bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of disinfectants and detergents on skin irritation
Authors: Slotosch Caroline M. , Kampf Günter , Löffler Harald
Published: July 2007

We investigated the biological response of regular human skin to alcohol‐based disinfectants and detergents in a repetitive test design. Using non‐invasive diagnostic tools such as transepidermal water loss, laser‐Doppler flowmetry and corneometry, we quantified the irritative effects of a propanol‐based hand disinfectant (Sterillium®), its propanol mixture (2‐propanol 45% w/w and 1‐propanol 30% w/w), sodium lauryl sulfate (SLS) 0.5% and distilled water. The substances were applied in a 2‐D patch test in a repetitive occlusive test design to the back. Additionally, we performed a wash test on the forearms that was supposed to mimic the skin affection in the normal daily routine of health care workers. In this controlled half‐side test design, we included the single application of the hand rub, SLS 0.5% and water as well as a tandem application of the same substances. Patch test and wash test showed similar results. The alcohol‐based test preparations showed minimal irritation rather comparable to the application of water. However, the detergent SLS produced stronger barrier disruption, erythema and dryness than the alcohol‐based preparations. There was no additional irritation at the combined use of SLS and disinfectants. By contrary, there was even a decrease in barrier disruption and erythema induced by the tandem application of SLS followed by alcohol‐based disinfection compared with the use of SLS alone. These findings show a less irritant effect of alcohol‐based disinfectants on the skin than detergents. Our study shows that there is no summation of irritating effects of a common detergent and propanol and that the combination of washing and disinfection has a rather protective aspect compared with washing alone.
Efficient Electroporation of DNA and Protein into Confluent and Differentiated Epithelial Cells in Culture
Authors: Deora Ami A. , Diaz Fernando , Schreiner Ryan , Rodriguez‐Boulan Enrique
Published: July 2007

Electroporation‐mediated delivery of molecules is a procedure widely used for transfecting complementary DNA in bacteria, mammalian and plant cells. This technique has proven very efficient for the introduction of macromolecules into cells in suspension culture and even into cells in their native tissue environment, e.g. retina and embryonic tissues. However, in spite of several attempts to date, there are no well‐established procedures to electroporate polarized epithelial cells adhering to a tissue culture substrate (glass, plastic or filter). We report here the development of a simple procedure that uses available commercial equipment and works efficiently and reproducibly for a variety of epithelial cell lines in culture.
Mucolipin‐2 Localizes to the Arf6‐Associated Pathway and Regulates Recycling of GPI‐APs
Authors: Karacsonyi Claudia , Miguel Anitza San , Puertollano Rosa
Published: July 2007

In mammals, the mucolipin family includes three members mucolipin‐1, mucolipin‐2, and mucolipin‐3 (MCOLN1–3). While mutations in MCOLN1 and MCOLN3 have been associated with mucolipidosis type IV and the varitint‐waddlermouse phenotype, respectively, little is known about the function and cellular distribution of MCOLN2. Here we show that MCOLN2 traffics via the Arf6‐associated pathway and colocalizes with major histocompatibility protein class I (MHCI) and glycosylphosphatidylinositol‐anchored proteins (GPI‐APs), such as CD59 in both vesicles and long tubular structures. Expression of a constitutive active Arf6 mutant, or activation of endogenous Arf6 by transfection with EFA6 or treatment with aluminum fluoride, caused accumulation of MCOLN2 in enlarged vacuoles that also contain MHCI and CD59. In addition, overexpression of MCOLN2 promoted efficient activation of Arf6 in vivo,thus suggesting that MCOLN2 may have a role in the traffic of cargo through the Arf6‐associated pathway. In support of this we found that overexpression of a MCOLN2 inactive mutant decreases recycling of CD59 to the plasma membrane. Therefore, our results indicate that MCOLN2 localizes to the Arf6‐regulated pathway and regulates sorting of GPI‐APs.
Endosomal Trafficking and Proprotein Convertase Cleavage of cis Golgi Protein GP73 Produces Marker for Hepatocellular Carcinoma
Authors: Bachert Collin , Fimmel Claus , Linstedt Adam D.
Published: July 2007

Serum GP73 levels are significantly increased in patients with hepatocellular carcinoma (HCC), potentially providing a marker for early detection. However, GP73 is an integral membrane protein localized to the cis Golgi and is not known to be secreted. Based on its presence in sera, we sought to determine whether GP73 might normally be released from cells and to elucidate the mechanism of this release. Indeed, a soluble form of GP73 was released from cultured cells and compared with the Golgi‐localized full‐length protein, the molecular weight was slightly reduced, suggesting that cleavage releases the GP73 ectodomain. Sequence analysis revealed a proprotein convertase (PC) consensus site, and, indeed, the ubiquitous PC furin was capable of cleaving purified GP73. Further, alanine substitutions in the PC site blocked both the in vitro and the in vivo cleavage of GP73. Using a cleavage‐specific antibody, cleaved GP73 was found in the trans Golgi network and endosomes, suggesting that GP73 cleavage occurs as GP73 cycles distal to the early Golgi. We conclude that the endosomal trafficking of GP73 allows for PC‐mediated cleavage, resulting in GP73 secretion, and provides a molecular mechanism for its presence as a serum biomarker for HCC.
Rebuilding the Ruined Churches of France
Authors: Gwynn Denis
Published: July 2007

With the beginning of Lent the bishops of nine of the French dioceses in the devastated districts issued an appeal to the public for a loan of 200 million francs. The experiment is in itself a very considerable contribution to solving the problem of reconstruction in the Regions Libérées.

