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Rheo-acoustical study of the shear disruption of reversible aggregates. Ultrasound scattering from concentrated suspensions of red cell aggregates

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JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA 2000年第3期107卷 1715-1726页

作者： Haider, L Snabre, P Boynard, M Inst Sci & Genie Mat & Procedes UPR 8521 F-66125 Font Romeu France UFR Biomed GRPB F-75270 Paris 06 France

Shear-induced disruption of reversible aggregates or clusters in a concentrated suspension is investigated by ultrasound backscattering in the low shear regime. Fractal aggregates are considered as non-Brownian scatterers much smaller than the wavelength with acoustic properties close to those of the surrounding liquid, so that the attenuation of the coherent field is weak and multiple scattering can be neglected, The concept of variance in local particle volume fraction is used to deduce a first-order expression of the ultrasound scattering cross section per unit volume for Rayleigh scatterers in a dense suspension. On the basis of a scaling law for the shear-induced disruption of aggregates, the shear stress dependence of the ultrasonic scattered intensity from a dense suspension of clusters is derived. In a second part, the shear breakup of hardened red blood cell aggregates is investigated in plane-plane flow geometry by ultrasound scattering. Rheo-acoustical experiments are analyzed within the framework of the self-consistent field approximation and the scaling laws currently used in microrheological models. Finally, the ability of ultrasonic, light reflectometry and viscometry methods to provide quantitative information about red blood cell aggregation and membrane adhesiveness is discussed. (C) 2000 Acoustical Society of America. [S0001-4966(00)01203-0].

关键词：声学红细胞/诊断显像红细胞/生理学模型生物学体积描记术阻抗/方法超声学超声检查人类

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E2F4 is essential for normal erythrocyte maturation and neonatal viability

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MOLECULAR CELL 2000年第2期6卷 281-291页

作者： Humbert, PO Rogers, C Ganiatsas, S Landsberg, RL Trimarchi, JM Dandapani, S Brugnara, C Erdman, S Schrenzel, M Bronson, RT Lees, JA MIT Dept Biol Cambridge MA 02139 USA MIT Div Comparat Med Cambridge MA 02139 USA Childrens Hosp Dept Hematol Oncol Boston MA 02115 USA Childrens Hosp Dept Lab Med Boston MA 02115 USA Tufts Univ Sch Med Dept Pathol Boston MA 02111 USA Tufts Univ Sch Vet Med Dept Pathol Boston MA 02111 USA

The retinoblastoma protein (pRB) plays a key role in the control of normal development and proliferation through the regulation of the E2F transcription factors. We generated a mutant mouse model to assess the in vivo role of the predominant E2F family member, E2F4. Remarkably, loss of E2F4 had no detectable effect on either cell cycle arrest or proliferation. However, E2F4 was essential for normal development. E2f4(-/-) mice died of an increased susceptibility to opportunistic infections that appeared to result from craniofacial defects. They also displayed a variety of erythroid abnormalities that arose from a cell autonomous defect in late stage maturation. This suggests that E2F4 makes a major contribution to the control of erythrocyte development by the pRB tumor suppresser.

关键词：动物新生细胞周期细胞分裂颅面骨畸形/遗传学 DNA结合蛋白质类/缺乏 DNA结合蛋白质类/遗传学 DNA结合蛋白质类/代谢疾病易感性 E2F4转录因子胚胎和胎儿发育/遗传学红细胞/生理学胎儿生长迟缓/遗传学小鼠基因敲除机会致病菌感染/遗传学重组蛋白质类/代谢转录因子/缺乏转录因子/遗传学转录因子/代谢动物小鼠

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Red blood cell substitutes: Evolution of approaches to demonstrating efficacy

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ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY 1999年第1期27卷 1-9页

