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Enhancement of erythropoietin production by selective adenosine A2 receptor agonists in response to hypoxia. 选择性腺苷A2受体激动剂在缺氧反应中增强促红细胞生成素的产生。
T Ohigashi, J Nakashima, S Aggarwal, J Brookins, K Agrawal, J W Fisher

The purpose of this study was to characterize the effects of two new adenosine A2 agonists, 2-(p-(2-carboxyethyl)phenethyl amino)-5'-N-ethylcarboxamidoadenosine (CGS-21680) and N6-(2(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)-adenosine (DPMA), on erythropoietin (EPO) production in vivo and in vitro. Intravenous injections of CGS-21680 (100 to 500 nmol/kg mouse/day) and DPMA (50 to 500 nmol/kg mouse/day) for 4 days produced significant increases in serum levels of EPO in exhypoxic polycythemic mice. CGS-21680 (10(-7) to 10(-6) mol/L) and DPMA (10(-8) to 10(-5) mol/L) also produced significant increases in medium levels of EPO in a cloned EPO-producing Hep3B hepatocellular carcinoma cell line after 18 hours of incubation in 1% O2. Both compounds also increased cellular cAMP levels significantly in a dose-dependent manner after 1 hour of incubation. A2 receptor binding assays with tritiated CGS-21680 revealed a single type of adenosine receptor binding site on Hep3B cell membranes with a dissociation constant of 132.9 nmol/L and a binding capacity of 270.6 fmol/mg protein. The Ki competition binding values versus tritiated CGS-21680 were 217 nmol/L for CGS-21680 and 86.8 nmol/L for DPMA. These results indicate that adenosine A2 receptor activation amplifies EPO production in response to hypoxia, both in vivo and in vitro.

本研究的目的是表征两种新的腺苷A2激动剂2-(对-(2-羧乙基)苯基氨基)-5'- n -乙基羧氨基腺苷(CGS-21680)和N6-(2(3,5-二甲氧基苯基)-2-(2-甲基苯基)乙基)-腺苷(DPMA)对体内和体外促红细胞生成素(EPO)产生的影响。静脉注射CGS-21680 (100 ~ 500 nmol/kg小鼠/天)和DPMA (50 ~ 500 nmol/kg小鼠/天)4天后,缺氧红细胞增多症小鼠血清EPO水平显著升高。CGS-21680 (10(-7) ~ 10(-6) mol/L)和DPMA (10(-8) ~ 10(-5) mol/L)在1% O2中培养18小时后,也能显著提高克隆的EPO产生肝癌Hep3B细胞的EPO水平。两种化合物在孵育1小时后也以剂量依赖的方式显著增加细胞cAMP水平。用氚化CGS-21680进行A2受体结合实验,发现Hep3B细胞膜上存在一种单一类型的腺苷受体结合位点,解离常数为132.9 nmol/L,结合能力为270.6 fmol/mg蛋白。CGS-21680与氚化CGS-21680的Ki竞争结合值分别为217 nmol/L和86.8 nmol/L。这些结果表明,体内和体外缺氧时,腺苷A2受体的激活会增加EPO的产生。
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引用次数: 0
Thrombotic risk factors and oral contraception. 血栓形成的危险因素和口服避孕药。
Pub Date : 1995-09-01 DOI: 10.3109/09513599609045652
M. Bokarewa, G. Falk, M. Sten-Linder, N. Egberg, M. Blombäck, K. Bremme
Eighty-one women with a history of thrombosis were classified into three groups: group I (n = 29), women in whom thrombosis developed during oral contraception; group II (n = 33), those who used oral contraceptives (OC) without complications but experienced vascular occlusion in other risk situations; group III (n = 19), women who never used OC. The level of antibodies to anionic phospholipids (PLa), a response to activated protein C (APC), and the presence for the mutation in the coagulation factor V gene causing APC resistance were studied. In the studied groups, APC resistance was present in 14% to 42% of patients. PLa were elevated in about half of APC-resistant patients. The incidence of APC resistance correlated with the recurrency of the thrombotic events within the groups. In most cases it was tightly connected to the mutation in the factor V gene. Women in whom thrombosis developed while they were taking OC (group I) differed from the others, having a remarkable disagreement between the lowest incidence of APC resistance and a relatively increased number of the mutation (14% vs 38%, p < 0.025). This finding suggested that the APC response is flexible. An influence of OC that predisposes a reduction in APC response is discussed.
81名有血栓形成史的女性被分为三组:第一组(n = 29),在口服避孕药期间出现血栓形成的女性;II组(n = 33),使用口服避孕药(OC)无并发症,但在其他危险情况下发生血管闭塞的患者;III组(n = 19),从未使用过OC的女性。研究了阴离子磷脂(PLa)抗体水平、活化蛋白C (APC)抗体水平以及引起APC耐药的凝血因子V基因突变的存在。在研究组中,14% - 42%的患者存在APC耐药。约半数apc耐药患者PLa升高。APC耐药发生率与组内血栓事件的复发率相关。在大多数情况下,它与因子V基因的突变密切相关。在服用OC期间发生血栓形成的女性(I组)与其他组不同,APC耐药最低发生率与突变数量相对增加之间存在显著差异(14% vs 38%, p < 0.025)。这一发现表明APC反应是灵活的。讨论了OC对APC反应降低的影响。
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引用次数: 20
Renal and systemic-hemodynamic response to isovolemic exchange transfusion with hemoglobin cross-linked with bis (3,5-dibromosalicyl) fumarate or albumin. 与富马酸(3,5-二溴水杨基)或白蛋白交联的血红蛋白等容交换输血对肾脏和全身血流动力学的反应。
B Matheson-Urbaitis, Y S Lu, C Fronticelli, E Bucci

