Overproduction Factor Research Articles

Role of cysteinyl-leukotrienes in the pathogenesis of nasal polyposis in patients with asthma

Cysteinyl leukotrienes (CysLTs: leukotrienes C4, D4, and E4) have long been implicated in the pathogenesis of allergic diseases such as asthma. CysLTs are potent bronchoconstrictors that have the additional effects of edema, mucous secretion, and eosinophilic accumulation, and airway remodeling. LTE4 has been identified as a major metabolite of LTC4, and urinary LTE4 (U-LTE4) is considered as the most reliable analytic parameter for monitoring the endogenous synthesis of CysLTs. From our extensive study of U-LTE4 in adult asthma, we identified four factors for hyperleukotrienuria. These factors were aspirin-intolerance, eosinophilic nasal polyposis (ENP), vasculitis, and severe asthma. In ENP there is prominent infiltration of eosinophils in the sinus and polyp tissues, which is linked to adult asthma and aspirin-sensitivity, and ENP is the most important factor for overproduction of CysLTs in asthmatics. We demonstrated that there is a significant decrease in the U-LTE4 concentration after the sinus surgery of asthmatics with and without aspirin intolerance. Recent studies reported that ENP tissue contain and produce a large amount of CysLTs, and there is a close relationship between CysLT production and eosinophil accumulation in ENP. These observations suggest that ENP is not only a local allergic disease, but also a systemic inflammatory disease with CysLT overproduction.

Intestinal Insulin Resistance and Aberrant Production of Apolipoprotein B48 Lipoproteins in an Animal Model of Insulin Resistance and Metabolic Dyslipidemia

Postprandial dyslipidemia is recognized as an important complication of insulin-resistant states, and recent evidence implicates intestinal lipoprotein overproduction as a causative factor. The mechanisms linking intestinal lipoprotein overproduction and aberrant insulin signaling in intestinal enterocytes are currently unknown. Intestinal insulin sensitivity and lipid metabolism were studied in a fructose-fed hamster model of insulin resistance and metabolic dyslipidemia. Intestinal lipoprotein production in chow-fed hamsters was responsive to the inhibitory effects of insulin, and a decrease in circulating levels of triglyceride-rich apolipoprotein (apo)B48-containing lipoproteins occurred 60 min after insulin administration. However, fructose-fed hamster intestine was not responsive to the insulin-induced downregulation of apoB48-lipoprotein production, suggesting insulin insensitivity at the level of the intestine. Enterocytes from the fructose-fed hamster exhibited normal activity of the insulin receptor but reduced levels of insulin receptor substrate-1 phosphorylation and mass and Akt protein mass. Conversely, the protein mass of the p110 subunit of phosphatidylinositol 3-kinase, protein tyrosine phosphatase-1B, and basal levels of phosphorylated extracellular signal-related kinase (ERK) were significantly increased in the fructose-fed hamster intestine. Modulating the ERK pathway through in vivo inhibition of mitogen-activated protein/ERK kinase 1/2, the upstream activator of ERK1/2, we observed a significant decrease in intestinal apoB48 synthesis and secretion. Interestingly, enhanced basal ERK activity in the fructose-fed hamster intestine was accompanied by an increased activation of sterol regulatory element-binding protein. In summary, these data suggest that insulin insensitivity at the level of the intestine and aberrant insulin signaling are important underlying factors in intestinal overproduction of highly atherogenic apoB48-containing lipoproteins in the insulin-resistant state. Basal activation of the ERK pathway may be an important contributor to the aberrant insulin signaling and lipoprotein overproduction in this model.

The s-process weak component: uncertainties due to convective overshooting

Using a new s-nucleosynthesis code, coupled with the stellar evolution code Star2003, we performed simulations to study the impact of the convection treatment on the s-process during core He-burning of a 25 Msun star (ZAMS mass) with an initial metallicity of Z=0.02. Particular attention was devoted to the impact of the extent of overshooting on the s-process efficiency. The results show enhancements of about a factor 2-3 in s-process efficiency (measured as the average overproduction factor of the 6 s-only nuclear species with $60\lesssim A\lesssim 90$) with overshooting parameter values in the range 0.01-0.035, compared to results obtained with the same model but without overshooting. The impact of these results on the p-process model based on type II supernovae is discussed.

