported for specific examples ofnegative selection. Using a panel of TCR transgenic lines inwhich negative selection occurs at different stages of thymocytedevelopment, we have used TUNEL staining to analyse the anatomicalsites of thymocyte apoptosis. For the first time we have beenable to compare directly the sites of deletion induced by theendogenous cognate peptides or by endogenous superantigen. Weshow that generalization from the medullary deletion of Vß5+,Vß11+ or Vß17a+ cells by the endogenoussuperantigens Mtv 8 and 9 and from limited examples of corticaldeletion by exogenous peptide administered to TCR transgenicmice is over-simplified. Apoptotic thymocytes in mice lackingMtv superantigens are indeed localized in the cortex. However,when deletion is induced by cognate self peptide, apoptosiscan occur in the cortex, the medulla or at the junction betweenthe two. 相似文献
12.
13.
Acute porphyria is rare in orientals. We describe a Chinese woman with recurrent generalised tonic-clonic seizures and abdominal pain. Genomic DNA studies identified a heterozygous base substitution from guanine to adenine at nucleotide position 503, resulting in substitution of arginine by histidine at position 168 of the protein (R168H). This genetic abnormality is similar to the mutation reported in Caucasians with variegate porphyria. To the best of our knowledge, this is the first report in the English literature a Chinese patient with variegate porphyria with an identifiable mutation. A brief review of porphyria is presented. 相似文献
14.
Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation. 相似文献
15.
van Kranen HJ; van Iersel PW; Rijnkels JM; Beems DB; Alink GM; van Kreijl CF 《Carcinogenesis》1998,19(9):1597-1601
The variation in colorectal cancer (CRC) incidence worldwide strongly
suggests a role for dietary influences. Based on epidemiological data,
protective effects of vegetables and fruit intake on CRC are widely
claimed, while other data indicate a possible increased CRC risk from
(higher) dietary fat intake. Therefore, we have investigated single and
interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in
the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this
study, four different diets (A-D) were compared, which were either low in
fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In
addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced
by a freeze-dried VFM. The diets were balanced so that they only differed
among each other in fat/carbohydrate content and the presence of specific
plant-constituents. Because the initiation of intestinal tumors in ApcMin
mice occurs relatively early in life, exposure to the diets was started in
utero. Without the addition of VFM, mice maintained at a high-fat diet did
not develop significantly higher numbers of small or large intestinal
adenomas than mice maintained at a low-fat diet. VFM added to a low-fat
diet significantly lowered multiplicity of small intestinal polyps (from
16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male
ApcMin mice only. Strikingly, addition of VFM to female mice maintained on
a low-fat diet and to both sexes maintained on a high-fat diet
significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7
polyps/mouse). In conclusion, our results indicate that neither a lower fat
intake nor consumption of VFM included in a high-fat diet decreases the
development of polyps in mice genetically predisposed to intestinal tumor
development.
相似文献
16.
17.
Olivia Fletcher Lorna Gibson Nichola Johnson Dan R Altmann Jeffrey M P Holly Alan Ashworth Julian Peto Isabel Dos Santos Silva 《Cancer epidemiology, biomarkers & prevention》2005,14(1):2-19
We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely. 相似文献
18.
Psychophysical measurements were carried out with a microcomputer-controlled matrix of 32 X 32 light emitting diodes to determine temporal parameters of figure-ground separation processes. The task was to detect a figure that was dispersed in time. Between each two figure elements n noise elements were interspersed. The results of these experiments indicate that the discrimination of figures hidden in dynamic noise is possible even if figure elements are dispersed in time over several hundred milliseconds. The maximal dispersion time still compatible with figure discrimination (Tmax) depends critically on the number n of interspersed noise elements, on the subject's expectancy and on the number of elements used for the generation of the figure. For simple figures such as triangles Tmax could be as long as 1.5 sec when n was 4. Our experimental results suggest that the neuronal representation of the briefly displayed (less than 6 msec) pattern elements outlasts their physical presence by at least 400 msec. This persistence of neuronal representations must occur at a level of processing where retinotopy is still preserved, since the only cue for figure-ground discrimination is the difference in the local density of figure and noise elements. 相似文献
19.
Dr. M. Altmann 《Journal of molecular medicine (Berlin, Germany)》1927,6(18):854-855
Ohne Zusammenfassung 相似文献
20.
K. Altmann Meirowsky Carl Bruck Fritz Juliusberg Harald Boas Max Joseph Weiler F. Krzysztalowicz J. Ullmann Marg Stern R. Volk Otto Clingestein Theodor Baer Oskar Müller Felix Münchheimer Edgar Braendle Loewenhardt L. Halbenlaedter Edgar Braendle L. Lalberstaedter 《Archives of dermatological research》1912,112(4):480-517
Ohne Zusammenfassung 相似文献