Of the twelve dioceses which suffered partial or complete devastation in the war only nine are included in the list of co-operative reconstruction societies in whose names this appeal for public subscriptions is issued. The diocese of Nancy, which was the first to originate the idea of applying to the reconstruction of the ruined churches the legal privileges accorded to important syndicates of claimants to reparation money, has already successfully floated a preliminary loan for 15 million francs on its own account. It speaks well for the success of this more ambitious project that the whole amount asked for by the diocese of Nancy was subscribed locally within a few weeks. The present issue is the result of an agreement among the nine dioceses which suffered the most serious devastation, that they would make a joint appeal to the public so that none should be penalised by being behindhand in organising the necessary co-operative societies.

The prospectus of the loan has now been distributed, and the first subscriptions are beginning to come in. There is no doubt, however, that the large amount asked for will take some time to materialise.

Even the 200 million francs is only a fraction of the total amount that will be required to repair all the three thousand ruined churches of the Regions Liberies, and it is as well to state at once that the promoters of the loan are anxious to collect money wherever they can find generous friends.
On Waterloo Bridge
Authors: Essex Edwin
Published: July 2007

Though starless is the sky to-night And clouds are sailing free,

A thousand fairy points of light Go dancing to the sea.

Reflections from the river-side Of lights both meek and bold,

They fall along the outward tide In silver, red, and gold.

They ripple on each tiny crest And tremble on the foam,

The river will not let them rest Or shine for us at home.

But onward from the magic town,

If men would look with me,

Its argosy it carries down From London to the sea.

Edwin Essex, O.P.
Canon Dimnet and Democracy
Authors: Foster Paul U.
Published: July 2007

Once,’ says Canon Dimnet, ‘I heard a shepherd saying that “the wind sat in France,”’ for the Canon was born in that frontier district of his country that was formerly part of the old Middle Kingdom of Lotharingia and later of the Duchy of Burgundy. Dimnet is a Frenchman born and bred; in My Old World he has created an unforgettable picture of the typical small town that was his birthplace, Trélon, with its gray spire dominating the flat landscape; but though the life of Trélon is French, its memories are of older allegiance, and the shepherd was recording in his phrase a time when, to the inhabitants of Trélon and all about Cambrai, the French were ‘foreigners.’

It is perhaps not too fanciful to see in this frontier background an explanation of Canon Dimnet’s extraordinary feeling for a language and a culture not his own. An uncle early taught him ‘simple English words; door, window, pen, book . . . and had given our dog quite a standing in the street by calling him, for some reason, Euston.’ The little flame lighted by his uncle grew during school days until at last, on going to teach at Douai, Ernest Dimnet came into contact with the English Benedictine community in that town. The effect upon him was startling. Even in their Catholicism they betrayed a new world: ‘I used to think my Benedictine friends, monks though they were, even more unclerical than I was.
Catechism for Adults:
Authors: Hislop Ian
Published: July 2007

We, writes St Paul, are chosen in him before the foundation of the world, that we should be holy and unspoiled in his sight in charity (Ephesians 1, 4). It is only in so far as man is chosen in Christ and one with Christ, that he belongs to God. Christ, raised from the dead, rules and is made ‘head over all the Church’ (Ephesians 1, 22). The Church is the body of Christ (Ephesians 1, 23); and to this body all those who at one time were afar off are joined, or in St Paul’s phrase ‘are made nigh’ (Ephesians 2, 13). All men are born under the condemnation of Adam and are therefore afar off from God, but ‘in the blood of Christ’ they are made near to God. Made near because Christ ‘is our peace’ (Ephesians 2, 23). It is Christ who ‘has made both one’ and who breaks down ‘the middle wall of partition, the enmities in his flesh... that he might make the two in himself into one new man, making peace, and might reconcile both to God in one body by the cross, killing the enmities in his flesh’ (Ephesians 2, 14-16).

The cross of Christ, which is the presence in the world of God’s judgment and love, is creative of that peace or unity that overcomes all division and enmity. The divisions that arise from sin or pride, all conflict as between flesh and spirit, Jew and Gentile, slave and free, are transcended in Christ. The death of Christ created a new unity, that of those who are called apart to live in charity in the presence of God. No escape from the world, but a transformation of all that goes to make up the world. This holiness of life is the basic category of life—the only purpose of existence. By it not merely the middle wall of partition between men is destroyed but the division between man and God, opened by sin, is closed. ‘You are no more strangers and foreigners, but you are fellow citizens with the saints and domestics of God’ (Ephesians 2, 14).
Heard and Seen: La Dolce Vita
Authors: Butcher Maryvonne
Published: July 2007

In the latest issue of the Revue Internationale du Cinema, the journal of the international Catholic cinema office, there is an article on the moral assessment of certain recent co-production films, as applied in various national centres. This demonstrates how the same film may get very different ratings from country to country: when we see that La Dolce Vita has been put into the ‘a proscrire’ category in Italy, the point is well taken. For now that it has reached the commercial screen in England it is difficult, from the Anglo-Saxon point of view, to see what all the fuss was about. From this side of the Channel it looks even more like a scathing moral indictment of a way of living that may be over-stated but is, as we all know, true enough in its essentials. Signor Fellini has said in a London interview that the Rome he has portrayed is his idea of Rome, not necessarily the true Rome; but this is no more, after all, than any creator’s way with his material and need not in any way surprise us.

