Positron re-emission, reflection, and diffraction from W(100) surface at very low energies.

The energy distributions of scattered and re-emitted low-energy positrons from a W(100) surface were measured as a function of incident positron energy from 0 to 25 eV. Given that tungsten has a negative work function of about -3 eV for positrons, one can envisage three scenarios of very low-energy positron scattering from such a surface. First, a positron approaching the sample surface with energy say 1 eV above the vacuum level will see a potential barrier of about 2 eV height and will be reflected back to the vacuum. Second, when the energy of incident positrons increases up to the top of the surface potential barrier (positron work function), they start entering the solid and, therefore, the reflectivity of positrons from the surface reduces. Positrons entering the solid are thermalised within few picoseconds and have a chance to escape back to the vacuum with kinetic energy about 3 eV above the vacuum level undergoing so-calledre-emission. Third, coherent scattering of low-energy positrons may occur on the crystal surface, i.e. positron diffraction. All the three scenarios of low-energy positrons scattering are studied here experimentally. Measured spectra are very sensitive to the surface conditions of the sample: they change dramatically after surface oxidation or thin film deposition.

Auger-mediated sticking of positrons to surfaces: evidence for a single-step transition from a scattering state to a surface image potential bound state.

We present the observation of an efficient mechanism for positron sticking to surfaces termed here Auger-mediated sticking. In this process the energy associated with the positrons transition from an unbound scattering state to a bound image potential state is coupled to a valence electron which can then have sufficient energy to leave the surface. Compelling evidence for this mechanism is found in a narrow secondary electron peak observed at incident positron kinetic energies well below the electron work function.

Smoking habits of UK military personnel on deployment: Exercise SAIF SAREEA 3.

INTRODUCTION: Changes of environment brought about by deployments are often attributed to an increase in smoking of service personnel. Electronic cigarettes are recognised as being a viable aid to quitting smoking but are currently banned from sale in Oman and were therefore banned during exercise SAIF SAREEA 3 (SS3). This paper sought to establish whether smoking increased on this exercise and for what reasons. Also, if deployed smoking cessation services are likely to be used, if available. METHODS: Questionnaires were distributed to deployed troops at various locations in theatre for data collection. RESULTS: Smoking prevalence increased by 5.2% (29) in the deployed population by the end of the exercise. The largest increase was seen in those smoking 20 cigarettes a day or more, rising by 269.8% (73) with a mean increase of 9 cigarettes per day. During the exercise the number of personnel using electronic cigarettes decreased and individuals' rate of electronic cigarette use also decreased. Those who smoked less during the exercise did mainly through choice (56.8%). 50% (280) of all individuals who increased smoking habits during the exercise did so out of boredom. CONCLUSIONS: During exercise SS3 the number of individuals who smoked and the quantity they smoked increased. The ban on electronic cigarettes in Oman and while on exercise potentially had an effect on the increased smoking habits. There is an argument to include smoking cessation material in medical modules to prevent ex-smokers from restarting, continue to aid those quitting and potentially lessen severity of increasing smoking habits while deployed.

Miniature electrostatic electron energy analyzers and S-shaped deflector.

An instrument has been developed to avoid the rotation of large electron sources and detectors in quantum single particle scattering experiments. The rotation of an electron beam has been achieved by combining three small cylindrical electrostatic electron energy analyzers in series such that the first analyzer is fixed and the other two rotate together around the exit axis of the first; it is a development from an S-shaped deflector used by Hegemann et al. [J. Phys. B 26, 4607 (1993)]. Novel design and construction, using copper, aluminum, and stainless steel parts mounted on polyvinyl printed circuit board, enabled an efficient, small-sized high vacuum compatible instrument. The characteristics and versatility of the instrument have been shown by measurements of angular and spin asymmetries of electron scattering phenomena.

Normal contractile state of hypertrophied myocardium after pulmonary artery constriction in the cat.

