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。     

Circular dichroic studies of the DNA and RNA of nucleoli

Circular dichroism (CD) in the 240-300-nm region was used to study the conformation of DNA and RNA complexed with proteins in isolated nucleoli form HeLa cells. Deoxyribonuclease or ribonuclease digestion was employed to obtain (1) the individual CD spectra of nucleolar DNA or RNA in complex form with proteins, or in free form; and (2) the experimental CD baseline correction to exclude contributions from nonnucleic acid sources such as light scattering artifacts and proteins. The CD spectrum of nucleolar DNA in DNA-protein complexes was highly reduced in ellipticity in comparison with protein-free DNA. It showed a positive peak at 283 nm with a molar ellipticity [theta]283 = 1200 deg cm2 dmol-1 and a crossover at 262 nm. Addition of sodium dodecylsulfate shifted the peak to 276 nm with [theta]276 8000 deg cm2 dmol-1 and a crossover at 254 nm. The CD spectrum of nucleolar RNA in RNA-protein complexes was also reduced in comparison with protein-free RNA, showing a peak at 269 nm ([theta]269 = 6900 deg cm2 dmol-1), and a crossover at 250 nm. Addition of sodium dodecyl sulfate shifted the peak to 265 nm with [theta]265 = 18 000 deg cm2 dmol-1 and a crossover at 246 nm. The low ellipticity of both nucleolar DNA and RNA when complexed with proteins was increased by treatment with sodium chloride, urea, or heparin. This suggests that some ionic, hydrophobic, and hydrogen bondings are involved in the nucleic acid-protein interaction in nucleolar chromatin similar to that observed in nuclear chromatin.     

Implantation of multiple intracochlear electrodes for rehabilitation of total deafness: preliminary report

Many instances of total deafness are due to destruction of the organ of Corti but with partial or complete preservation of the function of the cochlear nerve. In such cases, it is possible to restore some hearing by electrically stimulating the fibers of the cochlear nerve with the help of implanted electrodes. Preoperative testing with electric shocks applied to the round window have aroused sensations of noise in 45 cases of total bilateral deafness with a great variety of etiologies. The only negative results were in two cases of operated acoustic neuromas. Our operation places up to eight intracochlear electrodes, each with a separate fenestration opening into an electrically isolated compartment of the scala tympani. Stimulation of each electrode yields a different sound sensation of a pitch that depends on its location along the cochlea. Electric filters direct different frequency bands to the appropriate electrodes, with the necessary compression of dynamic range. In three experimental cases of unilateral deafness, pitch matches to the normal ear were made. In seven therapeutic operations on adult cases of acquired total bilateral deafness, speech recognition was usually relearned within a month or two. Improvement of voice quality was also dramatic. The intracochlear electrodes have been well tolerated for months, but the method of connection to the external equipment still presents difficulties.     

Teaching language to mentally retarded deaf children: a review of the literature and a description of one classroom program

Premature infants with hyaline membrane disease and related disorders are frequently hypovolemic. Furthermore, they frequently require repeated phlebotomies for laboratory evaluation of electrolytes, pH, oxygen tension, and other parameters. Adequate care of such infants is aided by small transfusions of heparinized blood. The walking donor program at the Sacramento Medical Center premature nursery furnishes these transfusions without exposing the infants to the hazards of receiving blood from many different donors. The program is described in detail, and the shortcomings of some of the alternative programs are pointed out.