Early therapy with interferon for acute hepatitis C acquired through a needlestick

Chinese hamster lung fibroblast V79 cells have been widely used in studies of DNA damage and DNA repair. Since the p53 gene is involved in normal responses to DNA damage, we have analyzed the molecular genetics and functional status of p53 in V79 cells and primary Chinese hamster embryonic fibroblast (CHEF) cells. The coding product of the p53 gene in CHEF cells was 76 and 75% homologous to human and mouse p53 respectively, and was 95% homologous to the Syrian hamster cells. The V79 p53 sequence contained two point mutations located within a presumed DNA binding domain, as compared with the CHEF cells. Additional immunocytochemical and molecular studies confirmed that the p53 protein in V79 cells was mutated and nonfunctional. Our results indicate that caution should be used in interpreting studies of DNA damage, DNA repair and apoptosis in V79 cells.     

The significance of colocalization of plasminogen activator inhibitor-1 and vitronectin in hepatic fibrosis

BACKGROUND: We examined the relationships among vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) in liver diseases to evaluate the presence of plasmin cascade in human hepatic fibrosis. METHODS: Blood and liver tissues were obtained from 57 patients with liver disease. Plasma VN, PAI-1 antigen, and PAI-1 activity levels were evaluated. Biopsied liver specimens were observed by light and electron microscopy after immunohistochemical staining. Morphometric analysis was performed on these specimens. RESULTS: Plasma VN and PAI-1 activity levels decreased significantly with the progression of hepatic fibrosis and were particularly marked in the liver cirrhosis group. Plasma PAI-1 antigen level increased significantly. The immunolocalization of the active form of TGF-beta became more intense with the progression of hepatic fibrosis, whereas that of the dual-stained positive areas of PAI-1 and VN (PAI-1.VN) decreased. There was a positive correlation between TGF-beta and PAI-1, whereas there was a negative correlation between TGF-beta and PAI-1.VN. Immunoelectron microscopy showed the localization of PAI-1-VN in the extracellular space around the sinusoidal cells or surface of aggregating platelets, TGF-beta mainly in Ito cells, and VN in hepatocytes near the focal necrotic area or fibrous septa. CONCLUSIONS: These findings suggest that VN and PAI-1 are related to the active form of TGF-beta and that it is possible that the plasmin cascade is present in the human liver.     

Ion exchange membranes and separation processes with chemical reactions

Recent research trends in the development of ion exchange membranes and their use in separation processes with chemical reactions are reviewed. Emphasis in research on the ion exchange membrane is trending toward analysis of micro-structure of the membranes and to development of new functionalized ion exchange membranes in response to industrial requirements. Separation processes with chemical reactions are discussed according to the following classifications: (1) double decomposition of electrolytes; (2) production of acid and base by bipolar ion exchange membrane processes; (3) separators for electrolysis; (4) separators for batteries; (5) use as solid polyelectrolytes; (6) active transport through ion exchange membranes; (7) acceleration of chemical reactions by ion exchange membranes; (8) carrier transport in ion exchange membranes; (9) transducers for electrical signals from chemical reactions; and (10) modified electrodes.     

Temperature Control of a Bench‐Scale Batch Polymerization Reactor for Polystyrene Production

Batch polymerization reactors commonly use optimal temperature control as the strategic operation parameter. This strategy allows for better operability and a more economic process. The main objective of the batch polymerization reactor control is to obtain acceptable product quality. Direct measurement of polymer quality is rarely achievable, which makes the online control of the reactor difficult. Temperature is the most controllable operational variable in the polymer reactor, which is seen to have a direct effect on the polymer properties. Temperature is chosen as the set point by using either the isothermal temperature or optimal temperature trajectory. Online control of the optimal temperature profile of a bench‐scale batch polymerization reactor was experimentally investigated in this study. The temperature trajectory was used as the target for controllers to follow. The time‐profile temperature was obtained with the objective of obtaining the desired conversion and number‐average chain length within the minimum time. Two advanced controls of fuzzy logic control and generic model control were applied to the polymer reactor. A comparison of the controllers reveals that both performed better than conventional controllers.     

