bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-Analysis Finds Use of Inhaled Corticosteroids During Pregnancy Safe: A Systematic Meta-Analysis Review
Authors: Rahimi R , Nikfar S , Abdollahi M
Published: August 2006

Inhaled corticosteroids (ICs) are the drug of choice for asthmatic women during pregnancy, but the results on the effects of these medications on obstetrical and perinatal outcomes are not conclusive. Meta-analysis is the statistical analysis of a collection of analysis results from individual studies for the purpose of integrating the findings. Meta-analysis techniques are necessary because only summary statistics are available in the literature. In order to determine the risk of exposure to ICs, we pooled data from all clinical studies that evaluated the pregnancy and perinatal outcomes in women exposed to this group of drugs during pregnancy by the meta-analytic technique.

PUBMED, OVID, EMBASE and SCOPUS databases were searched for studies that investigated birth outcome following exposure to ICs during pregnancy. Data were collected from 1997 to 2005 (up to 31 December). Types of outcome investigated were major malformations, pre-term delivery, low birth weight and pregnancy-induced hypertension. The criteria for inclusion of studies in this meta-analysis were exposure of women to any therapeutic dosage of any ICs (fluticasone, beclomethasone, budesonide, triamcinolone and flunisolide) during pregnancy.

The results showed that ICs do not increase the risk of major malformations, preterm delivery, low birth weight and pregnancy-induced hypertension. In conclusion, ICs do not increase the rates of any obstetrical outcomes investigated in the present study and interestingly improve the symptoms and are helpful in the management of asthma and thus can be used comfortably during pregnancy.
Effect of Low-Dose Cyclosporine A in the Treatment of Refractory Proteinuria in Childhood-Onset Lupus Nephritis
Authors: Baca V , Catalán T , Villasís-Keever M , Ramón G , Morales AM , Rodríguez-Leyva F
Published: August 2006

We performed a prospective study to evaluate the efficacy and safety of low-dose cyclosporine A (CSA) treatment in paediatric lupus nephritis refractory to conventional therapy. Seven children with biopsy-proven Class III—IV lupus nephritis were treated with CSA (2—4 mg/kg/day) combined with low-dose prednisone for one year. All patients had failed to achieve sustained proteinuria remission with corticosteroids and cytotoxic drugs. Proteinuria decreased from median value of 2.5 g/24 hours (range, 1.2—4.9) to 0.14 g/24 hours (range, 0.0—0.84) after treatment ( P = 0.018). Median values of creatinine clearance and serum creatinine did not change significantly. Median systemic lupus erythematosus disease activity index score decreased from 12 (range, 6—16) to 4 (range, 0—8) at end of treatment ( P = 0.027). However, two patients experienced flares of extrarrenal manifestations and complement levels did not improve. Moreover, most patients relapsed with proteinuria within a few months of stopping CSA therapy. Side effects were not significant. In conclusion, low-dose of CSA combined with steroids appears to be useful to reduce proteinuria in paediatric proliferative lupus nephritis refractory to steroids and cytotoxic drugs; however, relapses are common after CSA discontinuation. Further studies are needed to define the precise role of CSA in paediatric lupus nephritis.
Relationship between Damage Accrual, Disease Flares and Cumulative Drug Therapies in Juvenile-Onset Systemic Lupus Erythematosus
Authors: Bandeira M , Buratti S , Bartoli M , Gasparini C , Breda L , Pistorio A , Grassi S , Alpigiani MG , Barbano G , Janz-Junior LL , Martini A , Ravelli A
Published: August 2006

Our objective was to investigate the pattern of damage accumulation in patients with juvenile-onset systemic lupus erythematosus (JSLE) and the relationship between damage accrual, disease flares and cumulative drug therapies. All patients with SLE followed prospectively in three tertiary care centres were identified. Only patients who presented within 12 months of diagnosis and were followed for at least three years were included. Damage was measures based on chart review using the SLICC/ACR damage index (SDI), which was modified (M-SDI) by adding the item growth failure. Mild-moderate and severe disease flares were defined by the increase in SLEDAI-2K. The cumulative duration of drug therapies was calculated in each patient. Fifty-seven patients were included. The mean M-SDI score for the whole patient group increased over time, from 0.1 at one year to 0.8 at three years to 1.5 at five years. Ocular and renal damage and growth failure were observed most frequently. Compared to patients with stable damage, patients who accrued new damage had a significantly greater frequency of severe disease flare in the first three years of follow-up. No significant difference was observed in any cumulative drug therapy between patients who accrued damage and those who did not. Damage accrual was associated with severe disease flares, suggesting that judicious use of immunosuppressive agents to achieve prompt control of severe exacerbation of disease activity is important in minimizing damage in patients with JSLE.
Antinucleosome Antibodies in Patients with Juvenile Systemic Lupus Erythematosus
Authors: Campos LMA , Kiss MHB , Scheinberg MA , Mangueira CLP , Silva CA
Published: August 2006

