The IGF-I Receptor in Mitogenesis and Transformation of Mouse Embryo Cells: Role of Receptor Number

The type 1 receptor for insulin-like growth factors (IGF-IR) plays an important role in the growth and transformation of several types of cells. We have investigated the role of IGF-IR number in IGF-I-mediated mitogenesis and transformation of mouse embryo fibroblasts. We have used R⁻cells (3T3-like cells originating from mouse embryos with a targeted disruption of the IGF-IR genes) transfected with a plasmid expressing the human IGF-IR cDNA to generate clones with receptor numbers ranging from zero to 10⁶receptors per cell. In this model, between 15,000 and 22,000 receptors per cell are sufficient to render mouse embryo cells competent to grow in serum-free medium supplemented solely with IGF-I. For growth in soft agar, 30,000 receptors per cell seem to be the minimum requirement. These experiments indicate that a small increment in the number of receptors per cell, well within the physiological range, can modulate the mitogenic and transforming activities of the IGF-IR in 3T3-like cells.     

Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability

Bush, Michele L., Patrick T. Asplund, Kristen A. Miles,Abdellaziz Ben-Jebria, and James S. Ultman. Longitudinaldistribution of O₃ absorption inthe lung: gender differences and intersubject variability.J. Appl. Physiol. 81(4):1651-1657, 1996.Because the National Ambient Air QualityStandard for ozone (O₃) isintended to protect the most sensitive individuals in the generalpopulation, it is necessary to identify sources of intersubjectvariation in the exposure-dose-response cascade. We hypothesize thatdifferences in lung anatomy can modulate exposure-dose relationshipsbetween individuals, and this results in differences between theirresponsiveness to O₃ at a fixedexposure condition. During quiet breathing, the conducting airwaysremove the majority of inhaled O₃,so the volume of this region should have an important impact onO₃ dose distribution. Employingthe bolus inhalation method, we measured the distribution ofO₃ absorption with respect topenetration volume (V_P), and using the Fowler single-breath N₂washout method, we determined the dead space volume(VD) in the lungs of 10 menand 10 women at a fixed respiratory flow of 250 ml/s. On average, thewomen absorbed O₃ at smallerV_P than the men, and the women hadsmaller VD than the men. Whenexpressed in terms ofV_P/ VD,the absorption distribution of the men and women was indistinguishable.Moreover, an interpretation of theO₃ distribution in terms of anintrinsic mass transfer parameter(Ka) indicated that differencesbetween the O₃ dosimetry in allsubjects, whether men or women, could be explained by a uniquecorrelation with anatomic dead space: Ka (ins¹) = 610 VD^1.05(in ml). Application of this result to measurements ofO₃ exposure response indicatedthat previously reported gender differences may be due to a failure inproperly accounting for tissue surface within the conducting airways.

     

A first linkage map of Cichorium intybus L. using a one-way pseudo-testcross and PCR-derived markers

We have used a one-way pseudo-testcross mapping strategy in combination with different types of PCR-based markers (RAPD, AFLP, SAMPL) to construct a first linkage map for variegated chicory (Cichorium intybus L. var. silvestre Biskoff, n=9), a self-incompatible vegetable species. The success of such a strategy depends on the presence of sufficiently high levels of heterozygosity in the individual plant which is being mapped and on the informativeness of the marker system that is used. A total of 371 markers, comprising 16 RAPDs, 72 SAMPLs and 283 AFLPs, were scored in 46 F₁ individuals obtained from an interspecific cross between a C. intybus outbred individual and a C. endivia inbred line. Grouping of the markers at a LOD score of 4.0 resulted in 13 linkage groups covering 1330 cM. A framework map covering 1201.4 cM was assembled by using all markers that could be ordered with a LOD greater than 2.0. We estimate the total genome size of chicory to be ca. 1405 cM, thus considerably smaller than that estimated for lettuce (1950 cM). The usefulness of the different marker systems that were applied is analysed in terms of level of heterozygosity and marker index, i.e. number of different genetic loci that may be simultaneously analysed per experiment. Out of the 371 markers, 50 of them showed segregation distortion which is discussed in terms of the hybrid origin of the variegated chicory.     

