首页 > 最新文献

Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine最新文献

英文 中文
Peptide YY stimulates the expression of apolipoprotein A-IV gene in Caco-2 intestinal cells. 肽YY刺激Caco-2肠细胞载脂蛋白A-IV基因的表达。
K. Sonoyama, K. Suzuki, T. Kasai
The effect of peptide YY, a gastrointestinal hormone, on the expression of the apolipoprotein A-IV gene in the intestinal epithelial cell line Caco-2 was examined by semiquantitative RT-PCR followed by Southern hybridization with an inner oligonucleotide probe. Apolipoprotein A-IV mRNA levels were increased in response to peptide YY in a dose- and time-dependent fashion. Western blotting revealed that the exogenous peptide YY increased the intracellular concentration of apolipoprotein A-IV. In contrast, apolipoprotein A-I, B, and C-III mRNA did not respond to peptide YY. Differentiated Caco-2 cells expressed Y1- but not Y2- and Y5-receptor subtype mRNA. The present results suggest that peptide YY modulates apolipoprotein A-IV gene expression, likely via the Y1-receptor subtype in intestinal epithelial cells.
采用半定量RT-PCR +内寡核苷酸探针Southern杂交技术研究胃肠激素YY肽对小肠上皮细胞系Caco-2载脂蛋白a - iv基因表达的影响。载脂蛋白a - iv mRNA水平随YY肽剂量和时间的变化而升高。Western blotting结果显示外源肽YY使细胞内载脂蛋白A-IV浓度升高。相比之下,载脂蛋白A-I、B和C-III mRNA对肽YY没有反应。分化后的Caco-2细胞表达Y1-而不表达Y2-和y5受体亚型mRNA。目前的研究结果表明,YY肽可能通过肠上皮细胞中y1受体亚型调节载脂蛋白A-IV基因的表达。
{"title":"Peptide YY stimulates the expression of apolipoprotein A-IV gene in Caco-2 intestinal cells.","authors":"K. Sonoyama, K. Suzuki, T. Kasai","doi":"10.1111/J.1525-1373.2000.22338.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22338.X","url":null,"abstract":"The effect of peptide YY, a gastrointestinal hormone, on the expression of the apolipoprotein A-IV gene in the intestinal epithelial cell line Caco-2 was examined by semiquantitative RT-PCR followed by Southern hybridization with an inner oligonucleotide probe. Apolipoprotein A-IV mRNA levels were increased in response to peptide YY in a dose- and time-dependent fashion. Western blotting revealed that the exogenous peptide YY increased the intracellular concentration of apolipoprotein A-IV. In contrast, apolipoprotein A-I, B, and C-III mRNA did not respond to peptide YY. Differentiated Caco-2 cells expressed Y1- but not Y2- and Y5-receptor subtype mRNA. The present results suggest that peptide YY modulates apolipoprotein A-IV gene expression, likely via the Y1-receptor subtype in intestinal epithelial cells.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"253 1","pages":"270-5"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73762817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Transport of toxic heavy metals across cell membranes. 有毒重金属跨细胞膜的运输。
E. Foulkes
Membrane transport of nonessential toxic heavy metals (type D heavy metals) not only controls their access to intracellular target sites but also helps determine their uptake, distribution, and excretion from the body. The critical role of membranes in the toxicology of class D metals has attracted the attention of many investigators, and extensive information has been collected on the mechanism(s) of metal transfer across membranes. Characteristics of metal transport in different cells, or even on opposite sides of the same cell, or under different physiological conditions, are not identical, and no unitary hypothesis has been formulated to explain this process in all cells. However, it seems possible that the mechanisms proposed for different cells represent variations on a few common themes.
