Type I hypersensitivity reactions in intestinal mucosae from rats infected with Fasciola hepatica

Type I hypersensitivity reactions in the intestinal tract of sensitized animals may contribute to resistance to reinfection with Fasciola hepatica. Colonic mucosae isolated from previously infected rats were voltage clamped in Ussing chambers. Antigen was prepared as a crude homogenate from adult liver fluke. Assay of serum antibodies against fluke antigen confirmed sensitization. Antigen challenge evoked a rapid onset, transient inward current in sensitized but not in control preparations. Chloride secretion accounted for at least part of the response since the loop diuretic bumetanide reduced the effect of antigen by 61%. Anti-rat IgE mimicked the response to antigen and desensitized tissues to subsequent antigen challenge. Local synthesis of eicosanoids may mediate the response to antigen since the cyclo-oxygenase inhibitor piroxicam reduced the response by 76%. In contrast, mepyramine which is a histamine receptor antagonist did not alter the ion transport response evoked by antigen. Tetrodotoxin reduced the response to antigen by 53% implicating intrinsic neurons within the lamina propria as effector cells in the responses of this tissue to antigen. We propose that antigen stimulation of electrogenic chloride movement and consequent fluid secretion in vivo may contribute to a local effector mechanism in prevention of reinfection of previously sensitized hosts.     

Evidence that PGE2 in the dorsal and median raphe nuclei is involved in LPS-induced anorexia in rats

Anorexia is an element of the acute-phase immune response. Its mechanisms remain poorly understood. Activation of inducible cyclooxygenase-2 (COX-2) in blood-brain-barrier endothelial cells and subsequent release of prostaglandins (e.g., prostaglandin E2, PGE2) may be involved. Therefore, we sought to relate the effects of prostaglandins on the anorexia following gram-negative bacterial lipopolysaccharide treatment (LPS) to neural activity in the dorsal and median raphe nuclei (DRN and MnR) in rats. COX-2 antagonist (NS-398, 10 mg/kg; IP) administration prior to LPS (100 μg/kg; IP) prevented anorexia and reduced c-Fos expression the DRN, MnR, nucleus tractus solitarii and several related forebrain areas. These data indicate that COX-2-mediated prostaglandin synthesis is necessary for LPS anorexia and much of the initial LPS-induced neural activation. Injection of NS-398 into the DRN and MnR (1 ng/site) attenuated LPS-induced anorexia to nearly the same extent as IP NS-398, suggesting that prostaglandin signaling in these areas is necessary for LPS anorexia. Because the DRN and MnR are sources of major serotonergic projections to the forebrain, these data suggest that serotonergic neurons originating in the midbrain raphe play an important role in acute-phase response anorexia.     

p185,p170、Ki-67和CD44V6的表达与原发性乳腺癌预后的关系

目的 探讨p185、p170、Ki-67和CD44V6表达与原发性乳腺癌分期、淋巴结转移和预后的关系。方法 采用免疫组化S-P法对160例原发性乳腺癌组织进行p185、p170、Ki-67和CD44V6的检测。结果 随着肿瘤分期的提高,p185、p170、Ki-67和CD44V6的阳性表达均明显增加。p185、Ki-67和CD44V6表达在腋窝淋巴结转移病例明显高于无腋窝淋巴结转移病例(P<0.05或P<0.001),p170表达在转移组亦有增高趋势(X2=2.4)。4种标志物在死亡组病例的表达高于生存组(P<0.05或P<0.001)。结论p185、p170、Ki-67和CD44V6联合检测对于判断乳腺癌预后和指导治疗有实用价值。     

Overexpression of cyclin E isoforms correlates with poor prognosis in rectal cancer

Aims

To investigate the expression of cyclin E isoforms in rectal cancer and its relations to clinicopathological factors and survival.

Materials and methods

Cyclin E expression was assessed by Western blot in 360 resected rectal cancer patients of stage I to III. Multivariate analysis was applied to indicate the independent prognostic markers in this cohort.

Results

Nineteen percent, 24% or 29% patients exhibited elevated levels of full-length (FL) cyclin E, low-molecular-weight (LMW) cyclin E or total cyclin E in their tumors respectively. Significant correlation was observed between cyclin E expression with blood vessel invasion, deeply invasive tumors, histology grade and lymph node metastasis. Moreover, patients with high levels of LMW-cyclin E or total cyclin E had a poorer 5-year overall survival than did patients with low levels of LMW-cyclin E or total cyclin E. In multivariate analysis, both the LMW-cyclin E and total cyclin E, but not FL-cyclin E, remained independent prognostic indicators in both patients with stage I to III and in those with early stage. Patients with elevated LMW- or total cyclin E levels had a hazard ratio for death from rectal cancer of 6.302 (95% CI, 1.903-17.81, p = 0.001) or 4.332 (95% CI, 1.298-16.362, p = 0.001).

