Inhibition of Expression of Hypoxia-inducible Factor-1α mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats

Hypoxiaisadirectfactorcausinghypoxicpul monaryhypertension (HPH) .hypoxiainduciblefac tor 1α (HIF 1α)isfoundtobethemostcrucialfactorsofarwhichmediatesthecellularresponsetohypoxi a[1] .OurpreviousstudyrevealedthatoverexpressionofHIF 1andendothelin 1(ET 1…     

Anorexia and adipsia: dissociation from fever after MIP-1 injection in ventromedial hypothalamus and preoptic area of rats.

Certain cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) act centrally to affect eating behavior and thermoregulation and may be involved in the physiological mechanisms leading to anorexia, adipsia and loss in body weight. The newly discovered macrophage inflammatory protein-1 (MIP-1) infused into the anterior hypothalamic, preoptic area (AH/POA) evokes an intense hyperthermia. The present experiments were designed to determine whether MIP-1 affects the feeding mechanism in the ventromedial hypothalamus (VMH) independently of the thermoregulatory mechanism in the AH/POA. For the microinjection of MIP-1, guide cannulae were implanted stereotaxically in the rat just above the VMH or AH/POA. Following postoperative recovery, each unrestrained rat was adapted to procedures whereby body temperature and intakes of food and water available ad lib were monitored at predetermined intervals. When an efficacious dose of 5.6 picograms (pg) MIP-1 was microinjected in a volume of 0.5 microliters into the VMH, the intake of food in the rat was reduced significantly in the short term and throughout the following 22 h. Within intervals of 30 min and 4.0 h following MIP-1, the amount of food consumed was 4.0 and 10 g, respectively, below that eaten by control rats given the saline solvent vehicle injected at the same site in the VMH. Over the entire test period, the intake of water was similarly significantly below that of the control rats. Whereas MIP-1 injected into the AH/POA evoked fever accompanied by a transient decline in feeding, the body temperature of the rats was unaffected by the cytokine injected in the VMH.(ABSTRACT TRUNCATED AT 250 WORDS)     

A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases.

We have constructed a new capsid-modified adenovirus (Ad) vector that specifically replicates in tumor cells and expresses TNF-related apoptosis-inducing ligand (TRAIL). The Ad capsid contains short-shafted fibers derived from Ad serotype 35, which allow for efficient infection of malignant tumor cells, and largely avoids innate toxicity after intravenous application. Replication-dependent homologous recombination in Ad genomes was used to achieve tumor-specific expression of Ad E1a (to mediate viral replication) and TRAIL (to mediate apoptosis and enhance release of progeny virus from infected cells). We demonstrated that our oncolytic vector (Ad5/35.IR-E1A/TRAIL) induced apoptosis in human tumor cell lines derived from colorectal, lung, prostate, and liver cancer. Both in vitro and in vivo tumor models showed efficient intratumoral spread of this vector. In a model for metastatic colon cancer, tail vein infusion of Ad5/35.IR-E1A/TRAIL resulted in elimination of preestablished liver metastases. Intravenous injection of this vector caused a transient elevation of serum glutamic pyruvic transaminase in tumor-bearing mice, which we attributed to factors released from apoptotic tumor cells. Liver histology analyzed at day 14 after virus injection did not show signs of hepatocellular damage. This new oncolytic vector represents a potentially efficient means for gene therapy of metastatic cancer.     

Myoepitheliomas of the soft palate: helical CT findings in two patients.

We describe the enhancement patterns of myoepithelioma in two patients with a soft palate mass. In the first case, helical CT revealed a faintly enhancing mass. Histologically, the tumor was composed of plasmacytoid cells in a background of rich myxoid stroma. Immunostaining for CD34 showed scanty blood vessels. In the second case, helical CT revealed an intensely enhancing mass. Histologically, the mass was a cellular tumor with fibrous stroma. Immunostaining for CD34 also showed frequent blood vessels.     

双特异抗体介导的人单核—巨噬细胞对荷人肝癌裸鼠的抑制作用

观察双特异性单克隆抗体介导的人单核－巨噬细胞在裸鼠体内对肝癌生长的抑制作用。用化学交联法制备双特异性单克隆抗体ＨＡｂ１８－ＭＡｂ７及ＨＡｂ１８Ｆ（ａｂ）２－ＭＡｂ７Ｆ（ａｂ＇＿２，并将其与单核－巨噬细胞－同注入荷人肝癌裸鼠体内，观察肿瘤体积的变化。     

