Insulin and insulin-like growth factor-I signal transduction requires p21ras

We have investigated the role of cellular p21ras protein in insulin and insulin-like growth factor-I (IGF-I) signaling pathways. Insulin stimulation increased Ras-GTP formation in Rat-1 fibroblasts overexpressing normal human insulin receptors (HIRc-B), far greater than in parental Rat-1 fibroblasts, indicating that competent insulin receptors mediate this response. Cellular microinjection of a dominant-negative mutant p21ras protein (N17 ras) or anti-p21ras monoclonal antibody (Y13-259) into HIRc-B cells reduced insulin- and IGF-I-stimulated DNA synthesis by 75-90%. Insulin-induced c-fos protein expression was also inhibited by 74%. Microinjection of oncogenic p21ras (T-24 ras) into HIRc-B cells activated the mitogenic pathway, and coinjection of N17 ras and T-24 ras showed that oncogenic p21ras rescued the cells from the N17 ras blockade. This later finding indicates that T-24 ras acts downstream of N17 ras. In conclusion, 1) microinjection of a dominant interferring ras mutant into quiescent cells abrogated subsequent insulin and IGF-I mitogenic signaling; 2) oncogenic ras protein rescued cells from the N17 ras blockade, indicating that T24 ras action is downstream of the site of N17 inhibition; and 3) p21ras is an intermediate signaling molecule in the insulin/IGF-I signal transduction pathway and is required for gene expression and DNA synthesis.     

Biotransformation and toxicity of the lipoxygenase inhibitor 2-hydroxy-5-methyllaurophenone oxime (FLM 5011) on Hep G2 cells

2-Hydroxy-5-methyllaurophenone oxime (FLM 5011) is an inhibitor of lipoxygenase with antiinflammatory and antiallergic actions. We incubated FLM 5011 on the human immortal cell line Hep G2 and found a similar metabolite spectrum as in rat urine and faeces. We also measured the cytotoxicity of FLM 5011 on Hep G2 monolayers by the amido black assay and found that the influence of cell proliferation is partly due to apoptotic activities. Although the metabolic activity of Hep G2 cells is lower compared to rat hepatocyte cultures they are a suitable test system for biotransformation studies. Their higher proliferation rate allows toxicity to be characterised more exactly.     

Human lung cancer antigens recognized by autologous antibodies: definition of a novel cDNA derived from the tumor suppressor gene locus on chromosome 3p21.3

Supplementation with high doses of alpha-tocopherol has increased the oxidation resistance of LDL in many clinical trials. There have been only a few placebo-controlled trials in healthy persons of alpha-tocopherol doses usually contained in dietary supplements. We carried out a single-blind, placebo-controlled, randomized trial to examine the effect of 200 mg RRR-alpha-tocopheryl acetate/d on the oxidation resistance of atherogenic lipoproteins (VLDL+LDL including intermediate-density lipoproteins) in 40 smoking men. VLDL+LDL oxidation resistance was assessed as conjugated dienes after copper induction and hemin degradation after hydrogen peroxide induction. Also, the LDL total peroxyl-radical trapping antioxidant parameter (LDL TRAP) and plasma malondialdehyde were measured at baseline and after 2 mo of supplementation. Plasma RRR-alpha-tocopherol concentrations were measured at 2-h intervals for 12 h at baseline and after 2 mo of supplementation. Compared with placebo, 200-mg RRR-alpha-tocopheryl acetate supplementation elevated plasma and VLDL+LDL alpha-tocopherol concentrations, LDL TRAP, and oxidation resistance of VLDL+LDL. Plasma alpha-tocopherol increased by 88% (P < 0.0001), VLDL+LDL alpha-tocopherol increased by 90% (P < 0.0001), and LDL TRAP by 58% (P < 0.0001). The time to the start of oxidation (lag time) was prolonged by 34% when assessed with a copper-induced method and by 109% when assessed with a hemin + hydrogen peroxide-induced method; the time to maximal oxidation was prolonged by 21% (copper-induced method) in the vitamin E-supplemented group. Changes in plasma alpha-tocopherol, lipid-standardized alpha-tocopherol, and VLDL+LDL alpha-tocopherol correlated significantly with changes in LDL TRAP, lag time, and time to maximal oxidation. Differences in changes between groups in the area under the curve for plasma alpha-tocopherol were significant (P < 0.009). Our results suggest that 200 mg oral RRR-alpha-tocopheryl acetate/d had a clear effect on the in vitro oxidation of VLDL+LDL in smoking men.     

