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41.
In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis. 相似文献
42.
The in vitro production of factor VII-like material and of tissue factor activity by murine thioglycollate exudate macrophages was measured by amidolytic assays. Tissue factor activity was inducible by endotoxin, and its induction was inhibited by 1 microgram/mL of actinomycin D, 10 micrograms/mL of cycloheximide, and 0.2 micrograms/mL of tunicamycin. Soluble factor VII-like material was secreted by macrophages into culture supernatants. The amount produced was not influenced by further activation of the cells by endotoxin, nor was its production inhibited significantly by 1 microgram/mL actinomycin D or 0.2 micrograms/mL tunicamycin. The production of the factor VII-like material was inhibited by 10 micrograms/mL of cycloheximide, and its appearance in culture supernatants was enhanced significantly by the addition of vitamin K1. When lysates of activated macrophages were suspended in ultracentrifuged culture supernatants, a particulate factor X activator was formed. Centrifugation at 100,000 g pelleted the factor X activator and left no factor VII-like material in the supernatant. The data indicate that thioglycollate-induced exudate macrophages make and excrete factor VII-like material, and this production is not modulated by further activation. However, activation of the macrophages induces tissue factor production. The factor X activator appears to result from the interaction and complexing of the soluble factor VII-like material and the membrane-bound tissue factor. 相似文献
43.
Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans 总被引:3,自引:0,他引:3
Granowitz EV; Porat R; Mier JW; Orencole SF; Callahan MV; Cannon JG; Lynch EA; Ye K; Poutsiaka DD; Vannier E 《Blood》1993,82(10):2985-2990
Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra. 相似文献
44.
BACKGROUND AND OBJECTIVES: Currently, plasma fractionation involves multiple processing steps using established methods such as ethanol precipitation and column chromatography. The known limitations associated with conventional purification techniques, combined with strict regulations on safety and high demand for particular plasma proteins, have resulted in a shortage of plasma-derived therapeutics such as intravenous immunoglobulin G (IgG). MATERIALS AND METHODS: In this study, IgG was purified from human plasma using Gradiflow technology, an electrophoresis-based separation technology. RESULTS: IgG was isolated from plasma to high purity, with 94 +/- 5% recovery in a short processing time. CONCLUSIONS: The technology has been shown to be linearly scalable and has the capacity to contribute to increased production of important plasma fraction therapeutics. 相似文献
45.
A high frequency of nonhemolytic hereditary ovalocytosis in Malayan aborigines is thought to result from reduced susceptibility of affected individuals to malaria. Indeed, Kidson et al. recently showed that ovalocytes from Melanesians in Papua New Guinea are resistant to infection in culture by the malarial parasite Plasmodium falciparum. In order to determine if protection against parasitic invasion in these ovalocytes might be the result of some altered membrane material property in these unusual cells, we measured their membrane and cellular deformability characteristics using an ektacytometer . Ovalocytic red cells were found to be much less deformable in comparison to normal discoid red cells. Similar measurements on isolated membrane preparations revealed a marked reduction in ovalocytic membrane deformability. To produce equal deformation of ovalocytic and normal membranes, ovalocytes required an 8-10-fold increase in applied shear stress, indicating that their membrane was capable of deforming under sufficient stress. To test the possibility that this increased membrane rigidity might confer resistance to parasitic invasion, we performed an in vitro invasion assay using Plasmodium falciparum merozoites and Malayan ovalocytes of varying deformability from seven different donors. The level of infection of the ovalocytes ranged from 1% to 35% of that in control cells, and the extent of inhibition appeared to be closely related to the reduction in membrane deformability. Moreover, we were able to induce similar resistance to parasitic invasion in nonovalocytic normal red cells by increasing their membrane rigidity with graded exposure to a protein crosslinking agent. Our findings suggest that resistance to parasite invasion of Malayan ovalocytes is the result of a genetic mutation that causes increased membrane rigidity. 相似文献
46.
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48.
