BACKGROUND & AIMS: Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-induced signals in the induction of melanoma cell migration.

背景与目标： 白细胞介素-1（IL-1 alpha）在多种良性细胞类型中以及某些但不是全部恶性细胞系中诱导细胞运动。这项研究的特点是表达I型和II型IL-1受体的侵略性人黑素瘤细胞系的IL-1α诱导的运动。我们测试了包括针对I型和II型IL-1受体的功能阻断性单抗的单克隆抗体对黑素瘤细胞运动的影响，以确定哪个受体参与了IL-1α诱导的黑素瘤细胞运动的信号转导。 IL-1α使用改良的Boyden室测定法以剂量依赖性方式显着增加MM-RU黑色素瘤细胞迁移，其浓度比明显抑制细胞生长的浓度低10至100倍。计算机辅助的延时图像分析表明，通过中和针对IL-1α的抗体，可以以剂量依赖性的方式抑制运动性。针对I型或II型IL-1受体的功能阻断性单克隆抗体显示出对细胞因子诱导的细胞迁移增强的显着抑制作用。当两种抗IL-1受体抗体一起添加时，运动反应完全被阻断至对照水平。数据合计表明，IL-1α诱导的MM-RU黑色素瘤细胞的运动是通过I型和II型IL-1受体介导的。通过中和IL-1α或阻断任何一个IL-1受体或两个IL-1受体来显着抑制运动性，这表明在黑素瘤细胞迁移的诱导中整合了IL-1诱导的信号。

BACKGROUND & AIMS: :Studies were performed to elucidate the possible relationship between microvessel density, proliferative activity and angiogenesis in eutopic endometrium from women with and without endometriosis and peritoneal endometriotic lesions. The question whether changes in these parameters in endometriotic lesions were reflected by the level of vascular endothelial growth factor-A (VEGF-A) in serum and peritoneal fluid was also studied. Biopsy specimens of both eutopic endometrium and peritoneal endometriotic lesions from women with endometriosis (n = 25) as well as eutopic endometrium from women without endometriosis (n = 14) were analysed immunohistochemically regarding microvessel density, proliferative activity, and expression of VEGF-A and its receptors vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2) in stroma, glands and blood vessels. The VEGF-A concentration was measured in peritoneal fluid and serum. Secretory phase eutopic endometrium from women with endometriosis had significantly higher microvessel density, expression of VEGF-A in glandular epithelium and VEGFR-2 in endometrial blood vessels than those from women without endometriosis. Endometriotic lesions with high proliferative activity had a higher microvessel density and showed higher vascular expression of VEGFR-2 as well as being accompanied by higher levels of VEGF-A in peritoneal fluid and serum, compared with lesions with low proliferative activity. In conclusion, there seems to be a dysregulation of angiogenic activity in the eutopic endometrium of women with endometriosis and endometriotic lesions with high proliferative activity were accompanied by higher local angiogenic activity and higher levels of VEGF in serum and peritoneal fluid.

背景与目标： ：进行了研究以阐明患有和不患有子宫内膜异位和腹膜子宫内膜异位病变的女性在位子宫内膜的微血管密度，增殖活性和血管生成之间的可能关系。还研究了是否通过血清和腹膜液中血管内皮生长因子-A（VEGF-A）的水平反映子宫内膜异位病变中这些参数的变化的问题。对子宫内膜异位症妇女（n = 25）和非子宫内膜异位症妇女（n = 14）的对位子宫内膜和腹膜子宫内膜异位病变的活检标本进行了免疫组织化学分析，涉及微血管密度，增殖活性，VEGF-A和其受体位于基质，腺体和血管中的血管内皮生长因子受体1和2（VEGFR-1和VEGFR-2）。测定腹膜液和血清中的VEGF-A浓度。子宫内膜异位症女性的分泌期异位子宫内膜比无子宫内膜异位症女性的子宫内膜微血管密度，腺上皮中的VEGF-A表达和子宫内膜血管中的VEGFR-2显着更高。与具有低增殖活性的病变相比，具有高增殖活性的子宫内膜异位病变具有更高的微血管密度，并在腹膜液和血清中具有较高的VEGFR-2血管表达以及较高的VEGF-A水平。总之，子宫内膜异位症妇女的异位子宫内膜血管新生活性似乎异常，具有高增殖活性的子宫内膜异位病变伴有较高的局部血管新生活性和血清和腹膜液中较高的VEGF水平。

