A non-peptide substance P antagonist down-regulates SP mRNA expression in human mononuclear phagocytes

Substance P (SP), a potent modulator of neuroimmunoregulation, exerts its activity by binding to the neurokinin-1 receptor (NK-1R). The SP-NK-1R interaction is important in inflammation and viral infections, including HIV infection of human immune cells. We recently demonstrated that SP modulates HIV replication and that a non-peptide SP antagonist CP-96,345 inhibits HIV replication in human monocyte-derived macrophages (MDM) by affecting the SP-NK-1R interaction. In order to examine the effect of the SP antagonist on SP mRNA expression, MDM was incubated with or without CP-96,345 in the presence or absence of HIV infection. SP mRNA expression in these cells was then determined by real-time PCR technology. The effect of CP-96,345 on chemokine gene expression was also investigated by using a cDNA array assay. CP-96,345 down-regulated SP mRNA expression and antagonized exogenous SP-enhanced SP expression at the mRNA level, suggesting that SP autocrine regulation was interrupted by CP-96,345. CP-96,345 inhibited HIV replication in MDM, associated with down-regulated SP mRNA expression in comparison to HIV infection controls. In parallel with down-regulated SP and CCR5 mRNA expression, cDNA array assays indicated that CP-96,345 treatment also inhibited IL-8 gene expression, while enhancing expression of fractalkine and monocyte chemotactic protein-3 (MCP-3). Since SP plays an important role in inflammation and viral infections, these studies may have potential applications for therapeutic intervention of inflammation and viral infection of immune cells.     

Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated demyelinating disease of the central nervous system (CNS). Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catabolizes tryptophan, which can result in the death of T lymphocytes. This effect of IDO is inhibited by 1-methyl-tryptophan (1-MT). We used a murine model of EAE to demonstrate: (1) opposing patterns of spinal cord IDO and interferon-gamma (INF-gamma) mRNA expression through the preclinical, acute and remission I phases of EAE; (2) a change in the kynurenine-to-tryptophan (K/T) ratio during these same phases; and (3) 1-MT-induced exacerbation of clinical and histologic disease parameters during EAE. These results suggest that IDO may contribute to the regulation of T cell activity associated with the different phases of this animal model of multiple sclerosis (MS).     

‘军字一号’工程的门诊医生工作站在我院的运用

门诊医生工作站系统是医院信息管理系统中的重要组成部分 ,本文对'军字一号'中门诊医生工作站在我院的应用情况及其主要特点进行了比较详细介绍.     

Quantitative evaluation of canine renal blood flow with contrast-enhanced ultrasound]

OBJECTIVE: To evaluate the accuracy of contrast-enhanced ultrasound (CEU) in renal blood flow quantification. METHODS: Regional renal perfusion was quantified with CEU in 10 dogs at the baseline level and after treatment with 3 doses of dopamine (3, 8 and 16 mg.kg(-1).min(-1)), and renal arterial flow (RAF) was measured with ultrasonic flow probes deployed directly on the renal artery simultaneously. Normalized RAF was calculated as RAF divided by renal weight (ml.min(-1).g(-1)). RESULTS: Compared with the baseline level, a progressive increase in RAF was induced by dopamine treatment at the doses of 3 and 8 mg.kg(-1).min(-1) (P<0.05), but at a higher dose of 16 mg.kg(-1).min(-1), the increment in RAF was reduced in comparison with that with the two lower doses (P<0.05). The same changes in cortical nutrient blood flow derived from CEU were observed. Significant positive correlation was found between normalized RAF and CEU-derived cortical nutrient blood flow (y=39.8x + 44.3, r=0.88, P<0.001). CONCLUSION: CEU can be used to accurately quantify renal blood flow in dogs.     

