BACKGROUND & AIMS: Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface, classically provided by activated platelets. We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells (VSMCs) undergoing apoptosis after serum withdrawal. In this study, using a chromogenic assay, we have shown thrombin generation by apoptotic VSMCs expressing c-myc (VSMC-myc) with an area under the thrombin-generation curve (AUC) of 305 +/- 17 nmol x min/L and a peak thrombin (PT) of 154 +/- 9 nmol/L. The thrombin-generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets (P = .003 for AUC; P = .0002 for PT) and similar to calcium-ionophore activated platelets (AUC of 332 +/- 15 nmol x min/L, P = .3; PT of 172 +/- 8 nmol/L, P = .2). Thrombin activation was also seen with apoptotic human VSMCs (AUC of 211 +/- 8 nmol x min/L; PT of 103 +/- 4 nmol/L) and was inhibited by annexin V (P < .0001 for AUC and PT). VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal (P = .0002 for AUC and PT). VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin (AUC of 260 +/- 2 nmol x min/L; PT of 128 +/- 4 nmol/L). We conclude that apoptotic VSMCs possess a significant thrombin-generating capacity secondary to phosphatidylserine exposure. Apoptotic cells within atherosclerotic plaques may allow local thrombin activation, thereby contributing to disease progression.

背景与目标： 凝血酶的活化需要活化的凝血因子的凝血酶原酶复合物在阴离子磷脂表面上的组装，这通常是由活化的血小板提供的。先前我们已经表明，在撤离血清后，发生凋亡的大鼠血管平滑肌细胞（VSMC）会暴露出阴离子磷脂酰丝氨酸。在这项研究中，我们使用发色试验显示了表达c-myc（VSMC-myc）的凋亡VSMC的凝血酶生成，其凝血酶生成曲线（AUC）下方的面积为305 /-17 nmol x min / L，凝血酶峰值（PT）为154 9 nmol / L。凋亡的VSMC-myc细胞的凝血酶生成潜能大于未激活的血小板（对于AUC，P = .003；对于PT，P = .0002），类似于钙离子载体激活的血小板（AUC为332 /-15 nmol） xmin / L，P ＝ 0.3； PT为172 / 8-nmol / L，P ＝ 0.2）。在凋亡的人VSMC中也观察到凝血酶活化（AUC为211 /-8 nmol x min / L； PT为103 /-4 nmol / L），并被膜联蛋白V抑制（对于AUC和PT，P <.0001）。血清中维持的VSMC-myc细胞产生的凝血酶少于血清中止后产生的凝血酶（对于AUC和PT，P = .0002）。源自甚至在血清中也会凋亡的人冠状动脉粥样硬化斑块的VSMC也会产生凝血酶（AUC为260 /-2 nmol x min / L； PT为128 /-4 nmol / L）。我们得出结论，凋亡性VSMC具有继磷脂酰丝氨酸暴露后的显着凝血酶生成能力。动脉粥样硬化斑块中的凋亡细胞可能允许局部凝血酶活化，从而促进疾病进展。

BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.

背景与目标： ：Etanercept是一种重组人类可溶性肿瘤坏死因子（TNF-alpha）受体融合蛋白，可抑制TNF-alpha（一种在移植物抗宿主病（GVHD）发病机理中的主要介体）。我们的研究目的是评估依那西普治疗21例激素抵抗性急性GVHD（aGVHD）（n = 13）和慢性GVHD（cGVHD）（n = 8）患者的安全性和有效性。每周两次皮下给予Etanercept 25 mg，持续4周，然后每周25 mg，持续4周。在开始使用依那西普时，有14例皮肤，13例胃肠，5例肝，5例肺和4例经口受累。 12名患者（57％）完成了12剂治疗。总体上，21例患者中有11例（52％）对依那西普治疗有反应，其中6例（46％）患有aGVHD [n = 4完全缓解（CR），n = 2部分缓解（PR）]和5例（62 ％）和cGVHD（n = 1 CR，n = 4 PR）。临床反应最常见于顽固性肠aGVHD患者，其中55％的患者为CR，9％的患者为PR。 CMV重新激活发生在48％的患者中，细菌感染发生在14％的患者中，而真菌感染发生在19％的患者中。自依那西普开始接受中位随访429天（71-1007天）后，有14名患者（67％）还活着。 7例患者死亡，3例感染，2例难治性aGVHD死亡，2例疾病进展。总之，我们的初步数据表明，依那西普耐受性好，在类固醇难治性aGVHD和cGVHD患者中可引起较高的应答率，特别是在胃肠道受累的情况下。