Experiments were done in anesthetized rats to determine systemic hemodynamic and renal functional effects of isovolemic exchange transfusion with either 5% albumin or hemoglobin cross-linked with bis (3,5-dibromosalicyl) fumarate (XLHb) in volumes ranging from 1 to 6.3 ml.100 gm-1. Hematocrit decreased in proportion to increasing exchange volumes with either fluid. Exchange with increasing volumes of albumin led to progressive decreases in blood pressure. Exchange of 1 ml.100 gm-1 of XLHb was associated with an increase in blood pressure, whereas with larger exchanges, blood pressure returned to and was maintained at control values even for exchanges as large as 6.3 ml.100 gm-1. An increase of similar magnitude in glomerular filtration rate occurred with both fluids. Net and fractional sodium excretion (FENa) increased significantly with both transfusion fluids; the increase was significantly larger for XLHb than for albumin. Maximal FENa excretion with albumin was about 8% but exceeded 6% with XLHb. Pretreatment with indomethacin (5 mg.kg-1.day-1 for 3 days) did not blunt the diuresis that occurred with an exchange of 2 ml.100 gm-1 XLHb. It is concluded that 5% XLHb, as compared with 5% albumin, better supports systemic blood pressure, especially as exchange volume increases, possibly as a result of hemoglobin-induced increased vascular tone. Although a decrease in hematocrit may play a role in the diuresis observed with either fluid, the greater diuresis with XLHb must be due to some additional factor; the mechanism does not appear to involve prostaglandins.

在麻醉大鼠中进行实验,以测定5%白蛋白或血红蛋白与富马酸(3,5-二溴水杨基)交联(XLHb)的等容量交换输注对全身血流动力学和肾功能的影响,交换量为1至6.3 ml.100 gm-1。红细胞压积随两种液体交换量的增加成比例下降。随着白蛋白量的增加,交换导致血压逐渐下降。交换1 ml.100 gm-1 XLHb与血压升高相关,而更大的交换,即使交换6.3 ml.100 gm-1,血压也恢复并保持在控制值。两种液体肾小球滤过率均出现相似幅度的增加。两种输注液体均显著增加净钠排泄量和分数钠排泄量(FENa);XLHb的增加明显大于白蛋白。白蛋白组最大fea排泄量约为8%,XLHb组超过6%。用吲哚美辛(5 mg.kg-1)预处理。2 ml.100 gm-1 XLHb交换后出现的利尿并未减弱。由此可见,5% XLHb与5%白蛋白相比,能更好地支持全身血压,特别是当交换量增加时,这可能是由于血红蛋白诱导的血管张力增加。虽然红细胞压积的降低可能在两种液体的利尿中起作用,但XLHb的更大利尿一定是由于一些额外的因素;这一机制似乎与前列腺素无关。
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引用次数: 0
Thrombotic risk factors and oral contraception. 血栓形成的危险因素和口服避孕药。
M I Bokarewa, G Falk, M Sten-Linder, N Egberg, M Blombäck, K Bremme

