Acute Myelogenous Leukemia Cells Secrete Factors that Stimulate Cellular LDL Uptake via Autocrine and Paracrine Mechanisms

Leukemic cells isolated from most patients with acute myelogenous leukemia (AML) have higher low density lipoprotein (LDL) uptake than normal mononuclear blood cells. Little is known, however, about the mechanism behind the elevated LDL uptake. We investigated if AML cells secrete factors that stimulate cellular LDL uptake. Mononuclear blood cells were isolated from peripheral blood from 42 patients with AML at diagnosis. Cellular LDL uptake was determined from the degradation rate of ¹²⁵I-labelled LDL. Conditioned media from AML cells stimulated the LDL degradation in the leukemic cell lines KG1 and HL60, and in isolated AML cells. The stimulatory effect correlated with the LDL degradation in the AML cells directly after isolation from blood. Conditioned media also autostimulated LDL degradation in the AML cells themselves. Concentrations of IL-6 and IL-8 in AML cell conditioned media correlated with the LDL degradation in AML cells directly after isolation from blood. Addition of R-TNF-α, but not IL-6 or IL-8, stimulated LDL degradation in HL60, KG1, and AML cells. The LDL degradation in AML cells could be inhibited by a LDL receptor blocking antibody. AML cells secrete factors that stimulate LDL uptake in a paracrine and autocrine pattern which open up therapeutic possibilities to inhibit the uptake of LDL by administration of antibodies to these factors.     

Affinity-assisted in vivo folding of a secreted human peptide hormone in Escherichia coli

We show that coexpression of a specific binding protein in Escherichia coli can significantly improve the relative yields of correctly folded human insulin-like growth factor I (IGF-I). A glutathione redox buffer was used during growth to allow formation and breakage of disulfide bonds in the periplasm of the bacterial host. Both the binding protein and the peptide hormone were produced as affinity fusions, which allowed purification of the in vivo formed heterodimer by alternative affinity purification methods. The use of affinity-assisted in vivo folding has general implications for expression, folding, and purification of recombinant proteins.     

Multidimensional companding quantization of the Gaussian source

Multidimensional companding quantization is analyzed theoretically for the case of high-resolution and mean-squared-error distortion. The optimality of choosing the expander function to be the inverse of the compressor function is established first. Heuristic derivations of the point density and moment of inertia of companding are given, which combined result in the distortion formula by Bucklew. Further, the interaction between the lattice quantizer (LQ) and compressor function is studied. Optimality is achieved with a second moment optimal LQ, shaped by a compressor-dependent linear transform. High rate theory for a radial compander and spherically symmetric sources is reviewed. The result is used to evaluate the performance on an independent and identically distributed (i.i.d.) Gaussian source. The radial compander clearly outperforms both a product scalar quantizer and a spherical quantizer for dimensions higher than two. Radial companding is also generalized to the correlated Gaussian source. Finally, a comparison of theory and practical companders is made in a Gaussian framework.     

A Genetic Analysis of Population Differences in Pheromone Production and Response Between Two Populations of the Turnip Moth,Agrotis segetum

The genetic basis of the differences in female pheromone blend ratio and male behavioral response in the turnip moth,Agrotis segetum, was examined by crossing individuals derived from Scandinavian and Zimbabwean populations. These two populations differ both in the ratio of the three major female pheromone components,Z5–10:OAc,Z7–12:OAc, andZ9–14: OAc and in the behavioral response of the males in both wind-tunnel and field-trapping assays. The female pheromone blend in this study is treated as the log ngZ5–10:OAc/ngZ7–12:OAc and log ngZ9–14:OAc/ngZ7–12:OAc for statistical analysis. The mean log ngZ5–10:OAc/ngZ7–12:OAc, is under control by a major autosomal factor or factors, but it is unclear what genetic factor or factors may control the mean log ngZ9–14:OAc/ngZ7–12:OAc. Frequency distributions of the proportions of each component show wide individual variation and also suggest control ofZ5–10:OAc andZ7–12:OAc by major autosomal factors, which forZ5–10:OAc may show partial dominance. Analysis of male behavioral response to synthetic blends in the wind tunnel yields inconclusive results, but suggests thatA. segetum may have a broad window of response that reflects the range of individual variation in female blends.     

NORCHIP,a silicon brokers model

A Nordic Multi-Project-Chip organization with 26 design groups and 22 follow-up groups from five Nordic countries is described. The model for cooperation, the economy of the project, the applied technique and the impact on both industry and university research are dealt with. So far, 70 designs in three runs have been completed and 9 runs with 200 designs with extensive use of cell libraries are under way in 1983.Aiming towards submicron technology MPC might be the only possible way for smaller companies and universities to have circuits made.     

