硫酸葡聚糖伍用G-CSF对小鼠外周血造血干细胞动员作用研究

研究了硫酸葡聚糖(DS)和粒细胞集落刺激因子(G-CSF)单独应用及联合应用对小鼠外周血造血祖细胞的动员作用。联合用药方式为小鼠连续5天静脉注射G-CSF10μg/d,第5天腹腔注射DS15mg/k 体重,DS给药后2小时检测外周血白细胞,单个核细胞和CFU-GM,结果发现应用DS和G-CSF及二者联合用药后,外周血白细胞比给药前分别增高了2.5,1.8和2.8倍,外周血单个核细胞比给药前分别增高了1.9,1.7和2.5倍。DS与G-CSF联合用药,可以使粒系祖细胞数量分别高于单独使用DS和G-CSF组的53.4％和15.3％,统计学处理有显著性意义(P<0.05)。结论提示,DS与G-CSF联合应用对外周血造血祖细胞的动员产生了协同作用,其机制可能在于二者动员的途径不同。     

造血干细胞动员剂硫酸葡聚糖的毒性及其与含硫量的关系

本文研究了硫酸葡聚糖(DS)的不同含硫量与过敏反应的关系,初步找到了一个可供人体静脉注射用的DS含硫量的范围。DS的分子量在10000以下,这个范围大约为10.6％～11.8％(以进口的葡聚糖为原料)和12.0％～13.0％(以国产葡聚糖为原料)。初步探讨了影响小鼠外周血白细胞变化的某些因素,为DS作为造血干细胞动员剂用于临床展现了良好的前景。     

丹参素对小鼠外周血造血干细胞动员作用的研究

目的:探讨丹参素对小鼠外周血造血干细胞的动员作用及其对小鼠外周血细胞和骨髓基质细胞黏附分子的影响。方法:30只BALB/c小鼠随机分为三组:丹参素组、G-CSF组、生理盐水组,腹腔注射d1～d7,每日1次,第2～8天,采用外周血WBC和MNC计数、流式细胞术、造血祖细胞体外培养、免疫细胞化学等检测各组给药后对外周血WBC、MNC、CD34+细胞、CD49d阳性细胞、CFU-GM、CFU-MK、CFU-E的产率及小鼠骨髓基质细胞VCAM-1阳性细胞百分率的影响。结果:丹参素组给药第7天外周血WBC、MNC数量达到高峰,分别为给药前的3倍和3.5倍;丹参素组外周血CD34+、CD49d阳性细胞及骨髓基质细胞VCAM-1阳性细胞百分率分别为(1.03±0.24)%、(12.59±2.64)%和(50.86±8.77)%,均明显高于生理盐水组(P<0.05);其CFU-GM、CFU-MK和CFU-E产率分别为(14.90±2.88)%、(12.50±4.06)%和(16.10±6.36)%,均明显高于生理盐水组(P<0.01)。结论:丹参素对小鼠外周血造血干细胞有一定的动员作用,且这一作用可能与其上调小鼠外周血细胞和骨髓基质细胞黏附分子的表达有关。     

异基因外周血干细胞的动员与衡量

目的 :探讨异基因外周血干细胞移植的动员及阈剂量。方法 :重组粒细胞集落刺激因子动员 HL A配型相合的同胞供者 ,动员前后检测外周血及采集物中的单个核细胞、CD34 细胞及幼粒细胞。结果 :6例造血功能恢复迅速 , 12～ 14 d WBC≥ 1× 10 9/L , 9～ 2 4 d PL T≥ 2 0× 10 9/L ,染色体分析或血型检测证实为供者型。结论 :重组粒细胞集落刺激因子 7～ 10μg/(kg· d)连用 5 .5～ 6 d,适合临床常规使用。幼粒细胞≥ 1.38× 10 8/kg,单个核细胞≥ 6 .0 7× 10 8/kg联合应用可作为阈剂量。     

