特发性肺间质纤维化病人外周血单核细胞中DcR3基因表达的意义

目的　探讨外周血单核细胞 (PBMC)中DcR3基因表达水平与特发性肺间质纤维化 (IPF)的关系。方法　 1 4名IPF病人和 1 0名健康对照各取 5ml静脉血 ,肝素抗凝 ,密度梯度离心法分离PBMC ,异硫氰酸胍 酚 /氯仿法提取PBMC总RNA ,用半定量RT PCR法检测PBMC中DcR3基因的相对表达水平 ,并用t检验进行比较。结果　IPF病人组PBMC中DcR3基因的相对表达水平为 0 375± 0 0 88,与正常对照组 (0 2 59±0 0 84)相比有明显差异 (P <0 0 5)。结论　IPF病人PBMC中DcR3基因的表达水平增高。     

初次诊断的特发性间质性肺炎患者外周血DcR3含量的检测

目的 检测初次诊断的间质性肺炎(IIP)患者血清中DcR3水平的变化并探讨其临床价值.方法 采用双抗体夹心BAS-ELISA法和RT-PCR分别检测103例IIP患者和81例健康对照组血清中DcR3水平和外周血PBMC中DcR3基因相对表达水平.结果 IIP组血DcR3水平[(3.825 2±1.421 8)ng/dl]高于正常对照组[(1.007 9±0.479 3 ng/dl)](P＜0.01);IIP组患者PBMC中DcR3基因的相对表达水平(0.421±0.076)高于正常对照组(0.213±0.067 )(P＜0.05).结论 检测血清DcR3水平有助于诊断早期IIP.     

特发性肺纤维化患者诱导痰中SDF-1的表达与高分辨CT表现的相关性研究

目的探讨特发性肺纤维化(IPF)患者血清和诱导痰中基质细胞衍生因子-1(SDF-1)的表达水平与肺功能及胸部高分辨CT表现的相关性。方法选取IPF患者32例及健康体检者30例,收集血清和诱导痰标本并检测SDF-1表达水平,IPF患者行肺功能和胸部高分辨CT检查,并对结果作相关分析。结果 IPF患者的诱导痰中SDF-1的表达水平为(705.21±11.71)ng/ml,高于健康体检组的(252.82±10.62)ng/ml,P0.05差异有统计学意义。血清中SDF-1的表达水平(5.29±0.13)ng/ml高于健康体检组的(4.93±0.14)ng/ml,但P0.05,没有统计学意义。IPF患者肺功能均有限制性通气功能障碍和弥散功能障碍;影像学表现为程度不一的磨玻璃影、网格影和蜂窝肺,HRCT评分与诱导痰中的SDF-1表达水平呈正相关(r=0.287,P0.05)。结论 SDF-1在IPF患者诱导痰中表达明显升高,并与患者病情严重程度(胸部高分辨CT表现)呈正相关,对IPF诊断和治疗具有潜在的参考价值。     

陷阱因子3在类风湿关节炎患者血清及外周血单核细胞中的表达研究

目的 研究类风湿关节炎(RA)患者血清及外周血单核细胞中DcR3的表达情况.方法 选取已确诊的60例类风湿因子(RF)(+)的RA患者并按照DAS28评分将其分为RAa组和RAb组,以30名体检健康者作为对照,酶联免疫吸附试验( ELISA)法检测各组血清可溶性陷阱因子3(DcR3)的表达情况.同时荧光实时定量聚合酶链反应(PCR)检测各组外周血单核细胞中DcR3的表达情况.采用t检验和X2检验进行统计学分析.结果 DcR3血清表达水平在DAS28＞2.6的RAb组为(264+72) ng/ml较健康对照组为(48±39) ng/ml明显升高(r=0.251,P＜0.05).而在DAS28＜2.6的RAa组则没有差异.DcR3基因的扩增倍数在RAb组为23.5±5.4,健康对照组为8.3±3.6,差异具有统计学意义(r=0.336,P＜0.05).结论 DcR3在RA患者血清及外周血单核细胞中表达增高,而其血清表达水平在风湿活动较高的患者则更加明显.     

