• 【MRI引导的阿尔茨海默病内侧颞叶血流的SPECT测量。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Julin P,Lindqvist J,Svensson L,Slomka P,Wahlund LO
    BACKGROUND & AIMS: UNLABELLED:In this study, we assessed the accuracy and reliability of MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's disease (AD).

    METHODS:Interactively aligned three-dimensional MP-RAGE MRI and 99mTc-HMPAO SPECT images were used for MRI-guided measurement of medial temporal lobe CBF in eight control subjects and eight patients with probable AD. Intraoperator reliability was assessed by repeated alignment and measurement by one experienced operator. Accuracy was assessed by examining two subjects with fiducial markers.

    RESULTS:The alignment error was less than 1 SPECT pixel size (3.5 mm) and the coefficient of variation in repeated measures of medial temporal-to-cerebellar CBF ratios was 3.2%. The difference in mean medial temporal-to-cerebellar CBF ratios between eight control subjects and eight AD patients was 12%. Also by using three-dimensional seed-grow defined healthy brain reference regions, there were significant differences between control subjects and AD patients in medial temporal blood flow. Furthermore, the volumes of the MRI-defined medial temporal ROIs were smaller in the AD patients. The best separation between AD patients and control subjects was achieved by combining MRI measurements of atrophy and SPECT measurements of CBF.

    CONCLUSION:These data show that the accuracy and reliability of MRI-guided SPECT measurements of medial temporal CBF clearly allow the detection of changes in AD. Also, a direct comparison of structural and functional changes is possible by this methodology, which might improve the early diagnosis of AD.

    背景与目标: 未标记 : 在这项研究中,我们评估了MRI引导的SPECT测量阿尔茨海默氏病 (AD) 内侧颞叶血流的准确性和可靠性。
    方法 : 交互式对齐的三维MP-RAGE MRI和99mTc-HMPAO SPECT图像用于MRI引导的8名对照受试者和8名可能患有AD的患者的内侧颞叶CBF测量。一位经验丰富的操作员通过重复对准和测量来评估操作员内部的可靠性。通过检查两个具有基准标记的受试者来评估准确性。
    结果 : 对齐误差小于1 SPECT像素大小 (3.5毫米),并且重复测量的变异系数内侧颞-小脑CBF比3.2%。12% 了八名对照受试者和八名AD患者之间平均内侧颞与小脑CBF比率的差异。同样,通过使用三维种子生长定义的健康大脑参考区域,对照组和AD患者在内侧颞血流方面存在显着差异。此外,在AD患者中,MRI定义的内侧颞roi的体积较小。通过结合萎缩的MRI测量和CBF的SPECT测量,可以实现AD患者与对照组之间的最佳分离。
    结论 : 这些数据表明,MRI引导的内侧颞CBF SPECT测量的准确性和可靠性显然可以检测AD的变化。此外,通过这种方法可以直接比较结构和功能变化,这可能会改善AD的早期诊断。
  • 【囊性纤维化患者在呼气正压和振荡呼气正压胸部理疗期间血气紧张的即时变化。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Lagerkvist AL,Sten GM,Redfors SB,Lindblad AG,Hjalmarson O
    BACKGROUND & AIMS: OBJECTIVE:To assess and compare immediate effects of chest physiotherapy with positive expiratory pressure (PEP) versus oscillating PEP on transcutaneously measured blood-gas tensions in patients with cystic fibrosis. METHODS:Fifteen patients (mean age 12.5 y, range 6.9-21.5 y) participated. The treatments were randomized and performed on 2 separate occasions, 8 weeks apart. Spirometry was conducted before and after each treatment. We transcutaneously measured oxygen tension (P(tO2). RESULTS:There were no changes in spirometry values. During PEP, different trends in blood-gas tension were seen, and there were no consistent changes. During oscillating PEP, P(tO2) increased and P(tCO2) decreased. During oscillating PEP, P(tCO2) was lower and the intra-individual change in P(tCO2) was more pronounced than during PEP. The results obtained immediately after oscillating PEP showed a higher P(tO2) and a lower P(tCO2) than with PEP. CONCLUSION:PEP and oscillating PEP can both cause transitory effects on blood gases in patients with cystic fibrosis. However, oscillating PEP alters blood-gas tensions more than does PEP, and hyperventilation during oscillating PEP may reduce treatment time.
    背景与目标:
  • 【冠状动脉患者预后评估: 通用严重度指标的性能和定制。】 复制标题 收藏 收藏
    DOI:10.1378/chest.111.6.1666 复制DOI
    作者列表:Sarmiento X,Rué M,Guardiola JJ,Toboso JM,Soler M,Artigas A
    BACKGROUND & AIMS: STUDY OBJECTIVE:To assess the prognostic performance of general severity systems (APACHE II [acute physiology and chronic health evaluation], simplified acute physiology score [SAPS II], and mortality probability models [MPM II]) in coronary patients and to derive new customized indexes for coronary patients using a reduced number of variables.

