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991.
Induction of oral tolerance to antigens that are targets of self-reactive immune responses is an attractive approach to antigen-specific
immune therapy of autoimmune diseases. Oral tolerization has indeed proven to be safe and effective in amelioration of autoimmune
diseases in animal models. In humans, results have been somewhat controversial. The emphasis given to clinical outcome rather
than to immunomodulation, and the difficulty in identifying appropriate candidate antigens contribute to the controversy.
Heat shock proteins are promising targets for immune intervention. Immune reactivity to heat shock proteins has indeed been
correlated with autoimmune arthritis in animal models, and abnormal immune responses to heat shock proteins have been described
in human arthritis as well. Despite significant recent progress, little is known at a molecular level regarding the mechanisms
which are responsible for a switch from autoimmunity to tolerance in humans. This is particularly true with respect to sequential
analysis of several molecular and immunologic markers during both the course and treatment of disease. Novel approaches are
currently under way to fill the gaps. We will briefly detail here the experience gained to date, and identify some of the
avenues which future research will explore. 相似文献
992.
Heat shock proteins and the antitumor T cell response 总被引:14,自引:0,他引:14
Heat shock proteins (HSP) have been shown to participate in the antitumor T cell response. First, HSP play a crucial role
in the intracellular pathway for antigen processing where HSP can make complexes with a broad spectrum of cellular proteins
and peptides through their chaperone functions. In this pathway, macrophages are required for processing the chaperoned peptides
to make stable molecules with the major histocompatibility complex (MHC) class I molecules, even when HSP-peptide complexes
are exogenously administered. Through this pathway, vaccination with HSP-peptide complexes is thus able to elicit the response
of CD8+ T cells specific for the chaperoned peptides. These findings suggest an essential role of HSP in ‘cross-priming’ and their
usefulness for antitumor vaccination with tumor peptides. Second, HSP have been suggested to be expressed on the cell surface
by transformation and, in addition, to function as antigen-presenting molecules for double negative T cells. Third, HSP derived
from tumor cells have reportedly been recognized by T cells with either T cell receptor (TCR)-αβ or TCR-γδ. These lines of evidence therefore indicate that HSP may be potentially promising target molecules for antitumor T cell immunotherapy. 相似文献
993.
Osmotic shock and lysozyme/EDTA methods were used to recover secreted recombinant proteins from protease negative mutant strains of E. coli. Up to 80% of protein A--lactamase fusion protein was recovered from protease negative mutants by simple osmotic shock. Fractionation by lysozyme/EDTA treatment, increased the recovery of protein A--lactamase fusion protein from the mutant strain up to 93%. Mild fractionation condition allowed efficient recovery of secreted protein from protease negative mutant strains, but not from the parent strain possessing proteases. © Rapid Science Ltd. 1998 相似文献
994.
995.
Heat shock protein expression in fish 总被引:19,自引:0,他引:19
Iwama George K. Thomas Philip T. Forsyth Robert B. Vijayan Mathilakath M. 《Reviews in Fish Biology and Fisheries》1998,8(1):35-56
Heat shock proteins (HSP) are a family of proteins expressed in response to a wide range of biotic and abiotic stressors. They are thus also referred to as stress proteins. Their extraordinarily high degree of identity at the amino acid sequence level and the fact that this cellular stress response has been described in nearly all organisms studied, make this group of proteins unique. We provide a brief historical overview of HSP research, as a background to summarizing what is known about HSP expression in fish. The expression of HSPs in fish has been described in cell lines, primary cultures of various cells, and in the tissues of whole organisms. Collectively, the data show that the expression of HSPs are affected in a wide variety of fish cells and tissues, in response both to biological stressors such as infectious pathogens, as well as to abiotic stressors such as heat and cold shock, and environmental contaminants. HSP research in fish is in its early stages and many studies are describing the expression of proteins in response to various stressors. Several studies have contributed to our understanding of the molecular nature and the molecular biology of HSPs in fish. Recent studies have shown a relationship between HSP expression and the generalized stress response in fish, but further research is needed to clarify the complex relationships between stress hormones and the cellular HSP response. In general, the HSP response seems to be related to the sensing of the stressor and the subsequent cellular effects which may adapt the cells to cope with the stressors. Consequently, such data may be of central importance in understanding the significance of HSP expression to the whole organism. We conclude with sections on laboratory methods used in HSP research and on potential applications of this knowledge in biomonitoring. 相似文献
996.