趋化因子及其受体对造血细胞调控作用的研究进展

细胞的增殖分化受正负信号的调控 ,造血细胞也有增殖、分化和生长抑制的调节机制。近年来的研究发现 ,一些参与炎症及免疫反应的趋化因子是造血负调控因子的主要成员。现介绍一些对造血干细胞或祖细胞增殖具有抑制作用的趋化因子及其受体对造血细胞的调节作用。1　趋化因子的分类及其受体趋化因子超家族的成员多为相对分子质量 80 0 0～12 0 0 0的小分子蛋白 ,主要由白细胞分泌 ,能引起粒细胞、单核巨噬细胞及淋巴细胞的定向迁移 ,并对这些细胞的活化、功能的发挥及淋巴细胞再循环、组织定位和免疫应答等有重要作用。近年来趋化因子及其受体…     

G-CSF和DS动员干细胞作用与不同来源干细胞移植的比较

以近交系BALB/c小鼠为实验对象,分别观察了粒细胞集落刺激因子(G-CSF)和硫酸葡聚糖(DS)对外周血干细胞的动员作用。结果显示,经每天用G-CSF10μg/kg,共5天,小鼠外周血中有核细胞数及CFU-GM,BFU-E均见升高;分别为16.3±7.6×10~9/L,20.41±6.71/10~5MNC,15.14±3.27/10~5MNC;DS120mg/kg1次静脉注射后3小时分别为14.9±3.4×10~9/L,14.06±4.26/10~5MNC,12.37±5.63/10~5MNC。另外以致死剂量(8Gy)照射的小鼠作为造血功能衰竭模型,以雌性为受体,雄性为供体,分别观察了骨髓干细胞(BMSC1×10~8/kg),单纯外周血干细胞(PBSC2×10~9/kg),以及两者混合移植(BMSC0.5×10~8/kg PBSC1×10~9/kg)后造血重建过程。结果表明,对照组小鼠在8—10天相继死亡,而其它各组有1—2只死亡。移植后8天时,PBSCT及BMSCT PBSCT组外周血WBC计数均≥0.5×10~9/L,而单纯骨髓组仍<0.5×10~9/L。移植后12天骨髓移植组中CFU-GM,BFU-E亦较其它两组低(P<0.05)。实验证实G-CSF和DS均有动员外周血干细胞的作用,并且外周血干细胞及联合移植组造血重建较单纯骨髓组迅速。为证实植入,移植后10周对受体进行了染色体C带显色法检测嵌合体,确定有供者的细胞存在(含有Y染色体)。在实验中首次提出“等量移植”即各组所输CFU-GM数必须相等,使各组结果更具     

外周血干细胞的动员和采集及移植后造血重建研究

对２４例外周血干细胞（ＰＢＳＣ）移植的三种动员方案、采集及移植后的ＰＢＳＣ数量与造血重建关系进行研究。２４例中急性白血病１３例，多发性骨髓瘤６例，非霍奇金淋巴瘤４例，晚期乳癌１例。三组动员方案：化疗＋四氢叶酸＋氟美松；化疗＋ｒｈＧＭ－ＣＳＦ＋氟美松；化疗＋ｒｈＧ－ＣＳＦ＋氟美松。用流式细胞仪双染色直接免疫荧光法测定ｒｈＧ－ＣＳＦ组中９例ＣＤ３４＋ＣＤ３３＋细胞。结果表明：ｒｈＧ－ＣＳＦ组ＰＢＳＣ产率最高，平均每例单个核细胞（９．８６±６．０１）×１０８／ｋｇ，ＣＦＵ－ＧＭ（２１．０８±１６．８６）×１０４／ｋｇ，ＣＤ３４＋细胞数与ＣＦＵ－ＧＭ正相关（ｒ＝０．６８）。动员后再用ｒｈＧ－ＣＳＦ１周，ＣＤ３４＋细胞显著增多，可连续每日采集，当≥５×１０６／ｋｇ即可停止；采集与回输的ＰＢＳＣ数与造血重建时间密切相关。     