bcr-abl逆转录病毒介导的小鼠慢性粒细胞白血病样模型的建立

目的:构建bcr-abl逆转录病毒介导的小鼠慢性粒细胞白血病(CML)样模型,为深入研究CML发病机制和治疗奠定基础.方法:bcr-abl逆转录病毒Mig210载体经Phoenix-Ampe细胞包装后,取上清液感染5-FU处理后的BALB/c雄性小鼠骨髓细胞,再经尾静脉移植入经致死剂量γ射线(900cGy)照射的同种雌性受体鼠中.用形态学、RT-PCR和Western Blot鉴定小鼠成模情况.结果:小鼠移植8～9 wk后,外周血白细胞达2×1010～3×1010/L(为对照鼠的5～8倍),外周血涂片幼稚细胞达到0.10～0.20;骨髓粒系细胞显著增高,易见幼稚细胞,肝脾也可见白血病细胞浸润;移植4～5wk后在受体鼠骨髓和脾脏检出bcr-abl融合基因,8～9 wk后在肝脏亦检测出bcr-abl融合基因,同时在骨髓和脾脏也检测到bcr-abl融合蛋白.建模成功的小鼠3～5 Ino后相继死亡.结论:成功建立bcr-abl逆转录病毒介导的小鼠CML模型,可用于后续CML信号通路和治疗机制的研究.     

HR-HPV在农村宫颈癌前病变高危年龄妇女中的感染状况调查

目的:探讨高危型人乳头瘤病毒(High risk-human papilloma virus,HR-HPV)在中国农村宫颈癌前病变高危年龄妇女中的感染状况,为宫颈癌前病变的防治及宫颈癌筛查方案的制定提供客观依据。方法:对宫颈癌高发区江西修水县人桥乡2499例年龄为30~49岁农村已婚妇女进行以人群为基础的宫颈癌及癌前病变筛查的横断面研究。采用了目前被普遍认可的多种筛查技术的联合筛查:包括宫颈薄层液基细胞学检查(TCT)、宫颈脱落细胞HPV DNA检查、醋酸染色肉眼观察(VIA)、碘染色肉眼观察(VILI)以及阴道镜检查等方法。不同方法间遵循独立、双盲原则。对其中任何一项检查异常的妇女进行宫颈活组织病理检查,以宫颈活组织病理检查作为诊断金标准。HPV DNA检测采用第二代杂交捕获实验(Hybrid capture-2,HC-Ⅱ)对受检妇女宫颈脱落细胞行HPV DNA半定量检测。观察农村宫颈癌前病变高危年龄妇女病变程度与HR-HPV感染的关系以及HR-HPV在宫颈癌前病变高危年龄妇女人群中的感染状况。结果:2499例受检妇女中,352例妇女因HPV DNA缺失被排除,其余2147例妇女纳入本研究,共检出无宫颈病变1966例、宫颈鳞状细胞化生81例、慢性宫颈炎271例、CINⅠ82例,CINⅡ37例、CINⅢ59例、宫颈癌3例。HR-HPV在不同程度宫颈病变的感染率分别为5.1%、54.9%、66.9%、80.5%、94.1%、98.1%、100.0%。HR-HPV检出妇女中总阳性率为20.63%,在30~34岁、35~39岁、40~44岁、45~49岁各年龄组的阳性率分别为21.07%、19.66%、21.29%及20.54%。宫颈癌前病变妇女HR-HPV感染率与慢性宫颈炎妇女比较,差异有统计学意义(P<0.05)。宫颈癌前病变高危年龄妇女不同年龄组HPV感染率无统计学差异(P>0.05)。结论:HR-HPV感染与宫颈病变程度呈正相关,与年龄无明显相关性。     