Inhibition of Helicobacter pylori by garlic extract (Allium sativum)

Abstract The antibacterial effect of aqueous garlic extract (AGE) was investigated against Helicobacter pylori . Sixteen clinical isolates and three reference strains of H. pylori were studied. Two different varieties of garlic were used. The concentration of AGE required to inhibit the bacterial growth was between 2–5 mg ml⁻¹. The concentration, for both AGE types, to inhibit 90% (MIC₉₀) of isolates was 5 mg ml⁻¹. The minimum bactericidal concentration (MBC) was usually equal to, or two-fold higher than, minimum inhibitory concentration (MIC). Heat treatment of extracts reduced the inhibitory or bactericidal activity against H. pylori ; the boiled garlic extract showed a loss of efficacy from two-to four-fold the values of MIC and the MBC obtained with fresh AGR. The antibacterial activity of garlic was also studied after combination with a proton pump-inhibitor (omeprazole) in a ratio of 250:1. A synergistic effect was found in 47% of strains studied; an antagonistic effect was not observed.     

Crowned dopa's,their dimers,cyclodimers and polymers: Synthesis and cation complexation

Optically pure protected L -[3,4-(1,4,7,10,13-pentaoxatridecamethylene) phenyl] alanine, its dipeptide, diketopiperazine and homopolymer, protected L -[3,4-(1,4,7,10,13,16-hexaoxahexadecamethylene) phenyl] alanine and its polymer have been synthesized and characterized. These crown ether derivatives complex the potassium and ammonium cations as well as protonated leucine and glycine in tetrahydrofuran and methanol. They are also phase-transfer agents. The cooperativity of the crown units was studied in detail for the dimeric ligands.     

Regional-dependent increase of sympathetic innervation in rat white adipose tissue during prolonged fasting.

White adipose tissue (WAT) is innervated by the sympathetic nervous system. A role for WAT sympathetic noradrenergic nerves in lipid mobilization has been suggested. To gain insight into the involvement of nerve activity in the delipidation process, WAT nerves were investigated in rat retroperitoneal and epididymal depots after prolonged fasting. A significant increase in tyrosine hydroxylase (TH) content was found in epididymal and, especially, retroperitoneal WAT by Western blotting. Accordingly, an increased immunoreactivity for TH was detected by immunohistochemistry in epididymal and, especially, retroperitoneal vascular and parenchymal noradrenergic nerves. Neuropeptide Y (NPY)-containing nerves were found around arteries and in the parenchyma. Double-staining experiments and confocal microscopy showed that most perivascular and some parenchymal noradrenergic nerves also contained NPY. Detection of protein gene product (PGP) 9.5, a general marker of peripheral nerves, by Western blotting and PGP 9.5-TH by double-staining experiments showed significantly increased noradrenergic nerve density in fasted retroperitoneal, but not epididymal depots, suggesting that formation of new nerves takes place in retroperitoneal WAT in fasting conditions. On the whole, these data confirm the important role of sympathetic noradrenergic nerves in WAT lipid mobilization during fasting but also raise questions about the physiological role of regional-dependent nerve adjustments and their functional significance in relation to white adipocyte secretory products.     

Risikofaktoren für Krebs und MS in Kuhmilch und Rindfleisch?

Dairy cattle meat and milk factors contributing to the risk of cancers and multiple sclerosis A global epidemiological analysis of the incidence of colon and breast cancers suggests that consumption of meat and milk products of Eurasian dairy cattle contributes to the risk for these malignancies. Our group isolated a number of novel single‐stranded DNAs from serum and milk of dairy cattle. These are circular molecules (～1000–3000 nucleotides) of putative viral origin. Apparently this DNA does not integrate into chromosomal DNA of the animal hosts, but persists in a non‐integrated (episomal) state. Following transmission into human cells, this DNA is genetically active. Related isolates have been obtained from two lesions of patients with multiple sclerosis. Concepts have been developed to explain the potential etiological role of such agents for specific human diseases. Their involvement in human cancers and neurological diseases is presently subject of intensive investigations.