This long film, whose spatial control is so precise and whose temporal control is often so slack, sprawls across nearly three hours in a series of episodes whose visual attack frequently packs a much heavier punch than their intellectual content. From the first moment when the helicopter bears down upon the Roman suburbs, with the statue of Christ the Worker slung beneath it—ruined viaduct and bare tenement wall taking the statue’s shadow like a stigmata—Fellini’s sheer cinematic virtuosity imposes itself without question.
Stories for a Self‐Made Merchant
Authors: Edwards Owen Dudley
Published: July 2007

Psmith, Journalist is history; and it is crusade. But it also has its place as the best novel Wodehouse had written to date. Psmith was the god from the machine; but he was also the god who made the machine. Instead of leaving a good idea to rot in the background of the failure which The Prince and Betty in the American edition is (and there is even less to be said for it in the English one), Wodehouse had hacked his material into shape, introduced his god to bring it to life, and maintained a splendid pace alternating excitement and humour. He had simultaneously been working on another social document, appropriately named Something Fresh, analysing the almost Byzantine absurdities of English country-house drones and the snobbery of their servants which helped to maintain them. It it important to stress that this, the first view of Blandings Castle, is in fact an extremely hostile one. We must view Wodehouse as the disciple of Conan Doyle in social attitudes to some degree; and just as Holmes is frequently employed to show up the effete aristocrats and immoral millionaires, Wodehouse time and again returns to the theme of resolute and hardworking young men and women as a foil to aristocratic drones. In both cases, it is the bourgeois attack on the privilege and non-productivity of the aristocracy. In this sense Wodehouse, both in relation to Britain and to America, was in 1915 very much a figure of that eminently bourgeois phenomenon which the Americans have termed Progressivism. Wodehouse was seldom quite so pointedly hard-hitting as he was in Something Fresh. But the argument continues to be made, pleasantly, yet firmly.
Liberation Theology for Britain
Authors: Corner Mark
Published: July 2007

So concluded Fergus Kerr in an editorial comment published by New Blackfriars last year. His remark leads us to consider what form a British liberation theology might take, and what obstacles lie in the way of its progress.

The question of a British version of the theology of liberation has received some attention in recent years. Two important public lectures considered it, Charles Elliott’s Heslington Lecture of January 1985, and the more well-known Hibbert lecture given by the Anglican Bishop of Durham, David Jenkins, in April of that year. David Jenkins’ lecture pointed out that the task would not be an easy one—certainly not a simple matter of translation from a third-world context to a first-world one:

British essays in liberation theology would not be mere echoes or reflections of liberation theology elsewhere. As I learnt from my contacts with some of those who developed liberation theology in Latin America and South East Asia, it would not be in the spirit of liberation theology if it were. As an article published in the Philippines in Manila in 1971 puts it, ‘the question is not “how can we adapt theology to our needs?”, but rather, “how can our needs create a theology which is our own?” ‘. Liberation theology rises out of the particular needs of a particular country for hope in relation to justice, peace and love.

As we shall see, there are some questions to be asked concerning Jenkins’ reluctance to envisage too close a parallel between a third-world and a first-world version of liberation theology.
Salvation of Soil
Authors: Echlin Edward P.
Published: July 2007

As soil organisms, people depend on other soil creatures. Biologist Thomas Lovejoy observed in a recent Reith Lecture, ‘All organisms need to eat. Even green plants which use the energy of the sun have to take in nutrients to live and grow.’ All earth creatures are an interdependent soil, or earth, community. While geological evidence shows that the community flourished before the arrival of humanity, people are not as expendable as ‘ecological age’ gaia gurus would have us believe. For especially through human hands and voices, and through sustainable cultivation, the soil community praises God in an ordered, biodiverse symphony. Sustainable horticulture in and near sustainable settlements provides a foretaste, a sign or parable, of God’s awaited kingdom.
The Language of Freedom in the American Presidency, 1933‐2006
Authors: COE KEVIN
Published: July 2007

Freedom is the most familiar symbol in American political culture, but little is known about how presidents have employed this symbol in their discourse. This study uses quantitative and qualitative analysis to examine the language of freedom in more than seventy years worth of presidential speeches. The findings reveal a presidential narrative of freedom that has been remarkably constant over time. However, within this broad narrative, presidents' political ideology and the context in which they spoke led to significant differences in the way they defined freedom and in the way they used the term to define the nation.
Above the Fray? The Use of Party System References in Presidential Rhetoric
Authors: COLEMAN JOHN J. , MANNA PAUL
Published: July 2007

Examining communication items from four presidents, we find that presidents link themselves to the party system rhetorically. Employment of party references is tested against recurrent features of the office and shifts in the political environment, including presidential approval, partisan independence, presidential successes and defeats in Congress, and the presence of divided government. Presidents strategically employ party system references with regard to audience and calendar. We find greater support for the rhetorical president as politician rather than as statesman above the fray, and we consider our findings in relation to the concept of political time. These findings suggest rethinking accounts of the contemporary presidency that presume that presidents determinedly place themselves “above politics” and “beyond party” when crafting their communications imagery.
Executive Clemency or Bureaucratic Discretion? Two Models of the Pardons Process
Authors: ERLER H. ABBIE
Published: July 2007

