靶向树突状细胞表面分子DEC-205长循环免疫脂质体稳定性模型的构建及其生物学特性

应用多相分散体系的动力稳定性和聚结稳定性理论,以薄膜分散法构建了靶向树突状细胞（dendritic cells,DCs）表面分子DEC-205长循环免疫脂质体（anti—DEC-205 iLPSM）的稳定性模型,并对其物理稳定性、生物学特性等进行了考察。结果表明经优化后的脂质体4℃贮存7d后粒径分布变化较小;FTTC-dextran累积泄漏率小于7％;耦联抗DEC-205的免疫脂质体（anti—DEC-205 iLPSM）可特异性地识别DCs,并作为良好载体将FITC-dextran带入DCs浆内。anti—DEC-205 iLPSM模型的构建为进一步研究抗原靶向DEC-205受体后的体内免疫应答情况提供了工作基础,有望开发一种新型DCs疫苗应用于临床。     

DEC-205单抗耦联长循环免疫脂质体的制备及其体外靶向

为使脂质体将所包封的药物或抗原高效地递呈给树突状细胞（dendritic cells,DCs）,诱导产生强烈的T细胞免疫应答或特异性免疫耐受,采用薄膜分散法制备了包裹FITC—dextran的纳米脂质体;用DSPE—PEG（2000）对脂质体膜进行修饰使之具有长循环功能;用异型双功能交联剂SPDP将抗小鼠DEC-205单克隆抗体耦联于脂质体表面使之具有主动靶向DCs的能力。稳定性实验表明脂质体在4℃贮存7d后粒径分布变化较小,FITC—dextran累积泄漏率小于7％;体外结合实验证明耦联抗DEC-205的免疫脂质体（anti—DEC-205 iLPSM）可特异性地识别DCs,并作为良好载体将FITC—dextran带入DCs浆内。成熟树突状细胞（mDC）与未成熟树突状细胞（iDC）均可高效摄取anti—DEC-205iLPSM,iDC摄取能力更强。anti-DEC-205iLPSM有望成为一种新型DC疫苗应用于临床。     

树突状细胞与肠道免疫

肠道黏膜免疫系统是肠道防御细菌和病毒感染的第一道防线,在维持肠道黏膜自稳方面发挥着重要的作用。肠道黏膜免疫系统持续不断的与来自外界的食物抗原和病原微生物及自身长期共存的肠道菌群相互作用,刺激机体对有害抗原产生免疫应答反应,诱导机体对无害抗原产生免疫耐受。树突状细胞（Dendritic cells,DCs）是目前已知的最强有力的一种专职抗原递呈细胞（Professional antigen presenting cells,APC）,     

树突状细胞与抗肿瘤免疫

提高免疫系统对肿瘤的杀伤能力是肿瘤免疫学上目的,随着对免疫肿瘤抗原的了解以及对T细胞免疫反应和肿瘤逃逸机制的进一步认识。方面军一目的已取得了进展,体内含量稀少的抗原递呈细胞-树突状细胞（DC8）是这些机制的关键。体外从外周血祖细胞诱导扩增这些细胞为肿瘤治疗开辟了新纪元。DC8作为肿瘤疫苗,在B细胞淋巴瘤、黑色素瘤、前列腺癌等病人身上已有了一定的疗效。     

树突状细胞与肿瘤免疫

树突状细胞（dendriticcells,Dcs）是目前已知的功能最强的抗原提呈细胞,具有调节免疫应答与诱导免疫耐受的能力。而树突状细胞所发挥的功能与其是否成熟有很大的关系,未成熟状态的树突状细胞具备致耐受性,而成熟状态的树突状细胞则对肿瘤免疫起着重要作用。该文将对DC的免疫学特性及Dc与肿瘤的关系予以综述。     

树突状细胞递呈抗原的分子机制

树突状细胞（ＤＣｓ）是重要的抗原递呈细胞,其参与免疫应答的机制十分复杂,首先要形成“三分子复合体”,加上ＤＣｓ表达的其他刺激因子和粘附分子等信号的传递才能完成。ＤＣｓ尚有一些其他功能,如表达ＩｇＥ受体或作为感觉受体等,其与其他非职业性ＡＰＣ有明显不同。     