BACKGROUND & AIMS: :Under normoxic conditions the alpha-subunit of hypoxia-inducible factor (HIF-1alpha) protein is targeted for degradation by the von Hippel-Lindau (VHL) tumor suppressor protein acting as an E3 ubiquitin ligase. Recently, we developed a hypoxia-targeting protein, TOP3, which consisted of procaspase-3 with the VHL-mediated protein destruction motif of HIF-1alpha. This design enables procaspase-3 to be regulated similarly with HIF-1alpha, being degraded under normoxia while stabilized under hypoxia. Furthermore, stabilized TOP3 was cleaved by the hypoxic stress-induced endogenous caspases and thus the procaspase-3 was converted to active caspase-3 specifically under hypoxic conditions. These data demonstrated that the VHL-mediated protein destruction motif of HIF-1alpha endowed procaspase-3 with hypoxia-specific cytotoxicity.

背景与目标： 在常氧条件下，缺氧诱导因子（HIF-1alpha）蛋白的α亚基被von Hippel-Lindau（VHL）肿瘤抑制蛋白（作为E3泛素连接酶）降解。最近，我们开发了一种低氧靶向蛋白TOP3，该蛋白由具有HIF-1alpha的VHL介导的蛋白破坏基序的procaspase-3组成。这种设计使procaspase-3与HIF-1alpha相似，在常氧下降解，而在低氧下稳定。此外，稳定化的TOP3被低氧应激诱导的内源性半胱天冬酶裂解，因此procaspase-3特别是在低氧条件下转化为活性caspase-3。这些数据表明，HIF-1α的VHL介导的蛋白质破坏基序赋予了procaspase-3具有缺氧特异性细胞毒性。

BACKGROUND & AIMS: Elderly patients with malignant glioma have a poor prognosis and the benefit of standard radical radiotherapy is equivocal. Twenty-two percent of the adult referral base with malignant glioma at our centre is of age 70 years or greater. A phase II study was undertaken to determine if a shorter course of therapy yields a comparable median survival to radical radiotherapy and thus constitutes an appropriate investigational palliative regimen. 25 patients were accrued between 1988-1995, all of whom had histologically proven malignant glioma, 23 glioblastoma multiforme and 2 anaplastic astrocytoma. The median age was 73 (range 70-78) and median Karnofsky Performance Status (KPS) was 70.40% had a stereotactic biopsy only for diagnosis. Radiotherapy was delivered to limited fields to a dose of 37.5 Gy in 15 daily fractions over 3 weeks. An intention-to-treat analysis was undertaken with survival determined from date of initial consultation. The median survival of the whole group was 8.0 months (95% CI 4.8-9.6). Patients with good performance status (KPS > 70) had a median survival of 10.4 months (95% CI 9.6-14.7). 37.5 Gy in 15 daily fractions appears to yield comparable median survival to that of other series of radical radiotherapy. A phase III study of this regimen is recommended in investigating optimal palliation of elderly malignant glioma patients.