This article examines the use of the president's pardon power from 1953 to 2000. Two different models are used to describe the pardons process: a presidential model and an agency model. The presidential model takes a top‐down approach to the pardons process by viewing the pardon power as a resource that the president can use to advance specific policy goals. In contrast, the agency model views the pardons process as a bottom‐up process, with the preferences of officials within the Department of Justice as the key determinant of the number of pardons issued. This article empirically tests both of these models and finds that the president's control over the pardons process is limited by officials within the Justice Department and the actions of past presidents. This is illustrated by an in‐depth case study of President Bill Clinton's controversial use of the pardon power.
The Political Fallout of Taking a Stand: The President, Congress, and the Schiavo Case
Authors: HAIDER‐MARKEL DONALD P. , CARR CAROL K.
Published: July 2007

Federal government involvement in the case of terminally ill Terri Schiavo provides an interesting opportunity to explore the potential impact of specific institutional actions on public approval of those institutions. We analyze national survey data from the period of federal intervention and a poll conducted several months later. Our analyses, which account for time and exposure to political news, suggest that presidential and congressional actions in the case were associated with a decline in approval for the president and congressional leaders. Thus, the president and Congress can pay a political price when they take high‐profile actions a significant majority of the public opposes.
Why Did Clinton Survive the Impeachment Crisis? A Test of Three Explanations
Authors: SILVA CAROL L. , JENKINS‐SMITH HANK C. , WATERMAN RICHARD
Published: July 2007

In Federalist no. 65, Alexander Hamilton wrote that the impeachment process is a decidedly political one. We use data from a national survey conducted in September and October 1998 to examine explanations for Bill Clinton's survival of the impeachment crisis: the robust economy, his own high popular standing with the public, and the concomitantly lower public evaluations of his principal investigators, Independent Counsel Kenneth Starr and the Republican‐controlled U.S. Congress. Our analysis demonstrates that the performance of the U.S. economy did directly influence public support for impeachment, resignation, continued congressional hearings, and censure (four potential punishment options), but not in the manner most often hypothesized. More favorable assessments of the U.S. economy actually were related to higher levels of support for punishing the president. Evaluations of the president proved to be a double‐edged sword. Although higher evaluations of Clinton's personal job approval ratings and of his personal ethics ratings are related to lower levels of support for punishment, Clinton benefited more from the former than the latter, as his approval ratings were high while the public held considerable doubts about his ethics. Finally, we show that higher public evaluations of Clinton's primary investigators, Starr and the U.S. Congress, were related to higher levels of support for punishing the president. As both actors had an exceedingly low average approval rating, however, this dynamic worked to Clinton's advantage.
Affective Evaluations of First Ladies: A Comparison of Hillary Clinton and Laura Bush
Authors: SULFARO VALERIE A.
Published: July 2007

This study examines affective evaluations toward Hillary Clinton and Laura Bush during their tenure as first ladies and during Hillary Clinton's subsequent time as a U.S. senator. It was hypothesized that first ladies, rather than being above partisan politics, are evaluated in the same partisan and ideological manner as most political candidates. It was also hypothesized that Laura Bush, as a more traditional first lady, may receive more support from those who are associated with more traditional lifestyles and values. Ultimately, the strongest sources of affect toward first ladies prove to be partisanship and ideology. Moreover, when comparing ideal first ladies, liberals and women prefer Hillary Clinton, and white males and conservatives tend to prefer Nancy Reagan to Laura Bush.
The Contemporary Presidency: Who Wants Presidential Supremacy? Findings from the Institutions of American Democracy Project
Authors: ABERBACH JOEL D. , PETERSON MARK A. , QUIRK PAUL J.
Published: July 2007

The George W. Bush administration has aggressively advanced claims of presidential supremacy in American government. We use data from surveys to explore the reactions to these claims on the part of three groups of governmental elites and the general public. Responses are shaped by partisanship and ideology, which overwhelm institutional loyalties. Democrats are generally unified in opposing practices that expand presidential power beyond established political or constitutional limits. Republicans are more divided. Some entirely reject those practices. Yet about three quarters of Republicans in all samples endorse presidential supremacy, partially or fully. We consider the implications of the findings for possible longer‐term outcomes with respect to these issues.
The Polls: Presidential Referendum Effects in the 2006 Midterm Elections
Authors: COHEN JEFFREY E.
Published: July 2007

Many commentators saw the 2006 midterm elections as a referendum on George W. Bush's presidency, especially his unpopular Iraq War policy. Presidential referendum effects may be highly likely given the degree of party polarization and the concomitant attachment of large numbers of voters to the Democratic and Republican parties. But local factors, especially incumbency effects, may also have affected the outcome of the 2006 midterm contests. Using state‐level presidential approval polls, analysis finds that Bush's approval, an indicator of referendum voting, had little impact on voting in Senate contests, once applying controls for the ideological and partisan composition of state voting populations. In contrast, even with these controls, Bush's approval influenced voting in gubernatorial contests. But Iraq War battle deaths affected voting for senators, suggestive of another type of referendum effect. Battle deaths, however, did not affect the gubernatorial races.
Elections: The Home State Effect in Presidential Elections: Advances in the Study of Localism
Authors: DISARRO BRIAN , BARBER JILLIAN , RICE TOM W.
Published: July 2007