Gastric mucosal biopsy via a nasogastric tube: a nonendoscopic method for diagnosing fundic and antral mucosal gastritis and Helicobacter pylori infection in man

Synthesis of poly(gamma-glutamate) metabolites of natural folates and antifolates is a critical process. Folypolyglutamates are essential for cell proliferation. Polyglutamates of glutamate (Glu)-containing antifolates are often critical for their cytotoxic action and are relevant to antifolate resistance. However, the role of polyglutamate synthesis in selectivity is less clear. We have undertaken a research program to further define the significance of polyglutamate metabolism and to devise ways to exploit this metabolism to achieve greater therapeutic selectivity in cancer chemotherapy. This article briefly reviews several approaches tested thus far. Inhibition of folypolyglutamate synthesis should lead to cell death. Current ornithine (Orn)-containing folate-based inhibitors of the enzyme responsible for their synthesis, folypolyglutamate synthetase (FPGS), are poorly transported, apparently because of interference by the protonated delta-amine. Replacement of Orn with 4, 4-difluoroOrn, the delta-amine of which has a much lower pKa and is thus less protonated at physiological pH, was explored. Since it is unclear how polyglutamylation contributes to selectivity, we explored generic means either to eliminate or to enhance polyglutamylation. The data indicate that substitution for Glu in an antifolate by some Glu analogs in which the gamma-COOH is either altered or replaced (e.g., gamma-tetrazole-Glu) leads to loss of both FPGS substrate activity and binding; antifolate target specificity is unchanged, while uptake is actually enhanced. Substitution of 3,3-difluoroGlu for Glu leads to enhanced polyglutamylation (although probably only to the diglutamate), retention of target specificity, and at least equal uptake. Comparative studies of the same antifolate containing different replacements for Glu, such as gamma-tetrazole-Glu (no polyglutamylation) or 3,3-difluoroGlu (enhanced polyglutamylation), will be useful in exploring the role and significance of polyglutamylation.     

Management of E. coli dependent factorial diseases in weaning piglets

The most important postweaning factorial diseases are at least partly caused by E. coli. The term postweaning coli complex can be subcategorized into the following manifestations: postweaning diarrhoea, edema disease, postweaning wasting and hemorrhagic gastroenteritis. In the presented study the effect of prophylactic zootechnique alone and zoo- and biotechnique in combination was evaluated during the first weeks postweaning. The results showed that combined zoo- and biotechnique is superior to simple zootechnique regarding food conversion (1.41 kg versus 1.73 kg), average daily weight gain (390 g versus 325 g) and postweaning piglet mortality (3.1% versus 4.9%). It is the opinion of the authors that combined postweaning zoo- and biotechnique should be performed in such pig production units where ETEC and/or SLTEC are present.     

Design of an X-band transformer-coupled amplifier withimproved stability and layout

The authors present a push-pull transformer-coupled amplifier for monolithic microwave applications, and discuss how its stability and layout have been improved with respect to conventional approaches by means of opposite-phase feedback and fully symmetrical layout. The circuit provides state-of-the-art performance (10-dB gain and 18-dBm saturated power in the 4-8-GHz band) with only 165-mW DC power consumption     

Study of Desorption and Adsorption During Grain Aeration

One requirement in designing and operating and operating system is to minimize the moisture change in stored grain. Moisture transfer during the aeration process is generally believed to be caused by the partial pressure difference between water in grain and water in air (P₃-P₄). A mathematical model was developed for rough rice, which predicts the partial pressure difference under various grain and ambient conditions. Observations of moisture change over 10 aeration tests confirmed the good correlation between sorption phenomena and partial pressure differences. Studies indicated that air relative humidity, air temperature, grain temperature and grain moisture are significant factors influencing the partial pressure differences and, thus, affecting     

Theoretical and Experimental Study of Water Transport in a Hollow Cylinder Applied to the Drying of Round Squid Mantle

Until now, attention has been focused solely in the drying of squid mantle from an experimental point of view, neglecting the transport phenomenon studies of water in squid muscle. This work studies the drying of squid mantle (Loligo brasiliensis), previously salted and smoked by liquid smoking (hickory extract), using a tubular dryer in closed cycle with a silicagel fixed bed in series. The mass transfer phenomenon during drying was studied, based on the Fick's second law, with the effective diffusivity supposed constant, which enabled an analytical solution to the problem. The drying curve calculated with the resulting equation was compared with experimental data. The model was applied to a hollow cylinder geometry (round squid mantle), with its internal surface isolated from the drying environment by a plastic film. The latter was given a tubular form and introduced inside the mantle cavity (impervious wall boundary condition).     

High speed p-type SiGe modulation-doped field-effect transistors

We report on the fabrication and characterization of high-speed p-type modulation-doped field-effect transistors (MODFETs) with 0.7-μm and 1-μm gate-lengths having unity current-gain cut-off frequencies (f_T) of 9.5 GHz and 5.3 GHz, respectively. The devices were fabricated on a high hole mobility SiGe heterostructure grown by ultra-high-vacuum chemical vapor deposition (UHV-CVD). The dc maximum extrinsic transconductance (g_m) is 105 mS/mm (205 mS/mm) at room temperature (77 K) for the 0.7-μm gate length devices. The fabricated devices show good pinch-off characteristics and have a very low gate leakage current of a few μA/mm at room temperature and a few nA/mm at 77 K