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排序方式: 共有975条查询结果,搜索用时 15 毫秒
91.
Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria 总被引:2,自引:3,他引:2
Endo M; Ware RE; Vreeke TM; Singh SP; Howard TA; Tomita A; Holguin MH; Parker CJ 《Blood》1996,87(6):2546-2557
The purpose of these studies was to determine the molecular basis of the phenotypic mosaicism that is a defining feature of paroxysmal nocturnal hemoglobinuria (PNH). Analysis of T cell clones from a female patient revealed four distinct phenotypes based on surface expression of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). When PIG-A (the gene that is mutant in PNH) from these clones was analyzed, four discrete somatic mutations were identified. Analysis of X chromosomal inactivation among the abnormal T cell clones was consistent with polyclonality. Together, these studies demonstrate that the phenotypic mosaicism that is characteristic of PNH is a consequence of genotypic mosaicism and that, at least in this case, PNH is a polyclonal rather than a monoclonal disease. That four distinct somatic mutations were present in a single patient suggests that in conditions that predispose to PNH PIG-A may be hypermutable. 相似文献
92.
In this investigation, we studied the importance of cellular glutathione (GSH) in the hexose monophosphate shunt (HMPS) activity of unstimulated human erythrocytes and the mechanism by which pyruvate stimulates the HMPS. The rate of HMPS activity was measured by the production of radioactive CO2 from 14C-1-glucose or 14C-1-ribose using a vibrating reed electrometer and ionization chamber. HMPS activity was not significantly impaired by N-ethylmaleimide (NEM) in concentrations which bound all red cell GSH. Red cells incubated under carbon monoxide (CO), an experimental condition which eliminates peroxide production, still had HMPS activity which was 44% of the value under air. Pyruvate stimulation of the HMPS was unaffected by doses of NEM which bound all cellular GSH or by incubation under CO. These data indicated that pyruvate stimulation of the HMPS occurs by pathways which do not involve peroxide formation, GSH, or oxygen. This study indicates that sulfhydryl blockade of GSH does not necessarily inhibit HMPS activity and that HMPS activity in red cells may respond to reactions not linked directly to glutathione reduction. 相似文献
93.
Datta P Chakrabarty SB Chakrabarty A Chakrabarti A 《Blood cells, molecules & diseases》2003,30(3):248-253
Among the few studies, producing contradictory results, done on the interaction of erythroid membrane skeletal spectrin with hemoglobin (Hb), none has been able to provide a quantitative estimate of the association of spectrin with Hb. In this work, studies on the interactions of erythroid spectrin with Hb have been elaborated upon using a novel fluorescence technique. The concentration-dependent change in the fluorescence intensity of fluorescein-conjugated spectrin (F-spectrin) in presence of oxy-Hb indicated binding with a dissociation constant of approximately 20 microM that has been directly evaluated from the increase in the extent of quenching of the fluorescein fluorescence of F-spectrin by reverse titration with the increasing concentrations of different Hb samples isolated from both normal and beta-thalassemic patients. The Hb compositions, with major components of the normal HbA, the fetal HbF, and the variant HbA2, of each individual were estimated using the Variant HPLC device of Bio-Rad. Results of the present study indicated that the dissociation constant, K(d), of spectrin binding to Hb decreased from 19.5 +/- 2 microM in normal individuals to of 6.5 +/- 0.5 microM in the presence of 73% HbA2 along with coeluted variants in the blood samples of patients suffering from beta-thalassemia, indicating differential interactions of the Hb variants with spectrin. 相似文献
94.
The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy 总被引:4,自引:1,他引:4
Grever MR; Siaw MF; Jacob WF; Neidhart JA; Miser JS; Coleman MS; Hutton JJ; Balcerzak SP 《Blood》1981,57(3):406-417
A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of this enzyme by 2'-deoxycoformycin in 15 patients with hematologic malignancies. Biochemical consequences of the administration of this agent were closely monitored in erythrocytes, nucleated peripheral blood and bone marrow cells, serum, and urine. A marked rise in erythrocyte dATP was accompanied by a depletion of ATP in those patients exhibiting toxicity. Most patients excreted large amounts of deoxyadenosine but not adenosine in the urine. Serum deoxyadenosine rose in patients demonstrating a marked decrease in cell mass. The biochemical disturbances and clinical toxicity, including hepatic, renal, and conjunctival abnormalities, were usually reversible. Central nervous system toxicity, which potentially was the most serious consequence, was associated with high erythrocyte dATP/ATP ratios and high levels of cerebrospinal fluid deoxyadenosine. In patients with lymphoma and leukemia, objective responses were observed but were short- lived. Patients with chronic lymphocytic leukemia receiving weekly low doses of the drug demonstrated minimal toxicity and some efficacy. The chemotherapeutic potential o 2'-deoxycoformycin, as either a single agent or in combination with Ara-A, merits further exploration. 相似文献
95.
A supracondylar fracture above a total knee arthroplasty (TKA) is a devastating complication for both the patient and surgeon. Various methods of treatment are available. We have treated seven cases of displaced supracondylar fractures above a total knee replacement with custom made implants. This technique allows rapid post-operative recovery and gives a good functional outcome. 相似文献
96.
Seth Iwan Chia-Min Lin Christopher Perreault Kallol Chakrabarty Cheng-Chien Chen Yogesh Vohra Rostislav Hrubiak Guoyin Shen Nenad Velisavljevic 《Materials》2022,15(9)
The high-entropy transition metal borides containing a random distribution of five or more constituent metallic elements offer novel opportunities in designing materials that show crystalline phase stability, high strength, and thermal oxidation resistance under extreme conditions. We present a comprehensive theoretical and experimental investigation of prototypical high-entropy boride (HEB) materials such as (Hf, Mo, Nb, Ta, Ti)B2 and (Hf, Mo, Nb, Ta, Zr)B2 under extreme environments of pressures and temperatures. The theoretical tools include modeling elastic properties by special quasi-random structures that predict a bulk modulus of 288 GPa and a shear modulus of 215 GPa at ambient conditions. HEB samples were synthesized under high pressures and high temperatures and studied to 9.5 GPa and 2273 K in a large-volume pressure cell. The thermal equation of state measurement yielded a bulk modulus of 276 GPa, in excellent agreement with theory. The measured compressive yield strength by radial X-ray diffraction technique in a diamond anvil cell was 28 GPa at a pressure of 65 GPa, which is a significant fraction of the shear modulus at high pressures. The high compressive strength and phase stability of this material under high pressures and high temperatures make it an ideal candidate for application as a structural material in nuclear and aerospace fields. 相似文献
97.
目的 建立一种快速、灵敏的高效液相色谱-串联质谱(HPLC-MS/MS)方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1~8.0 μg·mL-1范围内线性良好(r2 > 0.99),最低检测限为 0.1 μg·mL-1,提取回收率为91.0%~98.7%,日内和日间准确度分别为98.8%~111.3% (精密度:CV ? 9.03%)和94.9%~102.6% (精密度:CV ? 10.68%)。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%~105.79%,94.25%~101.54%和93.24%~101.02%,均落在生物等效可接受标准80.00%~125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。 相似文献
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