History shows that presidential candidates often win their home states by large margins. This phenomenon, which is sometimes called localism, has attracted the attention of scholars for decades. In this study, we improve upon previous localism research in several significant ways. Most important, we challenge the traditional conceptualization of the home state effect, arguing that a candidate's national showing is best thought of as a determinant of the effect instead of part of it, as has often been the case. We also devise three other new hypotheses to account for variation in the home state effect. All of these hypotheses find support in our empirical analyses, providing the most complete understanding of the home state effect to date.
Voltage‐gated ion channel Kv4.3 is associated with Rap guanine nucleotide exchange factors and regulates angiotensin receptor type 1 signaling to small G‐protein Rap
Authors: Potapova Irina A. , Cohen Ira S. , Doronin Sergey V.
Published: July 2007

The voltage‐gated potassium channel Kv4.3 was coexpressed with its β‐subunit Kv channel‐interacting protein 2 and the angiotensin type 1 receptor in HEK‐293 cells. Proteomic analysis of proteins coimmunoprecipitated with Kv4.3 revealed that Kv4.3 is associated with Rap guanine nucleotide exchange factors MR‐GEF and EPAC‐1. Previously, we demonstrated that Kv4.3 interacts with the angiotensin type 1 receptor in HE293 cells and cardiac myocytes. On the basis of this, we investigated the angiotensin type 1 receptor signaling to small G‐proteins Ras and Rap‐1 in the presence and absence of the Kv4.3–Kv channel‐interacting protein 2 macromolecular complex. Ras activation was not significantly affected by coexpression of Kv4.3 and Kv channel‐interacting protein 2. Ras exhibited a rapid activation–inactivation pattern with maximum activity at 2.5 min after addition of angiotensin II. In contrast, activation of Rap‐1 was affected dramatically by coexpression of Kv4.3 and Kv channel‐interacting protein 2 with the angiotensin type 1 receptor. In the absence of Kv4.3 and Kv channel‐interacting protein 2, stimulation of the angiotensin type 1 receptor resulted in steady activation of Rap‐1 that reached a plateau 25 min after addition of angiotensin II. In the presence of Kv4.3 and Kv channel‐interacting protein 2, Rap‐1 reaches a maximum activity 2.5 min after addition of angiotensin II and then deactivates rapidly, demonstrating a pattern of activation similar to that of Ras. Our findings show that Kv4.3 regulates angiotensin type 1 receptor signaling to the small G‐protein Rap‐1.
The use of recombinant protein and RNA interference approaches to study the reproductive functions of a gonad‐stimulating hormone from the shrimp Metapenaeus ensis
Authors: Tiu Shirley Hiu‐Kwan , Chan Siu‐Ming
Published: July 2007

Although the crustacean crustacean hyperglycemic hormone/molt‐inhibiting hormone/gonad‐inhibiting hormone neuropeptides have been studied extensively in the last two decades and several neuropeptides from the shrimp Metapenaeus ensis have been cloned, the functions of most of these neuropeptides remained putative. In this article, we describe the use of recombinant protein and an RNA interference approach to study the reproductive function of the previously reported molt‐inhibiting hormone (MeMIH‐B) in M. ensis. When hepatopancreas and ovary explants were cultured in medium containing recombinant MeMIH‐B, the vitellogenin gene (MeVg1) expression level was upregulated in a dose‐dependent manner, reaching a maximum in explants treated with 0.3 nm recombinant MeMIH‐B. Shrimp injected with recombinant MeMIH‐B showed an increase in vitellogenin gene expression in the hepatopancreas. Moreover, a corresponding increase in the vitellogenin‐like immunoreactive protein was detected in the hemolymph and ovary of these females. Injection of MeMIH‐B dsRNA into the female shrimp caused a decrease in MeMIH‐B transcript level in thoracic ganglion and eyestalk. These shrimp also showed reduction of vitellogenin gene expression in the hepatopancreas and ovary. Furthermore, the hemolymph vitellogenin level was also reduced in these animals. In summary, the results from recombinant protein and RNA interference experiments have demonstrated the gonad‐stimulatory function of MeMIH‐B in shrimp.
Tumor necrosis factor‐α‐induced caspase‐1 gene expression
Authors: Jain Nishant , Sudhakar Ch , Swarup Ghanshyam
Published: July 2007

Tumour necrosis factor‐α (TNF‐α) is a cytokine that is involved in many functions, including the inflammatory response, immunity and apoptosis. Some of the responses of TNF‐α are mediated by caspase‐1, which is involved in the production of the pro‐inflammatory cytokines interleukin‐1β, interleukin‐18 and interleukin‐33. The molecular mechanisms involved in TNF‐α‐induced caspase‐1 gene expression remain poorly defined, despite the fact that signaling by TNF‐α has been well studied. The present study was undertaken to investigate the mechanisms involved in the induction of caspase‐1 gene expression by TNF‐α. Treatment of A549 cells with TNF‐α resulted in an increase in caspase‐1 mRNA and protein expression, which was preceded by an increase in interferon regulatory factor‐1 and p73 protein levels. Caspase‐1 promoter reporter was activated by the treatment of cells with TNF‐α. Mutation of the interferon regulatory factor‐1 binding site resulted in the almost complete loss of basal as well as of TNF‐α‐induced caspase‐1 promoter activity. Mutation of the p53/p73 responsive site resulted in reduced TNF‐α‐induced promoter activity. Blocking of p73 function by a dominant negative mutant or by a p73‐directed small hairpin RNA reduced basal as well as TNF‐α‐induced caspase‐1 promoter activity. TNF‐α‐induced caspase‐1 mRNA and protein levels were reduced when p73 mRNA was down‐regulated by small hairpin RNA. Caspase‐5 gene expression was induced by TNF‐α, which was inhibited by the small hairpin RNA‐mediated down‐regulation of p73. Our results show that TNF‐α induces p73 gene expression, which, together with interferon regulatory factor‐1, plays an important role in mediating caspase‐1 promoter activation by TNF‐α.
Assessment of Acute Respiratory and Cardiovascular Toxicity of Casiopeinas in Anaesthetized Dogs
Authors: Leal‐García Marco , García‐Ortuño Luis , Ruiz‐Azuara Lena , Gracia‐Mora Isabel , Luna‐delVillar Jorge , Sumano Héctor
Published: July 2007