    DESIGN:Inception cohort.

    SETTING:Adult medical and surgical ICUs in 17 hospitals in Catalonia and the Balearic Islands.

    PATIENTS:Four hundred fifty-six patients with acute myocardial infarction.

    MEASUREMENTS AND RESULTS:The APACHE II, SAPS II, and MPM II variables and survival status at hospital discharge have been collected. Performance of the severity systems was assessed by evaluating calibration and discrimination. Logistic regression was used to customize the MPM II(24) and SAPS II indexes. Discrimination was high enough for all of the models. However, calibration of the MPM II(24) was not as satisfactory as for the other models. The MPM II(24) and SAPS II were both reduced to five variables (MPM II(24 cor:) age, PaO2, continuous vasoactive drugs, urinary output, and mechanical ventilation; SAPS II(cor:) age, PaO2/FI(O2) ratio, systolic BP, Glasgow coma score, and urinary output). Both models showed better calibration and discrimination than the original ones.

    CONCLUSIONS:Prognostic indexes developed for multidisciplinary patients show good performance when applied to patients with acute myocardial infarction, but customization can reduce the number of variables necessary to compute them without a loss of, and a possible improvement in, prognostic accuracy.

    背景与目标: 研究目标 : 评估一般严重程度系统 (APACHE II [急性生理学和慢性健康评估],简化的急性生理学评分 [SAPS II],和冠心病患者的死亡率概率模型 [MPM II]),并使用减少的变量数量为冠心病患者推导新的定制指标。
    设计 : 初始队列。
    设置 : 加泰罗尼亚和巴利阿里群岛17家医院的成人医疗和外科重症监护医师。
    患者 : 456例急性心肌梗死患者。
    测量和结果 : 已收集APACHE II,SAPS II和MPM II变量以及出院时的生存状态。通过评估校准和判别来评估严重性系统的性能。Logistic回归用于定制MPM II(24) 和SAPS II指数。歧视对于所有模型来说都足够高。但是,MPM II(24) 的校准不如其他模型令人满意。MPM II(24) 和SAPS II均降低为五个变量 (MPM II(24 cor :) 年龄,PaO2,持续血管活性药物,尿量和机械通气; SAPS II(cor :) 年龄,PaO2/FI(O2) 比,收缩压,格拉斯哥昏迷评分,和尿量)。两种模型均显示出比原始模型更好的校准和区分度。
    结论 : 为多学科患者开发的预后指标在应用于急性心肌梗死患者时显示出良好的表现,但是,自定义可以减少计算它们所需的变量数量,而不会损失预后准确性,并可能提高预后准确性。
  • 【通过微孔过滤测量的外周血中性粒细胞流变学很好地反映了白塞氏病的活动。】 复制标题 收藏 收藏
    DOI:10.1016/s0923-1811(97)00599-9 复制DOI
    作者列表:Iijima S,Otsuka F
    BACKGROUND & AIMS: Activated neutrophils take a long time to pass through a narrow lumen like a micropore, and are supposed to play a deteriorating effect on microcirculation. Although the activation of neutrophils has been demonstrated in Behçet's disease, nobody analyzes the clinical activity of the disease by means of the rheological measure of neutrophils activity. Using a micropore (pore diameter 5 microns) filtration technique, we measured the filtration time of peripheral blood neutrophils, as a rheological measure of their activity, in order to determine the clinical activity of Behçet's disease. Twenty-one patients with Behçet's disease and 14 healthy control individuals were enrolled in the study. Symptoms and signs exhibited in the patients led us to distinguish the Behçet's disease into inactive and active cases. The latter were further differentiated into cases with absent symptoms and with present symptoms. Neutrophil filtration times were 11.5 +/- 4.8 s in the active cases with present symptoms, which were significantly (P < 0.05) larger than those (7.4 +/- 1.9 s) in the active cases with absent symptoms. The latter filtration times were further significantly (P < 0.001) larger than values (3.7 +/- 1.3 s) in the inactive cases and also those (4.8 +/- 1.2 s) in control subjects. Furthermore, increases in the filtration time obtained immediately after the exposure of cells to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP10 nM) were significantly (P < 0.01) larger in the active cases with present symptoms than those in the active cases with absent symptoms. The latter were also larger, but not significantly, than those in the inactive cases, and were significantly (P < 0.01) larger than those in control subjects. The present results demonstrate that the micropore filtration method reflects well the rheological activity of neutrophils as well as the clinical status of Behçet's disease. This method is much better than the measurement of O2 production to differentiate between active cases with absent symptoms and inactive patients or even control individuals. Furthermore, it is more sensitive and useful than laboratory data like the CRP value or the number of peripheral blood neutrophils.