树突状细胞在抗真菌感染免疫中的作用

近年来,随着广谱抗生素、抗肿瘤药物和免疫抑制剂等药物的广泛使用,免疫功能降低患者数量的增加,侵袭性真菌感染性疾病的发病率逐年升高。树突状细胞(Dendritic Cells,DCs)是已知功能最强的专职抗原提呈细胞,作为宿主固有免疫和适应性免疫的联系枢纽,DCs在病原微生物抗原的识别与呈递过程中发挥核心作用。研究证明,DCs可通过其细胞表面的多种受体有效识别病原真菌的抗原,并在诱导宿主免疫应答过程中发挥重要作用。本文将对树突状细胞分类及其在抗真菌感染免疫中的识别作用进行系统叙述。     

树突状细胞在抗感染免疫研究中的最新进展

树突状细胞(Dendritic cell,DC)是体内功能最强的抗原提呈细胞,也是介导机体固有免疫应答和适应性免疫应答的桥梁,其作用也越来越受到科研工作者的关注,而树突状细胞体外培养技术的发展成熟,为设计和发展DC依赖性疫苗提供了科学依据,也为感染性和肿瘤性疾病的预防和治疗展示了很好的应用前景。因此,对树突状细胞抗感染免疫方面研究的最新进展做一综述。     

树突状细胞的靶向抗肿瘤治疗进

树突状细胞(dendritic cell,DC)是目前已知体内最强的抗原提呈细胞(ARC),其在肿瘤免疫中具有重要的作用.DC的靶向抗肿瘤治疗成为当今肿瘤免疫治疗的研究热点.本文就DC的抗肿瘤机制、DC基因修饰策略及DC疫苗的临床治疗进展进行综述.     

Factors Affecting Activity and Stability of the Kluyveromyces lactis Killer Toxin

A number of physical parameters determining the activity and stability of the killer toxin produced by the yeast Kluyveromyces lactis have been investigated. The toxin was active over a relatively narrow pH range of 4.4 to 5.8, with a maximum at the lower end of the range. However, it was stable up to at least pH 8.0 but appeared to be irreversibly inactivated below pH 4.4. The toxin was stable at 40°C but rapidly inactivated at 50°C. Strong agitation caused the inactivation of the toxin in one medium but not another; this seemed to be due to oxygen-mediated disulfide bond formation, which could be prevented by sulfhydryl protecting agents.     

Surface Proteins of Gram-Positive Bacteria and Mechanisms of Their Targeting to the Cell Wall Envelope

The cell wall envelope of gram-positive bacteria is a macromolecular, exoskeletal organelle that is assembled and turned over at designated sites. The cell wall also functions as a surface organelle that allows gram-positive pathogens to interact with their environment, in particular the tissues of the infected host. All of these functions require that surface proteins and enzymes be properly targeted to the cell wall envelope. Two basic mechanisms, cell wall sorting and targeting, have been identified. Cell well sorting is the covalent attachment of surface proteins to the peptidoglycan via a C-terminal sorting signal that contains a consensus LPXTG sequence. More than 100 proteins that possess cell wall-sorting signals, including the M proteins of Streptococcus pyogenes, protein A of Staphylococcus aureus, and several internalins of Listeria monocytogenes, have been identified. Cell wall targeting involves the noncovalent attachment of proteins to the cell surface via specialized binding domains. Several of these wall-binding domains appear to interact with secondary wall polymers that are associated with the peptidoglycan, for example teichoic acids and polysaccharides. Proteins that are targeted to the cell surface include muralytic enzymes such as autolysins, lysostaphin, and phage lytic enzymes. Other examples for targeted proteins are the surface S-layer proteins of bacilli and clostridia, as well as virulence factors required for the pathogenesis of L. monocytogenes (internalin B) and Streptococcus pneumoniae (PspA) infections. In this review we describe the mechanisms for both sorting and targeting of proteins to the envelope of gram-positive bacteria and review the functions of known surface proteins.     

Factors Affecting the Activity and Stability of Alkaline Phosphatase in a Marine Pseudomonad

Conditions optimum for the assay of alkaline phosphatase of marine pseudomonad B-16 (ATCC 19855) and for maintaining the activity of the enzyme have been determined. The pH for optimal activity of the cell-bound enzyme was 9.0, whereas that for the enzyme after its release from the cells exceeded 9.4. Release was effected by first washing the cells in 0.5 M NaCl and then suspending them in 0.5 M sucrose. In the absence of salts, the activity of the cell-bound enzyme decreased rapidly at 25 C and less rapidly at 4 C. This loss of activity could be arrested but not restored by adding Mg(2+). In the presence of Na(+), activity of the cell-bound enzyme dropped to about 50% of that prevailing initially, but in this case adding Mg(2+) restored enzyme activity completely. The activity of the enzyme after its release from the cells into 0.5 M sucrose was approximately 50% of that of the equivalent amount of enzyme in the original cells. This activity was relatively stable at both 25 and 4 C. Adding Mg(2+) to the released enzyme restored its activity to that of the cell-bound form. The synthesis of alkaline phosphatase by the cells was not affected by adding 50 mM inorganic phosphate to the growth medium. The K(m) of the released enzyme for p-nitrophenyl phosphate was found to be 6.1 x 10(-5) M.     