Obesity in youth and middle age and risk of colorectal cancer in men

To investigate an association between colon cancer and obesity during early adulthood—a potentially important period in the etiology of this disease—the authors assembled, by computer linkage, a population-based historical cohort of 52,539 men born between 1913 and 1927 residing in Hawaii (USA), for whom weight and height had been recorded in 1942–43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 737 incident cases of colorectal cancer for 1972–86. An average of 3.8 cancer-free controls were matched to each case on month and year of birth and ethnicity of the parents. A case-control analysis in each anatomic subsite of the large bowel revealed that both early and middle-age body mass increased the risk of sigmoid cancer in men in a dose-dependent fashion. The odds ratios (OR) for sigmoid cancer for the highest compared with the lowest tertiles of Quetelet index were: 2.1 (95 percent confidence interval [CI]=1.4–3.2) and 1.7 (CI=1.1–2.5), at ages 15–29 and in prediagnostic years, respectively. These associations were additive and idependent of socioeconomic status. Men who were above the median Quetelet index in 1942 and 1972 had an OR of 2.7 (CI=1.8–4.0), compared with those who were below the median in both periods. This study provides further evidence for an association of obesity with colon cancer in men and suggests that this association is limited to the sigmoid colon and may be related to both early and late events of colon carcinogenesis.The authors are with the Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii. Address correspondence to Dr Le Marchand, Epidemiology Program, Cancer Research Center of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA. This work was supported in part by Public Health Service grant 5-R29-CA44503 and contract NO1-CN-55424 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.     

Pten基因敲除对过氧化物酶家族表达和活性氧水平的影响

目的:探讨Pten基因敲除后对过氧化物酶家族(Peroxiredoxins,Prdxs)水平和活性氧水平的影响.方法:采用Western印迹和化学/荧光发光分析法分别检测了在Pten / MEF和Pten-/-MEF细胞中PRDXs的表达和细胞内活性氧水平.结果:Western印迹结果显示,与Pten / MEF细胞相比,Pten-/-MEF细胞PRDX Ⅰ,Ⅱ,Ⅴ,Ⅵ蛋白水平下调,PRDX Ⅲ不变,PRDX Ⅳ上调.DCFH探针标记后流式结果显示Pten-/-MEF 细胞活性氧荧光值显著高于对照Pten / MEF细胞(P＜0.05).结论:Pten基因敲除引起数种PRDXs表达下调,细胞内活性氧水平增高.     

实验性室间隔缺损心肌血管紧张素Ⅱ受体表达的变化

目的　探讨实验性室间隔缺损 ( VSD)动物左右心室心肌血管紧张素 受体的改变。方法　建立猪实验性室间隔缺损动物模型 ,术后 1月取左右心室组织 ,通过放射性配体受体结合分析法测定每 10 6个细胞上血管紧张素 受体 ( AT1 R、AT2 R)的最大结合量 ( Bmax)和平衡解离常数 ( KD)。结果　假手术组与正常组动物受体的 Bmax和KD改变无统计学意义 ,手术组动物左室 AT1 R、右室 AT1 R和 AT2 R的 Bmax值 (分别为 188.42± 13 3 .97、2 72 .14±2 3 2 .74、40 .42± 3 4.76fmol/ 10 6 ,对照组 AT1 R和 AT2 R的 Bmax值左室为 2 9.2 0± 19.5 0和 2 .90± 0 .64 ,右室为76.72± 5 1.2 1和 9.63± 1.2 7fm ol/ L )增高明显 ( P<0 .0 5 )。结论　心内左向右所引起的心室容量负荷过重 ,导致AT1 R的表达增高 ,是 VSD心室肥厚及重构的重要机制 ;AT2 R在右心室表达增高 ,可能是中等程度容量负荷的VSD容易出现左室肥厚而非右室肥厚的原因     

α-地中海贫血种植前基因诊断妊娠成功

【目的】探讨种植前基因诊断的临床应用。【方法】对 1例夫妇均为东南亚缺失型α 地中海贫血携带者 ,经超排取卵、卵母细胞单精子显微注射受精及胚胎细胞活检 ,吸取的单个卵裂球采用针对α SEA基因的 gap PCR引物和荧光探针用荧光定量PCR技术进行诊断 ,将诊断为不致病的 3个胚胎进行宫腔内移植。【结果】胚胎移植后 7周B超诊断单胎妊娠 ,18周羊膜腔穿刺产前诊断证实为不致病胎儿。【结论】应用成熟的显微操作技术进行胚胎细胞活检 ,活检的单个卵裂球用荧光定量PCR技术进行诊断 ,获得国内首例α 地中海贫血胚胎种植前基因诊断后妊娠成功。     

人胃癌组织中fibulin-5的表达及其临床意义

目的探讨fibulin-5在人胃癌组织中的表达及其临床意义。方法采用免疫组织化学染色结合图像分析法，对32例胃癌组织、癌旁组织及正常胃组织中fibulin-5的表达进行半定量分析。结果fibulin-5在胃癌组织中的表达强于癌旁组织和正常组织（P〈0．05），且表达强度与癌组织的分化程度有关，低分化癌组织的fibulin-5表达强（P〈O．05）。结论fibulin-5的表达可能与胃癌组织细胞的恶性转化及增殖有关。