非必需的有毒重金属(D型重金属)的膜转运不仅控制它们进入细胞内靶位,而且有助于决定它们的吸收、分布和从体内排泄。膜在D类金属毒理学中的关键作用引起了许多研究者的注意,并且关于金属跨膜转移的机制已经收集了大量的信息。金属在不同细胞中,甚至在同一细胞的两侧,或在不同的生理条件下的运输特性是不相同的,也没有一个统一的假设来解释所有细胞中的这一过程。然而,针对不同细胞提出的机制似乎可能代表了一些共同主题的变化。
{"title":"Transport of toxic heavy metals across cell membranes.","authors":"E. Foulkes","doi":"10.1111/J.1525-1373.2000.22334.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22334.X","url":null,"abstract":"Membrane transport of nonessential toxic heavy metals (type D heavy metals) not only controls their access to intracellular target sites but also helps determine their uptake, distribution, and excretion from the body. The critical role of membranes in the toxicology of class D metals has attracted the attention of many investigators, and extensive information has been collected on the mechanism(s) of metal transfer across membranes. Characteristics of metal transport in different cells, or even on opposite sides of the same cell, or under different physiological conditions, are not identical, and no unitary hypothesis has been formulated to explain this process in all cells. However, it seems possible that the mechanisms proposed for different cells represent variations on a few common themes.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"82 1","pages":"234-40"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89255440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 113
Nitroprusside attenuates myocardial stunning through reduced contractile delay and time. 硝普塞通过减少收缩延迟和时间来减弱心肌昏迷。
R. Leone, P. Scholz, H. Weiss
We hypothesized that myocardial stunning would be reversed through increased cyclic GMP caused by nitroprusside, and that this would be accomplished through a decreased proportion of regional work during diastole. Hearts were instrumented to measure left ventricular pressure, and regional myocardial mechanics were recorded using a miniature force transducer and ultrasonic dimension crystals in eight open-chest anesthetized dogs. Following baseline (CON), the left anterior descending coronary artery (LAD) was occluded for 15 min, followed by a 30-min recovery (STUN). Then intracoronary LAD infusion of sodium nitroprusside (NP) (4 microg/kg/ min) was begun. The time delay (msec) to regional shortening increased significantly from 18+/-13 to 73+/-13 following stunning, but was reduced to 49+/-18 by NP. Total regional work (g*mm/min) at baseline (1368+/-401 CON) was unchanged with stunning (1320+/-333 STUN), but reduced (961+/-240) following NP. Time to peak force development (msec) increased significantly with stunning from 284+/-13 (CON) to 333+/-11 (STUN), but was reduced to 269+/-12 following NP. The percentage work during systole was reduced from 96%+/-2% (CON) to 77%+/-7% (STUN), but returned to 98%+/-1% with NP. Regional O2 consumption was unaffected by either treatment. Cyclic GMP was unchanged by stunning (2.9+/-0.3-2.9+/-0.4 pmol/g) but increased significantly with NP (4.6+/-0.6). These data indicated that regional myocardial stunning could be attenuated by nitroprusside, which increased cyclic GMP, decreased contractile delay, increased the proportion of work done during systole, and reduced time of shortening.
我们假设硝普赛引起的环GMP增加可以逆转心肌昏迷,这可以通过舒张期局部功的减少来实现。对8只开胸麻醉犬进行心脏仪器测量左心室压力,并利用微型力传感器和超声尺寸晶体记录局部心肌力学。基线(CON)后,左冠状动脉前降支(LAD)闭塞15分钟,随后30分钟恢复(STUN)。然后开始冠状动脉内滴注硝普钠(NP) (4 μ g/kg/ min)。区域缩短的延迟时间(msec)从昏迷后的18+/-13显著增加到73+/-13,但NP将其减少到49+/-18。总区域工作(g*mm/min)在基线(1368+/-401 CON)与昏迷(1320+/-333 STUN)不变,但NP后减少(961+/-240)。达到力量发展峰值的时间(msec)在眩晕时从284+/-13 (CON)显著增加到333+/-11 (STUN),但在NP后减少到269+/-12。收缩期的作功百分比从96%+/-2% (CON)降低到77%+/-7% (STUN),但在NP组中又恢复到98%+/-1%。两种处理均未影响区域氧气消耗。环GMP在麻醉下没有变化(2.9+/-0.3-2.9+/-0.4 pmol/g),但在NP作用下显著增加(4.6+/-0.6)。这些数据表明硝普钠可以减轻局部心肌昏迷,增加循环GMP,减少收缩延迟,增加收缩时做功的比例,缩短缩短时间。
{"title":"Nitroprusside attenuates myocardial stunning through reduced contractile delay and time.","authors":"R. Leone, P. Scholz, H. Weiss","doi":"10.1111/J.1525-1373.2000.22337.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22337.X","url":null,"abstract":"We hypothesized that myocardial stunning would be reversed through increased cyclic GMP caused by nitroprusside, and that this would be accomplished through a decreased proportion of regional work during diastole. Hearts were instrumented to measure left ventricular pressure, and regional myocardial mechanics were recorded using a miniature force transducer and ultrasonic dimension crystals in eight open-chest anesthetized dogs. Following baseline (CON), the left anterior descending coronary artery (LAD) was occluded for 15 min, followed by a 30-min recovery (STUN). Then intracoronary LAD infusion of sodium nitroprusside (NP) (4 microg/kg/ min) was begun. The time delay (msec) to regional shortening increased significantly from 18+/-13 to 73+/-13 following stunning, but was reduced to 49+/-18 by NP. Total regional work (g*mm/min) at baseline (1368+/-401 CON) was unchanged with stunning (1320+/-333 STUN), but reduced (961+/-240) following NP. Time to peak force development (msec) increased significantly with stunning from 284+/-13 (CON) to 333+/-11 (STUN), but was reduced to 269+/-12 following NP. The percentage work during systole was reduced from 96%+/-2% (CON) to 77%+/-7% (STUN), but returned to 98%+/-1% with NP. Regional O2 consumption was unaffected by either treatment. Cyclic GMP was unchanged by stunning (2.9+/-0.3-2.9+/-0.4 pmol/g) but increased significantly with NP (4.6+/-0.6). These data indicated that regional myocardial stunning could be attenuated by nitroprusside, which increased cyclic GMP, decreased contractile delay, increased the proportion of work done during systole, and reduced time of shortening.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"184 1","pages":"263-9"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88473775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Introduction to editorials on crises in academic medicine: diagnoses and treatments 学术医学危机社论导论:诊断和治疗