Eighty-one women with a history of thrombosis were classified into three groups: group I (n = 29), women in whom thrombosis developed during oral contraception; group II (n = 33), those who used oral contraceptives (OC) without complications but experienced vascular occlusion in other risk situations; group III (n = 19), women who never used OC. The level of antibodies to anionic phospholipids (PLa), a response to activated protein C (APC), and the presence for the mutation in the coagulation factor V gene causing APC resistance were studied. In the studied groups, APC resistance was present in 14% to 42% of patients. PLa were elevated in about half of APC-resistant patients. The incidence of APC resistance correlated with the recurrency of the thrombotic events within the groups. In most cases it was tightly connected to the mutation in the factor V gene. Women in whom thrombosis developed while they were taking OC (group I) differed from the others, having a remarkable disagreement between the lowest incidence of APC resistance and a relatively increased number of the mutation (14% vs 38%, p < 0.025). This finding suggested that the APC response is flexible. An influence of OC that predisposes a reduction in APC response is discussed.

81名有血栓形成史的女性被分为三组:第一组(n = 29),在口服避孕药期间出现血栓形成的女性;II组(n = 33),使用口服避孕药(OC)无并发症,但在其他危险情况下发生血管闭塞的患者;III组(n = 19),从未使用过OC的女性。研究了阴离子磷脂(PLa)抗体水平、活化蛋白C (APC)抗体水平以及引起APC耐药的凝血因子V基因突变的存在。在研究组中,14% - 42%的患者存在APC耐药。约半数apc耐药患者PLa升高。APC耐药发生率与组内血栓事件的复发率相关。在大多数情况下,它与因子V基因的突变密切相关。在服用OC期间发生血栓形成的女性(I组)与其他组不同,APC耐药最低发生率与突变数量相对增加之间存在显著差异(14% vs 38%, p < 0.025)。这一发现表明APC反应是灵活的。讨论了OC对APC反应降低的影响。
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引用次数: 0
Maternal-to-fetal transfer of 5-methyltetrahydrofolate by the perfused human placental cotyledon: evidence for a concentrative role by placental folate receptors in fetal folate delivery. 5-甲基四氢叶酸通过灌注人胎盘子叶向胎儿转移:胎盘叶酸受体在胎儿叶酸输送中集中作用的证据。
G I Henderson, T Perez, S Schenker, J Mackins, A C Antony