Changes in Composition and Content of Mycolic Acids in Glutamate-OverproducingCorynebacterium glutamicum

Overproduction of glutamate by Corynebacterium glutamicum is induced by biotin limitation or by the supplementation of specific detergents, sublethal amounts of penicillin, or cerulenin. But, it remains unclear why these different treatments, which have different sites of primary action, produce similar effects. In this study, it was found that the cellular content of mycolic acids--characteristic constituents of Corynebacterineae that are synthesized from fatty acids and form a cell surface layer--decreased under all conditions that induced glutamate overproduction. Furthermore, short mycolic acids increased under conditions of biotin limitation and cerulenin supplementation. These results suggest that different treatments produce the same effect that causes defects in the mycolic acid layer. This is perhaps one of the key factors in overproduction of glutamate by C. glutamicum.

Overexpression of TGF-beta by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer.

Pancreatic cancer is often associated with an intense production of interstitial collagens, known as the desmoplastic reaction. To understand more about desmoplasia in pancreatic cancer, the expression of mRNA for type I and III collagens and potent desmoplastic inducing growth factors transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), acidic and basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) A and C and epidermal growth factor (EGF) was analysed by quantitative RT–PCR. Expression of both collagens in 23 frozen primary pancreatic cancer nodules was significantly higher than that in 15 non-neoplastic pancreatic tissues. The expressions of mRNAs for TGF-β, acidic FGF, basic FGF and PDGF C were likewise higher in surgical cancer nodules, while that of CTGF, PDGF A and EGF were not. Among these growth factors, the expression of TGF-β mRNA showed the most significant correlation with that of collagens (P<0.0001). By immunohistochemistry, TGF-β showed faint cytoplasmic staining in cancer cells. In contrast, isolated cells, mainly located on the invasive front surrounding cancerous nests, were prominently and strongly stained. These TGF-β-positive cells contained a segmented nucleus, were negative for anti-macrophage (CD68) and positive for anti-granulocyte antibodies, indicating their granulocytic nature. In conclusion, TGF-β seemed to play a major role among the various growth factors in characteristic overproduction of collagens in pancreatic cancer. Moreover, the predominant cells that express TGF-β were likely to be infiltrated granulocytes (mostly are neutrophils) and not pancreatic cancer cells.

Physiological responses of wild type and putrescine-overproducing transgenic cells of poplar to variations in the form and concentration of nitrogen in the medium.

We determined: (a) the physiological consequences of overproduction of putrescine in transgenic poplar (Populus nigra x maximoviczii) cells expressing an ornithine decarboxylase transgene; and (b) effects of variation in nitrogen (N) concentration of the medium on cellular polyamine concentration in transgenic and non-transgenic cells. Cells grown in the presence of supplemental (to the normal concentrations of N sources in the growth medium) and reduced amounts of NH4NO3 and KNO3 were used to study effects on membrane permeability, mitochondrial respiratory activity, protein accumulation, growth rates and changes in cellular polyamine concentration. The N concentration of the MS medium was not a limiting factor for continued overproduction of putrescine in transgenic cells. However, continued supplies of NH4+ and NO3- were required to maintain homeostatic amounts of putrescine in both cell lines. The presence of high amounts of putrescine in transgenic cells had significant effects on the physiological parameters measured. Compared with non-transgenic cells, transgenic cells had greater plasma membrane permeability, less tolerance to NH4NO3, more tolerance to KNO3, and accumulated higher amounts of soluble protein.