Knopp, Bartke
{"title":"Introduction to editorials on crises in academic medicine: diagnoses and treatments","authors":"Knopp, Bartke","doi":"10.1111/J.1525-1373.2000.22331.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22331.X","url":null,"abstract":"","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"172 1","pages":"227"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77341168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis. 肿瘤坏死因子(TNF)- α和TNF受体在病毒发病中的作用。
Georges Herbein, William A. O'Brien
Tumor necrosis factor-alpha (TNF-alpha) and TNF receptors (TNFR) are members of the growing TNF ligand and receptor families that are involved in immune regulation. The present report will focus on the role of the prototypic ligand TNF and its two receptors, TNFR1 and TNFR2, in viral pathogenesis. Although TNF was reported years ago to modulate viral infections, recent findings on the molecular pathways involved in TNFR signaling have allowed a better understanding of the molecular interactions between cellular and viral factors within the infected cell. The interactions of viral proteins with intracellular components downstream of the TNFR have highlighted at the molecular level how viruses can manipulate the cellular machinery to escape the immune response and to favor the spread of the infection. We will review here the role of TNF and TNFR in immune response and the role of TNF and TNFR signaling in viral pathogenesis.
肿瘤坏死因子- α (TNF- α)和TNF受体(TNFR)是生长中的TNF配体和受体家族的成员,参与免疫调节。本报告将重点关注原型配体TNF及其两种受体TNFR1和TNFR2在病毒发病机制中的作用。尽管多年前就有TNF调节病毒感染的报道,但最近关于TNF信号通路的发现使人们更好地了解了感染细胞内细胞因子和病毒因子之间的分子相互作用。病毒蛋白与TNFR下游细胞内成分的相互作用在分子水平上突出了病毒如何操纵细胞机制以逃避免疫反应并有利于感染的传播。我们将在此综述TNF和TNFR在免疫应答中的作用以及TNF和TNFR信号在病毒发病机制中的作用。
{"title":"Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis.","authors":"Georges Herbein, William A. O'Brien","doi":"10.1046/J.1525-1373.2000.22335.X","DOIUrl":"https://doi.org/10.1046/J.1525-1373.2000.22335.X","url":null,"abstract":"Tumor necrosis factor-alpha (TNF-alpha) and TNF receptors (TNFR) are members of the growing TNF ligand and receptor families that are involved in immune regulation. The present report will focus on the role of the prototypic ligand TNF and its two receptors, TNFR1 and TNFR2, in viral pathogenesis. Although TNF was reported years ago to modulate viral infections, recent findings on the molecular pathways involved in TNFR signaling have allowed a better understanding of the molecular interactions between cellular and viral factors within the infected cell. The interactions of viral proteins with intracellular components downstream of the TNFR have highlighted at the molecular level how viruses can manipulate the cellular machinery to escape the immune response and to favor the spread of the infection. We will review here the role of TNF and TNFR in immune response and the role of TNF and TNFR signaling in viral pathogenesis.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"1 1","pages":"241-57"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89162464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 201
Beta-adrenergic agonist hyperplastic effect is associated with increased fibronectin gene expression and not mitogen-activated protein kinase modulation in C2C12 cells. 在C2C12细胞中,β -肾上腺素能激动剂的增生性效应与纤维连接蛋白基因表达的增加有关,而与丝裂原激活的蛋白激酶调节无关。
E. Izevbigie, W. Bergen
Beta-adrenergic agonists (beta-AA) enhance protein accretion in skeletal muscles. This stimulation is characterized by increased protein synthesis, increased expression of myofibrillar protein genes and a depression in protein degradation in animals, and increased proliferation and DNA synthesis in muscle cells in vitro. The mechanism or signal path in muscle whereby beta-AA would elicit these physiological effects upon binding to the G protein-coupled beta-adrenergic receptor (beta-AR) is unclear. C2C12 myoblasts were used to determine beta-AR ligand binding characteristics, cyclic AMP synthesis in response to isoproterenol (ISO) stimulation, and effects of ISO on DNA synthesis, mitogen activated protein kinase (MAPK), and fibronectin (FN) gene expression. Results showed that C2C12 cells possess beta-AR which are specific, saturable, and of high affinity (Kd = 0.2 nM). Forskolin and ISO stimulated cAMP production by = 20-fold (P<0.001) and 17-fold (P<0.001), respectively. ISO and the cAMP analog, 8-bromo-cAMP (8-BC) stimulated DNA synthesis in proliferating cells by 150% (P<0.05) and 200% (P<0.01), respectively, without modulating MAPK activity, whereas addition of fetal bovine serum to culture resulted in a 500% increase (P<0.01) in DNA synthesis and MAPK activation. DNA synthesis in C2C12 cells treated with ISO, 8-BC, or FBS was abolished in the presence of 25 microM PD098059, an MAPK-kinase inhibitor, suggesting that an MAPK-dependent pathway is likely involved in C2C12 proliferation. During cAMP elevating agent stimulation, basal MAPK activity may be sufficient, in the presence of other putative signaling molecules, to support proliferation in these cells. ISO or 8-BC treatment increased FN mRNA by three- and seven-fold, respectively, in growing C2C12 cells implying a connection between increased DNA synthesis and FN gene expression.