Folates play a vital role in cellular processes that are essential for fetal growth and viability. Thus the human placenta, which contains high-affinity membrane-associated placental folate receptors (PFRs), maintains a concentrative maternal-to-fetal flux of the vitamin under conditions of minimal dependence on variations of maternal dietary intake. To define transplacental folate transport and the role of PFRs in this mechanism, we utilized the isolated perfused human placental cotyledon. In closed system perfusions with 10 nmol/L 5-methyltetrahydrofolate, placental binding was rapid and extensive (47%), with a gradual maternal-to-fetal transfer of 5-methyltetrahydrofolate. Although hydrophilic PFRs were released into the fetal perfusate, PFR-bound folates constituted only a fraction of net transplacental folate transport. Transfer was bidirectional, not saturable, not inhibited by anion channel blockers, and dependent on perfusate levels. Placental binding far exceeded transfer, and pulsing the maternal circuit with tritiated 5-methyltetrahydrofolate, followed by washout of unbound radiolabel and rechallenge with unlabeled 5-methyltetrahydrofolate or folate, led to release of bound tritiated 5-methyltetrahydrofolate, illustrating reversible binding. Perfusion with the N-hydroxysuccinimide ester of folic acid eliminated essentially all 5-methyltetrahydrofolate binding to PFRs, while increasing net maternal-to-fetal transfer of the vitamin. Finally, because it has been suggested that impaired placental transport of folate may be linked to the fetotoxic effects of ethanol, the effect of this compound on the above processes was examined. An acute 6-hour exposure to ethanol (2.5 to 3.1 mg/ml) had no effect (p > 0.05) on net maternal-to-fetal transfer of 5-methyltetrahydrofolate. These studies suggest that net maternal-to-fetal transfer is a process consisting of two steps. First is the concentrative component in which circulating 5-methyltetrahydrofolate is bound to (captured by) PFRs on the maternally facing chorionic surface. Although kinetics favor binding, there is a dynamic state wherein a gradual release of 5-methyltetrahydrofolate from this pool can add to incoming circulating folates to generate an intervillous blood level approximately 3 times that in the maternal blood. In the second step, folates are passively transferred to the fetal circulation along a downhill concentration gradient. This unique mechanism for transplacental folate transport may be applicable to other small relative molecular mass ligand nutrients that bind to high-affinity placental receptors.

叶酸在细胞过程中起着至关重要的作用,对胎儿的生长和生存能力至关重要。因此,含有高亲和膜相关胎盘叶酸受体(PFRs)的人胎盘,在对母体饮食摄入变化依赖最小的条件下,维持母体到胎儿的维生素浓度。为了确定经胎盘叶酸转运和PFRs在这一机制中的作用,我们使用了离体灌注的人胎盘子叶。在封闭系统灌注10 nmol/L 5-甲基四氢叶酸时,胎盘结合迅速而广泛(47%),5-甲基四氢叶酸逐渐从母体转移到胎儿。虽然亲水的pfr被释放到胎儿灌注液中,但pfr结合的叶酸仅占经胎盘叶酸运输的一小部分。转移是双向的,不饱和的,不受阴离子通道阻滞剂的抑制,并依赖于灌注水平。胎盘结合远远超过转移,用氚化的5-甲基四氢叶酸刺激母体回路,然后冲洗未结合的放射性标记物,用未标记的5-甲基四氢叶酸或叶酸重新挑战,导致结合的氚化5-甲基四氢叶酸释放,说明可逆结合。灌注叶酸的n -羟基琥珀酰亚胺酯基本上消除了所有与PFRs结合的5-甲基四氢叶酸,同时增加了维生素的母体向胎儿的净转移。最后,由于有人认为叶酸的胎盘运输受损可能与乙醇的胎儿毒性作用有关,因此研究了这种化合物对上述过程的影响。急性暴露于乙醇(2.5 ~ 3.1 mg/ml) 6小时对5-甲基四氢叶酸母婴净转移没有影响(p > 0.05)。这些研究表明,净母胎移植是一个由两个步骤组成的过程。首先是浓缩成分,其中循环的5-甲基四氢叶酸与面向母体的绒毛膜表面的pfr结合(被捕获)。虽然动力学上有利于结合,但在动态状态下,从这个池中逐渐释放的5-甲基四氢叶酸可以增加进入循环的叶酸,从而产生绒毛间血水平,大约是母体血水平的3倍。在第二步,叶酸被动地转移到胎儿循环沿着下坡浓度梯度。这种独特的经胎盘转运叶酸的机制可能适用于与高亲和力胎盘受体结合的其他小相对分子质量配体营养物质。