The contractile function of right ventricular papillary muscles from normal cats and cats in which the pulmonary artery had been constricted for 6 or 24 wk was examined. Acute pulmonary artery constriction reduced cross-sectional area by an average of 70%, resulting in a 30% mortality from congestive heart failure, all such deaths occurring within the first 3 wk after banding. The increase in right ventricular mass in animals surviving for 6 or 24 wk was similar, averaging 70%. No banded animals had evidence of congestive heart failure at the time of sacrifice, and cardiac output and right atrial pressures were similar to those in control animals.6 wk after banding, the active length-tension curve, maximal rate of rise of isometric force, force-velocity relations, and isometric force with paired stimulation and norepinephrine were all significantly depressed when compared to their respective values in control animals. In contrast, none of these variables was significantly different from control values in animals banded for 24 wk. These observations indicate that depressed contractile state is not a fundamental characteristic of pressure-induced hypertrophied myocardium and reemphasize the important temporal relationship between contractile state and the imposition of sudden sustained loads.

The effect of chronic digitoxin administration on the contractile state of normal and nonfailing hypertrophied myocardium.

To determine the effect of prolonged digitoxin administration on contractile function of nonfailing myocardium, right ventricular papillary muscle mechanics were examined after 6 or 24 wk of glycoside administration to control and pulmonary artery banded cats. Resting length-tension relations were not affected by digitoxin; however, isometrically developed force and the maximal rate of force development at the peak of the length-tension curve were increased in all treated groups. In untreated animals, banding resulted in a 28% incidence of deaths from heart failure. 6 wk after constriction, contractile function was depressed whereas normal function was observed 24 wk after banding. Digitoxin significantly reduced mortality from heart failure and enhanced the recovery of contractile function; contractile function in the 6 wk banded treated group approached that of untreated control and 24-wk banded groups. The long-term effects of digitoxin on contractile function were not importantly related to the temporal association between banding and institution of glycoside administration. Development of myocardial hypertrophy was comparable in treated and untreated banded groups.These results demonstrate that a significant positive inotropic effect persists in both normal and nonfailing hypertrophied myocardium during chronic digitoxin administration.

Effect of acute hypoxia and hypercapnic acidosis on the development of acetylstrophanthidin-induced arrhythmias.

The effect of acutely induced hypoxia, hypercapnic acidosis, and the combination of the two on the amount of acetylstrophanthidin (AS) required to produce cardiac arrhythmias was determined in anesthetized dogs. Each animal was studied during ventilation with room air and again during ventilation with gas mixtures of appropriate concentrations; 24 hr separated the study periods. AS was infused intravenously at a rate of 5 mug/kg per min. Significantly less AS was required to produce arrhythmias during hypoxia and hypercapnic acidosis together than during the period with normal arterial Po(2), Pco(2), and pH (10 animals). Included in this group were two animals which had undergone previous bilateral adrenalectomy and four animals in which heart rate was maintained at the same frequency during both study periods. A significant reduction in the toxic dose of AS also was demonstrated in eight animals, two with constant heart rate, during hypoxia with normal arterial Pco(2) and pH. Hypercapnic acidosis alone (eight animals) did not significantly alter the toxic dose of AS. After the administration of propranolol (six animals) or hexamethionium (six animals), no significant difference was observed between the toxic dose of AS during hypoxia and that during ventilation with room air. Thus although hypoxia and hypercapnic acidosis together do reduce the amount of AS required to produce arrhythmias, it is the hypoxia which exerts the predominant effect on the development of this increased sensitivity to AS. Furthermore, this effect of hypoxia occurs primarily as a result of reflexly augmented sympathetic stimulation of the heart.

Left ventricular function in patients with chronic obstructive pulmonary disease.