β -肾上腺素能激动剂(β - aa)增强骨骼肌中蛋白质的增加。这种刺激的特点是蛋白质合成增加,肌纤维蛋白基因表达增加,动物体内蛋白质降解抑制,体外肌肉细胞增殖和DNA合成增加。肌肉中β - aa与G蛋白偶联β -肾上腺素能受体(β - ar)结合时引发这些生理效应的机制或信号通路尚不清楚。利用C2C12成肌细胞测定β - ar配体结合特性、异丙肾上腺素(ISO)刺激下环AMP的合成,以及ISO对DNA合成、丝裂原活化蛋白激酶(MAPK)和纤维连接蛋白(FN)基因表达的影响。结果表明,C2C12细胞具有特异性、可饱和、高亲和力(Kd = 0.2 nM)的β - ar。foskolin和ISO分别刺激cAMP生成20倍(P<0.001)和17倍(P<0.001)。在不影响MAPK活性的情况下,ISO和cAMP类似物8-溴-cAMP (8-BC)分别能刺激增殖细胞DNA合成150% (P<0.05)和200% (P<0.01),而添加胎牛血清可使DNA合成和MAPK活性增加500% (P<0.01)。在25微米PD098059(一种mapk激酶抑制剂)的存在下,ISO、8-BC或FBS处理的C2C12细胞中的DNA合成被破坏,这表明mapk依赖性途径可能参与了C2C12的增殖。在cAMP升高剂刺激下,在其他可能的信号分子存在的情况下,基础MAPK活性可能足以支持这些细胞的增殖。在生长的C2C12细胞中,ISO或8-BC处理分别使FN mRNA增加了3倍和7倍,这表明DNA合成增加与FN基因表达之间存在联系。
{"title":"Beta-adrenergic agonist hyperplastic effect is associated with increased fibronectin gene expression and not mitogen-activated protein kinase modulation in C2C12 cells.","authors":"E. Izevbigie, W. Bergen","doi":"10.1111/J.1525-1373.2000.22343.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22343.X","url":null,"abstract":"Beta-adrenergic agonists (beta-AA) enhance protein accretion in skeletal muscles. This stimulation is characterized by increased protein synthesis, increased expression of myofibrillar protein genes and a depression in protein degradation in animals, and increased proliferation and DNA synthesis in muscle cells in vitro. The mechanism or signal path in muscle whereby beta-AA would elicit these physiological effects upon binding to the G protein-coupled beta-adrenergic receptor (beta-AR) is unclear. C2C12 myoblasts were used to determine beta-AR ligand binding characteristics, cyclic AMP synthesis in response to isoproterenol (ISO) stimulation, and effects of ISO on DNA synthesis, mitogen activated protein kinase (MAPK), and fibronectin (FN) gene expression. Results showed that C2C12 cells possess beta-AR which are specific, saturable, and of high affinity (Kd = 0.2 nM). Forskolin and ISO stimulated cAMP production by = 20-fold (P<0.001) and 17-fold (P<0.001), respectively. ISO and the cAMP analog, 8-bromo-cAMP (8-BC) stimulated DNA synthesis in proliferating cells by 150% (P<0.05) and 200% (P<0.01), respectively, without modulating MAPK activity, whereas addition of fetal bovine serum to culture resulted in a 500% increase (P<0.01) in DNA synthesis and MAPK activation. DNA synthesis in C2C12 cells treated with ISO, 8-BC, or FBS was abolished in the presence of 25 microM PD098059, an MAPK-kinase inhibitor, suggesting that an MAPK-dependent pathway is likely involved in C2C12 proliferation. During cAMP elevating agent stimulation, basal MAPK activity may be sufficient, in the presence of other putative signaling molecules, to support proliferation in these cells. ISO or 8-BC treatment increased FN mRNA by three- and seven-fold, respectively, in growing C2C12 cells implying a connection between increased DNA synthesis and FN gene expression.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"97 1","pages":"302-9"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90340599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Recent developments in the virus therapy of cancer. 癌症病毒治疗的最新进展。
Timothy A. Steele
Cancer is one of the leading causes of death in the United States. Although there has been significant progress in the areas of cancer etiology, diagnostic techniques, and cancer prevention, adequate therapeutic approaches for many cancers have lagged behind. One promising line of investigation is the virus therapy of cancer. This approach entails the use of viruses, such as retroviruses, adenovirus, and vaccinia virus, to modify tumor cells so that they become more susceptible to being killed by the host immune response, chemotherapeutic agents, or programmed cell death. This review discusses recent advances in the virus therapy of cancer from both basic science and clinical perspectives. Given the potential of viruses to kill tumor cells directly or transduce desired gene products to allow a vigorous host antitumor immune response, the virus therapy of cancer holds great promise in the treatment of cancer.