{"title":"Maternal-to-fetal transfer of 5-methyltetrahydrofolate by the perfused human placental cotyledon: evidence for a concentrative role by placental folate receptors in fetal folate delivery.","authors":"G I Henderson,&nbsp;T Perez,&nbsp;S Schenker,&nbsp;J Mackins,&nbsp;A C Antony","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Folates play a vital role in cellular processes that are essential for fetal growth and viability. Thus the human placenta, which contains high-affinity membrane-associated placental folate receptors (PFRs), maintains a concentrative maternal-to-fetal flux of the vitamin under conditions of minimal dependence on variations of maternal dietary intake. To define transplacental folate transport and the role of PFRs in this mechanism, we utilized the isolated perfused human placental cotyledon. In closed system perfusions with 10 nmol/L 5-methyltetrahydrofolate, placental binding was rapid and extensive (47%), with a gradual maternal-to-fetal transfer of 5-methyltetrahydrofolate. Although hydrophilic PFRs were released into the fetal perfusate, PFR-bound folates constituted only a fraction of net transplacental folate transport. Transfer was bidirectional, not saturable, not inhibited by anion channel blockers, and dependent on perfusate levels. Placental binding far exceeded transfer, and pulsing the maternal circuit with tritiated 5-methyltetrahydrofolate, followed by washout of unbound radiolabel and rechallenge with unlabeled 5-methyltetrahydrofolate or folate, led to release of bound tritiated 5-methyltetrahydrofolate, illustrating reversible binding. Perfusion with the N-hydroxysuccinimide ester of folic acid eliminated essentially all 5-methyltetrahydrofolate binding to PFRs, while increasing net maternal-to-fetal transfer of the vitamin. Finally, because it has been suggested that impaired placental transport of folate may be linked to the fetotoxic effects of ethanol, the effect of this compound on the above processes was examined. An acute 6-hour exposure to ethanol (2.5 to 3.1 mg/ml) had no effect (p > 0.05) on net maternal-to-fetal transfer of 5-methyltetrahydrofolate. These studies suggest that net maternal-to-fetal transfer is a process consisting of two steps. First is the concentrative component in which circulating 5-methyltetrahydrofolate is bound to (captured by) PFRs on the maternally facing chorionic surface. Although kinetics favor binding, there is a dynamic state wherein a gradual release of 5-methyltetrahydrofolate from this pool can add to incoming circulating folates to generate an intervillous blood level approximately 3 times that in the maternal blood. In the second step, folates are passively transferred to the fetal circulation along a downhill concentration gradient. This unique mechanism for transplacental folate transport may be applicable to other small relative molecular mass ligand nutrients that bind to high-affinity placental receptors.</p>","PeriodicalId":23085,"journal":{"name":"The Journal of laboratory and clinical medicine","volume":"126 2","pages":"184-203"},"PeriodicalIF":0.0,"publicationDate":"1995-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18640674","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
Pulmonary immune response of young and aged mice after influenza challenge. 幼龄和老年小鼠在流感侵袭后的肺免疫反应。
B S Bender, S F Taylor, D S Zander, R Cottey

