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In 1957, Jacobson et al performed bilateral nephrectomies on rats and showed that these animals no longer responsed to phlebotomy or cobalt administration with increased Ep production. Rats that only had their ureters ligated and that developed similar elevations of the blood urea nitrogen still responded to cobalt or phlebotomy in the usual fashion .Similiar results were found in mice , rabbits , baboons , and dogs .In humans , Ep levels were found to be low in the serum of anemic patients with severe uremia , but after successful renal transplantation increases in blood Ep levels and hematocrit were observed. Furthermore , erythropoietic activity was detected in the perfusates from isolated rabbit kidneys and was produced by renal cell cultures in vitro . Although the evidence to support the renal origin of Ep was substantial , Ep had not been extracted from normal kidneys or from various normal kidney fractions until very recently. To explain this difficulty , three different hypotheses have been proposed . Current evidence indicates that the stimulation of Ep production by hypoxia or ischemia may be mediated via increases in renal prostaglandin and cyclic AMP levels . The administration of cyclic AMP to plethoric mice increased Ep production and led to and increased red cell mass in normal mice . prostaglandin raised the renal cyclic AMP concentration in isolated perfused dog kidneys as well as the amount of Ep in the perfusates ;the administration of prostaglandin to polycythemic mice increased both prostaglandin E and Ep blood levels in dogs . The effect on both these parameters as well as on hypoxia-induced Ep production was blocked by indomethacin, a known inhibitor of prostaglandin synthesis .Since prostaglandins are located mainly in the renal medulla , while Ep has been identified by fluorescent antibodies in the renal cortex , these observations are most consistent with the hypothesis that renal hypoxia or ischemia produces a medullary release of prostaglandin which in turn elevates renal corticla cyclic AMP levels. The newly formed cyclic AMP THEN may activate a protein kinase that leads to increased Ep production , possibly through phosphorylation of a precursor renal erythropoietic factor. Although the kidney is the major site controlling Ep formation , after bilateral nephrectomy the production of hormone and erythropoiesis continues in most species , but at a considerably lower level .Anephric mice and rats retain about 10%of their original capacity to increase Ep production in the presence of hypoxia , while anephric patients who become very anemic have Ep in their plasma .The extrarenal Ep of rats appears to be similar to Ep of renal origin since it stimulates heme synthesis by marrow cells and is neutralized by antiserum to urinary Ep . Several lines of study point to the liver as the primary site of extrarenal Ep production. Ep is produced primarily in the liver during fetal life .Hepatectomy abolishes hypoxia-stimulated hormone production in anephric rats , but not in animals with intact kidneys . In partially hepatectomized rats , the extrarenal Ep response to hypoxia correlates directly with liver regeneration and is most increased during the period of greatest proliferation . Administration of colloidal carbon or zymosan, which induces liver reticuloendothelial cell hyperplasia, enhances Ep production in nephrectomized rats exposed to hypoxia .This effect, which is also blocked by hepatectomy , suggests that the liver reticuloendothelial system may be and important factor in extrarenal Ep production . |
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在1957年,Jacobson 等人對(duì)大鼠首先進(jìn)行雙側(cè)腎切除,之后放血或用鈷處理,發(fā)現(xiàn)Ep不增高,然而,如果預(yù)先只是將大鼠輸尿管結(jié)扎,其血液尿素含量增高,之后放血或用鈷處理,其Ep,和正常鼠一樣,增高。在小鼠,家兔,狒狒和狗身上做相同的實(shí)驗(yàn),獲得的結(jié)果相似。在人群中,伴有嚴(yán)重尿毒癥的白血病患者的血液Ep水平較低,但在腎移植手術(shù)成功后,血液Ep水平升高,且血細(xì)胞計(jì)數(shù)也有所增加。此外,對(duì)分離的家兔的腎灌流液,即體外培養(yǎng)的腎細(xì)胞的紅血球生成活性進(jìn)行檢測(cè)。雖然支持Ep 來(lái)源于腎的證據(jù)可靠,但直到現(xiàn)在,人們還沒能從正常的腎或不同的腎fractions提取出 Ep 。為了解釋這個(gè)難題,三個(gè)不同的假說(shuō)被提出。最新證據(jù)顯示,由組織缺氧和局部缺血誘導(dǎo)的 Ep的產(chǎn)生是通過(guò)上調(diào)腎臟前列腺素和cAMP水平來(lái)介導(dǎo)的。用cAMP處理多血癥小鼠可增加Ep的產(chǎn)生,處理正常小鼠可導(dǎo)致紅細(xì)胞塊的增加。前列腺可以上調(diào)體外灌流的狗腎臟的cAMP濃度,同時(shí)也可以上調(diào)灌流液中Ep含量。用前列腺素處理紅細(xì)胞增多小鼠,可以增加血液前列腺素E含量,也可以增加狗的血Ep含量。對(duì)這2個(gè)參數(shù)的影響和組織缺氧誘導(dǎo)的Ep增多可以被消炎藥茚甲新阻斷,茚甲新是前列腺素合成的抑制劑。由于前列腺素主要分布于腎髓,而Ep已通過(guò)熒光抗體被鑒定存在于腎皮質(zhì), 這些觀察結(jié)果與假設(shè)一致,即腎缺氧或缺血誘導(dǎo)腎髓釋放前列腺素,而前列腺素反過(guò)來(lái)又上調(diào)腎皮質(zhì)的cAMP濃度。新生成的cAMP,接下來(lái)可能可以激活蛋白激酶增加Ep的產(chǎn)生,很可能是通過(guò)磷酸化腎紅血球生成因子前體來(lái)實(shí)現(xiàn)的。 雖然腎是控制Ep生成的主要場(chǎng)所,在大多數(shù)物種經(jīng)歷雙腎切除手術(shù)之后,激素和紅血球產(chǎn)生過(guò)程仍然繼續(xù),只是以相當(dāng)?shù)偷乃俣。