背景与目标： 老年恶性神经胶质瘤患者预后较差，标准根治性放疗的益处是模棱两可的。我们中心的成人恶性神经胶质瘤转诊基数中有22％的年龄为70岁或更高。进行了II期研究，以确定较短的疗程是否可以产生与根治性放疗相当的中位生存期，从而构成一种适当的姑息治疗方案。 1988年至1995年期间，共有25例患者，均经组织学证实为恶性神经胶质瘤，23例多形性胶质母细胞瘤和2例间变性星形细胞瘤。中位年龄为73岁（范围为70-78岁），中位Karnofsky绩效状态（KPS）为70.40％，仅进行了立体定向活检以进行诊断。放射治疗在3周内分15天内分次以37.5 Gy的剂量传送到有限的领域。进行了意向性治疗分析，生存期从初次咨询之日起确定。整个组的中位生存期为8.0个月（95％CI 4.8-9.6）。表现良好状态（KPS> 70）的患者中位生存期为10.4个月（95％CI 9.6-14.7）。 15个每日剂量中的37.5 Gy似乎可以产生与其他系列放射疗法相当的中位生存期。建议对该方案进行III期研究，以调查老年恶性神经胶质瘤患者的最佳缓解情况。

BACKGROUND & AIMS: :The primary objectives of this study were to follow the temporal patterns of testicular LH and FSH receptor (LH-R and FSH-R) concentrations and affinity (Ka) during sexual maturation in bulls and to see if such patterns could help explain the control of rapid testicular growth that occurs after 25 weeks of age, when serum gonadotropin concentrations are low. Separate groups of Hereford x Charolais calves (n = 6) were castrated every 4 weeks from 5 to 33 weeks of age and at 56 weeks of age. A week prior to castrations, from 5 to 33 weeks of age, blood was collected every 15 min for 10 h. The transition from indifferent supporting cells to Sertoli cells in seminiferous tubules was rapid between 13 and 25 weeks and rapid testis growth occurred after 25 weeks of age. Serum LH and FSH concentrations were transiently elevated at 12 weeks of age (P < 0.05). LH-R concentrations decreased from 13 to 25 weeks of age and increased to 56 weeks of age (P < 0.05). LH-RKa decreased from 9 to 17 weeks of age, increased to 29 weeks of age and declined to 33 weeks of age (P < 0.05). FSH-R concentrations declined from 17 to 25 weeks of age then increased to 56 weeks of age (P < 0.05). FSH-RKa increased from 17 to 25 weeks of age (P < 0.05). High concentrations of gonadotropins and their receptors may be critical to initiate testis growth postnatally and support it after 25 weeks of age in the face of low serum gonadotropin concentrations.

背景与目标： ：本研究的主要目的是追踪公牛性成熟过程中睾丸LH和FSH受体（LH-R和FSH-R）浓度和亲和力（Ka）的时间模式，并观察这种模式是否有助于解释控制因素血清促性腺激素浓度低时，在25周龄后出现睾丸快速生长的情况。从5到33周龄和56周龄每4周cast割一次赫瑞福德x夏洛来牛犊（n = 6）组。 5至33周龄weeks割前一周，每15分钟收集一次血液，持续10 h。在13至25周之间，从生精小管中的冷漠支持细胞向Sertoli细胞的过渡迅速，并且25周龄后睾丸迅速生长。血清LH和FSH浓度在12周龄时短暂升高（P <0.05）。 LH-R浓度从13周龄降低到25周龄，增加到56周龄（P <0.05）。 LH-RKa从9周龄降低到17周龄，增加到29周龄，下降到33周龄（P <0.05）。 FSH-R浓度从17周下降到25周，然后上升到56周（P <0.05）。 FSH-RKa从17周龄增加到25周龄（P <0.05）。高浓度的促性腺激素及其受体对于出生后开始睾丸生长并在25周龄后面对低血清促性腺激素浓度的情况下支持睾丸生长可能至关重要。

BACKGROUND & AIMS: :Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.