After influenza challenge, aged mice have prolonged viral shedding that correlates with lower splenic cytotoxic T lymphocyte (CTL) activity. To evaluate the age-related pulmonary cell-mediated immune response to influenza, pulmonary lymphocytes were obtained from young and aged mice at various days after respiratory tract infection with nonlethal influenza A/PC/1/73 (H3N2) virus. In young mice, pulmonary CTL activity peaked at 48% +/- 2% on day 7 after infection. Pulmonary CTL activity peaked 1 day later in aged mice and at about half the activity (24% +/- 5%). The majority of the cells recovered from the lungs in both age groups were CD3+, CD8+ T cells. Histologic examination of the lungs revealed that aged mice had significantly less inflammation than young mice. Therefore, after influenza challenge there was a large influx of lymphocytes into the lungs of both young and aged mice, but the cells from young mice were more active on a per-cell basis. In a further experiment, challenge with a more virulent strain of influenza produced higher mortality in young mice than in aged mice. Thus the higher CTL activity of young animals leads to more rapid virai clearance, but this may be at a price to the host--that is, more immunopathologic damage.

在流感攻击后,老年小鼠有延长的病毒脱落,这与较低的脾细胞毒性T淋巴细胞(CTL)活性相关。为了评估年龄相关的肺细胞介导的流感免疫反应,在呼吸道感染非致死性流感病毒A/PC/1/73 (H3N2)后的不同天,从年轻和老年小鼠中获得肺淋巴细胞。在幼鼠中,肺部CTL活性在感染后第7天达到48% +/- 2%的峰值。老年小鼠肺CTL活性在1天后达到峰值,约为活性的一半(24% +/- 5%)。在两个年龄组中,从肺中恢复的细胞大部分是CD3+、CD8+ T细胞。肺部的组织学检查显示,老年小鼠的炎症明显少于年轻小鼠。因此,在流感攻击后,大量淋巴细胞涌入年轻和年老小鼠的肺部,但年轻小鼠的细胞在每个细胞的基础上更活跃。在进一步的实验中,用毒性更强的流感毒株攻击幼鼠,其死亡率高于老龄鼠。因此,幼龄动物较高的CTL活性导致更快的病毒清除,但这可能对宿主有代价——即更多的免疫病理损伤。
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引用次数: 0
Correlation of low histidine rich glycoprotein plasma levels with the occurrence of acute graft-versus-host disease after allogeneic bone marrow transplantation. 低富组氨酸糖蛋白血浆水平与异基因骨髓移植后急性移植物抗宿主病发生的相关性
C Mauz-Körholz, D Körholz, S Burdach

Histidine-rich glycoprotein (HRGP) is a potent inhibitor of T cell activation and production of cytokines such as (gamma-IFN). gamma-IFN released by activated T cells is increased during a short-term period at the onset of GvHD after allogeneic bone marrow transplantation. Therefore we investigated HRGP plasma levels in patients after BMT. Blood was collected from 20 children before and up to 6 weeks after BMT. In patients without GvHD, HRGP plasma levels decreased during the first week after BMT to 237 +/- 60 micrograms/ml, compared with 302 +/- 104 micrograms/ml before transplantation. However, no significant changes in mean HRGP plasma levels were observed during the following 5 weeks of the posttransplantation period. Acute GvHD occurred in 10 of 20 patients between the second and third week after BMT. HRGP levels (mean +/- SEM) in patients with GvHD dropped during the first week to 158 +/- 32 micrograms/ml, compared with pretransplant levels of 240 +/- 48 micrograms/ml). In contrast to results in patients without GvHD, a second and significant decrease was obtained between the second and third week after BMT in patients with GvHD (161 +/- 35 micrograms/ml vs 84 +/- 13 micrograms/ml; p < 0.01). In the third week after BMT, HRGP levels were significantly lower in patients with GvHD as compared with patients without GvHD (166 +/- 29 micrograms/ml; p < 0.01). The decrease in HRGP in the second and third posttransplantation week was not a result of steroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

富组氨酸糖蛋白(HRGP)是T细胞活化和细胞因子(γ - ifn)产生的有效抑制剂。同种异体骨髓移植后,激活T细胞释放的γ - ifn在GvHD发病的短期内增加。因此,我们研究了BMT后患者的HRGP血浆水平。采集了20名患儿在BMT前和BMT后6周的血液。在没有GvHD的患者中,HRGP水平在BMT后的第一周内下降到237 +/- 60微克/毫升,而移植前为302 +/- 104微克/毫升。然而,在移植后的5周内,平均HRGP血浆水平没有明显变化。20例患者中有10例在BMT后的第二至第三周发生急性GvHD。GvHD患者的HRGP水平(平均+/- SEM)在第一周内下降至158 +/- 32微克/毫升,而移植前的水平为240 +/- 48微克/毫升。与无GvHD患者的结果相比,GvHD患者在BMT后的第二周和第三周之间出现了第二次显著下降(161 +/- 35微克/ml vs 84 +/- 13微克/ml);P < 0.01)。在BMT后的第三周,GvHD患者的HRGP水平明显低于非GvHD患者(166 +/- 29微克/毫升;P < 0.01)。移植后第二周和第三周HRGP的下降不是类固醇治疗的结果。(摘要删节250字)
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引用次数: 0
Development of an enzyme-linked immunosorbent assay for human metallothionein-1 in plasma and urine. 血浆和尿液中金属硫蛋白-1酶联免疫吸附测定方法的建立。
D F Akintola, B Sampson, A Fleck