Prediction of Transgene integration by Noninvasive Bioluminescent Screening of Microinjected Bovine Embryos 总被引:1,自引:0,他引:1
Menck M. Celeste Mercier Yvan Campion Evelyne Lobo Raysildo B. Heyman Yvan Renard Jean-Paul Thompson Eric M. 《Transgenic research》1998,7(5):331-342
Transgenesis in domestic species, as a research tool and in biotechnological applications, has been limited by the expense of producing transgenic offspring by standard microinjection techniques. A major factor is the inefficiency of maintaining large numbers of recipient females, when a high percentage of these carry nontransgenic fetuses. There are two approaches to reduce this cost, the fusion of transfected fetal fibroblasts with enucleated oocytes, and the screening of microinjected embryos for transgene integration in blastocysts, prior to transfer. Here, we develop a luminescent screening system to select transgenic bovine embryos. A transgene with scaffold attachment regions flanking the murine HSP70.1 promoter linked to firefly luciferase cDNA, was microinjected into pronuclei of in vitro produced zygotes. At the blastocyst stage, the transgene was induced by heat shock (45 °C, 15 min) and 4–6 h later, luciferase expression was analyzed by photon counting imaging. Screened blastocysts were transferred to recipients and day 50 fetuses or calves were analyzed by PCR and Southern blot for transgene integration. When nonluminescent blastocysts were transferred, transgene integration was never observed. Of 13 fetuses derived from luminescent blastocysts, 3 contained integrated transgenes that were functional in all tissues examined. Image analysis of the signal emitted by positive blastocysts revealed that 9 nontransgenic fetuses were obtained from blastocysts that exhibited a localized luminescent signal. On the other hand, 3 of 4 fetuses derived from blastocysts that emitted light over more than 70% of their surface were transgenic. Thus, by selecting luminescent blastocysts on the basis of both signal intensity and distribution, the number of recipient females required to produce transgenic offspring can be greatly reduced. Using this technique it should also be possible to improve the efficiency of transgenesis by microinjection through studies in which vector design and integration conditions are examined at the blastocyst stage. 相似文献
997.
目的:观察失血性休克后血浆IL-1活性的变化及其与肠源性内毒素血症的关系。方法:复制容量控制失血性休克及肠源性内毒素血症模型,改良LAF法及显色基质偶氮法检测IL-1及ET。结果:普通SD大鼠30%失血后2~3h及6~10h血浆IL-1活性升高,3h后ET水平显著升高;失血前胃内灌注双岐杆菌或失血后静注rBPI,大鼠血浆ET水平无明显升高,IL-1活性第1峰仍然存在,但第2峰消失。无菌SD大鼠10%失血、灌注LPS后1h血浆ET水平升高,2h后IL-1活性升高。结论:失血性休克后IL-1活性呈双峰型升高,第1峰与内毒素无关,第2峰为内毒素刺激峰,内毒素主要来源于肠道 相似文献
998.
