Low density lipoprotein catabolism is enhanced by the cleaved form of alpha-1-antitrypsin

The frequent occurrence of hypocholesterolaemia following inflammatory processes is well known but unexplained. Elevated plasma levels of serine proteinase inhibitors (serpins) and their complexes with target enzymes have been demonstrated in inflammatory, malignant and infectious diseases which are also often accompanied by low plasma cholesterol levels. Under inflammatory conditions, uncomplexed, but cleaved inactive serpins arising from slow deacylation of the serpin-proteinase complex may be present in the circulation. To determine the influence of native and cleaved forms of serpins, such as alpha-1-antitrypsin (AAT), on lipoprotein metabolism, we investigated the effect of these forms on low density lipoprotein (LDL) catabolism in human HepG2 cell line. We have found that the cleaved form of AAT in concentrations from 125 to 2000 nmol l-1 stimulates LDL binding to the HepG2 cells, by up to 49% with a subsequent increase in LDL uptake and degradation of up to 79 and 65% respectively. Native AAT was also found to increase LDL binding and internalization by 20-25%, independently of the amount of AAT added, an effect most probably due to the cleaved form of AAT produced by local proteolysis of native AAT incubated in the cell culture. Moreover we have shown that the cleaved form of AAT interacts with LDL in vitro, and that such an interaction abolishes AAT ability to stimulate LDL binding and internalization. This study for the first time describes the ability of the cleaved form of AAT to stimulate LDL binding and internalization in HepG2 cell culture, and provides evidence that hypocholesterolaemia occurring during inflammatory processes may be mediated by cleaved forms of serpins.     

Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas

ND10 are recently characterized nuclear domains that are composed of 0.5 microm sized, precisely circumscribed dots in cultured human cell lines. To investigate the distribution and number of ND10 on various types of normal and neoplastic human tissues, we carried out immunostaining and immunoprecipitation analyses with monoclonal antibodies 138 and 1150. The number of ND10 varied from 1 to 10 or more in various tissues as did their size. ND10 were diffusely located in early embryonic and normal tissues, except for the exocrine and endocrine cells of the pancreas and for hepatocytes. In normal squamous mucosa, basal cells had more ND10 than did differentiated superficial squamous cells. The number and size of ND10 were markedly increased in malignant neoplasms but were similar in benign tumors and corresponding normal tissues. Sex hormone-related normal tissues, such as the endometrium or myometrium, and neoplasms strongly stained for ND10. The distribution pattern of ND10 in human tissues indicates that they are conserved nuclear substructures that are closely associated with cellular differentiation, hormonal stimulation, and oncogenesis.     

An antinociceptive effect of the intraperitoneal injection of nifedipine in rats, measured by tail-flick test

The tail-flick (TF) technique was used to assess the antinociceptive properties of nifedipine (NIF) given intraperitoneally (i.p.). First, the most suitable intensity of the noxious stimulus (temperature of the bulb) has been ascertained and used in the main study. Male Sprague-Dawley rats received NIF, dissolved in dimethyl sulfoxide (DMSO) at the doses of 0.0, 0.5, 2, 5, 10 and 15 mg/kg, or control with no injection. For the main study, the noxious stimulus was limited to 15 sec (cut-off time) and TF latencies were recorded up to 120 min. The antinociceptive response was expressed as the area under the curve for each rat and analyzed by one-way ANOVA. The antinociceptive response to the lower doses of NIF (0.5 and 2 mg/kg) did not differ from control (no injection) and DMSO alone. Significance was found at 5, 10 and 15 mg NIF with no difference among the doses. However, there was an increasing tendency of the mean values from 0.5 to 15 mg NIF resulting in a positive correlation. The correlation coefficient was 0.32483 (p = 0.015) and regression equation Y = (19.37) x dose + 1320. Our data suggest that spinal mechanisms are involved in NIF-induced antinociception.     

Pain threshold values during periodontal probing: assessment of maxillary incisor and molar sites

Probing pain threshold (PPT) assessments were conducted in the facial and oral sulci of maxillary central incisors and first molars of 10 periodontally healthy adults. All subjects were systemically healthy, free of pain, and reported no current medication usage. A computer-linked electronic probe, modified to deliver steadily increasing forces up to 200 grams, was used to collect the data. The system contained a subject operated "off-switch" which, upon activation, signaled the computer to record the subject's PPT. Assessments of each subject's PPTs were conducted on 3 separate occasions at 7-day intervals. Results indicated that the facial sulci of the incisors were the most pain sensitive. They displayed a mean PPT of 50.9 +/- 26.6 grams. The oral sulci of the incisors exhibited a mean PPT of 76.5 +/- 45.2 grams. Facial and oral sulci of the molars evidenced mean PPT values of 102.6 +/- 52.1 grams and 113.5 +/- 51.3 grams, respectively. These data suggest that sulci associated with incisor teeth are nearly twice as pain sensitive as sulci associated with molar teeth. In addition, facial sulci are significantly more pain sensitive than oral sulci. Data did not indicate a visit effect nor a side-of-mouth effect on PPT values.     