The development of a sensitive enzyme-linked immunosorbent assay (ELISA) for human metallothionein-1 is reported. Metallothionein was purified from postmortem human liver and used to raise high-titer antibodies in rabbits. The assay was specific for human metallothionein-1 (MT-1), and there was no significant cross-reaction with human metallothionein-2. The detection limit (sensitivity) of the assay was 5 ng/ml, and the added MT-1 could be fully recovered from plasma and urine. The normal reference range for MT-1 was 32 +/- 16 ng/ml in plasma and 10 +/- 6 ng MT-1 per micromole of creatinine in random samples of urine. No significant differences were found between the values for males and females. The concentration of MT-1 was greatly increased between 24 and 48 hours after surgery, indicating that the protein behaves like an acute phase reactant in human subjects.

报道了一种灵敏的人金属硫蛋白-1酶联免疫吸附试验(ELISA)的发展。从人死后肝脏中纯化金属硫蛋白,用于兔体内培养高效价抗体。该方法对人金属硫蛋白-1 (MT-1)具有特异性,与人金属硫蛋白-2无明显交叉反应。检测限(灵敏度)为5 ng/ml,添加的MT-1可从血浆和尿液中完全回收。血浆中MT-1的正常参考范围为32 +/- 16 ng/ml,随机尿液中肌酐为10 +/- 6 ng -1 /微摩尔。在男性和女性之间没有发现显著差异。MT-1的浓度在手术后24至48小时内大幅增加,表明该蛋白在人类受试者中表现得像急性相反应物。
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引用次数: 0
The effect of cell-free hemoglobin on intravascular clearance and cellular, plasma, and organ distribution of bacterial endotoxin in rabbits. 无细胞血红蛋白对兔血管内细菌内毒素清除及细胞、血浆和器官分布的影响。
M Yoshida, R I Roth, J Levin

Cell-free hemoglobin (Hb) and bacterial endotoxin (LPS) synergistically produce toxicity. To elucidate possible mechanisms, three groups of rabbits received LPS alone, LPS plus human serum albumin (HSA), or LPS plus Hb (Hb group). The intravascular retention of injected iodine 125-labeled LPS during the 30-minute period analyzed was significantly longer in the Hb group than in the LPS alone or HSA groups (p = 0.0007 and p = 0.03, respectively), especially during the initial 10 minutes. The intravascular half-life of LPS in the LPS control, HSA, and Hb groups was 2.8, 4.0, and 4.9 minutes, respectively; the area under the curve was 1369 +/- 483, 1594 +/- 360, and 1731 +/- 481, respectively (ng/ml x minutes, mean +/- SD); and the total body clearance was 24.7 +/- 9.2, 20.1 +/- 5.4, and 18.9 +/- 6.0 (ml/min, mean +/- SD), respectively. The proportion of LPS associated with blood cells was very small at the initial 1-minute time period, and this decreased even further during the 30-minute period analyzed (p = 0.0001). Over 96% of injected LPS was associated with the cell-free plasma, with 51% to 54% of LPS in the apoprotein fraction at the initial time point and 35% to 37% in the HDL fraction. The proportion of LPS increased significantly in the HDL fraction and decreased significantly in apoproteins during the 30-minute period analyzed (p = 0.0006 and p = 0.002, respectively). However, there were no differences between the three groups. The liver was the main distribution site (74%) of injected LPS among the six organs evaluated. In the Hb group the accumulation of 125I-labeled LPS in the spleen was significantly lower than that in the HSA group (p = 0.05). The synergism of the in vivo toxicity reported for LPS and Hb may be due, in part, to the decreased rate of intravascular clearance of endotoxin.