支气管肺泡灌洗液细胞类型与特发性肺纤维化预后的关联性研究

目的 探讨临床指标、肺功能和BALF中细胞类型与特发性肺纤维化(IPF)患者预后的关系.方法 经临床诊断的43例IPF患者进行肺功能和支气管肺泡灌洗检查.采用Kaplan-Meier检验比较组间生存率,采用Cox比例风险回归方法评价各参数的死亡风险度.结果 IPF患者存在限制性通气功能障碍和弥散功能障碍,FVC占预计值%、肺总量占预计值%和DLCO占预计值%分别为(61±18)%、(54±13)%和(48±14)%.在平均随访30.7个月内,IPF患者诊断后的中位生存期为28.5个月.糖皮质激素和(或)细胞毒类药物治疗不能改变IPF患者的预后.单因素Cox比例风险回归分析结果表明,FVC占预计值%、肺总量占预计值%、DLCO占预计值%、中性粒细胞和嗜酸粒细胞比例是影响IPF患者预后的因素,多因素Cox比例风险回归分析结果表明仅DLCO占预计值%和中性粒细胞比例是影响IPF患者预后的主要因素.结论 IPF患者主要为老年男性,存在限制性通气功能障碍和弥散功能障碍.糖皮质激素和(或)细胞毒类药物不能改变IPF患者的预后.DLCO占预计值%和中性粒细胞比例是影响IPF患者预后的主要因素,其中DLCO占预计值%和IPF患者的预后呈负相关,中性粒细胞比例和IPF患者的预后呈正相关.     

单核细胞趋化蛋白在强直性脊性炎患者中的表达与意义

目的 旨在通过检测强直性脊性炎(AS)病人的外周血单个核细胞(PBMC)、关节滑液单个核细胞(SFMC)和滑膜细胞中趋化因子单核细胞趋化蛋白(MCP)基因表达水平，了解它们在AS中的变化及其在关节炎发病机制中的作用和意义。方法 选取健康志愿者和AS病人的PBMC基因表达谱，通过含1176基因的cDNA微阵列扫描结果得到，筛选出的差异表达基因再以反转录-聚合酶链反应(RT-PCR)方法验证AS病人PBMC、SFMC和AS患者滑膜中的表达水平。结果 MCP-1在AS患者SFMC表达明显高于健康志愿者的PBMC和AS病人的PBMC。AS患者SFMC中的MCP-1水平与MCP-3水平呈正相关(r=0．76，P=0．003)；MCP-1在AS患者的关节滑膜细胞的表达水平明显高于健康对照者的关节滑膜细胞(P=0．0035)；脂多糖(LPS)刺激4h后，AS患者和健康志愿者的外周血单核细胞的MCP-1的表达显著增高。结论 MCP—1在AS病人SFMC和关节滑膜细胞中呈高表达，提示MCP-1可能在AS病人的炎症细胞向关节的归巢以及关节局部的炎症反应中起重要作用。     

肺结节病患者不同时期肺功能变化研究

目的通过测定肺结节病患者不同时期的肺通气功能,并就其之间的相关性进行分析。方法对肺结节病患者不同时期,行肺通气功能和弥散功能检测,肺结节病患者静息状态肺通气功能基本正常（P〉0．05）,单口呼吸法肺弥散功能（DL-CO％）减低（P〈0．05）,并有小气道功能障碍,尤以FEF50％减低明显（P〈0．05）。结果显示此类患者表现为限制性通气功能障碍并伴有弥散功能下降和小气道功能受限。结论肺弥散功能以及小气道功能的检查,可作为肺结节病病情活动性及指导治疗判断预后的一项重要参考指标。     