無(wú)腎小鼠和無(wú)腎大鼠在缺氧條件下仍然保留約10%生產(chǎn)Ep的能力,但無(wú)腎的病人,常表現(xiàn)為嚴(yán)重貧血,在血漿中含有Ep。大鼠腎外的Ep和腎來(lái)源的Ep很相似,也可以刺激骨髓細(xì)胞生成亞鐵血紅素,可以被抗尿Ep的抗血清中和。一些研究團(tuán)隊(duì)認(rèn)為肝臟是腎外Ep產(chǎn)生的最初部位。在胎兒期 Ep主要在肝臟中產(chǎn)生。在無(wú)腎大鼠中,肝臟切除可以阻斷低氧誘導(dǎo)激素的產(chǎn)生,但在有完整腎的動(dòng)物中肝臟切除不可阻斷。在部分肝臟切除的大鼠中, 腎外Ep對(duì)低氧的反應(yīng)直接與肝再生相關(guān),且在增殖最旺盛期腎外Ep增加最快。 用膠狀碳或酵母聚糖誘導(dǎo)肝網(wǎng)狀內(nèi)皮組織增生,可以促進(jìn)受低氧脅迫的腎切除大鼠的Ep的產(chǎn)生。這個(gè)效應(yīng)同樣可以被肝切除手術(shù)阻斷,提示肝網(wǎng)狀內(nèi)皮系統(tǒng) 可能是腎外Ep產(chǎn)生的重要因素。 第一次翻譯,湊活著看啊 |
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SP(side population)細(xì)胞 1996年, Goodell et al [2] 在用Hoechst33342熒光 染色對(duì)小鼠骨髓造血干細(xì)胞進(jìn)行檢測(cè)時(shí), 通過(guò) 紫外激發(fā)檢測(cè)雙波長(zhǎng)分別為450 nm的藍(lán)色熒光 和675 nm的紅色熒光, 發(fā)現(xiàn)不到0.1%的細(xì)胞發(fā) 出極弱的藍(lán)光和紅光, 在流式二維分析點(diǎn)陣圖 上, 這一小群細(xì)胞呈彗星狀分布在細(xì)胞主群的 一側(cè), 他們將這群細(xì)胞稱為SP(side population) 細(xì)胞. ; |
鐵桿木蟲 (著名寫手)
| In 1957, Jacobson et al performed bilateral nephrectomies on rats and showed that these animals no longer responsed to phlebotomy or cobalt administration with increased Ep production. 1957年,Jacobson等人對(duì)小白鼠進(jìn)行了雙腎切除實(shí)驗(yàn),雙腎切除后的小白鼠的上皮細(xì)胞數(shù)量增加,但對(duì)放血和鈷刺激無(wú)任何反應(yīng)。Rats that only had their ureters ligated and that developed similar elevations of the blood urea nitrogen still responded to cobalt or phlebotomy in the usual fashion .而輸尿管結(jié)扎并血液尿素氮的含量增加的小白鼠通常對(duì)放血和鈷刺激仍有反應(yīng)。Similiar results were found in mice , rabbits , baboons , and dogs .對(duì)老鼠,兔子,狒狒和狗進(jìn)行實(shí)驗(yàn),也發(fā)現(xiàn)了相同的結(jié)果。In humans , Ep levels were found to be low in the serum of anemic patients with severe uremia , 而人體實(shí)驗(yàn)表明嚴(yán)重尿毒癥患者血清中上皮細(xì)胞數(shù)量低,but after successful renal transplantation increases in blood Ep levels and hematocrit were observed. 但經(jīng)成功的腎臟移植手術(shù)后,血液中的上皮細(xì)胞數(shù)量增加并觀察到有血細(xì)胞(hematocrit,這個(gè)單詞查了,還是不清楚)Furthermore , erythropoietic activity was detected in the perfusates from isolated rabbit kidneys and was produced by renal cell cultures in vitro . 另外,我們從切割下的兔子的腎臟中和在試管中培養(yǎng)的腎細(xì)胞中檢測(cè)到了紅細(xì)胞。Although the evidence to support the renal origin of Ep was substantial , Ep had not been extracted from normal kidneys or from various normal kidney fractions until very recently.雖然目前有足夠的證據(jù)能證明上皮細(xì)胞來(lái)源于腎臟,但是也只是最近才在正常的腎臟中或腎臟的不同組織中才提取出上皮細(xì)胞To explain this difficulty , three different hypotheses have been proposed .為了解釋這個(gè)問題,人們提出了三種假設(shè)。 |