Rp-process nucleosynthesis at extreme temperature and density conditions

We present nuclear reaction network calculations to investigate the influence of nuclear structure on the rp-process between Ge and Sn in various scenarios. Due to the lack of experimental data for neutron-deficient nuclei in this region, we discuss currently available model predictions for nuclear masses and deformations as well as methods of calculating reaction rates (Hauser-Feshbach) and β-decay rates (QRPA and shell model). In addition, we apply a valence nucleon ( N p N n) correlation scheme for the prediction of masses and deformations. We also describe the calculations of 2p-capture reactions, which had not been considered before in this mass region. We find that in X-ray bursts 2p-capture reactions accelerate the reaction flow into the Z ≥ 36 region considerably. Therefore, the rp-process in most X-ray bursts does not end in the Z = 32–36 region as previously assumed and overproduction factors of 10 7–10 8 are reached for some light p-nuclei in the A = 80–100 region. This might be of interest in respect of the yet unexplained large observed solar system abundances of these nuclei. Nuclei in this region can also be produced via the rp-proces in accretion disks around low mass black holes. Our results indicate that the rp-process energy production in the Z > 32 region cannot be neglected in these scenarios. We discuss in detail the influence of the various nuclear structure input parameters and their current uncertainties on these results. It turns out that rp-process nucleosynthesis is mainly determined by nuclear masses and β-decay rates of nuclei along the proton drip line. We present a detailed list of nuclei for which mass or β-decay rate measurements would be crucial to further constrain the models.

Na +-dependent glucose uptake and collagen synthesis by cultured bovine retinal pericytes

This study was performed to clarify the presence of sodium-dependent glucose uptake and its role in the synthesis of type IV and type VI collagen by cultured bovine retinal pericytes. The glucose uptake by retinal pericytes and retinal endothelial cells was measured using 3 H - d-glucose in the presence or absence of sodium. Glucose uptake in the presence of sodium was twice as high as that observed in the presence of phlorizin and sodium or in the absence of sodium. Sodium-dependent glucose uptake was observed at different sodium concentrations, and its half-maximal stimulation occurred at 48 mM. These findings were not observed in retinal endothelial cells. Levels of type IV and type VI collagen produced by retinal pericytes were significantly increased at glucose concentrations higher than 20 mM. Phlorizin decreased both collagen synthesis and glucose consumption by retinal pericytes incubated with 30 mM of glucose to the levels observed with 5 mM of glucose. These data suggest that sodium-dependent glucose uptake is present in retinal pericytes and that excessive glucose entry into the cell is an important factor for overproduction of collagen. Phlorizin normalized the synthesis of type IV and type VI collagen with decreasing glucose consumption under high glucose conditions.

On the Synthesis of [TSUP]7[/TSUP]Li and [TSUP]7[/TSUP]Be in Novae

The production of 7Li and 7Be during the explosive hydrogen burning that occurs in nova explosions is computed by means of a hydrodynamic code able to treat both the accretion and the explosion stages. Large overproduction factors with respect to solar abundances are obtained, the exact value depending mainly on the chemical composition of the envelope. Although the final ejected masses are small, these results indicate that novae can contribute to the 7Li enrichment of the interstellar medium. Furthermore, since 7Be decays by emitting a gamma ray (478 keV), with a half-life of 53.3 days, the synthesis of 7Li could be tested during the INTEGRAL mission.

XENON, OSMIUM, AND LEAD FORMED IN O‐SHELLS AND C‐SHELLS OF MASSIVE STARS

In this paper we show that the explosive products from O‐shells of massive stars which contain 124Xe with large overproduction factors do not contain any of the naturally occurring isotopes of Os and Pb. We show further that the explosive products from C‐shells (explosive carbon burning) do contain Os and Pb along with Xe which is strongly enriched in r‐Xe of anomalous isotopic composition. The composition of Os in this matter is probably s‐like rather than r‐like. Pb in this matter is enriched in 208Pb. The results and arguments of this paper have implications for studies of isotopic compositions of Xe, Os, and Pb in residues of the Allende and other carbonaceous chondrites.