狼疮性肾炎患者肺功能损害特征及其相关因素分析

目的　探讨狼疮性肾炎患者肺功能损害的特征及其相关因素。方法　测定 40例狼疮性肾炎患者的肺容量、通气功能、小气道功能、弥散功能和血红蛋白、BUN及血压。结果　肺活量 (VC)、残气容积与肺总量之比值 (RV/TLC)、第一秒肺活量 (FEV1)、最大通气量 (MVV)、一氧化碳弥散量 (DLCO)、每升肺泡通气量之CO弥散量 (DLCO/VA)与对照组比较 ,差异有显著性 (P <0 .0 5 ) ,其中 30 %的患者呈现肺气肿现象 ,30 %的患者肺通气功能减低 ,小气道阻塞和可疑小气道阻塞者高达 6 0 % ,更有高达 85 %的患者弥散功能减退 ;相关因素分析表明 ,DLCO与TLC明显正相关关系 (r =0 .42 ,P <0 .0 5 )。结论　狼疮性肾炎患者肺功能损害以弥散功能减退为主 ,限制性通气障碍与阻塞性通气障碍并存 ,且以限制性通气障碍为主要发展趋势 ,与其他结缔组织疾病一样弥散功能障碍先于肺X线表现 ,但其呼吸困难症状几乎与弥散功能同步出现 ,则与其他结缔组织疾病有所不同     

重症急性呼吸综合征患者康复期肺功能变化临床观察

目的　通过观察重症急性呼吸综合征 (SARS)患者康复期肺功能的变化 ,了解SARS患者是否遗留有肺功能的长期损害。方法　对 82例SARS患者出院 3个月后进行肺功能检查 (实验组 ) ,并对肺功能异常者出院6个月后再次行肺功能检查 ,并以 2 8例健康人的肺功能做为对照组进行比较分析。结果　实验组肺功能检测发现一氧化碳弥散量 (DLCO % )为 (78 4± 17 4 ) % ,对照组为 (93 8± 13 6 ) % (P <0 0 1)。出院后 3及 6个月实验组中分别有 4 6例和 30例存在弥散功能障碍 (DLCO % <80 % ) ,37例和 16例有小气道功能障碍 ,2 8例和 11例残总比增加 (RV/TLC >35 % ) ,9例和 5例有限制性通气功能障碍。按照患者住院期间胸片肺部阴影的范围 ,将患者分为轻、中、重 3组 ,其轻重程度与出院后 3个月及 6个月肺弥散功能损害呈正相关。重症患者使用机械通气治疗组与未使用机械通气治疗组肺功能损害差异不明显。结论　SARS患者治愈出院 3个月及 6个月后 ,部分患者遗留有肺功能损害 ,主要以弥散功能障碍为主 ,少数有小气道阻塞、残气增加和限制性通气功能障碍。     

特发性间质性肺炎小气道功能异常研究

目的探讨特发性间质性肺炎(idiopathic interstitial pneumonia,IIPs)患者的小气道功能改变。方法收集1999年1月至2007年2月北京朝阳医院住院确诊为IIPs的患者159例。特发性肺纤维化(IPF)患者113例,非特异性间质性肺炎(NSIP)患者23例,隐源性机化性肺炎(COP)患者23例。检测所有患者肺通气、肺换气以及小气道功能。结果 IIPs患者小气道功能指标明显降低,25%和50%肺活量时的最大呼气流速(V25%,V50%)均预计值的80%。IPF、NSIP、COP患者小气道功能障碍的发生率分别为51.32%、73.91%和69.56%,其中NSIP与IPF比较,差异有统计学意义(P0.05)。结论 IIPs患者不仅存在限制性通气功能和弥散功能障碍,也存在小气道功能障碍,不同类型IIPs小气道功能障碍发生率不同,NSIP发生率较IPF高;小气道功能测定可能会增加对IIPs患者生理功能异常的理解。     

Platelet HDL(3) binding sites are not related to integrin alpha(IIb)beta(3) (GPIIb-IIIa)