Our objective was to evaluate the frequency of antinucleosome antibodies (anti-Ncs) in juvenile systemic lupus erythematosus (JSLE) comparing it to that observed for anti-DNA and to correlate the presence of these antibodies with clinical manifestations and disease activity. Anti-Ncs and anti-DNA were detected by ELISA in 74 patients with JSLE and 64 normal controls. Clinical records were reviewed. Disease activity was assessed by SLEDAI score. Anti-Ncs and anti-DNA showed sensitivity of 52.7% and 54% and specificity of 98.4% and 95.3%, respectively. Disagreement between the two assays was found in 25.7% of the cases: isolated positive Anti-Ncs in nine cases (12.2%) and isolated positive anti-DNA in 10 cases (13.5%). Agreement was found in 74.3%: both positive antibodies in 30 cases and both negative in 25. The presence of anti-Ncs was significantly associated with malar erythema, hemolytic anemia, anti-DNA and low complement levels, but not with renal manifestations. The presence of anti-Ncs was associated with a higher SLEDAI median ( P < 0.001) and its titers correlated with the SLEDAI score ( r = 0.504; P < 0.001). The frequency, sensitivity and specificity values were similar between anti-Ncs and anti-DNA antibodies in patients with JSLE. Nevertheless, the discordance of 25.7% between the two assays suggests that both antibodies may have a complementary diagnostic role. The association and correlation between anti-Ncs and several disease activity parameters demonstrated its usufulness in the follow-up of these patients.
Use of Proteomics in Analysis of Autoimmune Diseases
Authors: Xiang Y , Kato T
Published: August 2006

Autoimmune diseases are common by diseases characterized by disorders of immune responses and autoimmune impairment involving multiple tissues, organs and systems. The autoantigens (Ags)/autoantibodies (Abs) are not only hallmarks but also involved in pathogenesis of autoimmune diseases. In recent years, proteomics technologies have been used and demonstrated effective in searching new Ags/Abs as well as disease biomarkers in autoimmune diseases.
Gene Expression Studies in Systemic Lupus Erythematosus
Authors: Mandel M , Achiron A
Published: August 2006

In a single assay, gene microarrays generate tens of thousands of measurements for the relative levels of messenger RNA expression, and thus hold promise to uncover the regulation of transcriptional responses behind clinical phenotypes of various diseases. Systemic lupus erythematosus (SLE) offers a unique opportunity to study gene expression both systemically and organ specific, as the tissues involved and specifically peripheral blood cells are readily accessible for molecular analysis. In the current review we highlight the current knowledge related to gene microarray in SLE. We approached the following questions: 1) Can gene microarray technology be used to translate molecular profiles into meaningful and applicable clinical information? 2) Does the assessment of differential gene expression provide specific signatures that may contribute to diagnostic and prognostic markers of SLE? 3) Can clinicians be helped in monitoring disease activity by identification of drug response gene profile? 4) Does evaluation of differential gene expression provide clues to detect previously unrecognized genes associated with the disease? It is evident that though not all questions can be currently answered appropriately, gene expression studies in SLE have important implications and will not only be beneficial for SLE patients, but will also lead to a better understanding of other autoimmune inflammatory diseases, thereby leading to novel diagnostic and therapeutic strategies in autoimmunity.
Stenosis in Antiphospholipid Syndrome: A New Finding with Clinical Implications
Authors: Ben-Ami D , Bar-Meir E , Shoenfeld Y
Published: August 2006

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a variety of clinical manifestations. Recent studies suggest arterial stenosis is involved in APS. Furthermore, arterial stenosis may be a relevant and treatable cause for hypertension, renal, CNS and gastrointestinal manifestations of APS. Our objective was to overview the published data regarding arterial stenosis in APS-the clinical presentation, diagnosis, suggested therapies and the possible mechanisms. We searched PUBMED (1951-2006) reference lists for the role of arterial stenosis in APS. APS patients might present with arterial stenosis. Its recognition has important diagnostic and therapeutic implications. Articles suggest that anticoagulation treatment with INR above three may reverse the artery stenosis and achieve subsequent clinical improvement. Currently, there are no specific guidelines for the management of APS patients with arterial stenosis. The exact mechanism of arterial stenosis in APS patients remains unclear.
Hand Arthritis in Systemic Lupus Erythematosus: An Ultrasound Pictorial Essay
Authors: Wright S , Filippucci E , Grassi W , Grey A , Bell A
Published: August 2006