癌症是美国人死亡的主要原因之一。尽管在癌症病因学、诊断技术和癌症预防方面取得了重大进展,但许多癌症的适当治疗方法仍落后。一个有希望的研究方向是癌症的病毒治疗。这种方法需要使用逆转录病毒、腺病毒和牛痘病毒等病毒来修饰肿瘤细胞,使它们更容易被宿主免疫反应、化疗药物或程序性细胞死亡杀死。本文从基础科学和临床两方面综述了肿瘤病毒治疗的最新进展。鉴于病毒有可能直接杀死肿瘤细胞或转导所需的基因产物,从而使宿主产生强烈的抗肿瘤免疫反应,癌症的病毒治疗在癌症治疗中具有很大的前景。
{"title":"Recent developments in the virus therapy of cancer.","authors":"Timothy A. Steele","doi":"10.1111/J.1525-1373.2000.22317.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22317.X","url":null,"abstract":"Cancer is one of the leading causes of death in the United States. Although there has been significant progress in the areas of cancer etiology, diagnostic techniques, and cancer prevention, adequate therapeutic approaches for many cancers have lagged behind. One promising line of investigation is the virus therapy of cancer. This approach entails the use of viruses, such as retroviruses, adenovirus, and vaccinia virus, to modify tumor cells so that they become more susceptible to being killed by the host immune response, chemotherapeutic agents, or programmed cell death. This review discusses recent advances in the virus therapy of cancer from both basic science and clinical perspectives. Given the potential of viruses to kill tumor cells directly or transduce desired gene products to allow a vigorous host antitumor immune response, the virus therapy of cancer holds great promise in the treatment of cancer.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"8 1","pages":"118-27"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87845880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Mediators and mechanisms of radiation nephropathy. 放射性肾病的介质和机制。
E. Cohen, S. Bonsib, E. Whitehouse, J. Hopewell, M. Robbins
Normal tissue radiation injury occurs after sufficient irradiation, thus limiting the curative potential of x-ray therapy. In the kidney, radiation injury results in fibrosis and, ultimately, renal failure. The mediators of fibrosis in radiation nephropathy have received scant attention. Therefore, we evaluated the sequential presence of alpha smooth muscle actin (alphasma), fibrin, collagen, and TGFbeta1 in a porcine model of radiation nephropathy using 9.8 Gy single-dose local kidney irradiation. During the 24-week study, there was progressive and significant collagen accumulation in glomeruli and in interstitium. In glomeruli, this was associated with significant mesangial alphasma expression by 2 weeks after irradiation, a further rise at 4 weeks, and then a gradual fall to baseline. Glomerular fibrin deposition was significant by 4 weeks after irradiation, and remained elevated thereafter. There was little or no glomerular TGFbeta1 expression at any time point. Tubular fibrin deposition was significant at 4 weeks after irradiation but declined thereafter. There was little or no tubulo-interstitial alphasma expression at any time after irradiation. At 6 weeks after irradiation, there was a significant peak of tubular epithelial TGFbeta1 expression that declined thereafter. The early glomerular injury is evident as mesangial alphasma expression but is not proceeded by TGFbeta1 expression. There is sustained glomerular fibrin deposition with deposition of fibrin in tubular lumens, suggesting that tubular fibrin derives and flows out from injured glomerular tufts. We conclude that i) alphasma expression is an early marker of glomerular radiation injury, presaging scarring; ii) fibrin deposition is involved in glomerular and tubular radiation injury; and iii) TGFbeta1 is not an early event in radiation nephropathy, and not apparent in glomeruli in this model, but may correlate with later tubulo-interstitial fibrosis. Thus, the mediators of scarring in this model differ according to time after injury and also according to the affected tissue compartment.