Early studies considered that fibrinogen receptor (glycoprotein [GP] IIb-IIIa or platelet integrin alpha(IIb)beta(3)) is the binding site for low-density lipoprotein (LDL) and high-density lipoprotein type 3 (HDL(3)). Recent data, however, do not support the hypothesis that the binding of LDL to human intact resting platelets is related to integrin alpha(IIb)beta(3). In this study we present evidence that platelet integrin alpha(IIb)beta(3) is also not involved in the interaction of HDL(3) and human intact resting platelets. Firstly, specific ligands for platelet integrin alpha(IIb)beta(3), such as fibrinogen, vitronectin, von Willebrand factor and fibronectin, were unable to inhibit the binding of HDL(3) to intact resting platelets. Secondly, the HDL(3) binding characteristics (K(d) and B(max) values), the activation of protein kinase C (PKC) and the inhibition of thrombin-induced inositoltriphosphate (IP(3)) formation and calcium (Ca(2+)) mobilization mediated by HDL(3) particles were similar in platelets from control subjects and patients with type I and type II Glanzmann's thrombasthenia, which are characterized by total and partial lack of GPIIb-IIIa and fibrinogen, respectively. In contrast, nitrosylation of tyrosine residues of HDL(3) by tetranitromethane fully abolished both the ability of particles to interact with its specific binding sites and the functional effects. Thirdly, polyclonal antibodies against the GPIIb-IIIa complex (edu-3 and 5B12), human antiserums against platelet alloantigens (anti-Bak(a/B) and anti-PL(A1/2)), anti-integrin subunits (anti-alpha(V) and anti-beta(3)), and a wide panel of monoclonal antibodies (mAbs) against well-known epitopes of GPIIb (M3, M4, M5, M6, M8 and M95-2b) and GPIIIa (P23-7, P33, P37, P40, and P97) did not affect the binding of HDL(3) particles to human intact resting platelets. Overall results show that neither the GPIIb-IIIa complex nor GPIIb or GPIIIa individually are the membrane binding proteins for HDL(3)on intact resting platelets.     

Obamacare's (3) Day(s) in Court

Before the oral arguments in late March, the vast majority of legal scholars felt confident that the Supreme Court of the United States would uphold the individual mandate against the constitutional challenge that 26 states have levied against it. Since the oral arguments, that confidence has been severely shaken. This article asks why legal scholars were so confident before the argument and what has made us so concerned since the argument. The article posits that certain fundamental characteristics of health insurance, particularly its unusual role in steering health-care consumption decisions, which distinguishes health insurance from standard kinds of indemnity insurance, should make the constitutional question easy, but the Obama Administration's legal team was understandably hesitant to highlight those unique characteristics in its arguments. Because the Supreme Court justices seemed not to understand the uniqueness of health insurance without the government's help and because the justices seemed unusually willing to adopt a new constitutional constraint in this case, the individual mandate appears to be in far greater jeopardy than we legal scholars anticipated.     

类风湿关节炎患者红细胞C3b受体数目改变及基因多态性分析

目的　分析类风湿关节炎（ＲＡ） 患者Ｃ３ｂ受体（Ｃ３ｂＲ） 表达数目及Ｃ３ｂＲ 基因多态性分布规律,探讨Ｃ３ｂＲ 数目改变的可能原因。方法　分别测定６３ 例ＲＡ 患者及健康献血员６０ 人的红细胞Ｃ３ｂ 受体花环率（Ｃ３ｂＲＲ） 及免疫复合物花环率（Ｃ３ｂＩＣＲ） 。用限制性片段长度多态（ＲＦＬＰ） 分析及Ｓｏｕｔｈｅｒｎ ｂｌｏｔｔｉｎｇ 杂交技术检测Ｃ３ｂＲ基因多态性。结果　ＲＡ 患者红细胞Ｃ３ｂＲＲ 和Ｃ３ｂＩＣＲ 分别显著低于和高于正常对照组。Ｃ３ｂＲ基因的两个等位基因基因型和表现型频率在ＲＡ 组和对照组均无显著差异。结论　ＲＡ 患者Ｃ３ｂＲ数目下降可能与基因变异无关,可能是受体基因转录和翻译过程异常所致。设法增加红细胞Ｃ３ｂＲ 数目以加速免疫复合物的清除,可能是治疗ＲＡ的有效途径之一。     

3'-Azido-2',3'-dideoxyuridine (AzddU): comparative pharmacokinetics with 3'-azido-3'-deoxythymidine (AZT) in monkeys