Conclusion

Overexpression of the LMW-cyclin E or total cyclin E is a strong predictor for poorer survival in patients with rectal cancer. Therefore, evaluating cyclin E expression may provide useful prognostic information for resectable rectal cancer patients.     

甲状腺乳头状癌BRAF基因突变的检测及临床意义

目的 了解甲状腺乳头状癌(papillary thyroid carcinoma,PTC)BRAF基因T1799A点突变的情况与临床病理学特征的关系.方法 应用聚合酶链反应及DNA直接测序法对43例PTC患者,20例非PTC甲状腺病变患者及40份正常甲状腺组织对照的新鲜标本进行BRAF基因检测.分析BRAF基因突变与性别、发病年龄、原发灶大小、甲状腺包膜外浸润、颈淋巴结转移及远处转移等临床病理学特征的关系.结果 43例PTC中1 7例检出BRAF基因T1799A点突变.检出率为39.5%,而在非PTC甲状腺病变患者和40份正常甲状腺组织未发现T1799A点突变.BRAF基因突变与PTC甲状腺包膜外浸润及颈淋巴结转移密切相关(P<0.05及P<0.05),与性别、发病年龄、原发灶大小及远处转移无关.结论 BRAF基因突变与颈淋巴结转移和甲状腺包膜外浸润密切相关,突变可能增加PTC的侵袭性并影响预后.     

Study on prevalence and genotype of hepatitis E virus isolated from Rex Rabbits in Beijing,China

Summary. A novel genotype of hepatitis E virus (HEV) isolated from rabbits is reported. The aim of this study was to confirm and further investigate the prevalence of the novel HEV genotype in rabbits in China. Sera and faecal samples were collected from farmed rex rabbits in Beijing, China. All serum samples were tested for anti‐HEV antibody by EIA. Both the serum and the faecal samples were evaluated for detection of HEV RNA using a nested RT‐PCR assay. The nucleotide sequences of rabbit HEV were then analysed, and sequence homology of rabbit HEV compared against human HEV genotypes 1–4, and avian HEV. Results: The prevalence of positive serum anti‐HEV from rex rabbits was 54.62% (65/119). The detection rate of HEV RNA using ORF2 primers was 6.96% (8/115) amongst rabbit faecal samples. All eight amplicons shared 98.3–100% nucleotide homology with each other and had identities of 75.8–78.6%, 73.9–75.0%, 77.5–81.0%, 74.2–78.6% and 54.8–57.6% with the corresponding regions of genotypes 1–4 and avian HEV, respectively. Phylogenetic analysis showed that the eight sequences formed one individual branch and were on the same branch with GDC9 and GDC46, both of which were reported to be a novel genotype of HEV isolated from rabbits. The conclusion is that this study provides further information about HEV infecting rabbits, which may be a new animal host of HEV, as well as genetical evidence of a new mammalian genotype of HEV.     

Prognostic utility of spontaneous erythroid colony formation and JAK2 mutational analysis for thrombotic events in essential thrombocythaemia

Background: Thrombotic events in essential thrombocythaemia (ET) are difficult to predict with current risk stratification based on age and prior history of thrombosis. Aims: We aimed to assess the predictive value of the JAK2 V617F mutation (JAK2) and spontaneous erythroid colony (SEC) growth for the development of thrombotic events post diagnosis in patients with ET. Methods: Consecutive patients with ET were retrospectively identified, and clinical and laboratory correlates were evaluated. Thrombotic events were categorized according to their occurrence at or prior to diagnosis (prior thrombosis), and any time post diagnosis of ET (subsequent thrombosis). JAK2 analysis was performed by allele‐specific PCR on whole blood or bone marrow. Results: A total of 62 patients was identified, median age 63 years; 67% (41/61) JAK2‐positive and 47% (25/53) SEC‐positive. Median follow‐up was 33 months (range, 1 to 137). JAK2‐positive patients showed a trend to increased prior thrombosis (27% vs 5%, P= 0.08), and a significant increase in the development of subsequent thrombosis (5‐year event rate 31% vs 6%, P= 0.04), which persisted when stratified for a history of prior thrombosis (P= 0.04). Survival was not affected by JAK2 status. The SEC assay predicted an increased rate of baseline thrombosis (16% vs 0%, P= 0.04), but was not found to be predictive of any subsequent thrombotic events. Conclusions: Patients with ET who are JAK2‐positive by whole blood allele‐specific PCR appear to be at increased risk of thrombotic complications, which is independent of a prior history of thrombosis.     

七宝美髯丹对衰老生物学影响的综合实验研究

实验表明 ,七宝美髯丹具有延长家蚕寿命、提高人胚肺二倍体细胞传代次数、改善老年动物SOD、LPO与大脑脂褐素、提高T淋巴细胞转换率、增强耐缺氧、抗疲劳能力和记忆力、改善血清微量元素、血脂及血浆胰岛素等作用。