Left ventricular function was assessed in six patients with essentially normal cardiopulmonary function, in five patients with primary myocardial disease, and in 16 patients with chronic obstructive pulmonary disease by determining the response of the ventricle to an increased resistance to ejection. Studies were performed at the time of cardiac catheterization and increased resistance to left ventricular ejection was produced by the intravenous infusion of methoxamine. In the control patients, methoxamine produced an increase in stroke volume index (SVI), in stroke work index (SWI), and stroke power index (SPI), whereas left ventricular end-diastolic pressure (LVEDP) increased only moderately. In contrast SVI, SWI, and SPI fell, whereas LVEDP increased inordinately in the patients with myocardiopathy. The patients with chronic obstructive pulmonary disease responded to the infusion with an increase in SVI, SWI, SPI, and LVEDP comparable to the control patients. Furthermore, in this latter group of patients, a quantitatively similar response was observed in those with essentially normal resting hemodynamics, in those with resting pulmonary hypertension, and in those whose disease had progressed to the stage of right ventricular failure. This study provides no evidence that chronic obstructive pulmonary disease results in chronic impairment of left ventricular function, but on the contrary, has demonstrated that the left ventricle responds normally to an increased pressure load in these patients.

Hydroxyproline and passive stiffness of pressure-induced hypertrophied kitten myocardium.

Passive stiffness and hydroxyproline content of myocardium hypertrophied by pressure-loading were determined in kittens 2, 8-16, and 24-52 wk after pulmonary artery banding, which initially elevated right ventricular systolic pressure by 10-15 mm Hg. Right ventricular mass increased by approximately 75%, three-quarters of which occurred during the first 2 wk after banding. Passive stiffness was assessed from resting length-tension relations of isometrically contracting isolated right ventricular papillary muscles. Stiffness constants, alpha and beta were determined from the relationship sigma = alpha (e beta epsilon - 1) where sigma = stress and epsilon = Lagrangian strain. Elastic stiffness (d sigma/d epsilon) was derived from: d sigma/d epsilon = beta sigma + beta alpha. Right ventricular hydroxyproline increased in proportion to muscle mass so that hydroxyproline concentration remained unchanged after banding. Both alpha, beta, and elastic stiffness-stress relations were similar to values in nonbanded controls. Thus, we did not observe an increase in passive stiffness or hydroxyproline concentration of pressure-stiffness or hydroxyproline concentration of pressure-induced hypertrophied myocardium in contrast to most previous studies.

Myocardial hydroxyproline and mechanical response to prolonged pressure loading followed by unloading in the cat.

To determine the myocardial response to prolonged pressure-loading and unloading, kittens weighing 0.8-1.2 kg underwent pulmonary artery banding, which initially elevated right ventricular (RV) systolic pressure by 10-15 mm Hg. 52 and 76 wk later; RV weight/body weight had increased by approximately 80%. Total RV hydroxyproline had increased significantly, whereas hydroxyproline concentration was unchanged from that of nonbanded animals of comparable age. In isometrically contracting RV papillary muscles, peak active force was significantly less at 76 wk (3.3 +/- 0.8 [SD] g/mm2 than at 52 wk (5.1 +/- 0.8 g/mm2) or in nonbanded animals (4.8 +/- 0.8 g/mm2). Velocity of muscle shortening at comparable loads was unchanged after 52 wk but was significantly less after 76 wk. In nonstimulated, slowly stretched muscles, passive stiffness constants, alpha and beta, derived from delta = alpha(e beta epsilon - 1), where delta is instantaneous stress and epsilon is Lagrangian strain, were unchanged by banding. The band was removed after 52 wk in additional animals that were studied 24 wk later. In those animals with normal RV pressures at death, hypertrophy had regressed and hydroxyproline concentration was comparable to that of nonbanded and banded animals; Active and passive mechanical function remained normal. In this model, changes in hydroxyproline parallel changes in muscle mass, and passive stiffness remains normal during development and regression of hypertrophy. Removal of the pressure load after prolonged hypertrophy prevents or retards the late development of myocardial dysfunction.

Endotoxin contamination in the dental surgery.

Dental waterlines contain large numbers of Gram-negative bacteria. Endotoxin, a component of such organisms, has significant health implications. Paired samples of dental unit water and the aerosols generated during dental procedures were collected, and assayed for bacteria and endotoxin levels, using heterotrophic plate counts and the Limulus amoebocyte lysate test. Consistent with published studies, the extent of bacterial contamination in the dental waters sampled for this investigation surpassed the levels associated with potable water, with counts in excess of 2.0x10(6) c.f.u. ml(-1) in some samples. Correspondingly high concentrations of endotoxin [up to 15 000 endotoxin units (EU) ml(-1)] were present in the water. A statistically significant Spearman correlation coefficient of rho=0.94 between endotoxin (EU ml(-1)) and bacterial load (c.f.u. ml(-1)) was demonstrated. All of the aerosol samples contained detectable endotoxin. Further studies of the consequences of dental endotoxin exposure, and evaluation of means to prevent exposure, are warranted.