鐵桿木蟲 (著名寫手)
| Current evidence indicates that the stimulation of Ep production by hypoxia or ischemia may be mediated via increases in renal prostaglandin and cyclic AMP levels . 目前已證明缺氧或缺血促進(jìn)上皮細(xì)胞的產(chǎn)生,腎前列腺素和環(huán)磷酸腺苷的增加也可能會(huì)導(dǎo)致上皮細(xì)胞的產(chǎn)生。The administration of cyclic AMP to plethoric mice increased Ep production and led to and increased red cell mass in normal mice . 環(huán)磷酸腺苷促進(jìn)多血癥老鼠的上皮細(xì)胞數(shù)量增加,而對(duì)正常鼠則會(huì)增加紅細(xì)胞的數(shù)量。prostaglandin raised the renal cyclic AMP concentration in isolated perfused dog kidneys as well as the amount of Ep in the perfusates 在灌注狗實(shí)驗(yàn)中,前列腺素會(huì)提高腎臟中環(huán)磷酸腺苷的濃度,上皮細(xì)胞的數(shù)量也會(huì)增多;the administration of prostaglandin to polycythemic mice increased both prostaglandin E and Ep blood levels in dogs此外,前列腺素會(huì)提高多血癥鼠(polycythemic 單詞沒查出來(lái)什么意思)的前列腺素E,增加狗血液中的上皮細(xì)胞量 . The effect on both these parameters as well as on hypoxia-induced Ep production was blocked by indomethacin, a known inhibitor of prostaglandin synthesis 消炎痛是一種常用的前列腺素產(chǎn)生抑制劑,前列腺素對(duì)前列腺素E及血液中上皮細(xì)胞和缺氧生成的上皮細(xì)胞的作用會(huì)受到消炎痛的抑制.Since prostaglandins are located mainly in the renal medulla , while Ep has been identified by fluorescent antibodies in the renal cortex ,有種猜想認(rèn)為腎臟缺氧或缺血導(dǎo)致腎髓質(zhì)釋放前列腺素,進(jìn)而前列腺素促進(jìn)皮質(zhì)中環(huán)磷酸腺苷的產(chǎn)生,新生成的環(huán)磷酸腺苷可能通過(guò)身形紅細(xì)胞生成因子的磷酸化作用,刺激蛋白激酶產(chǎn)生上皮細(xì)胞。因?yàn)榍傲邢偎刂饕嬖谟谀I髓質(zhì)中,腎臟皮層的上皮細(xì)胞可以用熒光抗體進(jìn)行識(shí)別,實(shí)驗(yàn)觀測(cè)結(jié)果與上述猜想相吻合。these observations are most consistent with the hypothesis that renal hypoxia or ischemia produces a medullary release of prostaglandin which in turn elevates renal corticla cyclic AMP levels. The newly formed cyclic AMP THEN may activate a protein kinase that leads to increased Ep production , possibly through phosphorylation of a precursor renal erythropoietic factor. |
鐵桿木蟲 (著名寫手)
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1957年,Jacobson等人對(duì)小白鼠進(jìn)行了雙腎切除實(shí)驗(yàn),雙腎切除后的小白鼠的上皮細(xì)胞數(shù)量增加,但對(duì)放血和鈷刺激無(wú)任何反應(yīng)。而輸尿管結(jié)扎并血液尿素氮的含量增加的小白鼠通常對(duì)放血和鈷刺激仍有反應(yīng)。對(duì)老鼠,兔子,狒狒和狗進(jìn)行實(shí)驗(yàn),也發(fā)現(xiàn)了相同的結(jié)果。