    背景与目标: 活化的中性粒细胞需要很长时间才能通过像微孔一样的狭窄管腔,并且应该对微循环起到恶化的作用。尽管在beh ç et病中已经证明了中性粒细胞的激活,但没有人通过中性粒细胞活性的流变学测量来分析该疾病的临床活性。使用微孔 (孔径5微米) 过滤技术,我们测量了外周血中性粒细胞的过滤时间,作为其活性的流变学指标,以确定白塞氏病的临床活性。21名beh ç et病患者和14名健康对照者参加了这项研究。患者表现出的症状和体征使我们将白塞氏病区分为不活跃和活跃的病例。后者进一步分为无症状和现有症状的病例。有症状的活动病例的中性粒细胞过滤时间为11.5 +/- 4.8 s,显著 (P < 0.05) 大于无症状的活动病例的中性粒细胞过滤时间 (7.4 +/- 1.9 s)。后者的过滤时间进一步显著 (P < 0.001) 大于非活性情况下的值 (3.7 +/- 1.3 s),也大于对照受试者中的值 (4.8 +/- 1.2 s)。此外,在细胞暴露于趋化肽甲酰基-甲硫酰基-亮氨酸-苯丙氨酸 (fmlp10nm) 后立即获得的过滤时间的增加在存在症状的活动病例中比在不存在症状的活动病例中显着 (P < 0.01) 大。后者也比不活跃的情况更大,但不显著,并且显著 (P < 0.01) 大于对照组。目前的结果表明,微孔过滤方法很好地反映了嗜中性粒细胞的流变活性以及白塞病的临床状况。此方法比O2产生的测量要好得多,可以区分无症状的活跃病例和不活跃的患者甚至对照组。此外,它比CRP值或外周血中性粒细胞数量等实验室数据更敏感和有用。
  • 【雌二醇通过上调Fas和Fas配体的表达来增加人冠状动脉内皮细胞的凋亡。】 复制标题 收藏 收藏
    DOI:10.1210/jc.2006-1225 复制DOI
    作者列表:Seli E,Guzeloglu-Kayisli O,Cakmak H,Kayisli UA,Selam B,Arici A
    BACKGROUND & AIMS: CONTEXT:In animal models, estrogen inhibits atherogenesis by inhibiting many of the early steps of atherosclerotic plaque formation. However, the lack of cardioprotective effect by postmenopausal hormone replacement therapy and possible increase in cardiovascular events observed during the first year after the initiation of hormone replacement therapy may suggest that once the plaque is formed, estrogen may have additional effects that may counteract its beneficial outcomes. Indeed, the effect of estrogen on plaque stability has not been identified. OBJECTIVE:We hypothesized that 17beta-estradiol (E2) may cause increased apoptosis in human coronary artery endothelial cells (HCAECs). This effect would explain an adverse effect on plaque stability in vivo. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S):The effect of E2 on apoptosis, cell proliferation, and expression of proapoptotic molecules Fas and Fas ligand (FasL) in cultured HCAECs was evaluated. RESULTS:HCAECs in culture treated with E2 showed an increase in DNA strand breaks and nuclear fragmentation indicative of apoptosis. E2 treatment also induced a significant concentration-dependent increase in Fas mRNA and protein expressions in HCAECs. Moreover, the expression of FasL mRNA and secretion of FasL protein by HCAECs were enhanced in response to E2 treatments. CONCLUSIONS:E2 increases the apoptosis in cultured HCAECs. Enhanced Fas and FasL expressions in response to E2 suggest that activation of the Fas/FasL pathway may be a mediator of the proapoptotic effects of E2 in these cells.
    背景与目标:
  • 【全髋关节置换术中血液稀释与其他血液回输技术。】 复制标题 收藏 收藏
    DOI:10.1097/00003086-199706000-00018 复制DOI
    作者列表:Oishi CS,D'Lima DD,Morris BA,Hardwick ME,Berkowitz SD,Colwell CW Jr
    BACKGROUND & AIMS: Acute normovolemic hemodilution has been reported to result in blood savings varying from 18% to 90%. Very few of these are randomized prospective studies. This study attempts to determine the blood transfusion savings if acute normovolemic hemodilution is used in combination with autologous predonated blood and cell saver. Thirty-three patients undergoing total hip arthroplasty were assigned randomly to one of two groups (control, n = 16; hemodilution, n = 17). Patients in both groups entered an autologous predonation program if cleared medically and were placed on Cell Saver intraoperatively and in the postanesthesia care unit. In addition, the hemodilution group underwent acute normovolemic hemodilution preoperatively. Only 41% of the patients in the hemodilution group required any autologous blood transfusion as compared with 75% of the control group. In addition, the hemodilution group required a mean lower quantity of autologous blood transfusion (41% of the estimated blood loss) as compared with the control group (71%). The net anesthesia time increased by an average of 11.4 minutes in the hemodilution group. Acute normovolemic hemodilution is a safe procedure even in an older patient population. Hemodilution resulted in fewer patients needing autologous predonated blood transfusions. The major benefit of hemodilution was seen when predonation was not possible.