作者： Fratantoni, JC CL McIntosh & Associates Rockville MD 20852 USA

There has been a striking advancement in our understanding of red cell substitutes over the past decade. Throughout this period, regulatory oversight influenced many aspects of product development. The approach to demonstrating efficacy was an important example. I will review some events of the decade so that we may consider the question, "If we had it to do over again could we do any better?" At the start of the decade, there were sufficient data on the mechanism of hemoglobin-induced renal toxicity to reach consensus among investigators that the content of alpha beta-dimers in any hemoglobin product must be strictly limited. An array of additional, unexpected reactions were seen in early clinical studies, reactions that led to several conclusions: hemoglobin is a pharmacologically active material;more basic studies are needed;and it would all be so much easier if communications between investigators were open and unhindered. Meaningful studies of efficacy could not be approached until the safety issues had been solved or until the community was convinced that they were not serious. The initial approach was based on the meager experience gained with previous products, e.g., Fluosol. That experience led to policies which required that, for example, if the product was to be used as a red cell substitute, it must be compared with red cells, and if it was to be used as an oxygen carrier, it must be shown to support organ function. Endpoints of clinical trials were based on delivery of a clear clinical benefit to the patient - surrogate endpoints could be used only if their relationship to clinical benefit had been demonstrated. Now, as we approach the end of the decade, it is time to ask whether progress would have been greater had policies regarding demonstration of efficacy been different. That question will be approached with specific examples and consideration of the possible outcomes.

关键词：生物转运血液代用品/药理学红细胞/生理学军事医学氧/代谢美国美国食品和药物管理局人类

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Effects of sialic acid substitutions on recognition by Sambucus nigra agglutinin and Maackia amurensis hemagglutinin

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ANALYTICAL BIOCHEMISTRY 2002年第1期303卷 98-104页

作者： Brinkman-Van der Linden, ECM Sonnenburg, JL Varki, A Univ Calif San Diego Dept Med Glycobiol Res & Training Ctr La Jolla CA 92093 USA Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA

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MONOCYTE-INDUCED INCREASE IN OSMOTIC FRAGILITY OF HUMAN RED-CELLS SENSITIZED WITH ANTI-D ALLOANTIBODIES

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BRITISH JOURNAL OF HAEMATOLOGY 1978年第3期40卷 439-446页

作者： FLEER, A KOOPMAN, MG VONDEMBORNE, AEGK ENGELFRIET, CP NETHERLANDS RED CROSS BLOOD TRANSFUS SERVDEPT IMMUNOHAEMATOLCENT LAB POB 9190 AMSTERDAM NETHERLANDS UNIV AMSTERDAM CLIN & EXPTL IMMUNOL LAB AMSTERDAM 1004 NETHERLANDS

The mechanism by which human monocytes increase the osmotic fragility of red cells sensitized with Rh anti-D alloantibodies was studied in vitro. The increase in osmotic fragility and the lysis of red cells by monocytes were enhanced by cytochalasin B and inhibited by hydrocortisone. These effects were similar to the effects of these agents on lysosomal enzyme release by monocytes. Hydrocortisone was completely ineffective when added 1 h after mixing monocytes and sensitized red cells. The damage responsible for the fragility increase and lysis may be completed within 1 h and may be due to lysosomal enzymes released by the monocytes. Since for the full expression of the osmotic fragility increase and lysis an incubation time much longer than I h is required, the latter phenomena apparently are the non-specific sequelae of damage inflicted on the red cell by released lysosomal enzymes.

关键词：细胞松弛素B/药理学红细胞/免疫学红细胞/生理学溶血/药物作用氢化可的松/药理学同种抗体单核细胞/免疫学渗透脆性/药物作用 Rh-Hr血型系统时间因素人类

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The oxyhemoglobin reaction of nitric oxide

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1999年第16期96卷 9027-9032页

作者： Gow, AJ Luchsinger, BP Pawloski, JR Singel, DJ Stamler, JS Duke Univ Med Ctr Howard Hughes Med Inst Durham NC 27710 USA Duke Univ Med Ctr Dept Med Durham NC 27710 USA Montana State Univ Dept Chem & Biochem Bozeman MT 59717 USA Duke Univ Dept Cell Biol Durham NC 27710 USA

