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571.
572.
A constitutively activated chimeric cytokine receptor confers factor- independent growth in hematopoietic cell lines 总被引:3,自引:1,他引:2
The high-affinity receptor for granulocyte-macrophage colony- stimulating factor (GMR) comprises at least 2 distinct subunits, alpha and beta common (beta c), whereas the normal erythropoietin receptor (nEpoR) comprises only one known subunit. An arginine to cysteine (R129C) mutation of the extracytoplasmic domain of the murine EpoR leads to Epo-independent growth in transduced cells (cEpoR). To investigate the proliferative functions of the cytoplasmic regions of each GMR subunit separately and the potential of the R129C EpoR mutation to induce factor-independent growth through heterologous receptor regions, we constructed four hybrid receptors: the extracellular region of either murine nEpoR or cEpoR linked to the transmembrane and cytoplasmic regions of either the human GMR alpha or beta c subunit (nE alpha, nE beta, cE alpha, and cE beta). We then expressed them in an interleukin-3-dependent murine cell line, Ba/F3. Expression of nE beta led to Epo-dependent growth, whereas expression of cE beta conferred factor-independent growth. Surprisingly, expression of cE alpha also resulted in factor-independent cell growth, whereas nE alpha did not respond to Epo. Furthermore, the functional hybrid receptors showed Epo-dependent (nE beta) or constitutive (cE alpha and cE beta) tyrosine phosphorylation of the cytoplasmic kinases JAK1 and JAK2. We reasoned that the proliferative signal of cE alpha was transduced either through the alpha tail itself or through an accessory protein such as the endogenous murine beta common subunit (mu beta c). To distinguish these possibilities, the chimeric receptor cE alpha was expressed in the interleukin-2-dependent murine cell line, CTLL-2, that does not express mu beta c. cE alpha did not induce cell growth in CTLL-2; however, when mu beta c was coexpressed with cE alpha in CTLL-2, factor-independent growth was reconstituted. In conclusion, the cytoplasmic domain of the GMR alpha subunit requires a beta chain for transduction of a proliferative signal. Furthermore, the R129C EpoR mutation can constitutively activate heterologous receptors to mediate factor-independent proliferation. 相似文献
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Transvenous inferior vena caval filters were placed in 32 patients (21 bird's nest [BN] and 11 Kimray-Greenfield [K-G] filters). Positive contrast cavography was performed before and immediately after filter placement as well as during long-term follow-up studies. In 23 patients, computed tomographic (CT) scanning was also performed; in 10 patients, real-time ultrasound (US) study was used as an adjunct. CT scans of the BN filter showed one case of hemorrhage and one case of air embolism, both of which were not recognized at cavography. CT scanning of the K-G filter demonstrated two cases of deep penetration of the prongs and one large retroperitoneal hematoma. Real-time US scanning played a major role in checking the final position of the filter and in determining its stability during repositioning of the upper prongs of one BN filter. Noninvasive examinations, including CT and US scanning, are valuable adjuncts in immediate and long-term follow-up study of patients with inferior vena caval filters. 相似文献
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Wood GS; Hardman DL; Boni R; Dummer R; Kim YH; Smoller BR; Takeshita M; Kikuchi M; Burg G 《Blood》1996,88(5):1765-1770
579.
Rifampicin-associated acute renal failure: pathophysiologic, immunologic, and clinical features 总被引:1,自引:0,他引:1
AS De Vriese DL Robbrecht RC Vanholder DP Vogelaers NH Lameire 《American journal of kidney diseases》1998,31(1):108-115
A 71-year-old woman was treated for a relapsing pulmonary tuberculosis with reinstitution of rifampicin after a medication-free interval of 2 years. After ingestion of the second dose, she developed severe hemolytic anemia and acute renal failure (ARF) necessitating dialysis. We demonstrated the presence in the patient's serum of rifampicin-dependent immunoglobulin G (IgG) and IgM antibodies, which caused red blood cell lysis through interaction with the I antigen on the erythrocyte surface. A review of the literature yielded 48 cases of rifampicin-associated renal failure. A subgroup of 37 patients could be distinguished, which, analogous to our case, suddenly developed ARF and frequently also developed hemolytic anemia and/or thrombocytopenia during intermittent or interrupted treatment. Regarding the pathogenesis of the ARF, renal biopsy consistently revealed tubular lesions. Although intravascular hemolysis with hemoglobinuria may play a role, it is not uniformly present. Our demonstration of an antibody with anti-I specificity provides a possible explanation. The I antigen is also expressed on tubular epithelium and may, therefore, be the target structure through which rifampicin-antibody complexes lead to tubular cell destruction. The other cases of rifampicin-associated ARF were unrelated to this subgroup: two cases of rapidly progressive glomerulonephritis, five cases of acute interstitial nephritis, and four cases of light chain proteinuria were recorded. 相似文献
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