背景与目标： 基质金属蛋白酶（MMPs）的表达与妇科肿瘤的侵袭性有关。这项研究的目的是确定子宫内膜恶性肿瘤中MMP-2，MMP-7和MMP-9以及金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2的表达及其与临床和组织学参数的关系。用特异性单克隆抗体对1999年至2004年间接受治疗的50例子宫内膜癌患者的福尔马林固定，石蜡包埋的肿瘤样品进行染色。根据FIGO分类将肿瘤分组。将染色结果与组织学和临床数据进行比较。 MMP和TIMP表达的半定量分析显示，根据组织学亚型，TIMP-2表达存在显着差异（P = 0.03），并且MMP-9表达也呈现差异的趋势（P = 0.05）。随着组织学分级的升高，MMP-2表达增加而TIMP-2表达下降（分别为P = 0.0007，P <0.0001）。 MMP-2表达与淋巴结转移相关（P = 0.04），而TIMP-2表达与肌层浸润深度（P = 0.01），血管淋巴间隙受累（P = 0.02）和淋巴结转移（P = 0.0003）相关）。这些结果支持MMP和TIMP参与子宫内膜肿瘤的生长和进展。 MMP-2的高表达和TIMP-2的低表达是子宫内膜肿瘤最有效的标志物，具有局部和远处扩散的高风险。

BACKGROUND & AIMS: The effect of nutritional status on IGF-I mRNA expression in the liver and brain of juvenile barramundi (Lates calcarifer) was investigated. Fish were either fed a satiety ration (SAT) or starved (STV) for 6 weeks. Starved fish demonstrated significantly lower condition factor and hepatic IGF-I mRNA expression at 3 and 6 weeks, when compared with the SAT group. IGF-I mRNA expression in the brain was 10 fold lower than the liver and was not affected by ration size. These results suggest the liver is the major site of IGF-I mRNA synthesis and hepatic but not brain IGF-I mRNA expression is regulated by food availability in juvenile barramundi.

背景与目标： 研究了营养状况对少年肺鱼（Lates calcarifer）肝脏和脑中IGF-I mRNA表达的影响。给鱼喂饱口粮（SAT）或饿死（STV）6周。与SAT组相比，在3周和6周时，饥饿的鱼表现出明显较低的条件因子和肝脏IGF-I mRNA表达。脑中IGF-I mRNA表达比肝脏低10倍，并且不受口粮大小的影响。这些结果表明，肝脏是IGF-I mRNA合成的主要部位，肝而不是脑IGF-I mRNA的表达受幼鱼的食物供应量的调节。

BACKGROUND & AIMS: :The objective of this study was to confirm whether hemoglobin (Hb) levels during chemoradiotherapy are associated with survival in patients with locally advanced cervical carcinoma and to assess impact of the Hb level on survival according to lymph node (LN) metastasis. A retrospective review of 85 cervical carcinoma patients treated with concurrent chemoradiotherapy was conducted. The stage of disease ranged between FIGO stage IB and stage IVA. Disease-free and overall survivals were evaluated by univariate and multivariate analyses. After median follow-up of 35.7 months, 24 patients developed recurrence of disease and 14 patients died from their disease. Stage, LN metastasis, and squamous cell carcinoma antigen and Hb levels during chemoradiation were correlated significantly with survival (P < 0.05). Maintenance of Hb above 10.0 g/dL was associated with better survival (P < 0.05). However, no such benefits were observed in patients with LN metastasis by magnetic resonance imaging (MRI). Multivariate Cox regression hazard model showed that Hb levels during chemoradiation were an independent prognostic factor in patients without LN metastasis by MRI. Maintenance of Hb during chemoradiation is of benefit in cervical carcinoma patients without LN metastasis but not with LN metastasis by MRI.

背景与目标： ：这项研究的目的是确定放化疗期间的血红蛋白（Hb）水平是否与局部晚期宫颈癌患者的生存相关，并根据淋巴结（LN）转移评估Hb水平对生存的影响。回顾性回顾了85例同时放化疗的宫颈癌患者。疾病的阶段在FIGO的IB阶段和IVA阶段之间。通过单因素和多因素分析评估无病生存期和总生存期。在中位随访35.7个月后，有24例患者复发疾病，有14例患者死于疾病。化学放疗期间的分期，LN转移，鳞状细胞癌抗原和血红蛋白水平与生存率显着相关（P <0.05）。维持Hb高于10.0 g / dL与更好的生存率相关（P <0.05）。但是，通过磁共振成像（MRI）在LN转移患者中未观察到此类益处。多元Cox回归风险模型显示，放化疗期间Hb水平是无LN转移的患者（通过MRI）的独立预后因素。对于没有LN转移但没有MRI的LN转移的宫颈癌患者，放化疗期间维持Hb有益。