而人體實(shí)驗(yàn)表明嚴(yán)重尿毒癥患者血清中上皮細(xì)胞數(shù)量低, 但經(jīng)成功的腎臟移植手術(shù)后,血液中的上皮細(xì)胞數(shù)量增加并觀察到有血細(xì)胞(hematocrit,這個(gè)單詞查了,還是不清楚)另外,我們從切割下的兔子的腎臟中和在試管中培養(yǎng)的腎細(xì)胞中檢測(cè)到了紅細(xì)胞。雖然目前有足夠的證據(jù)能證明上皮細(xì)胞來(lái)源于腎臟,但是也只是最近才在正常的腎臟中或腎臟的不同組織中才提取出上皮細(xì)胞為了解釋這個(gè)問題,人們提出了三種假設(shè)。 目前已證明缺氧或缺血促進(jìn)上皮細(xì)胞的產(chǎn)生,腎前列腺素和環(huán)磷酸腺苷的增加也可能會(huì)導(dǎo)致上皮細(xì)胞的產(chǎn)生。環(huán)磷酸腺苷促進(jìn)多血癥老鼠的上皮細(xì)胞數(shù)量增加,而對(duì)正常鼠則會(huì)增加紅細(xì)胞的數(shù)量。在灌注狗實(shí)驗(yàn)中,前列腺素會(huì)提高腎臟中環(huán)磷酸腺苷的濃度,上皮細(xì)胞的數(shù)量也會(huì)增多。此外,前列腺素會(huì)提高多血癥鼠(polycythemic 單詞沒查出來(lái)什么意思)的前列腺素E,增加狗血液中的上皮細(xì)胞量 . 消炎痛是一種常用的前列腺素產(chǎn)生抑制劑,前列腺素對(duì)前列腺素E及血液中上皮細(xì)胞和缺氧生成的上皮細(xì)胞的作用會(huì)受到消炎痛的抑制.有種猜想認(rèn)為腎臟缺氧或缺血導(dǎo)致腎髓質(zhì)釋放前列腺素,進(jìn)而前列腺素促進(jìn)皮質(zhì)中環(huán)磷酸腺苷的產(chǎn)生,新生成的環(huán)磷酸腺苷可能通過(guò)身形紅細(xì)胞生成因子的磷酸化作用,刺激蛋白激酶產(chǎn)生上皮細(xì)胞。因?yàn)榍傲邢偎刂饕嬖谟谀I髓質(zhì)中,腎臟皮層的上皮細(xì)胞可以用熒光抗體進(jìn)行識(shí)別,實(shí)驗(yàn)觀測(cè)結(jié)果與上述猜想相吻合。 |
鐵桿木蟲 (著名寫手)
| 1957年,Jacobson等人對(duì)大鼠做了雙側(cè)腎切除,發(fā)現(xiàn)這些動(dòng)物不再對(duì)放血或鈷處理產(chǎn)生Ep升高的反應(yīng)。而只是結(jié)扎了輸尿管并出現(xiàn)類似血液尿素氮水平升高現(xiàn)象的大鼠仍能夠?qū)Ψ叛外捥幚懋a(chǎn)生正常反應(yīng)。在小鼠、兔、狒狒和狗中也發(fā)現(xiàn)了類似的結(jié)果。在人類中,有嚴(yán)重尿毒癥的貧血癥患者血清Ep水平較低,但是成功腎移植后,血液Ep濃度和血細(xì)胞比容升高。此外,切除的兔腎的灌注液具有促紅細(xì)胞生成活性,體外培養(yǎng)的腎細(xì)胞也產(chǎn)生紅細(xì)胞生成活性。盡管大量證據(jù)支持Ep產(chǎn)生自腎,但直到最近才從正常腎或各種正常腎組分中提取到Ep。為解釋這種現(xiàn)象,人們提出了三種假說(shuō)。目前證據(jù)顯示低氧或缺血刺激引起的Ep生成可能是通過(guò)腎前列腺素和cAMP升高調(diào)節(jié)的。給予多血癥小鼠cAMP能夠增加Ep生成,而在正常小鼠中會(huì)導(dǎo)致紅細(xì)胞數(shù)量增加。前列腺素能夠提高分離灌注的狗腎的腎cAMP濃度,以及灌注液中的Ep含量。在多血癥小鼠中,前列腺素能夠提高前列腺素E水平,在狗中,前列腺素能夠增加血液Ep含量。前列腺素對(duì)這些參數(shù)以及低氧引起的Ep生成的影響受到消炎痛的阻斷,而消炎痛是已知的前列腺素合成抑制劑。前列腺素主要存在于神髓質(zhì),通過(guò)免疫熒光抗體發(fā)現(xiàn)Ep存在于腎皮質(zhì),這與一個(gè)假說(shuō)高度一致,這個(gè)假說(shuō)認(rèn)為腎低氧或缺血導(dǎo)致髓質(zhì)的前列腺素釋放,這又提高了皮質(zhì)cAMP的水平。新形成的cAMP可能激活一個(gè)蛋白激酶,通過(guò)磷酸化一個(gè)腎紅細(xì)胞生成因子的前體,導(dǎo)致Ep生成增加,盡管腎是控制Ep形成的主要位點(diǎn),但多數(shù)物種在雙側(cè)腎切除后繼續(xù)有激素和紅細(xì)胞生成,只是含量非常低。無(wú)腎小鼠和大鼠保留了大約10%的低氧時(shí)Ep生成增加的能力,而極度貧血的無(wú)腎病人血漿中含有Ep。大鼠腎以外Ep與腎來(lái)源Ep類似,因?yàn)槟I外Ep刺激骨髓細(xì)胞合成亞鐵血紅素,并能夠被尿Ep抗血清中和。有幾條線索提示肝臟是腎外Ep生成的主要位置。在胚胎時(shí)期,Ep主要是在肝臟中生成的。肝切除后,低氧引起的激素生成在無(wú)腎大鼠消失,但在腎完整動(dòng)物中不存在消失的情況。在部分肝切除的大鼠中,腎外Ep對(duì)低氧的反應(yīng)能力直接與肝重生相關(guān),并且在肝增生最強(qiáng)時(shí)反應(yīng)能力提升最快。膠態(tài)炭或酵母聚糖能夠引起肝網(wǎng)狀內(nèi)皮細(xì)胞增生,給予腎切除大鼠膠態(tài)炭或酵母聚糖后能夠增強(qiáng)低氧暴露的大鼠中Ep的生成。這一效應(yīng)也被肝切除阻斷,說(shuō)明肝網(wǎng)狀內(nèi)皮細(xì)胞系統(tǒng)可能是腎外Ep生成的一個(gè)重要因素。 |
至尊木蟲 (職業(yè)作家)
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