    背景与目标: 据报道,急性等容量血液稀释会导致血液节约从18% 到90% 不等。其中很少是随机前瞻性研究。这项研究试图确定如果将急性等容量血液稀释与自体预献血和细胞保护剂结合使用,则可以节省输血。将接受全髋关节置换术的33例患者随机分为两组之一 (对照组,n = 16; 血液稀释,n = 17)。如果经过医学批准,两组患者都进入了自体预捐赠计划,并在术中和麻醉后护理病房中放置在Cell Saver上。此外,血液稀释组术前进行了急性等容量血液稀释。与对照组的75% 相比,血液稀释组中只有41% 的患者需要任何自体输血。此外,与对照组 (71%) 相比,血液稀释组需要平均较低量的自体血回输 (41% 估计的失血量)。血液稀释组的净麻醉时间平均增加11.4分钟。即使在老年患者中,急性等容积量血液稀释也是一种安全的方法。血液稀释导致需要自体预输血的患者减少。当无法进行预捐赠时,可以看到血液稀释的主要好处。
  • 【通过血管内超声记录不稳定型心绞痛和急性心肌梗死中冠状动脉小动脉粥样硬化斑块上的血栓。】 复制标题 收藏 收藏
    DOI:10.1016/s0002-9149(97)00199-9 复制DOI
    作者列表:Birnbaum Y,Luo H,Fishbein MC,Samuels B,Siegel RJ
    BACKGROUND & AIMS: Rupture of atheromatous plaques leading to acute coronary syndromes usually occur in lipid-reach and well-developed coronary lesions. We describe 2 unusual patients with acute coronary syndromes in whom there was angiographic and intravascular ultrasound evidence of an intraluminal thrombus overlying a small, nonocclusive plaque in an enlarged coronary artery.

    背景与目标: 导致急性冠状动脉综合征的动脉粥样硬化斑块破裂通常发生在脂质到达和发达的冠状动脉病变中。我们描述了2例不寻常的急性冠状动脉综合征患者,其中有血管造影和血管内超声证据表明腔内血栓覆盖了扩大的冠状动脉中的一个小的非闭塞斑块。
  • 【正常成年大鼠血脑屏障缺陷区的丰富免疫环境。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-5728(97)00038-6 复制DOI
    作者列表:Pedersen EB,McNulty JA,Castro AJ,Fox LM,Zimmer J,Finsen B
    BACKGROUND & AIMS: The circumventricular organs (CVOs) in the brain are without a blood-brain barrier (BBB) and as such directly exposed to blood plasma constituents and blood-borne pathogens. In light of previous studies showing discrepancies regarding the immunocompetence of these organs, we initiated the present study to provide a comprehensive immunohistochemical analysis of the cellular expression of immune-associated antigens within the pineal gland, area postrema and the subfornical organ. In all CVOs, subpopulations of cells morphologically similar to complement receptor type 3 immunoreactive microglial/macrophage cells expressed major histocompatibility complex (MHC) class II antigen, leucocyte common antigen (LCA/CD45), as well as CD4 and ED1 antigen. Based on morphological criteria the MHC class II antigen expressing cells could be grouped into a major population of classical parenchymal and perivascular ramified microglial cells and a minor population presenting itself as scattered or small groups of rounded macrophage-like cells. CD4 and ED1 antigen were expressed by both cell types. CD45 was preferentially expressed by macrophage-like cells. MHC class I antigen was expressed by the vascular endothelium in both BBB-protected and BBB-deficient areas and was additionally present as a lattice-like network throughout the BBB-deficient parenchyma in all CVOs. The results suggest that the BBB-free areas of the brain besides being constantly surveyed by blood-borne macrophages, possess an intrinsic immune surveillance system based on resting and activated microglial cells, which may function as a non-endothelial, cellular barrier against blood-borne pathogens.