BACKGROUND & AIMS: OBJECTIVE:In the absence of immunodeficiency, only microchimerism (<0.1%) has been achieved in human fetal recipients or nonhuman primates following in utero hematopoietic cell transplantation (IUHCT). We hypothesized that enhanced long-term engraftment might be more reliably achieved in microchimeric systems if higher levels of chimerism existed during development of adaptive immunity. To evaluate this hypothesis, we stimulated the donor cells with vascular endothelial growth factor (VEGF) and stem cell factor (SCF) prior to IUHCT in a chimerism-resistant murine strain combination. METHODS:Donor Balb/c marrow was cultured in media with or without VEGF and SCF supplementation for 12 hours prior to IUHCT into B6 fetuses at 14 days postcoitum (dpc). Donor cell phenotype, homing, and chimerism were assessed at short and long-term time points and transplanted animals received skin allografts at 8 weeks. RESULTS:In pretreated allogeneic recipients, early chimerism rates were more than double that of controls (71% vs 33%, p = 0.01). These differences were associated with higher numbers of pretransplant donor cell colony-forming cells without change in donor cell homing. Despite prolonged skin allograft survival for pretreated recipients compared with controls (mean survival = 20.8 vs 8.2 days, p < 0.001), long-term engraftment was unchanged. CONCLUSIONS:These findings demonstrate that higher levels of early chimerism in recipients of cytokine-stimulated marrow result in improved short-term chimerism and tolerance. Future studies are needed to confirm the existence of a "threshold" level of chimerism necessary to sustain long-term engraftment.

背景与目标： 目的：在缺乏免疫缺陷的情况下，子宫内造血细胞移植（IUHCT）后，人类胎儿接受者或非人类灵长类仅获得微嵌合体（<0.1％）。我们假设，如果在适应性免疫发展过程中存在较高水平的嵌合体，则在微嵌合系统中可以更可靠地实现增强的长期植入。为了评估该假设，我们在抗嵌合体的鼠类菌株组合中，在IUHCT之前用血管内皮生长因子（VEGF）和干细胞因子（SCF）刺激了供体细胞。
方法：在IUHCT植入后的第14天（dpc）将IUBCT注入B6胎儿之前，在添加或不添加VEGF和SCF的培养基中培养供体Balb / c骨髓12小时。在短期和长期的时间点评估供体细胞的表型，归巢和嵌合，移植的动物在第8周接受皮肤同种异体移植。
结果：在经过预处理的同种异体受体中，早期嵌合率是对照的两倍以上（71％vs 33％，p = 0.01）。这些差异与更高数量的移植前供体细胞集落形成细胞相关，而未改变供体细胞归巢。尽管与对照组相比，经过预处理的接受者的皮肤同种异体移植存活时间延长（平均存活率= 20.8 vs 8.2天，p <0.001），但长期移植并未改变。
结论：这些发现表明，受细胞因子刺激的骨髓受体的早期嵌合水平较高，可改善短期嵌合和耐受性。需要进行进一步的研究，以确认是否存在维持长期植入所必需的“阈值”嵌合水平。