Jasper G Gerbers Martin Stevens Joris JW Ploegmakers Sjoerd K Bulstra Paul C Jutte 《Acta orthopaedica》2014,85(6):663-669
Background and purpose —
In orthopedic oncology, computer-assisted surgery (CAS) can be considered an alternative to fluoroscopy and direct measurement for orientation, planning, and margin control. However, only small case series reporting specific applications have been published. We therefore describe possible applications of CAS and report preliminary results in 130 procedures.Patients and methods —
We conducted a retrospective cohort study of all oncological CAS procedures in a single institution from November 2006 to March 2013. Mean follow-up time was 32 months. We categorized and analyzed 130 procedures for clinical parameters. The categories were image-based intralesional treatment, image-based resection, image-based resection and reconstruction, and imageless resection and reconstruction.Results —
Application to intralesional treatment showed 1 inadequate curettage and 1 (other) recurrence in 63 cases. Image-based resections in 42 cases showed 40 R0 margins; 16 in 17 pelvic resections. Image-based reconstruction facilitated graft creation with a mean reconstruction accuracy of 0.9 mm in one case. Imageless CAS was helpful in resection planning and length- and joint line reconstruction for tumor prostheses.Interpretation —
CAS is a promising new development. Preliminary results show a high number of R0 resections and low short-term recurrence rates for curettage.Oncological surgical treatment can be considered to be a trade-off between margins and function, with margins being the most important factor to consider. Accuracy is needed to achieve an efficient but oncologically safe result. To assist in this, most procedures in bone tumor surgery require intraoperative imaging with fluoroscopy and/or measurements with rulers for anatomical orientation and margin control. The best examples of this are pelvic resections. Cartiaux et al. (2008) demonstrated that 4 experienced surgeons could achieve a 10-mm resection margin, with 5-mm tolerance, on pelvic sawbones in only half of the resections. The supportive imaging and measuring modalities have, however, remained more or less unchanged for many years. In a 2-dimensional (2D) workflow such as fluoroscopy, there is still the requirement for an accurate frame of reference based on anatomical landmarks for adequate 3-dimensional (3D) margin control.In recent years, the use of computer-assisted surgery (CAS) in orthopedic surgery has become more common as an alternative for intraoperative imaging and measurements, providing the necessary precision in bone tumor surgery. The technique that is mostly used in orthopedic oncology is image-based navigation. The patient’s own anatomy (MRI and/or CT) is entered into the system and used during surgery. This provides real-time, continuous, 3D imaging feedback and may lead to more precise margin control, better tissue preservation, and new approaches to reconstruction while remaining oncologically safe. Several publications have supported CAS as being a safe navigation platform for planning and performing resections (Wong et al. 2007, So et al. 2010, Cho et al. 2012). A recent publication describes lessons in the technological approach and offers comments on CAS workflow (Wong 2010). However, to date the largest case series have involved only 20 and 31 cases (Cheong and Letson 2011, Jeys et al. 2013). The reported use has mostly been limited to complex tumor resections (e.g. pelvic), and due to the novelty of the technique, applications, approaches, and set-up times differ greatly (Saidi 2012). Here we describe possible applications of CAS in bone tumor surgery (also outside of complex resections), consider their usefulness, and report preliminary results from 130 CAS procedures performed at a single institution. 相似文献49.
Francisella tularensis is a gram-negative facultative intracellular pathogen and the causative agent of tularemia. Little is known about the immunopathogenesis of oral infection with this pathogen. Here, for the first time, we examined the susceptibility of mice to intragastric inoculation with virulent type A F. tularensis and characterized the course of infection and the associated host responses. Both immunocompetent and immunodeficient mice were relatively susceptible to intragastric inoculation of type A F. tularensis with a 50% lethal dose (LD(50)) of 10(6) organisms, which was 100,000-fold higher than the LD(100) for intradermal or respiratory routes of infection. Mice deficient in gamma interferon or tumor necrosis factor receptors 1 and 2 were more susceptible than wild-type controls to oral infection with a high dose of the pathogen. After oral inoculation, F. tularensis appeared first in the mesenteric lymph nodes (MLN) and then rapidly spread to the livers and spleens, where the organism multiplied to high numbers and induced marked neutrophilic infiltration and severe tissue necrosis. Infected mice showed rapid increases in tissue cytokine mRNA expression, which peaked in the MLN at 2 days postinfection (dpi) and in the liver and spleen at 3 dpi. The levels of gamma interferon, interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha, macrophage inflammatory protein 1alpha, KC, interferon-inducible protein 10, and monocyte chemotactic protein 1 were elevated from day 2 postinoculation onward. Moreover, mice intradermally immunized with the live vaccine strain of F. tularensis showed little survival advantage over naive mice after oral challenge with type A F. tularensis. These results suggest that type A F. tularensis is an effective oral pathogen that can cause fatal systemic infection and could pose a public health concern, particularly to immunocompromised individuals, if ingested in contaminated water and food. 相似文献
50.
目的:在前期微囊化基因工程细胞制备平台的基础上,构建分泌型人肿瘤坏死因子α的真核表达载体PSNAV2.0-TNFα重组质粒,并鉴定其蛋白的体外瞬时表达,为进一步利用该基因进行微囊化细胞移植治疗和改善疾病奠定基础。方法:实验于2006-06/2007-05在解放军总医院老年医学研究所细胞生物学实验室完成。①以含有人肿瘤坏死因子αcDNA序列的质粒为模板,通过PCR扩增获得人肿瘤坏死因子α基因片段;将其定向插入真核表达载体PSNAV2.0中,获得重组质粒PSNAV2.0-TNFα。采用SalⅠ和EcoRⅠ双酶切法、PCR法及插入片段序列测定法鉴定该质粒。②利用阳离子脂质体介导法,将其转染到人胚胎肾细胞HEK-293细胞中,构建可持续分泌人肿瘤坏死因子α的基因工程细胞,采用RT-PCR法和Western blot法检测转染细胞培养上清液中人肿瘤坏死因子蛋白的体外瞬时表达。结果:①通过SalⅠ和EcoRⅠ双酶切、PCR及测序鉴定证明:在HEK-293中插入片段正确。②采用RT-PCR和Western blot法检测表明HEK-293细胞培养上清中有人肿瘤坏死因子α蛋白,Mr17000。结论:成功构建了重组质粒PSNAV2.0-TNFα真核表达载体,转染HEK-293细胞后可有效分泌人肿瘤坏死因子α蛋白,并能分泌到细胞外。 相似文献