BACKGROUND & AIMS: :A photoplethysmographic (PPG) technique to assess blood flow in bone tissue has been developed and tested. The signal detected by the PPG consists of a constant-level (DC) component-which is related to the relative vascularization of the tissue-and a pulsatile (AC) component-which is synchronous with the pumping action of the heart. The PPG probe was applied on the skin over the patella. The probe uses near-infrared (804 nm) and green (560 nm) light sources and the AC component of the PPG signals of the two wavelengths was used to monitor pulsatile blood flow in the patellar bone and the overlying skin, respectively. Twenty healthy subjects were studied and arterial occlusion resulted in elimination of PPG signals at both wavelengths, whereas occlusion of skin blood flow by local surface pressure eliminated only the PPG signal at 560 nm. In a parallel study on a physical model with a rigid tube we showed that the AC component of the PPG signal originates from pulsations of blood flow in a rigid structure and not necessarily from volume pulsations. We conclude that pulsatile blood flow in the patellar bone can be assessed with the present PPG technique.

背景与目标： ：已经开发并测试了用于评​​估骨组织中血流的光电容积描记（PPG）技术。 PPG检测到的信号由与组织的相对血管形成有关的恒定水平（DC）分量和与心脏的泵浦动作同步的脉动（AC）分量组成。将PPG探针施加到over骨上的皮肤上。该探头使用近红外（804 nm）和绿色（560 nm）光源，并且使用两种波长的PPG信号的AC分量分别监视monitor骨和周围皮肤中的脉动血流。对二十名健康受试者进行了研究，动脉阻塞导致两种波长的PPG信号均被消除，而局部表面压力阻塞皮肤血流仅消除了560 nm处的PPG信号。在具有刚性管的物理模型的并行研究中，我们显示了PPG信号的AC分量源自刚性结构中的血流脉动，而不一定源自体积脉动。我们得出的结论是，可以使用当前的PPG技术评估the骨中的搏动性血流。

BACKGROUND & AIMS: :There is an abundance of clinical applications using human umbilical cord blood (HUCB) as a source for stem cell populations. Other than haematopoietic progenitors, there are mesenchymal, endothelial stem cells and neuronal precursors, in varying quantities, that are found in human umbilical cord blood. These may be useful in diseases such as immune deficiency and autoimmune disorders. Considering issues of safety, availability, transplant methodology, rejection and side effects, it is contended that a therapeutic stem cell transplant, utilizing stem cells from HUCB, provides a reliable repository of early precursor cells that can be useful in a great number of diverse conditions. Drawbacks of relatively smaller quantities of mononucleated cells in one unit of cord blood can be mitigated by in-vitro expansion procedures, improved in-vivo signalling, and augmentation of the cellular milieu, while simultaneously choosing the appropriate transplantation site and technique for introduction of the stem cell graft.

背景与目标： ：有大量的临床应用使用人类脐带血（HUCB）作为干细胞群体的来源。除造血祖细胞外，人类脐带血中还存在不同数量的间充质，内皮干细胞和神经元前体。这些可能对诸如免疫缺陷和自身免疫性疾病等疾病有用。考虑到安全性，可用性，移植方法，排斥反应和副作用等问题，可以认为，利用HUCB干细胞进行的治疗性干细胞移植可提供可靠的早期前体细胞库，该库可用于多种条件。可以通过体外扩增程序，改进的体内信号传导和细胞环境增强来缓解一单位脐带血中相对较少数量的单核细胞的缺点，同时选择合适的移植部位和技术引入干细胞移植。

BACKGROUND & AIMS: The analysis of brain extracellular fluid can provide essential information about both the physiology and the pathology of the human nervous system. The introduction of microdialysis into the clinical sciences has provided a new opportunity to study this environment. Using microdialysis, endogenous substances can be obtained and drugs can be delivered in very close proximity to the receptors and ion channels on neuronal membranes. In this sense, microdialysis can be regarded as a novel technique since it can continuously measure interstitial brain activity in living tissue while causing minimal adverse effects. Although it has been well established as an experimental technique for neurochemistry, the true utility of microdialysis as a clinical tool is still being defined. The potential clinical applications of microdialysis to characterize the human brain extracellular environment in patients with pathologic conditions has grown rapidly. The number of publications in which microdialysis has been performed in clinical studies has been increasing during recent years and this article gives a summary of those reports where microdialysis was applied in the study of human brain disorders.