BACKGROUND & AIMS: :The objective of this study was to determine whether paclitaxel and a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), can affect the activation of nuclear factor-kappa B (NF-kappaB) in SKOV-3 human ovarian cancer cell line and the effect of these two agents on the growth and apoptosis of the cancer cells. The cells were treated with various concentrations of paclitaxel and/or PDTC at various time intervals. Following treatments, cell growth and apoptosis were determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)-2H-tetrazolium (WST-8) (WST) assay and flow cytometry, respectively. Western blot assay was used to determine the nuclear p65 protein and cytoplasmic IkappaB-alpha protein. High doses of PDTC significantly inhibited the growth of SKOV-3 cells and caused apoptosis. Paclitaxel and lower doses of PDTC combined demonstrated additive inhibition of cell growth and increased levels of apoptosis. Treatment of paclitaxel alone showed increased nuclear p65 protein and decreased cytoplasmic IkappaB-alpha protein expression, while pretreatment of PDTC reversed this function. PDTC blocks the paclitaxel-induced activation of NF-kappaB leading to increased chemosensitivity to paclitaxel and enhanced apoptosis. Combining antioxidants and paclitaxel has significant potential to overcome the risk of paclitaxel resistance.

背景与目标： ：这项研究的目的是确定紫杉醇和强抗氧化剂吡咯烷二硫代氨基甲酸酯（PDTC）是否会影响SKOV-3人卵巢癌细胞系中核因子-κB（NF-kappaB）的活化及其作用两种药剂对癌细胞的生长和凋亡都有影响。在不同的时间间隔用不同浓度的紫杉醇和/或PDTC处理细胞。处理后，通过2-（2-甲氧基-4-硝基苯基）-3-（4-硝基苯基）-5-（2,4-二磺酰基）-2H-四唑鎓（WST-8）（WST）测定细胞生长和凋亡）分析和流式细胞术。蛋白质印迹法用于确定核p65蛋白和细胞质IkappaB-alpha蛋白。高剂量的PDTC显着抑制SKOV-3细胞的生长并引起细胞凋亡。紫杉醇和较低剂量的PDTC联合显示可抑制细胞生长和增加细胞凋亡水平。单独使用紫杉醇的治疗显示核p65蛋白增加，而细胞质IkappaB-α蛋白表达降低，而PDTC的预处理逆转了该功能。 PDTC阻止紫杉醇诱导的NF-κB活化，从而导致对紫杉醇的化学敏感性增加和细胞凋亡增强。抗氧化剂和紫杉醇的组合具有克服紫杉醇耐药性的巨大潜力。

BACKGROUND & AIMS: Studies concerned with the efficacy of cochlear implants have traditionally focused on measuring enhancements in speech perception associated with implantation. This paper reports the findings of a study concerned with qualitative and quantitative measures of psychosocial benefit associated with the adult cochlear implant programme. Cochlear implants enhanced implantees' interpersonal communication skills and social confidence, and were associated with a reduction in the user's social anxiety. Broader socioeconomic gains were not achieved by implantees, mainly because of an absence of adequate employment and community education programmes associated with implant programmes.

背景与目标： 传统上，有关耳蜗植入物功效的研究主要集中在测量与植入物相关的语音感知方面的增强。本文报告了一项研究的结果，该研究涉及与成人人工耳蜗计划有关的社会心理效益的定性和定量测量。人工耳蜗可以提高植入者的人际沟通技巧和社交信心，并可以减轻使用者的社交焦虑。种植者没有取得更广泛的社会经济收益，主要是因为缺乏与种植计划有关的充分就业和社区教育计划。

BACKGROUND & AIMS: The driving behaviors of dementia patients have received little in the way of empirical scrutiny except through retrospective reports of crash rates. Understanding the driving errors of dementia patients and how they differ from those of normal older and younger drivers is important. This knowledge is basic to the development of road tests and scoring procedures to evaluate the driving competence of older, experienced drivers, especially those whose fitness to drive may have been compromised by a medical illness that alters their mental abilities. We have drive tested over 100 currently driving elderly patients with clinically significant cognitive decline (mostly diagnosed as the early stages of Alzheimer disease) and compared their performance with that of normal drivers. The study identified the types of driving errors that distinguish and differentiate the cognitively impaired group as well as a set of driving errors typical of both cognitively impaired and normal experienced drivers but differing in the number and severity of errors. A set of errors was also identified that did not differentiate the groups and should not be used in evaluating a person's competence to drive.