正常组织放射损伤发生在足够的照射后,因此限制了x射线治疗的治愈潜力。在肾脏中,辐射损伤导致纤维化,最终导致肾衰竭。放射性肾病的纤维化介质很少受到关注。因此,我们在使用9.8 Gy单剂量局部肾照射的猪放射肾病模型中评估了α -平滑肌肌动蛋白(alphasma)、纤维蛋白、胶原蛋白和TGFbeta1的顺序存在。在24周的研究中,肾小球和间质有进行性和显著的胶原积累。在肾小球中,照射后2周时,这与肾小球系膜α蛋白表达显著相关,4周时进一步升高,然后逐渐下降到基线水平。照射后4周肾小球纤维蛋白沉积显著,此后保持升高。在任何时间点肾小球TGFbeta1的表达都很少或没有。照射后4周,小管纤维蛋白沉积显著,但此后逐渐减少。照射后的任何时间,小管间质α蛋白表达很少或没有表达。照射后6周,小管上皮TGFbeta1表达显著达到峰值,此后呈下降趋势。早期肾小球损伤表现为系膜α蛋白表达,但不表现为TGFbeta1表达。肾小球纤维蛋白持续沉积,纤维蛋白在小管腔内沉积,提示小管纤维蛋白来源于并流出损伤的肾小球簇。我们得出结论:1)α蛋白表达是肾小球辐射损伤的早期标志,预示着瘢痕形成;Ii)纤维蛋白沉积参与肾小球和小管辐射损伤;iii) TGFbeta1不是放射性肾病的早期事件,在该模型中肾小球中也不明显,但可能与晚期小管间质纤维化有关。因此,该模型中瘢痕形成的介质根据损伤后的时间和受影响的组织室不同而不同。
{"title":"Mediators and mechanisms of radiation nephropathy.","authors":"E. Cohen, S. Bonsib, E. Whitehouse, J. Hopewell, M. Robbins","doi":"10.1111/J.1525-1373.2000.22330.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22330.X","url":null,"abstract":"Normal tissue radiation injury occurs after sufficient irradiation, thus limiting the curative potential of x-ray therapy. In the kidney, radiation injury results in fibrosis and, ultimately, renal failure. The mediators of fibrosis in radiation nephropathy have received scant attention. Therefore, we evaluated the sequential presence of alpha smooth muscle actin (alphasma), fibrin, collagen, and TGFbeta1 in a porcine model of radiation nephropathy using 9.8 Gy single-dose local kidney irradiation. During the 24-week study, there was progressive and significant collagen accumulation in glomeruli and in interstitium. In glomeruli, this was associated with significant mesangial alphasma expression by 2 weeks after irradiation, a further rise at 4 weeks, and then a gradual fall to baseline. Glomerular fibrin deposition was significant by 4 weeks after irradiation, and remained elevated thereafter. There was little or no glomerular TGFbeta1 expression at any time point. Tubular fibrin deposition was significant at 4 weeks after irradiation but declined thereafter. There was little or no tubulo-interstitial alphasma expression at any time after irradiation. At 6 weeks after irradiation, there was a significant peak of tubular epithelial TGFbeta1 expression that declined thereafter. The early glomerular injury is evident as mesangial alphasma expression but is not proceeded by TGFbeta1 expression. There is sustained glomerular fibrin deposition with deposition of fibrin in tubular lumens, suggesting that tubular fibrin derives and flows out from injured glomerular tufts. We conclude that i) alphasma expression is an early marker of glomerular radiation injury, presaging scarring; ii) fibrin deposition is involved in glomerular and tubular radiation injury; and iii) TGFbeta1 is not an early event in radiation nephropathy, and not apparent in glomeruli in this model, but may correlate with later tubulo-interstitial fibrosis. Thus, the mediators of scarring in this model differ according to time after injury and also according to the affected tissue compartment.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"18 1","pages":"218-25"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82061992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
Microfilament network is needed for the endocytosis of water channels and not for apical membrane insertion upon vasopressin action. 水通道的内吞作用需要微丝网络,而抗利尿素作用下的顶膜插入不需要微丝网络。
A. Dibas, Abdul Mia, T. Yorio
In the current study, a novel role for the microfilaments in vasopressin-induced water transport in toad urinary bladders, a popular model for the mammalian collecting duct, was established. Vasopressin-induced water transport was not affected by cytochalasin D (CD, 20 microM) or latrunculin B (Lat B, 0.5-2 microM), microfilament-disrupting reagents, suggesting that the initial trafficking of vesicles containing water channels and insertion of membranes into the apical membrane are microfilament-independent. After the removal of vasopressin, bladders treated with CD or Lat B continued to transport water at least 2-3-fold greater than those that received the vehicle. Furthermore, the enhanced water transport was inhibited by HgCl2 (1 mM), a potent inhibitor of water channel-mediated water flow, suggesting that the enhanced water flow was through water channels. In addition, Lat B and CD inhibited vasopressin-induced endocytosis of horseradish peroxidase (HRP), a fluid endocytotic marker. These results suggested that although microfilaments are not needed for the initial trafficking of water channels to the apical side, the microfilament network is essential for the retrieval of water channels following their insertion into apical membranes.