Abstract:  The 99 lethal dose in an acute toxicity study of two anticancer novel molecules named casiopeinas® in dogs was calculated to be 200 mg/m2 for casiopeina III‐ia and 160 mg/m2 for casiopeina IIgly. Considering therapeutic dose ranges from 3.6 to 18 mg/m2 for the former and 1.2 to 3 mg/m2 for the latter, true therapeutic margin of safety varies from 4.7 to 23.6 mg/m2 and from 20 to 50 mg/m2, respectively. For both casiopeinas intravenous administration of the corresponding lethal dose in 100 ml of 5% dextrose solution in a time period of 30 min. induced death after an almost uneventful latency time period of 30–50 min. Then, after an apparently sudden onset, changes in blood gases indicated respiratory distress (PO2 from 82.5% to 26.5% for casiopeina III‐ia and from 88.6% to 37.5% for casiopeina IIgly; end‐tidal CO2 from 38 to 8.1 mmHg for the first and from 35.1 to 11.2 mmHg for the second, this was almost simultaneously confirmed by the onset of tachypnoea (from 16 to almost 60 breaths/min. for both casiopeinas) and by a drop in arterial blood pressure (from 117 to 51 mmHg for casiopeina III‐ia and from 108 to 49 mmHg for casiopeina IIgly). Reflex tachycardia occurs at the beginning of intravenous administration followed by bradycardia a few minutes later (from 158 to 63 beats/min. for casiopeina III‐ia and from 148 to 56 beats/min. for casiopeina IIgly). Finally, cardiac arrest occurred no later than 25 min. towards the end of these events lung oedema appeared as fluid dripping from the endotracheal tube. Death occurred in a mean of 15 ± 5 min. S.D. from the beginning of the end of the latency period. For both casiopeina's data allow the speculation that lung oedema is caused by a joined toxicity to the lung capillary bed, and particularly to the heart. Carvedilol premedication for 8 days delayed the outcome of lung oedema by approximately 8 hr but could not prevent it.
Influence of Endotoxin‐Induced Sepsis on the Requirements of Propofol‐Fentanyl Infusion Rate in Pigs
Authors: Bollen Peter J. A. , Nielsen Bjørn J. , Toft Palle
Published: July 2007

Abstract:  Endotoxin‐induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin‐induced sepsis, in order to prevent respiratory and cardiovascular depression, but the scientific evidence for this observation is lacking. Therefore, we measured the consumption of propofol and fentanyl at equal level of anaesthesia in pigs with (n = 5) and without (n = 5) endotoxin‐induced sepsis, using the cerebral state index (CSI) as measure of anaesthetic depth. Infusion rates of propofol (P < 0.01) and fentanyl (P < 0.05) were significantly lower in septic pigs. Pigs with endotoxin‐induced sepsis had an infusion rate of 2.2 mg/kg/hr (S.D. 0.5) for propofol and 12 µg/kg/hr (S.D. 2) for fentanyl, whereas healthy pigs had infusion rates of 3.5 mg/kg/hr (S.D. 0.6) and 17 µg/kg/hr (S.D. 4), respectively. CSI was equal in both groups throughout the experiment, and had a lowest average value of 47 (S.D. 10) at t = 30 in healthy pigs and reached a highest average value of 67 (S.D. 19) at t = 240 in pigs with endotoxin‐induced sepsis. Anaesthetic depth was sufficient, assessed clinically, throughout the experiment in both groups. We concluded that the consumption of propofol and fentanyl was significantly reduced in pigs with endotoxin‐induced sepsis. In the present study, we adjusted the level of anaesthesia according to clinical signs, and found good agreement with CSI.
[3H] Citalopram Binding to Serotonin Transporter Sites in Minnow Brains
Authors: Gould Georgianna G. , Brooks Bryan W. , Frazer Alan
Published: July 2007