基于级联卷积神经网络的疲劳检测

为了诊断热核聚变等离子体状态,研制了用于热 斑区等离子体诊断用的新型X射线光谱仪,能够同 时探测X射线光谱与聚爆靶图像信息。光谱检测功能由4块椭圆晶体分析器实现,材料分别 为α-石英(1010)、 α-石英(2023)、α-石英(1011)和Si(111),几乎能够覆盖2~20 keV能带范围内的X射线特 征光谱。光谱检测 结构为光源位于椭圆的一个焦点,其辐射光谱经过椭圆反射聚焦于椭圆另一焦点,由X射线 成像板(IP)接收。图 像检测功能由分幅相机匹配小孔阵列成像完成,理想状态能够得到20 幅不同时间的聚爆靶图像。在谱仪与 聚爆靶之间的调整台上设置厚为60μm的Be膜,以保护针孔与晶体避 免聚爆溅射碎片破坏。在中物院“神光- Ⅱ”升级装置上进行了打靶实验,获取了X射线光谱与聚爆靶图像信号。分析了光谱及图像 信息,并针对光谱 仪漏光问题改进了光谱仪结构,最后在神光-Ⅲ原型装置上进行了验证实验并获得比较理想 的图像信号,信噪比(SNR)数据达到15dB。     

Present morality in parkinson's disease: the ratio of observed to expected deaths with a method to calculate expected deaths

Excess mortality, i.e. more deaths than expected in a similar normal population, has been reduced in Parkinson's disease by levodopa. A California series and a large collaborative study throughout the United States show the ratio of observed to expected deaths to be normal. In contrast, a New York study was similar patients and a Montreal group of much more severely disabled patients showed greater mortality. The reasons for these differences are unclear, but some variations in results may be attributed to different methods of calculating expected deaths to derive the ratio of observed to expected deaths.     

The management of diabetes in the elderly

It appears inevitable that with increased longevity, the management of the elderly diabetic will place even greater demands on hospital services. It seems reasonable to adopt a more liberal attitude to the regulation of control of diabetes in the elderly than in younger patients. However, the view that diabetes in the elderly is always mild can be dangerously misleading. A significant number of elderly diabetics develop ketoacidosis or other serious forms of metabolic disturbance, and in these patients the mortality is high. Cardiovascular disease and peripheral vascular disease are major problems in the elderly, the former being the main cause of death. For best results, it is desirable that management of diabetes not be isolated from management of other, coexisting disorders, but rather that it be considered as part of the overall patient problem. As Malins pointed out, we should think in terms of diabetics rather than diabetes.     

Toxicity of various carrageenans in the mouse

Carrageenan toxicity was found to vary according to the biochemical nature and source of material injected. Ischaemic lesions of body extremities (acronecrosis) were produced by some but not all preparations. Histological examination of these sites and of both recent and old organ lesions (especially of liver and kidney) confirmed that the underlying pathology was disseminated intravascular coagulation. Evidence was also obtained that carrageenans are hepatotoxic.     

Lactate metabolism in the dog during shock from hemorrhage, cardiac tamponade or endotoxin

Serum IgE concentrations of patients with paragonimiasis were determined by a radioimmunosorbent test. The mean concentration was 3,462.3 IU/ml in a group of 13 cases of paragonimiasis miyazakii in which patients showed clinical symptoms and/or positive immunological diagnostic tests, and 1,026.6 IU/ml in a control group of 13 individuals who had eaten uncooked freshwater crabs, Potamon dehaani, but had been found to be free from the infection. Moreover, the IgE level of the pleural exudates obtained from four patients with paragonimiasis miyazakii on the day of bleeding or within several days after was significantly higher than that of their sera, ranging between 4,200 IU/ml and 10,000 IU/ml. This was true also in a case of paragonimiasis westermani. Sera and pleural exudates of patients with both forms of paragonimiasis were applied to immunosorbent columns of Sepharose 4B beads coupled with saline extracts of Paragonimus miyazakii, P. weetermani, or P. ohirai. IgE eluted from the corresponding column was considered to be specific, being around 5% to 10% of the total IgE.