食管癌中特异表达的人类omega蛋白(Igll3)基因的序列分析及意义

目的筛选食管癌中差异表达的基因,进一步了解食管癌发生的分子机制。方法利用荧光差异显示技术(DD-PCR)从食管癌组织相对癌旁组织中获得差异表达片段,对这些片段进行克隆和序列分析。通过在GenBank中同源性检索,查找差异片段相对应的同源基因。利用定量PCR检测验证该基因表达的差异性。设计引物获得该基因全长。结果通过DD-PCR得到3个差异片段,分别为人类10号常染色体上的开放阅读框99;人类信号转导和激活转录因子2及人类omega蛋白(Igll3)。定量PCR验证的结果表明,Igll3在食管癌组织中的表达量高于癌旁组织。设计引物得到该基因全长,测序表明该基因长为711bp,编码236aa。结论 Igll3在食管癌组织中异常表达,可能在食管癌发生过程中起着重要的作用。     

Age-related amyloidosis outside the brain: A state-of-the-art review

Inside and outside the brain, accumulation of amyloid fibrils plays key roles in the pathogenesis of fatal age-related diseases such as Alzheimer’s and Parkinson’s diseases and wild-type transthyretin amyloidosis. Although the incidence of all amyloidoses increases with age, for some types of amyloidosis aging is known as the main direct risk factor, and these types are typically diseases of elderly people. More than 10 different precursor proteins are known to cause age-associated amyloidosis; these proteins include amyloid β protein, α-synuclein, transthyretin, islet amyloid polypeptide, atrial natriuretic factor, and the newly discovered epidermal growth factor-containing fibulin-like extracellular matrix protein 1. Except for intracerebral amyloidoses, most age-related amyloidoses have been little studied. Indeed, in view of the increasing life expectancy in our societies, understanding how aging is involved in the process of amyloid fibril accumulation and the effects of amyloid deposits on the aging body is extremely important. In this review, we summarize current knowledge about the nature of amyloid precursor proteins, the prevalence, clinical manifestations, and pathogenesis of amyloidosis, and recent advances in our understanding of age-related amyloidoses outside the brain.     

GIP and Insulin Responses to a Test Meal in Healthy and Obese Subjects

Twenty-three obese and 17 control subjects were studied after ingestion of a heavy breakfast. Blood samples were drawn before and at 30, 60, 90, 120, 150, and 180 min after the start of the meal. The mean serum insulin level was significantly (p < 0.02) higher in the obese than in the control group throughout the study, whereas the mean blood glucose concentration was significantly (p < 0.02) higher in the obese group at 30, 60, and 90 min only. No significant differences between the two groups were noted in fasting or in postprandial plasma GIP, and it appears that hypersecretion of GIP is not responsible for the hyperinsulinemia seen in obesity.     

Glucagon-like Peptide 1 (7-36 hide) Secretion in Response to Luminal Sucrose from the Upper and Lower Gut: A Study Using α-Glucosidase Inhibition (Acarbose)

Background: After nutrient ingestion there is an early response of glucagon-like peptide 1 (GLP-1) immunoreactivity, although GLP-1 is mainly produced in endocrine cells from the lower gut (ileum and colon/rectum), suggesting that indirect stimulation is important after the ingestion of carbohydrates that are predominantly absorbed from the upper intestine.

Methods: To enable contact of sucrose with lower gut mucosa, sucrose was administered by mouth with and without the simultaneous ingestion of 100mg of the α-glucosidase inhibitor acarbose to six normal healthy volunteers.

Results: There was an early increment in GLP-1 15min after sucrose ingestion. With acarbose, sucrose reached the colon approximately 120min after ingestion, as indicated by an increment in breath hydrogen exhalation (p < 0.0001), and GLP-1 release was prolonged (p < 0.0001). The sucrose-related increments in glucose, insulin, C-peptide, and gastric inhibitory polypeptide (GIP) and the suppression of glucagon were only marginally affected by acarbose administration.

Conclusions: GLP-1 release appears to be influenced by indirect mechanisms (early response after sucrose) and by direct luminal contact with lower gut mucosal endocrine cells (late response with acarbose).     

Effects of a Gastric Partitioning Operation for Morbid Obesity on the Secretion of Gastric Inhibitory Polypeptide and Pancreatic Polypeptide

Nine morbidly obese subjects were studied with a test meal before and 3 months after a gastric partitioning operation. After the operation the postprandial release of plasma gastric inhibitory polypeptide was significantly increased, the plasma pancreatic polypeptide release was similar, and the serum insulin release significantly reduced as compared with the preoperative values.     

The role of Ntcp,Oatp2, Bsep and Mrp2 in liver injury induced by Dioscorea bulbifera L. and Diosbulbin B in mice

Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels. Following liquid chromatography-tandem mass analysis of the DIOB content of DB extract, male ICR mice were randomly orally administered DB or DIOB for 14 days. Liver injury was assessed by histopathological and biochemical analysis of liver fuction. The levels of transporter protein and mRNA were determined by western blotting and real-time PCR. Liver function and histopathological analysis indicated that both DB and DIOB could induce liver injury in mice, and that DIOB might be the primary toxic compound in DB. Moreover, down-regulation of Mrp2 blocked the excretion of bilirubin, glutathione disulfide, and bile acids, leading to the accumulation of toxic substrates in the liver and a redox imbalance. We identified down-regulated expression of Mrp2 as potential factors linked to increased serum bilirubin levels and decreased levels of glutathione in the liver and increased liver injury severity. In summary, our study indicates that down-regulation of Mrp2 represents the primary mechanism of DB- and DIOB-induced hepatotoxicity, and provides insight into novel therapies that could be used to prevent DB- and DIOB-mediated liver injury.     

The immunogenicity of insulin preparation. Antibody levels before and after transfer to highly purified porcine insulin

Summary Ninety-two insulin-dependent diabetics (aged 4–20 years, mean±SD: 13±4) with a duration of diabetes from 2 to 17 years (7±3) were transferred from Lente or NPH (5 × crystallised insulin) to Monotard insulin (highly purified insulin). Total serum immunoreactive insulin levels and concentrations of antibodies against insulin, porcine proinsulin, a-component and pancreatic polypeptide were determined prior to [I] and at a mean of 220 [II], 460 [III], 830 [IV], and 1170 [V] days after the change. All but two subjects had insulin antibodies (IgG) at the start, with a mean value of 2864 U/ml. There was a significant fall in the mean insulin antibody level between [I] and [II] to 2165 U/ml (p<10^-7), followed by an increase between [II] and [III] whereafter a slight decrease was observed being significant between [III] and [IV], as well as between [IV] and [V] (p<0.05); some patients showed a constant fall over the entire period, while others showed fluctuations. Total serum insulin showed a similar pattern, with a mean value of 1141 U/ml at [I] declining to 522 U/ml at [V]. The percentage fall between [I] and [V] was greater (54%) than that in the insulin antibodies (30%). Antibodies against acomponent, proinsulin and pancreatic polypeptide were present in 96%, 72% and 41% of the patients respectively before the change in therapy. There was a decline in these antibodies between each sampling (p values between <10^-3 and 10^-8) and, at the end of the investigation antibodies against a-component were above the detection limit in only 4 patients, and none of the patients showed antibodies against proinsulin or pancreatic polypeptide. Thus, removal of the impurities, including the hormonal contaminants of insulin, leads to a slow fall in antibodies to insulin and a much faster disappearance of antibodies against acomponent, proinsulin and pancreatic polypeptide.