在本研究中,微丝在抗利尿激素诱导的蟾蜍膀胱(一种常见的哺乳动物集尿管模型)中发挥了新的作用。抗利尿激素诱导的水运输不受细胞松弛素D (CD, 20微米)或拉runculin B (Lat B, 0.5-2微米)微丝破坏剂的影响,这表明含有水通道的囊泡的初始运输和膜插入顶膜是微丝无关的。在去除抗利尿激素后,用CD或Lat B处理的膀胱继续运输水,至少比接受载体的膀胱多2-3倍。此外,HgCl2 (1 mM)是一种有效的水通道介导的水流抑制剂,可以抑制水运的增强,这表明水流的增强是通过水通道进行的。此外,Lat B和CD抑制抗利尿激素诱导的辣根过氧化物酶(HRP)的内吞作用,这是一种液体内吞标志物。这些结果表明,虽然微丝并不需要初始的水通道运输到根尖侧,但微丝网络对于水通道插入根尖膜后的恢复是必不可少的。
{"title":"Microfilament network is needed for the endocytosis of water channels and not for apical membrane insertion upon vasopressin action.","authors":"A. Dibas, Abdul Mia, T. Yorio","doi":"10.1111/J.1525-1373.2000.22328.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22328.X","url":null,"abstract":"In the current study, a novel role for the microfilaments in vasopressin-induced water transport in toad urinary bladders, a popular model for the mammalian collecting duct, was established. Vasopressin-induced water transport was not affected by cytochalasin D (CD, 20 microM) or latrunculin B (Lat B, 0.5-2 microM), microfilament-disrupting reagents, suggesting that the initial trafficking of vesicles containing water channels and insertion of membranes into the apical membrane are microfilament-independent. After the removal of vasopressin, bladders treated with CD or Lat B continued to transport water at least 2-3-fold greater than those that received the vehicle. Furthermore, the enhanced water transport was inhibited by HgCl2 (1 mM), a potent inhibitor of water channel-mediated water flow, suggesting that the enhanced water flow was through water channels. In addition, Lat B and CD inhibited vasopressin-induced endocytosis of horseradish peroxidase (HRP), a fluid endocytotic marker. These results suggested that although microfilaments are not needed for the initial trafficking of water channels to the apical side, the microfilament network is essential for the retrieval of water channels following their insertion into apical membranes.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"33 1","pages":"203-9"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86050666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Regional fat deposition in the legs is useful as a presumptive marker of antiatherogenesity in Japanese. 在日本,腿部的区域性脂肪沉积可作为抗动脉粥样硬化的推定标志。
M. Tatsukawa, M. Kurokawa, Y. Tamari, H. Yoshimatsu, T. Sakata
To examine the pathological role of regional fat deposition in development of metabolic and cardiovascular disorders, regional fat distribution was evaluated using metabolites and hormones as measures of obesity-related disorders. The subjects enrolled were 100 sex-matched inpatients, who were admitted, regardless of their body mass index values, for further examination of unusual results from periodic medical screening tests, and for examination of obesity-induced complications and treatment of obesity. Body fat distribution was analyzed using dual energy X-ray absorptiometry (DEXA). Analysis of parameters regarding fat distribution showed that gender was one of the determinants affecting correlation between fat distribution and metabolites of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), or triglyceride (TG). However, regardless of gender, both leg trunk fat (L/Tr) and arm trunk fat (A/Tr) ratios negatively correlated with a total body fat (% total fat) ratio, whereas the intercept value of female regression line in L/Tr was greater than that in males, but not in A/Tr. Percentage total fat, L/Tr, and A/Tr in males correlated significantly with FPG, TC, TG, low-density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index (A.I.), and apoB/A1 only low density lipoprotein (LDL) was significantly correlated solely to L/Tr and A/Tr. These results indicate that regional fat distribution in males may not be a major determinant for development of metabolic disorders in obese patients. Unlike male regional fat distribution, female L/Tr correlated significantly not only with TC, TG, and LDL, but also with FPG and HbA1c, although both of the latter 2 glucose-related parameters in males showed no correlation with any parameters of fat deposition. The remaining female parameters of fasting plasma insulin, VLDL, A.I., and ApoB/A1 correlated with each of the three parameters of fat deposition, as similarly shown in males. The powerful and negative correlation was thus evident, particularly in females, between leg fat deposition and parameters of glucose and lipid metabolites. The resulting information provides a novel insight that regional fat deposition at the legs is useful as a marker for metabolic and cardiovascular disorders associated with obesity.