    背景与目标: 大脑中的心室器官 (CVOs) 没有血脑屏障 (BBB),因此直接暴露于血浆成分和血液传播的病原体。鉴于先前的研究显示这些器官的免疫能力存在差异,我们启动了本研究,以提供松果体,后区域和下器官内免疫相关抗原的细胞表达的全面免疫组织化学分析。在所有cvo中,形态上与补体受体3型免疫反应性小胶质细胞/巨噬细胞相似的细胞亚群表达主要组织相容性复合物 (MHC) II类抗原,白细胞共同抗原 (LCA/CD45) 以及CD4和ED1抗原。根据形态学标准,可以将MHC II类抗原表达细胞分为主要的经典实质和血管周围分支的小胶质细胞群,以及少量的呈分散或小群的圆形巨噬细胞样细胞群。两种细胞类型均表达CD4和ED1抗原。CD45优先由巨噬细胞样细胞表达。MHC I类抗原在BBB保护和BBB缺陷区域均由血管内皮表达,并且在所有cvo的BBB缺陷实质中还以晶格状网络的形式存在。结果表明,大脑的无BBB区域除了不断受到血源性巨噬细胞的调查外,还具有基于静息和活化的小胶质细胞的内在免疫监视系统,该系统可能是针对血源性病原体的非内皮细胞屏障。
  • 【心肌梗死溶栓治疗后出血的发生率和预测因素。链激酶和组织纤溶酶原激活剂在闭塞冠状动脉 (GUSTO) 中的全球利用。】 复制标题 收藏 收藏
    DOI:10.1161/01.cir.95.11.2508 复制DOI
    作者列表:Berkowitz SD,Granger CB,Pieper KS,Lee KL,Gore JM,Simoons M,Armstrong PW,Topol EJ,Califf RM
    BACKGROUND & AIMS: BACKGROUND:Although the benefit of thrombolytic therapy in reducing mortality in acute myocardial infarction is well established, the types of bleeding and risk factors for bleeding are less well described in large trials.

    METHODS AND RESULTS:We analyzed the baseline characteristics, outcomes, and incidence of bleeding by location, severity, and treatment assignment among 41,021 patients in the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903 patients for whom there were complete data, 1.2% suffered severe bleeding and 11.4% experienced moderate hemorrhage at a variety of sites. The most common sources of bleeding were procedure related. The thrombolytic regimen was strongly related to the incidence of bleeding; comparatively more bleeding was seen with the therapies of streptokinase plus intravenous heparin and the streptokinase and tissue plasminogen activator plus intravenous heparin combination. In multivariate analysis, the four most powerful independent predictors of hemorrhage were older age, lighter body weight, female sex, and African ancestry; they remained the most important predictors of bleeding when multivariate analysis was performed on patients who did not undergo invasive procedures. The presence of serious hemorrhage was associated with other undesirable outcomes (recurrent events, left ventricular dysfunction, arrhythmia, or stroke).

    CONCLUSIONS:Important predictors of bleeding in this population are increased age, lighter weight, female sex, African ancestry, and experiencing invasive procedures. Other nonhemorrhagic adverse clinical outcomes were associated with moderate and severe bleeding, which was in turn associated with increased length of hospital stay and mortality at 30 days.