Ornithine aminotransferase turnover in host tissues of tumor-bearing rats.

The activity of ornithine-oxo-acid aminotransferase (OAT) in the liver and kidneys of rats was notably decreased as a consequence of tumor bearing. The decrease in the activity of OAT was closely related to a concomitant decrease in the rate of synthesis of the enzyme in both host tissues, while the rate of enzyme degradation remained unchanged. These results are concluded to be consistent with the proposal that host tissues of tumor-bearing animals may become "dedifferentiated," and in this example the mechanism of the expression of the dedifferentiation involved the significant decrease in specific enzyme production.

A monoclonal antibody to a human breast tumor protein released in response to estrogen.

A panel of monoclonal antibodies was produced against cell surface antigens of the MCF-7 human breast cancer cell line. The monoclonal antibodies were selected by their ability to bind to live, intact MCF-7 cells in solid-phase radioimmunoassay, and to bind to human breast cancer cells in paraffin sections. One monoclonal antibody, designated UCD /AB 6.11, identified two cellular antigens and one extracellular antigen from MCF-7, and bound to 18 of 20 breast cancers in paraffin sections. The two cellular antigens were associated with Mr 54,000 and Mr 56,000 proteins, which could be identified in Western blots, and were localized to the cell surface by immune precipitation of lactoperoxidase-iodinated plasma membrane proteins. The extracellular antigen, a Mr 52,000 protein, was slightly more acidic and was only found in the media from estrogen-stimulated cells. Estrogen did not appear to have an effect on the production of the cell-associated antigens, Mr 54,000 and 56,000 proteins. We postulate that the cellular antigens are precursors to the secreted Mr 52,000 protein.

Effect of procainamide on myocardial contractile function and digoxin inotropy.

The effect of procainamide and digoxin, singly and together, on peak active force and rate of force development of isolated right ventricular papillary muscles from adult cats was examined. Procainamide (1.5 X 10(-5) M) increased force and rate of force development in each muscle with further increments in performance up to 2.4 X 10(-4) M in most muscles. The maximal increases in force (+/- SEM) averaged 75 +/- 13% above control values. Essentially no response to procainamide was observed when basal levels of contractile state were increased by increasing stimulus frequency or calcium concentrations of the bathing solution. Propranolol (10(-6) M) markedly reduced and verapamil (10(-7) M) abolished the inotropic effect of procainamide. Exposing muscles to procainamide (1.5 or 3 X 10(-5) M) before or after the administration of digoxin (2 or 4 X 10(-7) M) did not alter the inotropic action of either drug. Thus, procainamide in concentrations that are in the therapeutic range in human patients has potent positive inotropic effects that may be masked at high levels of contractile state. This action of procainamide appears to be due to an effect on calcium channels, which in part may be due to beta-adrenergic receptor stimulation. These concentrations of procainamide do not alter the inotropic response to digoxin.

E1A-based determinants of oncogenicity in human adenovirus groups A and C.