Factors Affecting the Distribution and Stability of Unoccupied 1,25-Dihydroxyvitamin D3 Receptors

Abstract

Recently our laboratory reported that unoccupied 1,25(OH)₂D₃ receptors are found in the nuclei/chromatin fraction under low salt conditions in vitro (J. Biol. Chem. 255, 6799–6805, 1980). Additionally, various conditions exert differential effects on receptor solubilization and stability in vitro, potentially leading to confusion when these effects are not fully appreciated. In order to facilitate future studies, we have compiled a review of these factors and their effects. The conditions discussed include dilution, ionic strength (KCl and molybdate), protease inhibitors (Trasylol, PMSF and TPCK), temperature, ligand, glycerol, dithiothreitol, and EDTA.     

Factors Affecting the Stability and Performance of Ipratropium Bromide; Fenoterol Hydrobromide Pressurized-Metered Dose Inhalers

The aim of the study was to investigate the factors affecting the stability and performance of ipratropium bromide and fenoterol hydrobromide in a pressurized-metered dose inhaler (pMDI). A factorial design was applied to investigate the effects of three parameters (propellant, water, and ethanol) on the performance of 27 designed formulations of a solution-based pMDI. The formulations that contained a hydrofluoroalkane (HFA) propellant lower than 72% v/v and an ethanol concentration higher than 27% v/v remained as clear solutions. Nine formulations that contained the HFA propellant higher than 74% v/v precipitated. The results indicated that it was not only the HFA propellant content of the formulations that was related to the formulation instability but also ethanol content. Only six formulations from the 18 formulations, that did not precipitate, produced drug contents that were within the acceptable range (80–120%). These six formulations generated aerosols with mass median aerodynamic diameters (MMAD) of approximately 2 μm with a fine particle fraction (FPF; particle size, <6.4 μm) between 45% and 52%. The MMAD and FPF did not change significantly after 6 months of storage (P > 0.05).KEY WORDS: fenoterol hydrobromide, ipratropium bromide, pressurized metered dose inhaler, stability     

Factors Affecting Uptake of Radioactive Phosphorus by Leaves and its Translocation to other Parts of the Plant

The rate of uptake of ³²P from labelled NaH₂PO₄ solutions sprayedon to one leaf of swedes (Brassica napus) or French beans (Phaseolusvulgaris) was rapid during the first few hours and fell to zeroafter 4 days. ²²P was detected in the root after 3 hours andcontinued to move out of the treated leaf for at least 6 daysafter application. A larger fraction of the applied ³²P wasabsorbed from repeated than from a single spraying. Swedes absorbed more ³²P from a single application to the lowersurface than to the upper surface of the leaf. Doubling theconcentration of the spray caused a small increase in the percentageof applied ²²P that was absorbed. Absorption by French-beanleaves decreased slightly when the area sprayed with a constantamount of ³²P was doubled, and decreased with increasing ageof leaf. Increasing the phosphorus supply to the roots of swedesaffected neither the initial rate nor the total amount of ³²Puptake by the leaves but decreased the quantity of ³²P thatwas translocated out of the treated leaf. Increasing the relative humidity of the air around the plantsalso increased³²P uptake. Shading usually decreased uptake andalways decreased translocation. Rewetting the leaf to whichthe ³²P had been applied, with water or sucrose solution, hadvariable effects. The significance of the results is discussed.     

影响腐霉发酵培养中菌丝形态的因素及其与EPA含量的关系

研究了发酵培养中影响腐霉菌丝形态的因素及其与EPA（二十碳五烯酸）含量的关系．结果表明．接种量、起始pH值、温度、添加物对腐霉菌丝形态影响较大,接种量3％-10％,培养温度25-30℃,起始pH4及pH6．5-9,添加植物油能使菌丝保持直径小于5mm的分散小球状态．同时,起始pH值及培养温度显著影响EPA含量．较低pH值和低温培养均有利于菌丝内EPA积累．