    背景与目标: 背景 : 尽管溶栓治疗在降低急性心肌梗死死亡率方面的益处已得到充分证实,但在大型试验中,出血类型和出血危险因素的描述较少。
    方法和结果 : 在GUSTO-I急性心肌梗死溶栓试验中,我们分析了41,021名患者的基线特征,结局和出血发生率,按位置,严重程度和治疗分配。在40,903例有完整数据的患者中,1.2% 例严重出血,11.4% 例在不同部位出现中度出血。最常见的出血来源与手术有关。溶栓方案与出血发生率密切相关; 链激酶加静脉肝素以及链激酶和组织型纤溶酶原激活剂加静脉肝素联合治疗的出血相对较多。在多变量分析中,出血的四个最有效的独立预测因子是年龄较大,体重较轻,女性和非洲血统; 当对未接受侵入性操作的患者进行多变量分析时,它们仍然是出血的最重要预测因子。严重出血的存在与其他不良结果 (复发事件,左心室功能障碍,心律失常或中风) 相关。
    结论 : 该人群出血的重要预测因素是年龄增加,体重减轻,女性,非洲血统,经历侵入性手术。其他非出血性不良临床结局与中度和重度出血相关,而中度和重度出血又与30天时的住院时间和死亡率增加相关。
  • 【识别外周血中野生型p53-derived表位的CD8 T淋巴细胞的频率增加与肝细胞癌患者中表位丢失肿瘤变体的存在相关。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22251 复制DOI
    作者列表:Cicinnati VR,Zhang X,Yu Z,Ferencik S,Schmitz KJ,Dworacki G,Kaczmarek E,Oldhafer K,Frilling A,Baba HA,Schmid KW,Grosse-Wilde H,Broelsch CE,DeLeo AB,Gerken G,Beckebaum S
    BACKGROUND & AIMS: :Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.
    背景与目标: : 野生型 (WT) 序列p53肽是广泛适用的癌症疫苗的有吸引力的候选者。这项研究的目的是评估WT p53-based免疫治疗方法对肝细胞癌 (HCC) 患者的潜力。通过在24例HCC患者中使用肽/HLA-A2.1四聚体,在外周血中直接鉴定了对WT p53(149-157) 和WT p53(264-272) hla-a * 0201限制性表位特异性的循环CD8 + T细胞。使用定量实时聚合酶链反应测定法,通过分析颗粒酶B和干扰素-γ mRNA转录来评估WT p53肽特异性刺激后的细胞毒性T淋巴细胞 (CTL) 活性。进行肿瘤免疫表型分析以评估新鲜分离的肿瘤细胞中的p53状态,主要组织相容性复合物 (MHC) 和共刺激分子的表达。与健康对照组相比,HCC患者表现出明显更高的WT p53-specific记忆CD8 + T细胞频率和更强的WT p53-specific CTL活性。p53-specific CD8 + T细胞的频率增加及其活性与肿瘤细胞的选择性HLA-A2等位基因丢失和共刺激分子表达降低相关。此外,p53-specific T细胞数量的增加与肿瘤细胞中高MHC II类表达相吻合,但与肿瘤淋巴结转移分期系统的T状态成反比。我们的结果表明存在自然免疫监视和肿瘤免疫逃避,涉及HCC患者针对WT p53肿瘤抗原的T细胞反应。这些发现可能对癌症疫苗的未来发展具有重要意义。
  • 【通过气管内施用编码人血小板生成素cDNA的腺病毒载体来增加血小板水平。】 复制标题 收藏 收藏
    DOI:10.1038/nbt0697-570 复制DOI
    作者列表:Cannizzo SJ,Frey BM,Raffi S,Moore MA,Eaton D,Suzuki M,Singh R,Mack CA,Crystal RG
    BACKGROUND & AIMS: :This study was designed to evaluate the hypothesis that administration of a replication-deficient, recombinant adenovirus vector to the epithelial surface of the respiratory tract can be used to deliver a recombinant protein to the systemic circulation in sufficient quantities to evoke a systemic response appropriate to the recombinant protein. We administered AdCMV.TPO-an adenovirus vector containing an expression cassette coding for the human thrombopoietin (TPO) cDNA-to the respiratory epithelium of immunocompetent Balb/c mice. Over the following week, serum human TPO levels were elevated, platelet levels increased more than sixfold, and megakaryocytosis was evident in bone marrow. This strategy may be a useful approach to the nonparenteral administration of a variety of therapeutic recombinant proteins, such as those relevant to clotting, endocrine function, and bone-marrow function.
    背景与目标: : 这项研究旨在评估以下假设: 将复制缺陷型重组腺病毒载体施用到呼吸道上皮表面可用于将重组蛋白以足够量递送到体循环,以引起适合的全身反应。重组蛋白。我们向具有免疫活性的Balb/c小鼠的呼吸道上皮施用AdCMV.TPO-一种含有编码人血小板生成素 (TPO) cDNA的表达盒的腺病毒载体。在接下来的一周中,血清人TPO水平升高,血小板水平增加了六倍以上,并且骨髓中巨核细胞增多。该策略可能是非胃肠外给药多种治疗性重组蛋白的有用方法,例如与凝血,内分泌功能和骨髓功能有关的蛋白。
  • 【人冠状动脉粥样斑块切除术中肝细胞生长因子的免疫组织化学分析: 与转化生长因子 β 亚型的比较。】 复制标题 收藏 收藏
    DOI:10.1007/s004280050050 复制DOI
    作者列表:Ueda H,Imazu M,Hayashi Y,Ono K,Yasui W,Yamakido M
    BACKGROUND & AIMS: The expression and localization of hepatocyte growth factor/scatter factor (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions retrieved by directional coronary atherectomy and compared with the localization of transforming growth factor beta isoforms (TGF-beta 1, -beta 2, and -beta 3). In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and 0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel, respectively. Immunoreactivity for HGF was much weaker than that for TGF-beta isoforms in these components except in thrombotic tissue. These cells exhibiting strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly demonstrated HGF-IR. In contrast, in control coronary arteries obtained at autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that HGF produced by macrophages play a part in the process of coronary plaque formation attributable to thrombus in man.