膜周部室间隔缺损介入治疗并发症的分析

目的　探讨膜周部室间隔缺损 (ventricularseptaldefect ,VSD)经导管介入治疗的并发症及其预防。方法　 2 0 0 2年 7月 - 2 0 0 4年 5月 ,2 6 2 (男 138,女 12 4 )例膜周部VSD患儿 ,年龄 2～ 18(9 3± 5 8)岁 ,体重 11.0～ 6 5 .0 (平均 30 5 )kg。 3例合并动脉导管未闭 ,4例合并房间隔缺损 ,1例合并动脉导管未闭和房间隔缺损。结果　 2 6 2例患儿术前经胸超声检测VSD大小为 2 7～ 13.0mm(平均 6 5mm) ,术中心室造影测量VSD大小为 1 3～ 14 .0mm(平均 6 8mm) ,2 5 6 /2 6 2例 (97 7% )封堵成功。所选封堵器大小为 4～ 16mm (平均 8 6mm)。严重并发症 8例 (3 1% )。其中高度房室传导阻滞(atrioventricularconductionblock ,AVB) 5例 (2 0 % ) ,溶血 2例 (0 8% )。封堵器明显移位 1例 (0 4 % )。5例AVB患儿治疗后除 1例术后 5 0d安装永久起搏器外 ,其余 4例均恢复正常窦性心律。溶血患儿经常规治疗后恢复正常。封堵器明显移位则采用心脏外科手术处理。其他并发症有 :1例 (0 4 % )术后 6个月复查有微量残余分流 ;5例 (2 0 % )术后新出现主动脉瓣微量返流 ;4例 (1 6 % )术后新出现三尖瓣少量返流 ;75例 (2 9% )术后出现间歇性加速性交界性心律或加速性室性自主心律伴干扰性房室脱节 ,治疗后均恢复     

Expression of Trio, a member of the Dbl family of Rho GEFs in the developing rat brain

Trio, a member of the Dbl family of guanine nucleotide exchange factors (GEFs), has a series of spectrin repeats, two GEF domains, protein interaction domains, and a putative kinase domain, potentially important in neuronal axon guidance and cell migration. Most knowledge about Trio is based on studies of Caenorhabditis elegans and Drosophila, while the function of Trio in vertebrates is unclear. The aim of these experiments was to establish the patterns of Trio expression in the postnatal rat brain. During postnatal (P) development, high levels of Trio mRNA are found in the cerebral cortex, hippocampus, thalamus, caudate/putamen, and olfactory bulb, with lower levels in the septal nucleus, nucleus accumbens, amygdala, and hypothalamus. Except for the cerebellum, Trio mRNA in major brain areas is highest at P1, decreasing gradually during development, with low but detectable levels at P30. In P14 cerebral cortex, pyramidal neurons with strongly staining soma and dendrites are observed primarily in layer 5. In hippocampus, strong staining is observed in pyramidal neurons, granule cells, and isolated interneurons. Cerebellar Purkinje neurons exhibit intense staining in the soma and in extensive dendritic arbors at P7 and P14. Levels of Trio mRNA and the intensity of Trio immunostaining in cerebellar Purkinje cells increase from P1 to P30. Consistent with the in situ hybridization pattern, Western blot analyses show that Trio levels in the hippocampus and cortex are high at P1, decreasing until P30. The data suggest that Trio plays an important role during neuronal development.     

Total cavopulmonary connection with off-pump technique

The aim of this study was to evaluate an off-pump technique for total cavopulmonary connection. Between May 2000 and June 2004, 16 patients underwent total cavopulmonary connection without cardiopulmonary bypass. There were 8 males and 8 females, with a mean age of 9.8 +/- 6.2 years and a mean weight of 27.7 +/- 14.9 kg. Preoperative percutaneous oxygen saturation was 75% +/- 6%, and pulmonary arterial pressure was 12.6 +/- 2.7 mm Hg. Postoperative outcomes were retrospectively compared with a group of 17 patients who underwent total cavopulmonary connection with an extracardiac conduit under cardiopulmonary bypass. Two patients died early postoperatively. Chylothorax occurred in 2 patients and 3 underwent reoperation for fenestration between the extracardiac conduit and the right atrium in the early postoperative period. All survivors were acyanotic. On discharge from hospital, the percutaneous oxygen saturation breathing air was 95% +/- 3%. Patients in the off-pump group demonstrated significantly shorter extubation time and intensive care unit stay. This connection technique is easy to perform and helpful in the early management of patients with a functional univentricular heart. However, much remains to be learned about this unique physiologic system.