Shigenori Katayama Hisato Shuntoh Shogo Matsuyama Chikako Tanaka 《Journal of neurochemistry》1994,62(6):2292-2299
Abstract: The effect of heat shock on agonist-stimulated intracellular Ca2+ mobilization and the expression of heat shock protein 72 (hsp72) in neuroblastoma × glioma hybrid cells (NG 108–15 cells) were examined. Hsp72 was expressed at 6 h after heat shock (42.5°C, 2 h), reached a maximum at 12 h, and decreased thereafter. Bradykinin-induced [Ca2+ ], rise was attenuated to 28% of control by heat shock at 2 h after heat shock, and reversion to the control level was seen 12 h later. When the cells were treated with quercetin or antisense oligodeoxyribonucleotide against hsp72 cDNA, the synthesis of hsp72 was not induced by heat shock, whereas bradykinin-induced [Ca2+ ]i rise was abolished and the [Ca2+ ]i rise was not restored. Recovery from this stressed condition was evident when cells were stimulated by the Ca2+ -ATPase inhibitor thapsigargin, even in the presence of either quercetin or antisense oligodeoxyribonucleotide. Inositol 1,4,5-trisphosphate (IP3 ) production was not altered by heat shock at 12 h after heat shock, whereas IP3 receptor binding activity was reduced to 45.3%. In the presence of quercetin or antisense oligodeoxyribonucleotide, IP3 receptor binding activity decreased and reached 27.2% of the control 12 h after heat shock. Our working thesis is that heat shock transiently suppresses the IPs-mediated intracellular Ca2+ signal transduction system and that hsp72 is involved in the recovery of bradykinin-induced [Ca2+ ]i rise. 相似文献
999.
Activation and Tyrosine Phosphorylation of 44-kDa Mitogen-Activated Protein Kinase (MAPK) Induced by Electroconvulsive Shock in Rat Hippocampus 总被引:1,自引:0,他引:1
Ung Gu Kang Kyung Sue Hong Hee Yeon Jung Yong Sik Kim Yeon-Sun Seong Yun Chung Yang Joo-Bae Park 《Journal of neurochemistry》1994,63(5):1979-1982
Abstract: Electroconvulsive shock (ECS) has been reported to induce the phosphorylation and activation of 42-kDa, but not 44-kDa, mitogen-activated protein kinase (MAPK) in rat hippocampus. We studied the activation and tyrosine phosphorylation of MAPKs in rat brain after ECS. We observed the increase of the activities of both 42- and 44-kDa MAPKs in rat hippocampus after ECS. The activities reached peak at 2 min and returned to basal levels by 15 min after ECS. We also observed the increased phsophorylation on the tyrosine residue of 42-kDa MAPK in rat hippocampus after ECS, but not on that of 44-kDa MAPK. However, when we examined the immunoprecipitated 44-kDa MAPK, we could demonstrate that the tyrosine phosphorylation of 44-kDa MAPK at 2 min after ECS was markedly increased, in accordance with the increase of kinase activity. These results indicate that ECS induces the transient activation and tyrosine phosphorylation of 44-kDa MAPK, as well as 42-kDa MAPK, in rat hippocampus, although the amount of tyrosine phosphorylation is far less and the kinase activity is lower in 44-kDa MAPK than in 42-kDa MAPK. 相似文献
1000.
Yasuyuki Ogata Tohru Mizushima Kazuhiro Kataoka Takeyoshi Miki Kazuhisa Sekimizu 《Molecular & general genetics : MGG》1994,244(5):451-455
The linking number of plasmid DNA in exponentially growingEscherichia coli increases immediately and transiently after heat shock. The purpose of this study was to search for DNA topoisomerases that catalyze this relaxation of DNA. Neither introduction of atopA deletion mutation nor treatment of cells with DNA gyrase inhibitors affected the DNA relaxation induced by heat shock. Thus, DNA topoisomerase I and DNA gyrase are apparently not involved in the process. However, the reaction was inhibited by nalidixic acid or by oxolinic acid in thetopA mutant and the reaction was resistant to nalidixic acid in atopA mutant carrying, in addition, thenalA26 mutation. These results are interpreted as indicating that both DNA topoisomerase I and DNA gyrase are involved in the DNA relaxation induced by heat shock. 相似文献