丹参素、川芎嗪对小鼠外周血造血干细胞动员作用的研究

目的探讨丹参素、川芎嗪对小鼠外周血造血干细胞的动员作用及其对小鼠外周血细胞和骨髓基质细胞粘附分子的影响。方法40只BALB／c小鼠，随机分为4组：丹参素组[300mg／（kg·d）]、川芎嗪组E50mg／（kg·d）]、rhG-CSF组[250μg／（kg·d）]、生理盐水组，腹腔注射d1～7，1次／d，第8天，采用外周血WBC、MNC计数、流式细胞术、造血祖细胞体外培养、免疫细胞化学等检测各组给药后对外周血WBC、MNC、CD34^＋细胞、CD49d阳性胞、CFU-GM、CFU-MK、CFU-E的产率及小鼠骨髓基质细胞VCAM-1阳性细胞百分率的影响。结果丹参素组给药第7天外周血WBC、MNC数量达到高峰，分别为给药前的3倍和3．4倍；丹参素组外周血CD34^＋、CD49d阳性细胞及骨髓基质细胞VCAM-1阳性细胞百分率分别为（1．03±0．24）％、（12．59±2．64）％和（50．86±8．77）％，均明显高于生理盐水组（P〈0．05）；其CFU-GM、CFU-MK和CFU-E产率分别为（14．90±2．88）％、（12．50±4．06）％和（16．10±6．36）％，均明显高于生理盐水组（P〈0．01）；川芎嗪组给药第7天外周血WBC、MNC数量达到高峰，分别为给药前的3．2倍和3．9倍；川芎嗪组外周血CD34^＋、CD49d阳性细胞及骨髓基质细胞VCAM-1阳性细胞百分率分别为（O．86±0．42）％、（12．91±2．84）％和（48．47±7．87）％，均明显高于生理盐水组（P〈0．05）；川芎嗪组CFU-GM、CFU-MK和CFU-E产率分别为（53．10±9．63）％、（20．40±5．36）％和624．50±5．35）％，均明显高于生理盐水组（P〈0．01）。结论丹参素、川芎嗪对小鼠外周血造血干细胞有一定的动员作用，且这一作用可能与其上调小鼠外周血细胞和骨髓基质细胞粘附分子的表达有关。     

低频超声波对人外周血造血干细胞作用的研究

目的观察低频超声波对人外周血造血干细胞的作用。方法正常人经外周血动员后Baxter CS-3000血细胞分离机采取外周血造血干细胞，分成照射组和对照组。分别于照射后6h，24h，48h用台盼蓝拒染法检测细胞存活率，流式细胞仪检测细胞凋亡，瑞氏染色光镜下观察细胞照射后有无出现凋亡，透射电镜观察照射后细胞的超微结构。结果台盼蓝拒染法结果为不同照射强度和不同照射时间组之间数值差异不显著；流式细胞仪未检测到明显凋亡；瑞氏染色光镜下未观察到细胞凋亡；透射电镜观察结果为照射后细胞的超微结构无明显改变。结论低频低强度超声波对人外周血造血干细胞的生长无明显影响。     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

Prospects for the control of neglected tropical diseases by mass drug administration

The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In spite of this and other striking successes, mass drug administration programs are faced with major challenges resulting from suboptimal coverage and lack of efficacy. At current suboptimal coverage rates, programs may need prolongation for an extended period, increasing costs and undermining sustainability. Community participation through health education and information appears to be crucial to improve coverage and to achieve sustainability. Implementation of complementary measures, such as vector control, improved hygiene and environmental sanitation, are important to further control transmission and to prevent re-emergence of the infection and, again, may only be achieved effectively through community-based initiatives. To reduce costs and to relieve pressure on the health system, combining neglected tropical disease programs in areas where diseases coexist and integration with existing control programs for malaria, tuberculosis and HIV/AIDS is advocated. The risk of developing drug resistance is of particular concern in view of the lack of alternative drugs, and reduced treatment efficacy due to emerging resistance is evident for the soil-transmitted helminths and onchocerciasis. Given the risk for the development of drug resistance and the need for a high degree of participation, close attention should be paid to the monitoring of the coverage and efficacy of the different program components.     