无细胞血红蛋白(Hb)和细菌内毒素(LPS)协同产生毒性。为了阐明可能的机制,三组兔子单独接受LPS, LPS加人血清白蛋白(HSA),或LPS加Hb (Hb组)。在分析的30分钟内,Hb组注射碘125标记LPS的血管内滞留时间明显长于单独注射LPS或HSA组(p = 0.0007和p = 0.03),特别是在最初的10分钟内。LPS对照组、HSA组和Hb组LPS的血管内半衰期分别为2.8、4.0和4.9分钟;曲线下面积分别为1369 +/- 483、1594 +/- 360、1731 +/- 481 (ng/ml x min,平均值+/- SD);总清除率分别为24.7 +/- 9.2、20.1 +/- 5.4和18.9 +/- 6.0 (ml/min, mean +/- SD)。在最初的1分钟时间内,与血细胞相关的LPS比例非常小,在分析的30分钟期间,这一比例进一步下降(p = 0.0001)。超过96%的注射LPS与无细胞血浆相关,初始时间点载脂蛋白部分为51% ~ 54%,HDL部分为35% ~ 37%。在分析的30分钟内,LPS在HDL部分的比例显著升高,载脂蛋白的比例显著降低(p = 0.0006和p = 0.002)。然而,三组之间没有差异。肝脏是6个脏器中注射LPS的主要分布部位(74%)。Hb组脾脏中125i标记LPS的积累明显低于HSA组(p = 0.05)。据报道,脂多糖和血红蛋白体内毒性的协同作用可能部分归因于血管内内毒素清除率的降低。
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引用次数: 0
Cyclic adenosine monophosphate and protein kinase C modulate fibronectin production in cultured human mesangial cells. 单磷酸环腺苷和蛋白激酶C调节培养的人系膜细胞中纤维连接蛋白的产生。
B H Rovin, L C Tan, K L Leonhart, N S Nahman

To identify potential intracellular mediators of mesangial cell fibronectin production, we examined the effect of cyclic adenosine monophosphate and protein kinase C on fibronectin biosynthesis in cultured human mesangial cells. We found that increasing intracellular cyclic adenosine monophosphate resulted in a 2.6-fold increase in fibronectin mRNA expression within 15 minutes; this reached a plateau after 1 hour and fell below control levels by 24 hours. Cyclic adenosine monophosphate significantly increased both immunoreactive fibronectin levels and the incorporation of [35S]-labeled methionine into fibronectin after 1 and 2 hours (251% +/- 3% and 157% +/- 18% of controls, respectively). The induction of protein kinase C with phorbol ester also increased fibronectin mRNA expression. The effect was time and dose dependent. Phorbol ester significantly increased both immunoreactive fibronectin levels and the incorporation of [35S]-labeled methionine after 1 and 2 hours (174% +/- 2% and 224% +/- 6% of controls, respectively). Inhibition of protein kinase C with calphostin C attenuated constitutive and phorbol ester induced fibronectin biosynthesis. These studies indicate that cyclic adenosine monophosphate and protein kinase C regulate mesangial cell fibronectin biosynthesis and that protein kinase C may contribute to control of constitutive fibronectin production.

为了确定系膜细胞纤维连接蛋白产生的潜在细胞内介质,我们研究了环磷酸腺苷和蛋白激酶C对培养的人系膜细胞纤维连接蛋白生物合成的影响。我们发现,增加细胞内环磷酸腺苷导致纤维连接蛋白mRNA表达在15分钟内增加2.6倍;1小时后达到平稳,24小时后降至控制水平以下。环磷酸腺苷在1和2小时后显著增加免疫反应性纤维连接蛋白水平和[35S]标记的蛋氨酸与纤维连接蛋白的结合(分别为对照组的251% +/- 3%和157% +/- 18%)。磷酸酯诱导蛋白激酶C也增加了纤维连接蛋白mRNA的表达。效果是时间和剂量依赖的。Phorbol酯在1和2小时后显著增加免疫反应性纤维连接蛋白水平和[35S]标记蛋氨酸的掺入(分别为对照组的174% +/- 2%和224% +/- 6%)。calphostin C抑制蛋白激酶C可减弱组成型和酚酯诱导的纤维连接蛋白生物合成。这些研究表明,单磷酸环腺苷和蛋白激酶C调节系膜细胞纤维连接蛋白的生物合成,蛋白激酶C可能有助于控制组成型纤维连接蛋白的产生。
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The Journal of laboratory and clinical medicine
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