Endothelial cell apoptosis induced by oxidized LDL is associated with the down-regulation of the cellular caspase inhibitor FLIP

Fas (CD-95/APO-1) is a death receptor that initiates an apoptotic signal when activated by its ligand, FasL. Normal vascular endothelial cells are resistant to Fas-mediated apoptosis though they express both Fas and FasL. Oxidized low density lipoprotein (OxLDL) or lysophosphatidylcholine (LPC), a major component of OxLDL, induces endothelial cell suicide by sensitizing endothelial cells to Fas-mediated apoptosis. Here, we show that endothelial cell apoptosis by OxLDL and LPC-C16:0 was dose-dependent and correlated with down-regulation of FLICE-inhibitory protein (FLIP), an intracellular caspase inhibitor. FLIP down-regulation also occurred when endothelial cells were treated with toxic doses of LPC-C18:0 or minimally modified low density lipoprotein (LDL). In contrast, FLIP was not down-regulated by native LDL, acetylated LDL, LPC-C12:0, cholesterol, or 7-ketocholesterol, which are not toxic to endothelial cells. The cytotoxicity of oxidized lipids was reversed by transfecting endothelial cells with a FLIP expression plasmid. The results demonstrate, for the first time, FLIP regulation under conditions that lead to pathological tissue destruction.     

Abnormal accumulation of endotoxin in biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis

We measured levels of glucose and glycated hemoglobin in the blood of three of the world's smallest nectarivorous birds, the Anna's (Calypte anna), Costa's (Calypte costae), and ruby-throated hummingbirds (Archilochus colubris). Plasma glucose levels of hummingbirds that were fasted overnight (17 mM) were higher than those in any mammal and are among the highest ever measured in a fasting vertebrate. Glucose levels in hummingbirds just after feeding were extreme, rising as high as 42 mM. The surprisingly high blood glucose concentrations in hummingbirds were accompanied by glycated hemoglobin levels that are the highest ever measured in birds but are lower than those of non-diabetic humans. How hummingbirds tolerate blood glucose levels that cause serious neurological and microvascular pathologies in diabetic humans and animals remains unknown.     

Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas

Glioblastoma multiforme, the most malignant human brain tumor, may develop de novo (primary glioblastoma) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). We present further evidence that primary and secondary glioblastomas constitute distinct disease entities which develop through the acquisition of different genetic alterations. We analyzed p53 mutations, p53 protein accumulation and epidermal growth factor receptor (EGFR) overexpression in 49 biopsies classified as primary or secondary glioblastoma according to clinical and histopathologic criteria. Patients with primary glioblastoma were selected on the basis of a clinical history of less than 3 months and histopathologic features of glioblastoma at the first biopsy (19 cases; mean age, 55 years). The diagnosis of secondary glioblastomas required at least two biopsies and clinical as well as histologic evidence of progression from low grade or anaplastic astrocytoma (30 cases; mean age, 39 years). DNA sequence analysis showed that p53 mutations were rare in primary glioblastomas (11%) while secondary glioblastomas had a high incidence of p53 mutations (67%), of which 90% were already present in the first biopsy. The incidence of p53 protein accumulation (nuclear immunoreactivity to PAb 1801) was also lower in primary (37%) than in secondary glioblastomas (97%). In contrast, immunoreactivity for the EGF receptor prevailed in primary glioblastomas (63%) but was rare in secondary glioblastomas (10%). Only one out of 49 glioblastomas showed EGFR overexpression and a p53 mutation. These data indicate that overexpression of the EGF receptor and mutations of the p53 tumor suppressor gene are mutually exclusive events defining two different genetic pathways in the evolution of glioblastoma as the common phenotypic endpoint.     

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.     

A study on product modelling for integration of CAD/CAM

Modelling capability for products to be designed and manufactured plays an important role in order to effectively construct and utilize CAD/CAM systems. Product models should represent all the information about products, which is utilized in manufacturing processes. Therefore it is required that they describe functional structures of machine products, and include not only geometric information but also various non-geometric data, such as physical, technological and management data. Presently there do not seem to exist definite methods or theories for constructing product models. In this paper, we first investigate the whole manufacturing process, and propose a system structure for integration of CAD/CAM, in which product modelling plays a fundamental role. Then requirements for product modelling are studied thoroughly, and a new representation framework for product models is proposed. It consists of an object concept called frame, relations among frames and attributes, and it can incorporate the existing various modelling capabilities, such as solid modelling. We use this representation framework in combination with our solid modelling package GEOMAP-III, and show the effectiveness of this approach by performing illustrative design experiments.