Bacterial meningitis: an update of new treatment options

The outcome of bacterial meningitis critically depends on the rapid initiation of bactericidal antibiotic therapy and adequate management of septic shock. In community-acquired meningitis, the choice of an optimum initial empirical antibiotic regimen depends on the regional resistance patterns. Pathogens resistant to antibacterials prevail in nosocomial bacterial meningitis. Dexamethasone is recommended as adjunctive therapy for community-acquired meningitis in developed countries. In comatose patients, aggressive measures to lower intracranial pressure <20 mmHg (in particular, external ventriculostomy, osmotherapy and temporary hyperventilation) were effective in a case–control study. Although many experimental approaches were protective in animal models, none of them has been proven effective in patients. Antibiotics, which are bactericidal but do not lyse bacteria, and inhibitors of matrix metalloproteinases or complement factor C5 appear the most promising therapeutic options. At present, vaccination is the most efficient method to reduce disease burden. Palmitoylethanolamide appears promising to enhance the resistance of the brain to infections.     

Modified micro-superior percutaneously-assisted total hip: early experiences & case reports

Because of the extensile nature and familiarity of the standard posterior-lateral approach to the hip, a family of "micro-posterior" approaches has been developed. This family includes the Percutaneously-Assisted Total Hip (PATH) approach, the Supercapsular (SuperCap) approach and a newer hybrid approach, the Supercapsular Percutaneously-Assisted Total Hip (SuperPATH) approach. Such approaches should ideally provide a continuum for the surgeon: from a "micro" (external rotator sparing) posterior approach, to a "mini" (external rotator sacrificing) posterior approach, to a standard posterior approach. This could keep a surgeon within his comfort zone during the learning curve of the procedure, while leaving options for complicated reconstructions for the more practiced micro-posterior surgeons. This paper details one author's experiences utilizing this combined approach, as well as permutations of this entire micro-posterior family of approaches as applied to more complex hip reconstructions.     

Imaging choices in occult hip fracture

Background: Hip fracture is a common injury, with an incidence rate of > 250,000 per year in the United States. Diagnosis is particularly important due to the high dependence on the integrity of the hip in the daily life of most people. Objectives: In this article we review the literature focused on hip fracture detection and discuss advantages and limitations of each major imaging modality. Discussion: Plain radiographs are usually sufficient for diagnosis as they are at least 90% sensitive for hip fracture. However, in the 3–4% of Emergency Department (ED) patients having hip X-ray studies who harbor an occult hip fracture, the Emergency Physician must choose among several methods, each with intrinsic limitations, for further evaluation. These methods include computed tomography, scintigraphy, and magnetic resonance imaging. Conclusion: We present an evidence-based algorithm for the evaluation of a patient suspected to have an occult hip fracture in the ED. Also outlined are future directions for research to distinguish more effective techniques for identifying occult hip fractures.     

Structure and function of "metalloantibiotics"

Although most antibiotics do not need metal ions for their biological activities, there are a number of antibiotics that require metal ions to function properly, such as bleomycin (BLM), streptonigrin (SN), and bacitracin. The coordinated metal ions in these antibiotics play an important role in maintaining proper structure and/or function of these antibiotics. Removal of the metal ions from these antibiotics can cause changes in structure and/or function of these antibiotics. Similar to the case of "metalloproteins," these antibiotics are dubbed "metalloantibiotics" which are the title subjects of this review. Metalloantibiotics can interact with several different kinds of biomolecules, including DNA, RNA, proteins, receptors, and lipids, rendering their unique and specific bioactivities. In addition to the microbial-originated metalloantibiotics, many metalloantibiotic derivatives and metal complexes of synthetic ligands also show antibacterial, antiviral, and anti-neoplastic activities which are also briefly discussed to provide a broad sense of the term "metalloantibiotics."