Abstract: Mammalian serotonin (SERT) and norepinephrine transporters (NET) are target sites for antidepressants and are affected by pesticide exposures. Herein, we examined whether golden shiner (Notemigonus crysoleucas) or fathead minnow (Pimphales promelas) SERTs and catecholamine transporters respond comparably to mammalian SERTs and NETs. We compared the pharmacological profiles of central SERT and NET binding sites of the golden shiner minnow to those of rats. Homogenate binding with the radioligand [3H] citalopram indicated that golden shiner SERT has a KDof 7 ± 3 nM and a Bmaxof 226 ± 46 fmol/mg protein. These values are similar to those of rat cortical SERT (KD1.4 ± 0.1 nM and Bmax240 ± 48 fmol/mg protein). We also examined SERT binding in fathead minnow brain, and found it similar to that of the golden shiner. A putative golden shiner NET, measured using [3H] nisoxetine, had KD = 12 ± 5 nM and Bmax = 187 ± 49 fmol/mg protein, whereas rat hippocampal NET had KD = 5 ± 2 nM and Bmax = 93 ± 8 fmol/mg protein. Minnow SERT and NET binding is displaceable by selective reuptake inhibitors. Finally, we exposed zebrafish (Danio rerio) to the serotonin reuptake inhibiting antidepressant sertraline or the organophosphate chlorpyrifos for 21 days. After either treatment, SERT binding was reduced by 50% (n = 3–6, P < 0.05). In summary, minnow central SERT and NET express slightly lower affinity for antidepressants than rats. However, magnitudes of affinity are similar, and minnow SERT binding is decreased by chronic sertraline or chlorpyrifos administration.
Influence of Tetrahydrocurcumin on Hepatic and Renal Functional Markers and Protein Levels in Experimental Type 2 Diabetic Rats
Authors: Murugan Pidaran , Pari Leelavinothan
Published: July 2007

Abstract:  Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti‐inflammatory agent. Tetrahydrocurcumin is one of the major metabolites of curcumin that exhibits many of the same physiologic and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than curcumin. Oral administration of tetrahydrocurcumin at 80 mg/kg body weight to diabetic rats for 45 days resulted in a significant reduction in blood glucose and significant increase in plasma insulin levels. In addition, the diabetic rats had decreased levels of plasma total protein, albumin, globulin and albumin/globulin ratio as compared to control rats. After treatment with tetrahydrocurcumin and curcumin total protein, albumin, globulin and albumin/globulin ratio were brought back to near normal. The activities of hepatic and renal markers were significantly elevated in diabetic rats as compared to control rats, and treatment with tetrahydrocurcumin and curcumin has reversed these parameters to near normal levels. In diabetic rats, the decreased levels of urea, uric acid and creatinine with increased levels of albumin and urine volume was observed, and treatment with tetrahydrocurcumin and curcumin reversed these parameters to near normal. Tetrahydrocurcumin appeared to have a better protective effect when compared to curcumin.
Substrate‐Dependent Modulation of UDP‐Glucuronosyltransferase 1A1 (UGT1A1) by Propofol in Recombinant Human UGT1A1 and Human Liver Microsomes
Authors: Mano Yuji , Usui Takashi , Kamimura Hidetaka
Published: July 2007

Abstract: Our previous study has shown that propofol, a probe substrate for human UDP‐glucuronosyltransferase (UGT) 1A9, activated the glucuronidation of 4‐methylumbelliferone (4‐MU) by recombinant UGT1A1 in a concentration‐dependent manner. In the present study, we investigated the mechanism of activation, and whether the stimulatory effect occurs when another substrate is used with human liver microsomes. The glucuronidation of 4‐MU followed Michaelis‐Menten kinetics with a Kmvalue of 101 µM in the absence of propofol. In the presence of 200 µM propofol, a concentration that causes heterotopic activation of 4‐MU glucuronidation (4‐MUG), the Vmaxvalue increased to 1.5‐fold, while the Kmvalue decreased to 0.53‐fold. In order to assess whether propofol activates UGT1A1 activity for a substrate other than 4‐MU, the effect of propofol on oestradiol 3β‐glucuronidation by recombinant UGT1A1 and in human liver microsomes was evaluated. In contrast to 4‐MUG activity, propofol inhibited UGT1A1‐catalysed oestradiol 3β‐glucuronidation in recombinant UGT1A1 as well as in human liver microsomes with IC50values of 59 and 228 µM, respectively. In addition, a known UGT1A1 modulator, 17α‐ethynyloestradiol, stimulated oestradiol 3β‐glucuronidation slightly at a concentration of 5 µM, while it inhibited 4‐MUG in recombinant UGT1A1 at all concentrations tested (5–100 µM). These findings indicate that the modulation of UGT1A1 by propofol is substrate‐dependent, and thus care should be taken when extrapolating the stimulatory effects of drugs for one glucuronidation substrate.
Amelioration of Corticosteroid‐Induced Type 2 Diabetes Mellitus by Rosiglitazone Is Possibly Mediated through Stimulation of Thyroid Function and Inhibition of Tissue Lipid Peroxidation in Mice
Authors: Jatwa Rameshwar , Parmar Hamendra Singh , Panda Sunanda , Kar Anand
Published: July 2007