背景与目标： 除非通过回顾性报告失速发生率，痴呆症患者的驾驶行为在实证研究中很少受到关注。了解痴呆症患者的驾驶错误及其与正常年龄段和年轻驾驶员的区别是很重要的。这些知识是开发道路测试和评分程序以评估年长，经验丰富的驾驶员（特别是那些可能会因精神疾病而患病的驾驶健康状况的驾驶员）驾驶能力的基础。我们已经对100多名目前正在驾驶的具有临床上明显的认知能力下降（主要被诊断为阿尔茨海默病的早期阶段）的老年患者进行了驾驶测试，并将他们的表现与正常驾驶者进行了比较。该研究确定了区分和区分认知障碍人群的驾驶错误类型，以及一组认知障碍和正常经验丰富的驾驶员典型的驾驶错误，但错误的数量和严重程度有所不同。还确定了一组错误，这些错误不会区分群体，因此不应用于评估一个人的驾驶能力。

BACKGROUND & AIMS: BACKGROUND:Germ cells are the only cell type that can penetrate from one generation to next generation. At the early embryonic developmental stages, germ cells originally stem from primordial germ cells, and finally differentiate into functional gametes, sperm in male or oocyte in female, after sexual maturity. This study was conducted to investigate a large-scale expressed sequence tag (EST) analysis in chicken PGCs and compare the expression of the PGC ESTs with that of embryonic gonad. RESULTS:We constructed 10,851 ESTs from a chicken cDNA library of a collection of highly separated embryonic PGCs. After chimeric and problematic sequences were filtered out using the chicken genomic sequences, there were 5,093 resulting unique sequences consisting of 156 contigs and 4,937 singlets. Pearson chi-square tests of gene ontology terms in the 2nd level between PGC and embryonic gonad set showed no significance. However, digital gene expression profiling using the Audic's test showed that there were 2 genes expressed significantly with higher number of transcripts in PGCs compared with the embryonic gonads set. On the other hand, 17 genes in embryonic gonads were up-regulated higher than those in the PGC set. CONCLUSION:Our results in this study contribute to knowledge of mining novel transcripts and genes involved in germline cell proliferation and differentiation at the early embryonic stages.

背景与目标： 背景：生殖细胞是唯一可以从一代渗透到下一代的细胞类型。在胚胎发育的早期阶段，生殖细胞最初起源于原始生殖细胞，并在性成熟后分化为功能性配子，雄性精子或雌性卵母细胞。进行这项研究以调查鸡PGC中的大规模表达序列标签（EST）分析，并将PGC EST与胚胎性腺的表达进行比较。
结果：我们从鸡的高度分离的胚胎PGC的cDNA文库中构建了10,851个EST。使用鸡基因组序列过滤掉嵌合和有问题的序列后，共有5,093个得到的独特序列，由156个重叠群和4,937个单重态组成。 PGC和胚胎性腺集之间第二级的基因本体项的皮尔逊卡方检验没有意义。但是，使用Audic's测试进行的数字基因表达谱分析显示，与胚胎性腺相比，PGC中有2个基因表达显着，且转录本数量更高。另一方面，胚胎性腺中的17个基因上调的程度高于PGC中的基因。
结论：我们在这项研究中的结果有助于了解在胚胎早期阶段涉及生殖细胞增殖和分化的新转录本和基因。

