Secretion by glucagonomas of a possible glucagon precursor

Five patients with glucagonomas had elevated plasma levels of total glucagon immunoreactivity. Gel filtrations of these plasma samples on Bio-Gel P30 columns showed that most of the immunoreactivity eluted in the 3,500-(true glucagon) and 9,000-dalton fractions. After the administration of alpha cell effectors, changes in total glucagon immunoreactivity were seen which were accounted for primarily by the 3,500-dalton species, but there were also changes in the 9,000-dalton moiety. Venous effluent plasma from tumors of two subjects contained elevated concentrations of glucagon immunoreactivity in both fractions. When material from both the 3,500- and 9,000-dalton peaks were serially diluted in a glucagon immunoassay, parallel displacement curves were found, suggesting that both have similar or identical antigenic determinants. Thus, with conversion to a neoplastic state, alpha cells of glucagonomas, much like beta cells of insulinomas, may secrete an increased amount of a larger, 9,000-mol wt glucagon species which may be a prohormone.     

Systematic disruption of 456 ORFs in the yeast Saccharomyces cerevisiae

In the framework of the European Network for Functional Analysis (EUROFAN), five packages of 96 ORFs from chromosomes III, IV, VII, XIII, XIV and XV were subjected to systematic deletions in an isogenic derivative of strain S288c. Deletions were constructed in diploid and haploid strains. Two questionable ORFs overlapping with larger ORFs and seven TY ORFs were discarded. A total of 456 heterozygous and 385 homozygous deletant diploids were obtained. Sixty-nine deletions, 25 of which had never been published before, were lethal in haploid strains and 30 caused slow cellular growth.     

Diagnostic ultrasound in the management of patients using intrauterine contraceptive devices

A group of 80 patients was scanned by ultrasound within 24 hours of insertion of an intrauterine contraceptive device (IUCD) and re-examined clinically and/or by ultrasound after the next menstrual period. An attempt was made to identify factors such as uterine size, uterine flexion and the position of the IUCD which might be related to its expulsion or removal when, on initial scanning, the device was not located in the fundal area; removal was necessary in 5 out of 6 patients. In patients with an endometrial cavity of less than 40 mm length and/or acute uterine flexion, the overall figure for expulsion and removal was 54 per cent (13 out of 24). It is hoped that a consideration of these factors will lead to a reduction of the failure rate of the IUCD.     

Emissions of volatile organic compounds originating from UK livestock agriculture

In this paper we estimate the quantity of non‐methane volatile organic compounds (NMVOCs) emitted from UK livestock. The final estimate is derived from published values and from direct measurements of NMVOC emissions from dairy cattle slurry and laying hen manure. Emission rates of NMVOCs were determined for fresh dairy cattle slurry and laying hen manure using a 40 m³ emissions chamber. Dimethyl sulphides dominated emissions from laying hen manure at 753 ± 263 g m^?3 day^?1. Emissions from dairy cattle slurry were dominated by volatile fatty acids (C₂? C₅, 6.3 ± 3.1 g m^?3 day^?1) and phenols (2.4 ± 1.2 g m^?3 day^?1). Many of these NMVOCs are decomposition products from protein sources from which ammonia is also a by‐product. There is a close association between ammonia and NMVOC production from manure, and on this basis we estimated the annual NMVOC emissions from UK livestock as 165 ± 56 kt for 2002. These emissions compare to those from the larger industrial and transport sectors and exceed the 50–100 kt C year^?1 currently determined as originating from biogenic sources including agriculture. These findings have implications for air quality, and these NMVOCs may affect the cleansing capacity of the troposphere. Copyright © 2004 Society of Chemical Industry     

Mitochondrial disease in superoxide dismutase 2 mutant mice

Oxidative stress has been implicated in many diseases. The chief source of reactive oxygen species within the cell is the mitochondrion. We have characterized a variety of the biochemical and metabolic effects of inactivation of the mouse gene for the mitochondrial superoxide dismutase (CD1-Sod2(tm1Cje)). The Sod2 mutant mice exhibit a tissue-specific inhibition of the respiratory chain enzymes NADH-dehydrogenase (complex I) and succinate dehydrogenase (complex II), inactivation of the tricarboxylic acid cycle enzyme aconitase, development of a urine organic aciduria in conjunction with a partial defect in 3-hydroxy-3-methylglutaryl-CoA lyase, and accumulation of oxidative DNA damage. These results indicate that the increase in mitochondrial reactive oxygen species can result in biochemical aberrations with features reminiscent of mitochondrial myopathy, Friedreich ataxia, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.     