The oxidation of nitric oxide (NO) to nitrate by oxyhemoglobin is a fundamental reaction that shapes our understanding of NO biology. This reaction is considered to be the major pathway for NO elimination from the body;it is the basis for a prevalent NO assay;it is a critical feature in the modeling of NO diffusion in the circulatory system;and it informs a variety of therapeutic applications, including NO-inhalation therapy and blood substitute design. Here we show that, under physiological conditions, this reaction is of little significance. Instead, NO preferentially binds to the minor population of the hemoglobin's vacant hemes in a cooperative manner, nitrosylates hemoglobin thiols, or reacts with liberated superoxide in solution. In the red blood cell, superoxide dismutase eliminates superoxide, increasing the yield of S-nitrosohemoglobin and nitrosylated hemes, Hemoglobin thus serves to regulate the chemistry of NO and maintain it in a bioactive state. These results represent a reversal of the conventional view of hemoglobin in NO biology and motivate a reconsideration of fundamental issues in NO biochemistry and therapy.

关键词：电子自旋共振谱学红细胞/生理学动力学模型化学一氧化氮/化学一氧化氮/代谢氧合血红蛋白/化学氧合血红蛋白/代谢分光光度法超氧化物类/血液人类

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Hemoglobin switching in unicellular erythroid culture of sibling erythroid burst-forming units: kit ligand induces a dose-dependent fetal hemoglobin reactivation potentiated by sodium butyrate

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BLOOD 2000年第11期95卷 3555-3561页

作者： Gabbianelli, M Testa, U Massa, A Pelosi, E Sposi, NM Riccioni, R Luchetti, L Peschle, C Thomas Jefferson Univ Kimmel Canc Ctr Philadelphia PA 19107 USA Ist Super Sanita Dept Hematol & Oncol I-00161 Rome Italy

Mechanisms underlying fetal hemoglobin (HbF) reactivation In adult life have not been elucidated;particularly, the role of growth factors (GFs) is controversial. Interestingly, histone deacetylase (HD) inhibitors (sodium butyrate, NaB, trichostatin A, TSA) reactivate HbF. We developed a novel model system to investigate HbF reactivation: (1) single hematopoietic progenitor cells (HPCs) were seeded in serum-free unilineage erythroid culture;(2) the 4 daughter cells (erythroid burst-forming units, [BFU-Es]), endowed with equivalent proliferation/differentiation and HbF synthesis potential, were seeded in 4 unicellular erythroid cultures differentially treated with graded dosages of GFs and/or HD inhibitors;and (3) HbF levels were evaluated in terminal erythroblasts by assay of F cells and gamma-globin content (control levels, 2.4% and 1,8%, respectively, were close to physiologic values). HbF was moderately enhanced by interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor treatment (up to 5%-8% gamma-globin content), while sharply reactivated in a dose-dependent fashion by c-kit ligand (KL) and NaB (20%-23%). The stimulatory effects of KL on HbF production and erythroid cell proliferation were strictly correlated. A striking increase of HbF was induced by combined addition of KL and NaB or TSA (40%-43%), This positive interaction is seemingly mediated via different mechanisms: NaB and TSA may modify the chromatin structure of the beta-globin gene cluster;KL may activate the gamma-globin promoter via up-modulation of tal-1 and possibly FLKF transcription factors. These studies indicate that KL plays a key role in HbF reactivation in adult life, furthermore, combined KL and NaB administration may be considered for sickle cell anemia and beta-thalassemia therapy. (Blood. 2000;95:3555-3561) (C) 2000 by The American Society of Hematology.