A small minority of systemic lupus erythematosus (SLE) patients may develop a deforming arthritis, typically with a non-erosive (Jaccoud’s) pattern, although erosive features indistinguishable from rheumatoid arthritis may also occur. High-resolution ultrasonography (HRUS) allows detailed ‘real time’imaging of joint and tendon morphostructural changes involving the hand in patients with several rheumatic diseases. The main aim of this pictorial essay is to provide the first descriptive HRUS and power Doppler (PD) findings of joint and tendon involvement of the hand and wrist in patients with SLE arthritis. Seventeen patients with SLE and hand involvement were examined. HRUS of the wrist, 2nd and 3rd MCP joints, 3rd PIP joint and 2nd, 3rd and 4th finger flexor tendons were studied in the dominant hand for each patient. Sixteen (94%) patients had joint effusion or synovial hypertrophy in the wrist. Twelve (71%) patients had joint effusion or synovial hypertrophy in 2nd or 3rd MCPJs. Eight (47%) patients had erosion at 2nd or 3rd MCPJs. In three cases erosions were not present radiologically. Eleven (65%) patients had evidence of tenosynovitis. In SLE, HRUS with PD detects a high prevalence of inflammatory pathology in the tendons and synovium of the hand and wrist, and a high prevalence of MCP joint erosions. HRUS offers a sensitive, real-time and readily repeatable assessment of soft-tissue, inflammatory and bony changes in SLE hands.
Aortitis and Aortic Thrombus in Systemic Lupus Erythematosus
Authors: Silver AS , Shao CY , Ginzler EM
Published: August 2006

Aortitis is an uncommon complication of systemic lupus erythematosus (SLE). Most cases of lupus-associated aortitis have been described in conjunction with aortic aneurysms or aortic dissection and have been documented either at autopsy or during surgery to repair a dissection. We describe an unusual case of aortitis associated with an aortic thrombus in a young man with SLE.
The Cardiac Safety of Chloroquine Phosphate Treatment in Patients with Systemic Lupus Erythematosus: The Influence on Arrhythmia, Heart Rate Variability and Repolarization Parameters
Authors: Wozniacka A , Cygankiewicz I , Chudzik M , Sysa-Jędrzejowska A , Wranicz JK
Published: August 2006

Antimalarials are used to treat cutaneous and systemic lupus erythematosus (SLE). Even though cardiac damage is a rare complication, over the last decade several reports have raised the issue of cardiotoxicity associated with antimalarials. Therefore, the aim of study was to evaluate the influence of seven-month chloroquine treatment with a 250 mg daily dose on arrhythmia, conduction disturbances as well as heart rate variability and repolarization parameters assessed in 24-hour Holter monitoring. The studied group included 28 SLE patients treated with chloroquine as a monotherapy. In all the patients standard 12 leads surface ECG (50 mm) and the 24-hour ECG Holter monitoring (Oxford Medilog Excel-2) were performed before and after chloroquine phosphate treatment. All subjects presented sinus rhythm both at the enrollment and after treatment. No episodes of paroxysmal arrhythmias or conduction disturbances were reported during the study. All the patients were characterized by tendency to tachycardia, but no significant differences in mean heart rate were found before and after chloroquine administration. Similarly, no changes in heart rate variability or repolarization parameters were observed.
Somatostatin Treatment Attenuates Proteinuria and Prevents Weight Loss in NZB/W F1 Mice
Authors: Paran D , Bernheim J , Golan I , Caspi D , Bernheim J , Benchetrit S
Published: August 2006