    背景与目标: 通过免疫组织化学检查了通过定向冠状动脉粥样斑块切除术检索的59例人冠状动脉病变中肝细胞生长因子/散射因子 (HGF/SF) 的表达和定位,并将其与转化生长因子 β 亚型 (tgf-β1,-β2和-β3) 的定位进行了比较。在59个标本中的21个 (35.6%) 中,HGF样免疫反应性 (hgf-ir) 被揭示。血栓组织中45% (14/31) 的HGF免疫阳性率显着 (P < 0.05) 高于纤维组织,新内膜增生和动脉粥样硬化稀粥中的7.3% (4/55),7.1% (3/42) 和0% (0/14)。分别。除血栓形成组织外,这些成分中HGF的免疫反应性比TGF-β 同工型的免疫反应性弱得多。这些表现出强hgf-ir的细胞是炎性细胞,例如血栓形成组织中,与血栓相邻的组织病变以及部分新生血管病变的毛细血管壁外部的单核细胞/巨噬细胞。平滑肌细胞 (smc) 几乎不显示HGF-IR。相反,在尸检获得的对照冠状动脉中,hgf-ir在smc中强烈表达。这些发现表明,巨噬细胞产生的HGF在人类血栓形成引起的冠状动脉斑块形成过程中发挥了作用。
  • 【使用MR数字减影血管造影评估儿童颅内病变的血液供应。】 复制标题 收藏 收藏
    DOI:10.1007/s00247-006-0268-1 复制DOI
    作者列表:Chooi WK,Connolly DJ,Coley SC,Griffiths PD
    BACKGROUND & AIMS: BACKGROUND:MR digital subtraction angiography (MR-DSA) is a contrast-enhanced MR angiographic sequence that enables time-resolved evaluation of the cerebral circulation. OBJECTIVE:We describe the feasibility and technical success of our attempts at MR-DSA for the assessment of intracranial pathology in children. MATERIALS AND METHODS:We performed MR-DSA in 15 children (age range 5 days to 16 years) referred for MR imaging because of known or suspected intracranial pathology that required a dynamic assessment of the cerebral vasculature. MR-DSA consisted of a thick (6-10 mm) slice-selective RF-spoiled fast gradient-echo sequence (RF-FAST) acquired before and during passage of an intravenously administered bolus of Gd-DTPA. The images were subtracted and viewed as a cine loop. RESULTS:MR-DSA was performed successfully in all patients. High-flow lesions were shown in four patients; these included vein of Galen aneurysmal malformation, dural fistula, and two partially treated arteriovenous malformations (AVMs). Low-flow lesions were seen in three patients, all of which were tumours. Normal flow was confirmed in eight patients including two with successfully treated AVMs, and in three patients with cavernomas. CONCLUSION:Our early experience suggests that MR-DSA is a realistic, non-invasive alternative to catheter angiography in certain clinical settings.
    背景与目标:
  • 【基于人群的样本中肾脏血浆对血管紧张素II的血流反应与血压之间的关系。】 复制标题 收藏 收藏
    DOI:10.1097/00004872-199715050-00004 复制DOI
    作者列表:Turner ST,Kardia SL
    BACKGROUND & AIMS: OBJECTIVE:To assess whether interindividual variation in renal plasma flow or in its response to angiotensin II infusion is associated with interindividual differences in blood pressure in a population-based sample of 287 non-Hispanic whites (143 women and 144 men), aged 20-49.9 years.

    METHODS:After seven days of eating a high-sodium diet (260 mmol/day), the renal plasma flow was determined by measuring the clearance of p-aminohippurate before and after infusion of 3 ng/kg per min angiotensin II. Multiple linear regression methods were used to assess whether measures of the renal plasma flow and of its response to angiotensin II infusion were predictive of systolic or diastolic blood pressures measured prior to administration of the high-sodium diet, on day 6 of the high-sodium diet, or during the renal clearance procedure on day 7 prior to angiotensin II infusion.