BACKGROUND & AIMS: Various practice parameters have emphasized a step-wise approach to the treatment of asthma utilizing high doses of inhaled corticosteroids, i.e., 2000 ug per day for the most difficult-to-manage asthmatic patient, along with maximum bronchodilator therapy. The use of such vigorous therapy presupposes that various triggers that perpetuate asthma have been considered and hopefully eliminated or diminished, such as occupational incitants, gastroesophageal reflux, and concomitant medication such as beta blockers and perhaps difficult-to-recognize allergen stimulation. As new therapies emerge, their role in the treatment of a severe subgroup of the population remains uncategorized and will only be clarified with personal experience and appropriate double-blind studies. For example, there are data to support the concept that salmeterol plus moderate dose aerosol corticosteroids is superior to high dose corticosteroid aerosols. Theoretically, the use of anti-leukotrienes for a patient with aspirin idiosyncrasy may be superior to other combinations as would be conjectured from aspirin challenge data. Lidocaine has recently been employed in severe asthmatics, and preliminary data suggest benefit. The purpose of this review is to summarize some of our knowledge regarding medications that are either steroid-sparing or that might be useful in a subgroup of asthmatic patients with severe asthma.

背景与目标： 各种实践参数都强调了逐步治疗哮喘的方法，即使用大剂量吸入皮质类固醇，即最难以治疗的哮喘患者每天2000 ug，同时采用最大的支气管扩张剂治疗。使用这种有力的治疗方法的前提是，已经考虑了各种可以使哮喘病永存的诱因，并希望这些诱因得以消除或减少，例如职业诱因，胃食管反流以及伴随的药物（例如β受体阻滞剂），以及可能难以识别的过敏原刺激。随着新疗法的出现，它们在治疗重症人群中的作用仍未分类，只有通过个人经验和适当的双盲研究才能阐明。例如，有数据支持沙美特罗加中剂量气溶胶皮质类固醇优于大剂量皮质类固醇气溶胶的概念。从理论上讲，针对阿司匹林特质的患者使用抗白三烯可能优于其他组合，正如从阿司匹林挑战数据中推测的那样。利多卡因最近已被用于严重哮喘患者，初步数据表明其获益。这篇综述的目的是总结一些我们对类固醇或对重度哮喘的亚型哮喘患者可能有用的药物的认识。

BACKGROUND & AIMS: :A mouse perfusion model using fluorescently labeled dextran has been developed to investigate the functionality of blood vessels during cutaneous wound healing. By immunostaining cryostat sections of perfused wounds with antibodies that identify vessels, we were able to assess their functionality. There was an increase in the proportion of CD31(+)-perfused vessels in all wound regions with time, although the vessels of the wound margins and superficial granulation tissue (GT) took the longest to become perfused. More than 50% of the latter vessels were not perfused at 10 days postwounding. This is consistent with the growth of functional vessels from the wound base proceeding to the more superficial GT. The CD34 marker was expressed by a subpopulation of CD31(+) vessels. However, in contrast to CD31(+) vessels, the functionality of CD34(+) vessels did not change significantly with time and 50-75% of CD34(+) vessels in the GT and wound margins were nonfunctional. This might be explained either by apoptosis of the CD34(+) vessels or the loss of the marker with time. This study has important implications for assays of wound-healing angiogenesis based on histology and immunohistochemical markers for vessels, because vessel functionality differs both spatially and temporally during wound healing.

背景与目标： ：已经开发了使用荧光标记的葡聚糖的小鼠灌注模型，以研究皮肤伤口愈合过程中血管的功能。通过用识别血管的抗体免疫染色灌注伤口的低温恒温器切片，我们能够评估其功能。尽管伤口边缘的血管和浅表肉芽组织（GT）的灌注时间最长，但所有伤口区域中CD31（）灌注血管的比例均随时间增加。受伤后10天，没有再灌注50％以上的血管。这与功能性血管从伤口基部到更浅层的GT的生长是一致的。 CD34标记由CD31（）血管的亚群表达。然而，与CD31（）血管相反，CD34（）血管的功能并未随时间而显着变化，GT中50-75％的CD34（）血管和伤口边缘均无功能。这可能是由于CD34（）血管凋亡或标记随时间流逝而造成的。这项研究对基于组织学和血管免疫组织化学标记的伤口愈合血管生成的测定具有重要意义，因为在伤口愈合过程中血管功能在空间和时间上都不同。