Abstract:   We investigated the possible involvement of thyroid hormones and lipid peroxidation in the antidiabetic potential of rosiglitazone (a peroxisome proliferator‐activated receptors γ‐agonist) on corticosteroid‐induced type 2 diabetes mellitus. Rosiglitazone was administered to dexamethasone‐induced hyperglycaemic male mice and the alterations in serum concentrations of thyroid hormones insulin, total cholesterol, triglycerides and fasting glucose were studied. Simultaneously changes in lipid peroxidation, reduced glutathione (GSH) content, superoxide dismutase and catalase activities in renal and cardiac tissues (which are commonly affected in diabetes mellitus), were also investigated. Administration of dexamethasone (1.0 mg/kg/day intramuscularly for 28 days) caused hyperglycaemia with a parallel increase in serum insulin, total cholesterol, triglycerides and tissue lipid peroxidation with a decrease in serum levels of both the thyroid hormones (triiodothyronine, T3 and thyroxine, T4) and in the activity of associated tissue antioxidants such as superoxide, catalase and glutathione. However, rosiglitazone administration (3.2 mg/kg/day orally for 21 days) along with an equivalent amount of dexamethasone reverted most of these changes, including a marked inhibition of tissue lipid peroxidation and an increase in the serum levels of both thyroid hormones. The present findings reveal that the test drug ameliorates corticosteroid‐induced type 2 diabetes mellitus through an increase in serum thyroid hormone concentrations and inhibition in tissue lipid peroxidation.
FACTORS AFFECTING COWORKERS‘ PROCEDURAL JUSTICE INFERENCES OF THE WORKPLACE ACCOMMODATIONS OF EMPLOYEES WITH DISABILITIES
Authors: COLELLA ADRIENNE , PAETZOLD RAMONAL. , BELLIVEAU MAURA A.
Published: July 2007

We examine coworkers' procedural justice inferences about the accommodation of another employee when they believe it is for disability‐related reasons. Legal constraints that prevent the release of information about the accommodation process may lead to negative inferences about fairness. However, we argue that other factors can help to make inferences about procedural justice more positive. We present a model of the process through which coworkers engage in making inferences about the procedural justice of accommodating a coworker with a disability and the individual and organizational level factors likely to influence those inferences. Consequently, we present propositions to be studied in future empirical research and suggestions to managers who desire to reduce negative coworker reactions to accommodating individuals with disabilities.
PREDICTORS OF JOB SEARCH BEHAVIOR AMONG EMPLOYED AND UNEMPLOYED PEOPLE
Authors: HOOFT EDWIN A. J. VAN , BORN MARISE PH. , TARIS TOON W. , FLIER HENK VAN DER , BLONK ROLAND W. B.
Published: July 2007

This study investigated job search behavior and its predictors among employed and unemployed people. Ajzen's (1985) theory of planned behavior (TPB) was used to predict job search intention and behavior in both groups. In addition, we examined the indirect effects of several other variables (i.e., job satisfaction, organizational commitment, work valence, expectancy, and financial need). Data were collected in a 2‐wave longitudinal design, using a sample of employed individuals (N = 989) and a sample of unemployed individuals (N= 317). Results supported the applicability of the TPB in the 2 groups. The attitude‐intention‐behavior relationship was stronger in the unemployed group than in the employed group. The TPB variables partially mediated the effects of the additional variables studied.
LEADERSHIP AND PROCEDURAL JUSTICE CLIMATE AS ANTECEDENTS OF UNIT‐LEVEL ORGANIZATIONAL CITIZENSHIP BEHAVIOR
Authors: EHRHART MARK G.
Published: July 2007

Despite an abundance of research conducted on organizational citizenship behavior (OCB) at the individual level of analysis, relatively little is known about unit‐level OCB. To investigate the antecedents of unit‐level OCB, data were collected from employees of 249 grocery store departments. Structural equation modeling techniques were used to test a model in which procedural justice climate was hypothesized to partially mediate the relationship between leadership behavior (servant‐leadership) and unit‐level OCB. Models were tested using both employee ratings and manager ratings of unit‐level OCB. The results gave general support for the hypotheses, although there were some differences depending on the source of the OCB ratings (supervisor or subordinate), whether the type of department was controlled for, and whether a common method variance factor was included. Overall, the evidence generally supported the association of both servant‐leadership and procedural justice climate with unit‐level OCB. Building on the current study, a multilevel framework for the study of OCB is presented in conjunction with a discussion of future research directions in four specific areas.
RECRUITMENT COMMUNICATION MEDIA: IMPACT ON PREHIRE OUTCOMES
Authors: ALLEN DAVID G. , SCOTTER JAMES R. VAN , OTONDO ROBERT F.
Published: July 2007

An unanswered question in recruitment research is whether and how the media used to communicate recruitment messages influence important outcomes. Drawing from research and theory on persuasive communication and media richness and features, we propose and test a model of the effects of media and media features (amount of information, opportunities for 2‐way communication, personal focus, social presence, symbolism) on communication outcomes (credibility and satisfaction), attitudes, intentions, and behavior associated with joining the organization. Results of an experiment with 989 undergraduate students show that a constant recruitment message delivered via different media (face‐to‐face, video, audio, text) influenced perceptions of featares, and perceptions of features were related to important pre‐hire outcomes.
WHEN THE PSYCHOMETRICS OF TEST DEVELOPMENT MEETS ORGANIZATIONAL REALITIES: A CONCEPTUAL FRAMEWORK FOR ORGANIZATIONAL CHANGE, EXAMPLES, AND RECOMMENDATIONS
Authors: MUCHINSKY PAUL M.
Published: July 2007

Our standards for the construction of psychological tests give scant attention to the organizational context in which the tests are to be used. This paper describes 10 Psychometric issues associated with the development of an electrical job knowledge test. The test was designed to replace seniority as a means of making promotional decisions within an organization. The 10 test‐related issues are presented as a means to understand the underlying process of organizational change associated with the implementation of the new test. It is suggested that a closer link between the science and practice of our profession can be attained by achieving a greater understanding of issues associated with the practical implementation of theory‐based interventions.