背景与目标： 对大脑细胞外液的分析可以提供有关人类神经系统生理和病理的基本信息。将微透析技术引入临床科学为研究这种环境提供了新的机会。使用微透析，可以获得内源性物质，并且药物可以非常靠近神经元膜上的受体和离子通道递送。从这个意义上讲，微透析可以被视为一种新颖的技术，因为它可以连续测量活组织中的间质性大脑活动，同时将不良影响降到最低。尽管已经将其很好地确立为神经化学的实验技术，但微透析作为临床工具的真正用途仍在定义中。微透析在表征病理状况患者中表征人脑细胞外环境的潜在临床应用迅速增长。近年来，在临床研究中进行微透析的出版物数量不断增加，本文总结了在人类脑部疾病研究中应用微透析的那些报道。

BACKGROUND & AIMS: PURPOSE:Peptide growth factors are known accelerators of corneal wound healing, probably mediated through increased proliferation of the cells; however, information about their effect on keratocyte motility is lacking. The influence of peptide growth factors on keratocyte migratory activity was investigated, using the following growth factors: platelet derived growth factor (PDGF-BB), epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I) and transforming growth factor-beta-1 (TGF-beta 1).

METHODS:Keratocytes were seeded on gels of type 1 collagen, growth factor added, and the cells left to migrate for 72 hours. Subsequently, the number of keratocytes at the different levels in the collagen gel was evaluated by optically sectioning the gel at 20 microns, intervals, with an inverted phase contrast microscope.

RESULTS:PDGF, EGF and bFGF at 10 ng/ml, all increased the number of keratocytes at the different levels of the gel as compared to a non-stimulated control (p < 0.05 or p < 0.01, students t-test). TGF-beta proved to be a strong inhibitor of keratocyte migration, decreasing the number of keratocytes observed at every level in the gel (p < 0.05 and p < 0.01, students t-test), whereas no effect of IGF-I and aFGF was found. During the 72 hours of migration, no contraction of the collagen gels was observed. Autoradiography of histological sections of the gels showed that during the 72-hour period only TGF-beta and 10% fetal bovine serum induced an increase in keratocyte proliferation.

CONCLUSION:PDGF, EGF and bFGF increase keratocyte migration, independent of proliferation in a collagen gel invasion assay and might promote corneal wound healing, not only by increasing cell proliferation, but also through increased motility.

背景与目标： 目的：肽生长因子是已知的角膜伤口愈合促进剂，可能是通过细胞增殖的增加来介导的。然而，缺乏有关它们对角膜细胞运动性影响的信息。使用以下生长因子研究了肽生长因子对角膜细胞迁移活性的影响：血小板衍生生长因子（PDGF-BB），表皮生长因子（EGF），酸性成纤维细胞生长因子（aFGF），碱性成纤维细胞生长因子（bFGF） ），胰岛素样生长因子I（IGF-I）和转化生长因子β-1（TGF-beta 1）。

方法：将角质形成细胞接种在1型胶原蛋白，添加了生长因子，细胞迁移了72小时。随后，通过倒置相差显微镜以20微米的间隔对凝胶进行光学切片，评估胶原蛋白凝胶中不同水平的角质形成细胞的数量。

结果：PDGF ，与未刺激的对照组相比，在10 ng / ml的EGF和bFGF均增加了凝胶水平不同时的角化细胞数量（p <0.05或p <0.01，学生t检验）。 TGF-β被证明是一种强烈的角膜细胞迁移抑制剂，可减少凝胶中各个水平上观察到的角膜细胞数量（p <0.05和p <0.01，学生t检验），而IGF-I和aFGF没有作用成立。在迁移的72小时内，未观察到胶原凝胶的收缩。凝胶组织学切片的放射自显影显示，在72小时内，只有TGF-β和10％的胎牛血清诱导了角膜细胞增殖的增加。

结论：PDGF，EGF bFGF和bFGF可以增加角膜细胞的迁移，而不受胶原凝胶入侵试验中的增殖的影响，不仅可以通过增加细胞增殖，而且可以通过增加运动性来促进角膜伤口愈合。