关键词：丁酸盐类/药理学细胞培养技术/方法细胞分化/药物作用细胞培养的红细胞/细胞学红细胞/药物作用红细胞/生理学红细胞生成素重组/药理学胎儿血红蛋白/生物合成基因开关珠蛋白类/生物合成粒细胞巨噬细胞集落刺激因子/药理学造血干细胞/细胞学造血干细胞/药物作用造血干细胞/生理学血红蛋白A/生物合成白细胞介素3/药理学重组蛋白质类/药理学干细胞因子/药理学成年人人类男(雄)性

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Acoustic measurement of compressibility and thermal expansion coefficient of erythrocytes

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PHYSICS IN MEDICINE AND BIOLOGY 1999年第5期44卷 1277-1287页

作者： Toubal, M Asmani, M Radziszewski, E Nongaillard, B Univ Valenciennes & Hainaut Cambresis Dept OAE IEMN CNRSUMR 9929 F-59304 Valenciennes France

Mechanical properties of human erythrocytes, namely adiabatic compressibility and thermal expansion coefficient, have been determined using a classical ultrasound velocity and attenuation burst transmission technique. The theoretical model concerns the corpuscular part of the elastic wave propagating in a suspension of viscous particles of small size compared with the wavelength. The thermal wave contribution was taken into account. Normal and stiffened red blood cells were suspended in saline of different NaCl concentration.

关键词：声学生物物理学现象生物物理学红细胞变形性/生理学红细胞/诊断显像红细胞/生理学模型生物学氯化钠溶液温度超声检查人类

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Welcome innovation in erythrocyte sedimentation testing

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AMERICAN JOURNAL OF CLINICAL PATHOLOGY 2002年第1期118卷 11-12页

作者： Koepke, JA Duke Univ Med Ctr Durham NC 27710 USA

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Pathogenesis of classical swine fever:: Renal haemorrhages and erythrodiapedesis

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JOURNAL OF COMPARATIVE PATHOLOGY 2000年第1期123卷 47-54页

作者： Gómez-Villamandos, JC Ruiz-Villamor, E Bautista, MJ Quezada, M Sánchez, CP Salguero, FJ Sierra, MA Univ Cardoba Fac Vet Dept Pathol Anat Cordoba 14014 Spain Univ Concepcion Dept Patol & Med Prevent Chillan Chile INIA Ctr Invest Sanidad Anim Madrid Spain

Thirty pigs were inoculated with a virulent isolate (Quillota strain) of classical swine fever (hog cholera) virus to establish the chronological occurrence of lesions in the kidney and to determine the mechanism responsible for renal haemorrhages. The study included the use of histopathological, ultrastructural, immunohistochemical (detection of viral antigen gp55, MAC387, lambda chains, CD3 and Clq) and morphometrical techniques (vascular area). Renal interstitial oedema and haemorrhages were detected from 7 da's post-inoculation (dpi), associated with a slight interstitial mononuclear infiltrate and evidence of viral infection in macrophages and fibroblasts, and in a small proportion of lymphocytes. Viral infection was not detected in capillary endothelial cells. An intense mononuclear infiltrate, with B cells, T cells and small numbers of macrophages, was detected from 10 dpi. In the final phase of the experiment (14 dpi, slight proliferation and degranulation of mast cells were observed. Increased expression of the Clq component of complement was also detected. A significant increase in vascular area was observed from 7 dpi. These results suggest that haemorrhages observed in the kidneys of pigs inoculated with the Quillota strain resulted from erythrodiapedesis and increased vascular permeability, probably aggravated by mast cell degranulation in the final stage of the experiment. The results suggested that mast cell degranulation was linked to activation of the complement system. (C) 2000 Harcourt Publishers Ltd.

关键词：抗原病毒/分析生物学标记/分析毛细血管/代谢毛细血管/超微结构毛细血管/病毒学毛细血管脆性/生理学毛细血管通透性/生理学细胞脱颗粒/生理学细胞运动/生理学猪瘟/病因学猪瘟/免疫学猪瘟/病理学猪瘟病毒/免疫学胞质小泡/生理学胞质小泡/超微结构水肿/病因学水肿/病理学内皮血管/代谢内皮血管/超微结构内皮血管/病毒学红细胞/细胞学红细胞/生理学出血/病因学出血/病理学肾疾病/病因学肾疾病/病理学肥大细胞/生理学肥大细胞/超微结构猪动物女(雌)性男(雄)性

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