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1.
Protein synthesis: its control in erythropoiesis   总被引:16,自引:0,他引:16  
Erythropoiesis in the fetal mouse provides a model to study several important aspects of the regulation of cell differentiation and differentiated protein synthesis. Changes in the patterns of hemoglobins formed during fetal and postfetal development are shown to be associated with the substitution of the liver erythroid cell line. In the course of differentiation of yolk sac erythroid cells there are at least two classes of proteins distinguishable with respect to dependence on continued RNA formatoin. The bulk of nuclear proteins, "nondifferentiated" proteins, appear to be dependent on relatively short-lived messenger RNA while synthesis of differentiated proteins, the hemoglobins, proceeds on relatively stable molecules of messenger RNA. Hemoglobin formation occurs in those cells which are actively synthesizing DNA and dividing. On the average, two to three cell divisions may occur after the formation and stabilization of the messenger RNA for globin. Yolk sac erythropoiesis, at least from day 10 of gestation, is unresponsive to erythropoietin. By comparison, in fetal liver erythropoiesis, the hormone, erythropoietin, acts selectively on the most immature erythroid cell precursor to induce differentiation, cell replication, and hemoglobin formation. The erythropoietin responsive cell in the liver is apparently differentiated from the progenitor, pluripotential stem cell and committed to erythroblast formation and hemoglobin synthesis on exposure to the hormone. The initial effects of erythropoietin on macromolecular synthesis are to stimulate RNA synthesis, which temporally is followed by cell replication and the increase in hemoglobin formation. During liver erythropoiesis, there appears to be a transition from hemoglobin synthesis dependent on RNA formation to hemoglobin synthesis directed by relatively stable messenger RNA.  相似文献   

2.
Arabinosylcytosine, a compound that inhibits DNA synthesis in rapidly dividing cells, stimulates fetal hemoglobin in adult baboons and produces significant perturbations in the pools of erythroid progenitors. It appears that changes in the kinetics of erythroid cell differentiation rather than direct action on the gamma genes underlie stimulation of fetal hemoglobin in the adult animals in vivo. These results also suggest that chemotherapeutic agents selected for their low carcinogenic or mutagenic potential could be used for therapeutic induction of fetal hemoglobin in patients with sickle cell anemia.  相似文献   

3.
A cell-free protein-synthesizing system made from rabbit reticulocytes was used to incorporate (14)C-amino acids into hemoglobin. Electrophoretic analyses of the soluble products of this cell-free system revealed a fraction containing rabbit (14)C-alpha chains in addition to the rabbit (14)C-hemoglobin. The addition of isolated human hemoglobin beta chains to this system during active synthesis inhibited the release of newly synthesized rabbit (14)C-beta chains into solution from the ribosome fraction. This inhibition was possibly a result of hybrid hemoglobin formation between rabbit alpha and human beta chains. A model of hemoglobin construction in which soluble alpha chains are intermediates is suggested. These alpha chains may aid in the release of beta chains from the polyribosomes during the completion of the hemoglobin molecule.  相似文献   

4.
Erythroid colonies, raised from erythroid stem cells circulating in the peripheral blood of normal adult individuals, synthesize considerable amounts of fetal hemoglobin. In cultures from persons with sickling disorders, amounts of hemoglobin F that are known to inhibit sickling in vivo are produced. The results provide evidence that primitive erythroid progenitors are able to express the hemoglobin F production program and that cultures of mononuclear cells of the adult blood can be used to investigate the mechanisms involved in regulation of gamma-globin gene switching.  相似文献   

5.
Synthesis and evaluation of a prototypal artificial red cell   总被引:3,自引:0,他引:3  
A new process allows microencapsulation of purified human hemoglobin and 2,3-diphosphoglycerate to form neohemocytes. The microcapsule membrane is composed of phospholipids and cholesterol. Neohemocytes are substantially smaller than erythrocytes, contain 15.1 grams per decaliter of hemoglobin, and have a P50 value (the partial pressure of oxygen at which the hemoglobin is half-saturated) of 24.0 torr. All rats given 50-percent exchange transfusions survived with only limited evidence of reversible toxicity. Normal serum glutamate-pyruvate-transaminase values at 1, 7, and 30 days after transfusion were consistent with minimal hepatotoxicity. The concentration of blood urea-nitrogen was elevated by 35 percent after 1 day but returned to normal by day 7. However, histopathology revealed normal kidneys on day 1 as well as on days 7 and 30. Neohemocytes cleared from the circulation of transfused rats with an apparent half-life of 5.8 hours.  相似文献   