Rapamycin pre-treatment preserves viability, ATP level and catabolic capacity during carbon starvation of Saccharomyces cerevisiae

Saccharomyces cerevisiae growing exponentially in anaerobic batch cultures that are suddenly exposed to carbon starvation will rapidly lose almost all ATP. This will cause an energy deficiency and adaptation to starvation conditions is prohibited. As a result, viability and fermentative capacity will be drastically reduced during prolonged starvation. However, if the cells are incubated in the presence of rapamycin (which will inactivate the TOR pathway) before carbon starvation ATP levels, viability and fermentative capacity will be preserved to a much larger extent compared to untreated cells. The beneficial effect of rapamycin cannot be explained by induction of a stationary phase phenotype. In fact, under these anaerobic well-controlled growth conditions, rapamycin-treated cells were still metabolically active and continued to grow, albeit not exponentially and with a reduced protein content. It is hypothesized that the loss of ATP during carbon starvation occurs because protein synthesis does not make an immediate arrest at the onset of starvation. Since there are no external or internal energy sources, this will rapidly deplete the cells of ATP. Rapamycin-treated cells, on the other hand, have already downregulated the protein-synthesizing machinery and are thus better suited to cope with a sudden carbon starvation condition. This hypothesis is strengthened by the fact that treating the cells with the protein synthesis inhibitor cycloheximide also improves the carbon starvation tolerance, although not to the same extent as rapamycin. The even better effect of rapamycin is explained by accumulation of storage carbohydrates, which is not observed for cycloheximide-treated cells.     

Weld Quality Assessment and Actions

Since 1989, Nordic industries, organizations and universities have co‐operated in numerous projects related to the design and fabrication of welded structures. In a current ongoing project, QFAB, over 20 participants are working together to improve the design, fabrication and cost effectiveness of complex welded structures. This paper describes the background to this project and will also discuss the process of quality assessment of welded construction machinery. The main part of the supporting framework on vehicles consists of welded steel structures. These welds contain defects and imperfections from the weld process itself and when severe load conditions are present, a finite life is at hand. The competition among manufacturers towards higher productivity and lower fuel consumption drives the engineers to design lighter structures preferably in high strength material. Such a design requires a higher weld quality and calls special attention to design and manufacturing of welds. A major issue is thus to form a scientific and consistent base which can be used when analysis and design is integrated with production and quality inspection of components. The goal is to build world class vehicles for operation without failures in service during the economic life.     

Electrophysiological and chemical analysis of sex pheromone communication system of the mottled umber,Erannis defoliaria (Lepidoptera: Geometridae)

(Z,Z,Z)-3,6,9-nonadecatriene (Z3,Z6,Z9–19Hy) and (Z,Z)-3,9-cis-6,7-epoxy-nonadecadiene (Z3,Z9-cis-6,7-epo-19Hy) were identified in pheromone gland extracts from femaleErannis defoliaria. The two components were found in a 13 ratio, with the main component,Z3,Z9-cis-6,7-epo-19Hy present at an amount of about 1.5 ng per female. The components were identified by means of gas chromatography-mass spectrometry, gas chromatography-electroantennography and gas chromatography-single sensillum recordings. Single sensillum measurements on the male antenna showed two physiological types of sensilla. One type was characterized by a large spike amplitude cell responding toZ3,Z9-cis-6,7-epoxy-19Hy and a small spike amplitude cell responding toZ3,Z6,Z9–19Hy. A second type responded only with a large spike amplitude cell to the epoxide, and this cell was inhibited by the triene. Of the two pheromone components, the epoxide gave the higher response in the EAG tests. Preliminary field tests support the identification of the pheromone components. The epoxide was also found to be present in the extract of the pheromone gland ofColotois pennaria, and males ofC. pennaria andAgriopis marginaria were trapped by the mixture of the identified compounds.     

Effects of respiratory alkalosis and acidosis on myocardial excitation

The adipokinetic activities, relative to isoproterenol as 1,000, in sedated, phenoxybenzamine pretreated unfasted mice were: norepinephrine 540, epinephrine 330, N-t-butylnorepinephrine 130, isoetharine 30 and N-cyclopentylbutanefrine 10. These relative activities correlate (r=0.88) with the medians of some previously defined beta1-adrenoceptor activities, but not (r=less than 0.1) with the medians of some previously defined beta2-adrenoceptor activities. These findings are in accord with the previously suggested view that an alpha, beta1-, beta2-, adrenoceptor concept is in better accord with experimental evidence that is an alpha- and beta-adrenoceptor one.