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91.
Erythropoietin structure-function relationships: high degree of sequence homology among mammals 总被引:7,自引:3,他引:4
Wen D; Boissel JP; Tracy TE; Gruninger RH; Mulcahy LS; Czelusniak J; Goodman M; Bunn HF 《Blood》1993,82(5):1507-1516
To investigate structure-function relationships of erythropoietin (Epo), we have obtained cDNA sequences that encode the mature Epo protein of a variety of mammals. A first set of primers, corresponding to conserved nucleotide sequences between mouse and human DNAs, allowed us to amplify by polymerase chain reaction (PCR) intron 1/exon 2 fragments from genomic DNA of the hamster, cat, lion, dog, horse, sheep, dolphin, and pig. Sequencing of these fragments permitted the design of a second generation of species-specific primers. RNA was prepared from anemic kidneys and reverse-transcribed. Using our battery of species-specific 5' primers, we were able to successfully PCR- amplify Epo cDNA from Rhesus monkey, rat, sheep, dog, cat, and pig. Deduced amino acid sequences of mature Epo proteins from these animals, in combination with known sequences for human, Cynomolgus monkey, and mouse, showed a high degree of homology, which explains the biologic and immunological cross-reactivity that has been observed in a number of species. Human Epo is 91% identical to monkey Epo, 85% to cat and dog Epo, and 80% to 82% to pig, sheep, mouse, and rat Epos. There was full conservation of (1) the disulfide bridge linking the NH2 and COOH termini; (2) N-glycosylation sites; and (3) predicted amphipathic alpha- helices. In contrast, the short disulfide bridge (C29/C33 in humans) is not invariant. Cys33 was replaced by a Pro in rodents. Most of the amino acid replacements were conservative. The C-terminal part of the loop between the C and D helices showed the most variation, with several amino acid substitutions, deletions, and/or insertions. Calculations of maximum parsimony for intron 1/exon 2 sequences as well as coding sequences enabled the construction of cladograms that are in good agreement with known phylogenetic relationships. 相似文献
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Internal mammary compartment: window to the mediastinum 总被引:1,自引:0,他引:1
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David W. Golde Noelle Bersch Shirley G. Quan Martin J. Cline 《American journal of hematology》1976,1(4):369-373
The effect of dexamethasone on mouse bone marrow granulocyte-monocyte precursor cells (CFU-C) was studied in vitro. Dexamethasone inhibited colony formation in the presence of maximally stimulating concentrations of colony-stimulating activity. A mean colony reduction of 55% occurred at 109 M dexamethasone and inhibition was observed at concentrations as low as 10?12 M. The dexamethasone suppression could be abrogated by progesterone. These studies provide evidence that the committed granulocyte-monocyte stem cell has a glucocorticoid receptor mechanism that when activated results in inhibition of cellular proliferation in vitro. 相似文献
96.
We have investigated the mechanism of splenic irradiation-induced granulocytopenia in two patients with myelofibrosis and marked splenomegaly. Serial assays were performed for circulating granulocyte-monocyte progenitors capable of colony formation in vitro (CFU-C). For comparison, similar studies were performed on two patients receiving whole brain irradiation for glioma. Splenic irradiation caused a significant decrease in circulating CFU-C in the myelofibrosis patients. There was no decrease in circulating CFU-C in the brain-irradiated patients. No radiation-induced humoral inhibitor of granulopoiesis and no increased CFU-C radiosensitivity could be demonstrated in the myelofibrosis patients. These observations, taken together with previous data on splenic blood flow and pooling, suggest that the major mechanism of irradiation-induced granulocytopenia in myelofibrosis is destruction of proliferating precursor cells in the splenic tissue and sinusoids. 相似文献
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R H Weisbart R Billing D W Golde 《The Journal of laboratory and clinical medicine》1979,93(4):622-626
Fifteen lymphoblast cell lines, including B cell, T cell, Null cell, and myeloblast cells, were examined for the production of human neutrophil migration-inhibition activity. Only one T lymphoblast cell line established from a patient with hairy cell leukemia produced a neutrophil migration-inhibition factor spontaneously and after stimulation with Con A and PHA. 相似文献
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