为了研究区域脂肪沉积在代谢和心血管疾病发展中的病理作用,我们使用代谢物和激素作为肥胖相关疾病的测量指标来评估区域脂肪分布。纳入的受试者是100名性别匹配的住院患者,无论其体重指数值如何,均入院接受定期医学筛查测试的异常结果的进一步检查,以及肥胖引起的并发症和肥胖治疗的检查。采用双能x线吸收仪(DEXA)分析体脂分布。脂肪分布参数分析显示,性别是影响脂肪分布与空腹血糖(FPG)、血红蛋白A1c (HbA1c)、总胆固醇(TC)或甘油三酯(TG)代谢物相关性的决定因素之一。但无论性别如何,腿干脂肪(L/Tr)和臂干脂肪(A/Tr)与全身脂肪(%总脂肪)比均呈负相关,而女性L/Tr的回归线截距值大于男性,而A/Tr的截距值小于男性。男性总脂肪百分比、L/Tr、A/Tr与FPG、TC、TG、低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)、致动脉粥样硬化指数(A.I.)显著相关,仅apoB/A1低密度脂蛋白(LDL)与L/Tr、A/Tr显著相关。这些结果表明,男性的区域脂肪分布可能不是肥胖患者代谢紊乱发展的主要决定因素。与男性区域脂肪分布不同,女性L/Tr不仅与TC、TG、LDL相关,还与FPG、HbA1c相关,尽管男性后2种葡萄糖相关参数与脂肪沉积参数均无相关性。其余女性空腹血浆胰岛素、VLDL、A.I和ApoB/A1参数与脂肪沉积的三个参数均相关,与男性相似。因此,腿部脂肪沉积与葡萄糖和脂质代谢物参数之间存在明显的负相关,尤其是在女性中。由此产生的信息提供了一种新的见解,即腿部区域脂肪沉积可作为与肥胖相关的代谢和心血管疾病的标志物。
{"title":"Regional fat deposition in the legs is useful as a presumptive marker of antiatherogenesity in Japanese.","authors":"M. Tatsukawa, M. Kurokawa, Y. Tamari, H. Yoshimatsu, T. Sakata","doi":"10.1111/J.1525-1373.2000.22321.X","DOIUrl":"https://doi.org/10.1111/J.1525-1373.2000.22321.X","url":null,"abstract":"To examine the pathological role of regional fat deposition in development of metabolic and cardiovascular disorders, regional fat distribution was evaluated using metabolites and hormones as measures of obesity-related disorders. The subjects enrolled were 100 sex-matched inpatients, who were admitted, regardless of their body mass index values, for further examination of unusual results from periodic medical screening tests, and for examination of obesity-induced complications and treatment of obesity. Body fat distribution was analyzed using dual energy X-ray absorptiometry (DEXA). Analysis of parameters regarding fat distribution showed that gender was one of the determinants affecting correlation between fat distribution and metabolites of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), or triglyceride (TG). However, regardless of gender, both leg trunk fat (L/Tr) and arm trunk fat (A/Tr) ratios negatively correlated with a total body fat (% total fat) ratio, whereas the intercept value of female regression line in L/Tr was greater than that in males, but not in A/Tr. Percentage total fat, L/Tr, and A/Tr in males correlated significantly with FPG, TC, TG, low-density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index (A.I.), and apoB/A1 only low density lipoprotein (LDL) was significantly correlated solely to L/Tr and A/Tr. These results indicate that regional fat distribution in males may not be a major determinant for development of metabolic disorders in obese patients. Unlike male regional fat distribution, female L/Tr correlated significantly not only with TC, TG, and LDL, but also with FPG and HbA1c, although both of the latter 2 glucose-related parameters in males showed no correlation with any parameters of fat deposition. The remaining female parameters of fasting plasma insulin, VLDL, A.I., and ApoB/A1 correlated with each of the three parameters of fat deposition, as similarly shown in males. The powerful and negative correlation was thus evident, particularly in females, between leg fat deposition and parameters of glucose and lipid metabolites. The resulting information provides a novel insight that regional fat deposition at the legs is useful as a marker for metabolic and cardiovascular disorders associated with obesity.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"12 1","pages":"156-62"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89414598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 29
期刊
Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1