Rapid platelet-function assay: an automated and quantitative cartridge-based method

BACKGROUND: The platelet glycoprotein (GP) IIb/IIIa receptor is important in mediating platelet thrombus formation, and the GP IIb/IIIa antagonist abciximab (c7E3 Fab; ReoPro) is effective in preventing thrombotic ischemic cardiovascular complications of unstable angina and percutaneous coronary interventions. Small-molecule antagonists of GP IIb/IIIa based on the Arg-Gly-Asp (RGD) sequence show similar benefit, and some of these agents are orally active. However, there may be significant interindividual variation in response to such antagonists, especially with chronic oral therapy. It will be essential to balance the beneficial antithrombotic effect of these drugs with their potential for causing bleeding. In response to this need, we have developed a rapid platelet-function assay (RPFA), a point-of-care system that provides a quantitative measure of the competence of the GP IIb/IIIa receptor as reflected in the ability of platelets to agglutinate fibrinogen-coated beads. METHODS AND RESULTS: Polystyrene beads were coated with fibrinogen and placed in a cartridge along with a lyophilized peptide that activates the thrombin receptor. Anticoagulated whole blood was added to the cartridge, and then a microprocessor-controlled operation mixed the reagents and detected agglutination between platelets and coated beads. Quantitative digital results were displayed within 3 minutes. Because there is no dilution of the blood, the assay can be used to measure platelet activity in samples that have been treated with GP IIb/IIIa antagonists with high dissociation rates. RPFA results of whole-blood samples treated with different GP IIb/IIIa antagonists correlated well with both conventional turbidimetric platelet aggregation (r2=0.95) and the percentage of free GP IIb/IIIa molecules in the sample (r2=0.96). The mean difference in measurements between RPFA and aggregometry was -4% (+/-4% SD), and the mean difference in measurements between RPFA and free GP IIb/IIIa receptors was -2% (+/-6% SD). CONCLUSIONS: The RPFA provides rapid information on platelet function that mirrors turbidimetric platelet aggregation and reflects GP IIb/IIIa receptor blockade.     

Effect of leukotriene inhibitor on otoacoustic emissions in salicylate ototoxicity

Our previous work showed that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and increased levels of leukotrienes (LTs) in the perilymph. Pretreatment with LT inhibitor was found to prevent salicylate ototoxicity. Other studies demonstrated that salicylate ototoxicity is associated with decreased cochlear blood flow, reversible changes in cochlear outer hair cells, and decreased otoacoustic emissions. The purpose of our study was to determine the effect of LT blocker (Sch 37224) on transient-evoked otoacoustic emissions (TEOAEs) in salicylate or LT ototoxicity. Chinchillas were divided into five groups. Transient-evoked otoacoustic emissions were measured after salicylate application on the round window membrane (RWM), with (Group 1) and without (Group 2) LT blockade; after LTC4 (a type of leukotriene) application on the RWM, with (Group 3) and without (Group 4) LT blockade; and in the control group after saline application on the RWM. The overall response differences from the baseline measurements over time in each case were compared with each other. Both salicylate and LTC4 application on the RWM were followed by significant decreases in TEOAEs, and the decrease was prevented by pretreatment with LT blocker. There was no significant change in TEOAEs in the control group. Salicylate ototoxicity appears to be mediated by the elevated levels of leukotrienes as a consequence of cyclooxygenase inhibition. This study also provides further evidence that the site of action in salicylate ototoxicity is the outer hair cell.     

Model of temperature dependence for gain shape of erbium-dopedfiber amplifier

The problem of modeling the temperature dependence of erbium-doped fiber amplifier (EDFAs) is important for multichannel optical WDM systems. A physical model is presented in this paper, which could be used to predict the gain change under temperature variations for such systems. Some of the input parameters for the model are the erbium energy sublevel density, excitation coefficients from lower sublevels to upper sublevels of erbium ions, and electron distribution over energy levels. It is difficult to measure these parameters. In order to use the model for gain shape calculations, some simplifications are demonstrated. These simplifications lead to two numerical models, which are shown to be consistent with experimental data with reasonable accuracy, and are based only on two spectral measurements for different temperatures. Both numerical models were tested for the signal band and the 980 nm pump band of a typical erbium-doped fiber