A broad spectrum of genetic and molecular investigations carried out with group C, Ad2 and Ad5, and with group A, Ad12, have shown that early region1 (E1) gene products are sufficient for complete transformation of rodent cells in vitro by these viruses. During the past quarter century, the processes by which E1A proteins, in cooperation with E1B proteins, perturb the cell cycle and induce the transformed phenotype, have become well defined. Somewhat less understood is the basis for the differential oncogenicity of these two groups of viruses, and the processes by which the E1A proteins of Ad12 induce a tumorigenic phenotype in transformants resulting from infection of cells in vivo and in vitro. In this chapter we review previous findings and present new evidence which demonstrates that Ad12 E1A possesses two or more independent functions enabling it to induce tumors. One of these functions lies in its capacity to repress transcription of MHC class I genes, allowing the tumor cells to avoid lysis by cytotoxic T lymphocytes. We have shown that class I repression is mediated through increased binding of repressor COUP-TF and decreased binding of NF-kB to the class I enhancer. In addition to mediating immune escape, E1A also determines the susceptibility of transformants to Natural Killer (NK) cell lysis, and in this case, also, Ad12 transformants are not susceptible. By using Ad12 mutants containing chimeric E1A Ad12-Ad5 genes, point mutations, or a specific deletion, we have shown that the unique spacer region of Ad12 E1A is an oncogenic determinant, but is not required for transformation in vitro. Given that the E1A regions responsible for class I repression are first exon encoded, we have examined a set of cell lines transformed by these altered viruses, and have found that while they display greatly reduced tumorigenicity, they maintain a wildtype capacity to repress class I transcription. Whether the spacer contributes to NK evasion remains unresolved. Lastly, we discuss the properties of the Ad2/Ad5 E1A C-terminal negative modulator of tumorigenicity, and examine the effects on transformation, tumor induction and transformant tumorigenicity, when the Ad5 negative modulator is placed by chimeric construction in Ad12 E1A.

Defective insulin receptor function in down-regulated HepG2 cells.

Insulin receptors on the surface of down-regulated HepG2 cells were studied, and multiple defects of receptor function were demonstrated. Insulin treatment led to a 58% decrease in cell surface receptor number, and the remaining receptors exhibited a 50% decrease in insulin internalization and degradation on a per receptor basis. Down-regulated cells internalized 36% of receptors photolabeled with 125I-NAPA-insulin vs. 56% of labeled receptors in control cells, indicating a 40% decrease in ligand-mediated receptor internalization. Total cellular receptors purified from down-regulated cells by wheat germ affinity chromatography demonstrated a 20% decrease in maximal autophosphorylation. Assessment of autophosphorylation of cell surface receptors in intact cells by restimulation of cells with insulin at 12 C (a temperature nonpermissive for receptor recycling), followed by immunoblotting with antiphosphotyrosine antibodies revealed a decrease of approximately 70% in insulin-stimulated autophosphorylation compared with controls. This method also revealed a comparable decrease in insulin-stimulable tyrosine phosphorylation of pp185, a putative endogenous substrate. When receptors were stimulated to undergo autophosphorylation with 125I-NAPA-insulin in intact cells and then solubilized, only 11% of 125I-NAPA-insulin receptor complexes from down-regulated cells were immunoprecipitated with antiphosphotyrosine antibodies compared with 35% of labeled control receptors. These results indicate that treatment with high concentrations of insulin results in the accumulation on the cell surface of a population of receptors that display multiple functional abnormalities. This probably results from preferential internalization and degradation of kinase-competent insulin receptors causing an accumulation of kinase-incompetent receptors on the cell surface. These receptors may in part be responsible for the postbinding defects in insulin action observed in down-regulated cells.

Deletion of the insulin receptor beta-subunit acidic domain results in enhanced metabolic signaling.

The contribution of the insulin receptor beta-subunit acidic domain, amino acids 1262-1291, to receptor function was analyzed. A mutant insulin receptor complementary DNA lacking this domain was created. Rat-1 fibroblasts were stably transfected with plasmids containing the mutant insulin receptor complementary DNA and clonal cell lines derived (hIR1262). Compared with cells overexpressing the wild type insulin receptor, metabolic signaling was enhanced in hIR1262 cells whereas the mitogenic response to insulin was unchanged. hIR1262 had normal kinase activity and insulin-stimulated receptor internalization in spite of substantially reduced autophosphorylation (70% decreased in vitro). Additionally, polylysine, a polycation postulated to interact with the insulin receptor beta-subunit acidic domain, increased autophosphorylation and facilitated insulin-induced phosphorylation of calmodulin in the wild type as well as the hIR1262 receptors. We conclude: 1) The acidic domain is not the site of interaction between the insulin receptor and polycations. 2) Removal of the acidic domain leads to enhanced metabolic signaling but 3) unchanged mitogenic activity. 4) The defect in autophosphorylation is not correlated with a defect in kinase activity. Thus, the observed changes in biological signaling indicate that specific pathways diverge at the level of the receptor itself and that neither kinase activity or biological activity necessarily correlates directly with diminished autophosphorylation when the tyrosine kinase domain remains intact.