    RESULTS:There was some evidence that measures of the renal plasma flow and of its response to angiotensin II infusion during the high-sodium diet were statistically significant predictors of measures of blood pressure in women; there was less evidence for this for blood pressures in men. Interindividual variation in measures of the renal plasma flow and of its response to angiotensin II infusion explained less than 10% of the interindividual variation in any measure of the blood pressure in both sexes.

    CONCLUSION:These results suggest that interindividual variation in renal plasma flow ad in its response to angiotensin II infusion during a high-sodium diet will be of limited utility in elucidating the basis for interindividual differences in blood pressure.

    背景与目标: 目的 : 在基于人群的287非西班牙裔白人 (143名女性和144名男性) 样本中,评估肾血浆流量或对血管紧张素II输注的反应的个体差异是否与血压的个体差异相关,年龄在20-49.9岁之间。
    方法 : 在食用高钠饮食 (260 mmol/天) 7天后,通过在每分钟输注3 ng/kg血管紧张素II之前和之后测量对氨基马尿酸盐的清除率来确定肾血浆流量。使用多元线性回归方法来评估肾血浆流量及其对血管紧张素II输注的反应的测量是否可以预测高钠饮食第6天在给予高钠饮食之前测得的收缩压或舒张压。钠饮食,或在输注血管紧张素II之前第7天的肾脏清除过程中。
    结果 : 有证据表明,高钠饮食期间肾脏血浆流量的测量及其对血管紧张素II输注的反应是女性血压测量的统计学显着预测指标; 男性血压的证据较少。肾血浆流量测量及其对血管紧张素II输注的反应的个体差异解释了男女血压测量中个体间差异的10%。
    结论 : 这些结果表明,在高钠饮食中对血管紧张素II输注的反应中,肾血浆流量ad的个体差异在阐明血压个体差异的基础方面将是有限的。
  • 【重症ICU患者的护理点和连续血糖分析的准确性和可行性。】 复制标题 收藏 收藏
    DOI:10.1186/cc5048 复制DOI
    作者列表:Corstjens AM,Ligtenberg JJ,van der Horst IC,Spanjersberg R,Lind JS,Tulleken JE,Meertens JH,Zijlstra JG
    BACKGROUND & AIMS: INTRODUCTION:To obtain strict glucose regulation, an accurate and feasible bedside glucometry method is essential. We evaluated three different types of point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The study was performed as a single-centre, prospective, observational study in a 12-bed medical ICU of a university hospital. METHODS:Patients with an expected ICU stay of more than 48 hours were included. Because the reference laboratory delivers glucose values after approximately 30 to 60 minutes, which is too slow to use in a glucose regulation protocol and for calibration of the subcutaneous continuous glucose monitoring system (CGMS) (CGMS System Gold), we first validated the ICU-based blood gas/glucose analyser ABL715 (part 1 of the study). Subsequently, part 2 was performed: after inserting (and calibrating) the subcutaneous CGMS, heparinised arterial blood samples were drawn from an arterial line every 6 hours and analysed on both the Precision PCx point-of-care meter using test strips and on the blood gas/glucose analyser ABL715. CGMS glucose data were downloaded after 24 to 72 hours. The results of the paired measurements were analysed as a scatter plot by the method of Bland and Altman and were expressed as a correlation coefficient. RESULTS:Part 1: Four hundred and twenty-four blood samples were drawn from 45 critically ill ICU patients. The ICU-based blood gas/glucose analyser ABL715 provided a good estimate of conventional laboratory glucose assessment: the correlation coefficient was 0.95. In the Clarke error grid, 96.8% of the paired measurements were in the clinically acceptable zones A and B. Part 2: One hundred sixty-five paired samples were drawn from 19 ICU patients. The Precision PCx point-of-care meter showed a correlation coefficient of 0.89. Ninety-eight point seven percent of measurements were within zones A and B. The correlation coefficient for the subcutaneous CGMS System Gold was 0.89. One hundred percent of measurements were within zones A and B. CONCLUSION:The ICU-based blood glucose analyser ABL715 is a rapid and accurate alternative for laboratory glucose determination and can serve as a standard for ICU blood glucose measurements. The Precision PCx is a good alternative, but feasibility may be limited because of the blood sample handling. The subcutaneous CGMS System Gold is promising, but real-time glucose level reporting is necessary before it can be of clinical use in the ICU. When implementing a glucose-insulin algorithm in patient care or research, one should realise that the absolute glucose level may differ systematically among various measuring methods, influencing targeted glucose levels.
    背景与目标:

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