The pharmacokinetics of the anti-human immunodeficiency virus type 1 nucleosides, 3'-azido-2',3'-dideoxyuridine (AzddU) and 3'-azido-3'-deoxythymidine (AZT) were characterized in rhesus monkeys. Half-life, total clearance, and steady-state volume of distribution were similar for both compounds. The observed pharmacokinetic parameters for AZT were comparable to those previously reported in humans. Oral absorption of AzddU and AZT was virtually complete after 60 mg/kg. However, bioavailability of both nucleosides was markedly lower (less than 50%) after 200 mg/kg, possibly indicating the involvement of a saturable absorption mechanism. The nucleosides were also well absorbed after subcutaneous administration. AzddU and AZT penetrated the cerebrospinal fluid (CSF) with concentration ratios in CSF:serum ranging from 0.05 to 0.25 one hour after drug administration. The glucuronides of AZT and AzddU were readily detected in urine. Hemogram and blood chemistry values for animals receiving short-term treatment (3 doses) with either AZT or AzddU did not exhibit any significant changes when compared with untreated control monkeys. The similar pharmacokinetic characteristics of AzddU compared with AZT suggest that clinical trials of AzddU are warranted.     

Missense mutations in the beta(3) subunit have a different impact on the expression and function between alpha(IIb)beta(3) and alpha(v)beta(3).

Alpha(IIb)beta(3) and alpha(v)beta(3) belong to the beta(3) integrin subfamily. Although the beta(3) subunit is a key regulator for the biosynthesis of beta(3) integrins, it remains obscure whether missense mutations in beta(3) may induce the same defects in both alpha(IIb)beta(3) and alpha(v)beta(3). In this study, it is revealed that thrombasthenic platelets with a His280Pro mutation in beta(3), which is prevalent in Japanese patients with Glanzmann thrombasthenia, did contain significant amounts of alpha(v)beta(3) (about 50% of control) using sensitive enzyme-linked immunosorbent assay. Expression studies showed that the His280Probeta(3) mutation impaired alpha(IIb)beta(3) expression but not alpha(v)beta(3) expression in 293 cells. To extend these findings, the effects of several beta(3) missense mutations leading to an impaired alpha(IIb)beta(3) expression on alpha(v)beta(3) function as well as expression was examined: Leu117Trp, Ser162Leu, Arg216Gln, Cys374Tyr, and a newly created Arg216Gln/Leu292Ser mutation. Leu117Trp and Cys374Tyr beta(3) mutations did impair alpha(v)beta(3) expression, while Ser162Leu, Arg216Gln, and Arg216Gln/Leu292Ser mutations did not. With regard to ligand binding function, Ser162Leu mutation induced especially distinct effects between 2 beta(3) integrins: it markedly impaired ligand binding to alpha(IIb)beta(3) but not to alpha(v)beta(3) at all. These data clearly demonstrate that the biosynthesis and the ligand binding function of alpha(IIb)beta(3) and those of alpha(v)beta(3) are regulated in part by different mechanisms. Present data would be a clue to elucidate the regulatory mechanism of expression and function of beta(3) integrins.     

Icosahedral quasicrystals as twins of cubic crystals containing large icosahedral clusters of atoms: The 1012-atom primitive cubic structure of Al(6)CuLi(3), the C-phase Al(37)Cu(3)Li(21)Mg(3), and GaMg(2)Zn(3)

Single-grain precession x-ray diffraction photographs of Al₆CuLi₃ have been successfully indexed on the basis of icosahedral twinning of cubic crystals with a 1012-atom primitive cubic unit with edge 25.70 Å, giving support to the proposal that the so-called icosahedral quasicrystals are twins of crystals containing eight large icosahedral clusters in the β-W arrangement. In this compound two of the clusters consist of 104 atoms and six consist of 136 atoms, with 24 atoms shared. The same structure is assigned to the C-phase, Al₃₇Cu₃Li₂₁Mg₃, and to GaMg₂Zn₃. A theory of icosahedral quasicrystals and amorphous metals is described.