Receptor-binding activity of highly purified bovine luteinizing hormone and thyrotropin, and their subunits.

Highly purified preparations of bovine TSH (bTSH) and LH (bLH) and their subunits have been obtained by affinity chromatography using immobilized antibodies directed against counterpart subunits. The purified preparations were assessed for biological activity in radioligand-receptor assays for TSH and LH. After affinity purification against bLH beta, a TSH preparation whose initial potency in the LH assay had been 0.15% that of LH, failed to compete with [125I]LH in amounts up to 100 microgram. Thus, it appears that bTSH does not bind to LH receptors in the rat testis and that interaction of less purified TSH with gonadotropin receptors is attributable to LH contamination. In contrast, LH, whose initial potency in the TSH receptor assay was 0.6% that of TSH, retained a potency of 0.004% of TSH (equivalent to 3.6 mU/mg) after immunoadsorption by anti-bTSH beta. The retention of TSH receptor-binding activity by affinity-purified LH indicates that the LH molecule (like hCG) has a low intrinsic thyroid-stimulating activity. Affinity-purified LH subunits have little or no demonstrable affinity for the LH receptor in vitro. Affinity-purified TSH subunits and affinity-purified LH, however, exhibit very weak receptor-binding activity in the TSH radioligand receptor assay. An evaluation of the capacity of the immunoadsorbents to remove TSH from artificial mixtures suggests that the residual binding does not result entirely from contamination, and therefore, that alpha-subunits as well as LH have some intrinsic TSH-binding activity.

Interaction of tissue transglutaminase with nuclear transport protein importin-alpha3.

Tissue transglutaminase is a multifunctional enzyme which has been involved in the regulation of cell growth, differentiation, and apoptosis. Recently, nuclear localization of tTG has been reported indicating the potential of active nuclear transport. In this study we use the yeast two-hybrid assay and co-immunoprecipitation to show that tTG interacts with the nuclear transport protein importin-alpha3. Using electron microscopy we demonstrate that nuclear expression of tTG in a non-small cell lung cancer cell line is induced by retinoic acid (RA). These data suggest that importin-alpha3 could mediate active nuclear transport of tTG which may be important for the regulation of critical cellular processes.

Lipid composition of metacestodes of Taenia taeniaeformis and lipid changes during growth.

A lipid analysis was performed on developing metacestodes of Taenia taeniaeformis removed from the livers of rats at times varying from 3 to 35 weeks post infection. Lipid accounted for 7-21% of the dry weight of the parasites. The highest proportions were found at the earlier stages. The distribution was as follows; neutral lipid 27-45%; glycolipid 5-11%; and phospholipid 50-61%. The major neutral lipid was cholesterol, and minor neutral lipids were sterol esters, triglycerides, diglycerides and monoglycerides. Hydrocarbons were present throughout development, but in the highest amounts at the earlier stages. Five different glycolipids were found, all of which were identified as glycosphingolipids. An increase in the proportion of more complex glycolipids was noted as parasites grew older. Ten different phospholipids were identified, with the major components being phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Other phospholipids were: lysophosphatides, phosphatidylinositol, phosphatidic acid, diphosphatidylglycerol, sphingomyelin, and an unknown phospholipid component. Changes in the relative amounts of the two major phospholipids were found when the early and late stages were compared. Two lipids found throughout development were identified as glycosylated dolichol phosphates, and they comprised between 1 and 3% of the total phospholipid fraction. Nineteen fatty acids were detected, and the fatty acid distribution for each lipid class at each stage was determined. Seven major fatty acids were common to each. These were: hexadecanoic, octadecanoic, oleic, linoleic, arachidonic, docosanoic, and docosahexaenoic.