6.
Activation of developmentally mutated human globin genes by cell fusion   总被引:6,自引:0,他引:6  
Human fetal globin genes are not expressed in hybrid cells produced by the fusion of normal human lymphocytes with mouse erythroleukemia cells. In contrast, when lymphocytes from persons with globin gene developmental mutations (hereditary persistence of fetal hemoglobin) are used for these fusions, fetal globin is expressed in the hybrid cells. Thus, mutations of developmental origin can be reconstituted in vitro by fusing mutant lymphoid cells with differentiated cell lines of the proper lineage. This system can readily be used for analyses, such as globin gene methylation, that normally require large numbers of pure nucleated erythroid cells, which are difficult to obtain.  相似文献   

7.
A striking similarity has been found between the composition of peptides obtained from tryptic digestion of normal adult hemoglobin (hemoglobin A) and fetal hemoglobin (hemoglobin F).  相似文献   

8.
A new soluble mediator was found in supernatant fluid from cultures of human peripheral blood leukocytes that were stimulated by phytohemagglutinin, or by antigenic material present in human dental plaque deposits. This soluble Jactor produced bone resorption in organ cultures of fetal rat bones as measured by increased release of calcium-45, and also increased the number of active osteoclasts.  相似文献   

9.
The mechanisms by which expression of the beta-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic (epsilon) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human epsilon-globin gene was linked to a 2.5-kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human epsilon-globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erythroid cells. The absence of epsilon gene expression in definitive erythroid cells suggests that the developmental regulation of the epsilon-globin gene depends only on the presence of the LCR and the epsilon-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of epsilon-globin gene developmental control distinguishes it from the competitive mechanism of regulation of gamma and beta-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching.  相似文献   

10.
Gene selection in hemoglobin and in antibody-synthesizing cells   总被引:11,自引:0,他引:11  
Close linkage of mutually exclusive genes occurs in the non-alpha chain hemoglobin genes and in the immunoglobulin genes of man and other mammals. The expression of one gene in the cluster precludes the expression of any other linked gene. A simple, testable theory of gene selection called "looping-out excision"which was designed only to explain this mutual exclusivity in the hemoglobin system is described. The theory is closely concordant with a wide range of previously unexplained findings concerning hematopoiesis- including the developmental changes of hemoglobins, the increases in immature or fetal forms of hemoglobin that accompany anemia, and with the distribution of adult and fetal hemoglobins among erythrocytes during normal embryogenesis and in various pathological conditions. One corollary of this theory is that erythroid tissue in the normal adult bone marrow is constantly recapitulating the developmental stages of its embryogenesis. Another corollary is that the selection from among the linked globin genes occurs independently on the two chromosomes of the diploid organism. Both of these corollaries are supported by the available data. The same theory of gene selection is also remarkably consistent with known data for immunoglobulin synthesis; it could explain not only the mutually exclusive activation of linked variable genes but also the splicing which occurs between genetically linked variable and constant region genes for the immunoglobulin polypeptide chains. The agreement between these two different tissues is considered to be strong evidence that the proposed mechanism is correct at least in broad outline. Evidence from the genetics of maize and of drosophila also supports this theory of somatic tissue variegation. On the basis of these comparisons, I suggest that looping-out excision probably occurs also in other tissues and may be one means of gene selection and activation in differentiating cells.  相似文献   

11.
Activation of hemoglobin C synthesis in sheep marrow culture   总被引:6,自引:0,他引:6  
Erythropoietin preferentially stimulates hemoglobin C synthesis in suspension cultures of marrow cells from sheep homozygous for hemoglobin A; the amount of synthesis is dependent on the dose of erythropoietin and is blocked by antiserum to erythropoietin. The results provide the first in vitro evidence that erythropoietin mediates the hemoglobin A --> C "switch" in sheep and indicate that bone marrow cultures may be used to investigate the mechanisms involved in the preferential gene activation characteristic of the hemoglobin A --> C system.  相似文献   

12.
为了有效利用猪血资源,减少猪血的环境污染,采用超声波酶解法水解血红蛋白制备血红素,研究了超声波破胞技术对血红素提取效果的影响。以血红素提取率为考察指标,通过单因素试验和正交试验确定了最佳工艺条件即:血红素与水的体积比1∶7,超声功率300W,超声次数60次,间歇比2∶5,破胞后经过酶水解,得到血红素。在此工艺条件下测得血红素提取率为652.71μg/mL。  相似文献   

13.
目的探讨妊娠期糖尿病的预防措施.方法以吉林市妇产医院和丰满区妇幼保健院2004~2006年收治的妊娠期糖尿病(GDM)患者53例作为研究组,与同期112例非患者作为对照组进行分析.结果两组比较羊水过多、妊高症、早产、胎儿窘迫、巨大儿、剖宫产有显著意义(P〈0.05).产后感染、酮症酸中毒、羊水过少、胎儿畸形、死胎无显著意义(P〉005).结论提示GDM的母婴并发症明显增加.进行糖尿病筛查,及时发现妊娠期糖尿病,能较好控制血糖,加强围生期GDM孕妇的管理,可降低GDM母婴的并发症.  相似文献   

