Endotoxin and cytokines increase hepatic sphingolipid biosynthesis and produce lipoproteins enriched in ceramides and sphingomyelin

Alterations in triglyceride and cholesterol metabolism often accompany inflammatory diseases and infections. We studied the effects of endotoxin (lipopolysaccharide [LPS]) and cytokines on hepatic sphingolipid synthesis, activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid synthesis, and lipoprotein sphingolipid content in Syrian hamsters. Administration of LPS induced a 2-fold increase in hepatic SPT activity. The increase in activity first occurred at 16 hours, peaked at 24 hours, and was sustained for at least 48 hours. Low doses of LPS produced maximal increases in SPT activity, with half-maximal effect seen at approximately 0.3 microg LPS/100 g body weight. LPS increased hepatic SPT mRNA levels 2-fold, suggesting that the increase in SPT activity was due to an increase in SPT mRNA. LPS treatment also produced 75% and 2.5-fold increases in hepatic sphingomyelin and ceramide synthesis, respectively. Many of the metabolic effects of LPS are mediated by cytokines. Interleukin 1 (IL-1), but not tumor necrosis factor, increased both SPT activity and mRNA levels in the liver of intact animals, whereas both IL-1 and tumor necrosis factor increased SPT mRNA levels in HepG2 cells. IL- produced a 3-fold increase in SPT mRNA in HepG2 cells, and the half-maximal dose was 2 ng/mL. IL-1 also increased the secretion of sphingolipids into the medium. Analysis of serum lipoprotein fractions demonstrated that very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein isolated from animals treated with LPS contained significantly higher amounts of ceramide, glucosylceramide, and sphingomyelin. Taken together, these results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis.     

The effect of adrenergic agonists on the systemic response to hemorrhage

An in vivo antitumor screening of extracts of Gomphrena martiana indicated positive activity in the petroleum ether extract, and its further bioactivity-directed fractionation resulted in a lipophilic flavonoid fraction. Upon inoculation of various doses of 5,6,7-trisubstituted flavones on two murine tumor lines, Sarcoma 180 and Ehrlich's carcinoma, a decrease of tumor growth was observed. An in vitro KB cultured cell screen indicated cytotoxicity.     

Expression of multiple apoptosis-regulatory genes in human breast cancer cell lines and primary tumors

Low molecular mass polypeptides (LMP) 2 and LMP7 and transporter associated with antigen processing (TAP) subunits TAP1 and TAP2 play a crucial role in antigen processing and cell surface expression of HLA class I molecules. Since monoclonal antibodies (mAb) to these molecules will facilitate the analysis of their expression, structure and function in normal and transformed cells, in the present study we have developed these reagents. Specifically anti-LMP2 and LMP7 mAb were generated from BALB/c mice immunized with specific peptides, and anti-TAP1 and TAP2 mAb from BALB/c mice immunized with respective recombinant proteins. mAb VF101-39F7 and VF101-39G5 were shown to be specific for LMP2, mAb VF103-5D5 and VF103-8C2 for LMP7, mAb VF108-1B3 and VF108-12D6 for TAP1 and mAb VF118-1E4 and VF118-2C5 for TAP2, since they reacted specifically with the corresponding immunogens in ELISA and with the corresponding LMP and TAP subunits when tested in Western blotting with human lymphoid cell extracts. Furthermore, the mAb immunoprecipitated components with the characteristic electrophoretic mobility from lymphoid cells. Both anti-LMP and anti-TAP mAb stained keratinocytes and infiltrating lymphocytes in frozen and formalin-fixed, paraffin embedded sections of normal skin in indirect immunoperoxidase reactions. Furthermore, all the mAb except mAb VF103-5D5 stained the cytoplasm of lymphoid cells in an intracytoplasmic staining reaction. The specificity and reactivity pattern of the mAb we have characterized indicate that they will be valuable reagents to analyze the cellular expression and tissue distribution of LMP and TAP subunits.     

INVESTIGATION OF THE ROLE OF RESIDUAL STRESSES IN THE WARM PRESTRESS (WPS) EFFECT. PART I—EXPERIMENTAL

Abstract— The role of residual stresses in the warm prestress (WPS) effect has been investigated. Three types of specimen have been tested in this investigation: smooth uniaxial tensile specimens, blunt notched single edge notched bend (SENB) specimens and sharply precracked SENB specimens. Room temperature prestraining of uniaxial tensile specimens leads to a dramatic decrease in the measured nominal fracture stress at — 196°C. Such an embrittling effect may be expected to reduce the beneficial increase in subsequent fracture toughness commonly observed in WPS sequences. The blunt-notched specimens were prestressed in tension and compression. Compressive prestressing was found to lead to a decrease in subsequent fracture load whereas tensile prestressing leads to an increase. The load decrease following a compressive WPS was greater than the load increase following a tensile WPS. Various sequences of loading, unloading and cooling have been investigated and the differences in the subsequent fracture behaviour of specimens have been explained qualitatively by superposition arguments. The theories of Chell and Curry have been supported by the general trend of results.     

Nutritional intervention and growth in children with chronic renal failure

During fifties there were at most few tens of persons in this country who believed in the future of computers and cybernetics. One group of such enthusiasts, headed by Antonín Svoboda, was working at a construction of the first Czech computer SAPO. The other group tried to analyse, anticipate, and prepare in advance various applications for the new systemic conceptions and for the information processing machines. Members of both groups met for discussions which opened prospects to the future and influenced many of other activities for a long time. At the early sixties, the Czechoslovak Cybernetic Society was established at the Czechoslovak Academy of Sciences and in 1962 the Main Problem Committee for the Medical Cybernetics was founded at the Department of Health. It coordinated majority of the research programmes in the medical cybernetics and informatics. In 1967-1969 the Committee prepared an extensive project of a medical information system (ZIS), but its accomplishment was finally blocked by the then authorities. However, interests for that topics kept growing and the new working places equipped with available computer technology were formed at the health and clinical centres. The first tentative lectures in medical cybernetics and biocybernetics at our faculty were introduced into the students curricula in the late sixties. Thematically, medical cybernetics subsequently differentiated into the medical informatics, simulations of biological and medical systems, and the biosignal analysis. The growing interest enabled to hold conferences since the middle of seventies, some of which were held periodically, sometimes with international participation. It is not possible in brevity to include the whole spectrum to those goal-directed activities nor to appraise adequately their future significance.     

Anatomy of a text analysis package

A model of a text processing package is described which is based on elementary set theory. This is used to describe procedures for computing indexes, concordances, and collocations. Aspects of the implementation of the model are given.