14.
由于食品的多样性和食品基质的复杂性,食品安全问题已成为全社会共同关注的热点问题,其中微生物引起的食源性疾病居全球食品安全问题之首。食源性致病菌的检测是食源性疾病预防与控制的关键环节。平板计数法被评为微生物检测的金标准,但在致病菌检测过程中信号的放大需要通过单个细胞生长成菌落来实现,因此检测周期较长(3—7 d)。此外,现有的准确检测致病菌的技术有聚合酶链式反应(PCR)和酶联免疫吸附法(ELISA)等,但由于预处理时间长、操作复杂、检测结果存在假阳性等问题,不适合对致病菌进行现场快速有效的检测。核酸适配体是利用指数富集的配体系统进化技术(SELEX)从核酸分子文库中得到的寡核苷酸片段,具有良好的特异性、稳定性、易于修饰和亲和力高等特点,在毒素、抗生素、重金属和致病菌等其他小分子的检测中有很大的潜力。目前,国内外学者已开发了各种基于适配体的检测方法。本文综述了食品中常见的食源性致病菌及其传统的检测方法和近十年来用于致病菌检测的光学和电化学适配传感器,涵盖每种方法的检测策略、检测时间、检测范围和检测限等信息,也提出了适配体传感器在食品安全检测中存在的主要问题,并对其未来研究的发展趋势进行了展望,这些将为今后的研究工作提供一定的基础。  相似文献   

15.
[目的]合理利用动物血液,优化冰醋酸提取猪血红素的方法.[方法]试验以新鲜猪血为原料,采用冰醋酸法提取新鲜猪血中的血红素,考察冰醋酸的添加量、反应温度、反应时间、氯化钠添加量等因素对血红素提取的影响.[结果]试验表明,冰醋酸法提取猪血红素的最佳工艺为:冰醋酸添加量为血球4倍,氯化钠添加量为血球的2.4%,反应时间30 min,反应温度为95℃,此条件下提取的血红素含量为40.2%.[结论]研究可为猪血资源的合理开发利用提供理论依据.  相似文献   

16.
Persistence of human fetal hemoglobin (HbF, α(2)γ(2)) in adults lessens the severity of sickle cell disease (SCD) and the β-thalassemias. Here, we show that the repressor BCL11A is required in vivo for silencing of γ-globin expression in adult animals, yet dispensable for red cell production. BCL11A serves as a barrier to HbF reactivation by known HbF inducing agents. In a proof-of-principle test of BCL11A as a potential therapeutic target, we demonstrate that inactivation of BCL11A in SCD transgenic mice corrects the hematologic and pathologic defects associated with SCD through high-level pancellular HbF induction. Thus, interference with HbF silencing by manipulation of a single target protein is sufficient to reverse SCD.  相似文献   

17.
Hemoglobin M variants, M Iwate, M Boston, M Saskatoon are easily and accurately identified by electron spin resonance with small amounts of patients' blood. In hemoglobin M Iwate and M Boston the electron spin resonance of both fresh blood (unprocessed) and isolated pure ferrihemoglobin M revealed similar signal shapes; whereas that of hemoglobin M Saskatoon was doublet in fresh blood and triplet in pure ferrihemoglobin M.  相似文献   

18.
There was decreased synthesis of the beta-globin chain in the peripheral blood, and equal synthesis of alpha- and non-alpha-chains in the bone marrow of three patients with hemoglobin Lepore trait, similar to the findings in patients with heterozygous beta-thalassemia. There is a relative instability of the synthetic mechanism for normal beta-chain in these patients.  相似文献   

19.
Direct analyses of solid phase formed by deoxygenating solutions of sickle-cell hemoglobin (Hb S) in the presence of certain other hemoglobin species show that hemoglobins A and C can participate in the filamentous fine structure characteristic of the sickling phenomenon. In contrast, fetal hemoglobin (Hb F) is nearly completely excluded.  相似文献   

20.
Urea tolerance as a molecular adaptation of elasmobranch hemoglobins   总被引:2,自引:0,他引:2  
Urea is maintained at moderately high concentrations in the blood and tissues of marine elasmobranchs. Functional properties of the hemoglobins fromn several elasmobranch species are unaffected by urea concentrations as high as 5 molar. This in. sensitivity to urea, which is not observed with human hemoglobin, is accompanied by an increased sensitivity to sodium chloride.  相似文献   

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