Somatostatin, a naturally occurring neuropeptide, is an immunomodulator which inhibits humoral and cell mediated immunity as well as secretion of proinflammatory cytokines. The objective of this study was to examine the effects of a somatostatin analogue on the severity of glomerulonephritis in the female NZB/W F1 murine model of systemic lupus erythematosus (SLE). Twenty female NZB/W F1 mice were treated at 23 weeks of age with 10 mg/kg of the somatostatin analogue Sandostatin-LAR, IM every four weeks. Ten control mice received IM injection of vehicle. Mice were assessed at four-week intervals for weight change, proteinuria, anti-DNA antibodies and splenocyte cytokine profile. The mice were sacrificed at age 34.5 weeks. Kidneys were collected and evaluated by light and immunofluorescence (IF) microscopy. Spleens were collected and splenocyte intracellular cytokines were measured by FACS analysis. In the treatment group significantly less proteinuria was observed four weeks after the second somatostatin analogue injection (dipstik scale: +2.07 ± 0.95 versus. +3.5 ± 1.08, P = 0.0002). The treated mice did not lose weight while the control group lost weight over time (P = 0.016). No differences were noted between the groups in anti-DNA antibody titres, cytokine profile or the severity of lupus nephritis as assessed by light and IF microscopy. Somatostatin analogue treatment attenuated proteinuria and prevented weight loss in NZB/W F1 mice, suggesting a possible beneficial effect on renal parameters and systemic manifestations of the disease. Further studies will be needed to assess the value of somatostatin analogue treatment in lupus nephritis, utilizing higher doses, at different stages of the disease, for longer periods.
Bristol COPD Knowledge Questionnaire (BCKQ): testing what we teach patients about COPD
Authors: White R , Walker P , Roberts S , Kalisky S , White P
Published: August 2006

Health professionals recommend education of patients about COPD. There is no satisfactory instrument to measure their knowledge and therefore to assess the results of education. A multiple-choice questionnaire (BCKQ) has been designed and tested. Each of 13 topics contains five statements for which there is a right or wrong answer. Its validity and consistency has been assessed, and the test re-test reliability and responsiveness measured after an interval of eight weeks. A copy of the multiple-choice questionnaire is given in the Appendix. The questionnaire was judged by patients and health professionals to have good content and face validity. It has good internal consistency for the 65 items. (Cronbach’s alpha 0.73). It can be completed and scored within twenty minutes. The average score in subjects who had not received prior education was 54.7%. In a group not receiving education there was good test-retest reliability ( r - 0.71). Following an eight-week education programme there was a significant improvement of 18.3 percentage points, and most of the increase was maintained for six months without any further formal education. BCKQ is suitable for both clinical and research purposes. It will test knowledge that is appropriate for COPD patients and can be used as an assessment tool for individual patients, or as a broad cross-sectional survey instrument. It will enable the effectiveness of education to be assessed and will be of value in developing and comparing different educational interventions.
‘The damned word’: Culture and Its (In)compatibility with Law
Authors: Fitzpatrick Peter
Published: August 2006

The compatibility and incompatibility between law and culture are identified through an analysis of relation. By way of exploring the elusiveness of conceptions of culture and of law, a commonality relating them is arrived at, one that indicates not only what they constituently share but also what distinguishes them from each other. So far an abstract abstract. The abstractness of the comment itself is relieved by references to a case study and by resorting to etymologies.
Making a Mess of Things: The Trifles of Legal Pleasure
Authors: Reichman Ravit
Published: August 2006

This essay argues for an approach to legal studies that concentrates on law's wider cultural resonances. It examines the genre of the mystery novel, focusing on Wilkie Collins's The Moonstone, and analyzes legal writings by such figures as Oliver Wendell Holmes. By centering on the figure of the trifle, it emphasizes issues that are deemed irrelevant by an approach to the law that privileges matters of doctrine and procedure. To engage the trivial requires addressing questions of pleasure – an underexamined aspect of the law that can only be engaged by a cultural approach to its study.
Legal Claims to Culture in and Against the Market: Neoliberalism and the Global Proliferation of Meaningful Difference
Authors: Coombe Rosemary J.
Published: August 2006

Under conditions of neoliberalism legal claims to protect, preserve, maintain, and to exploit culture have assumed a new urgency. Cultural diversity has become a matter of state concern and fears of cultural homogenization animate movements to promote a revitalized realm of cultural policy. Municipal governments see cultural amenities, attractions, and social values as important resources to attract labor and capital and engage in cultural planning exercises as they seek to brand urban space. Rural spaces become culturalised as traditions are constructed to establish market distinctions for local goods and traditional knowledge is valorized in international environmental treaties. But if culture is clearly delineated for the purposes of state management and the creation of new intellectual properties, it is also evoked in anti-globalization movements that contest growing forms of corporate hegemony. Finally, we witness the emergence of a new cultural politics of difference in place-based movements that draw upon international indigenous and human rights traditions to establish their claims to livelihood resources, territories, and cultural survival. Critical scholarship is needed to explore the conditions under which neoliberal regimes of govern-mentality are supported and challenged by the legal recognition of cultural assertions and the stakes and limitations of cultural claims.
Zizek against Democracy
Authors: Dean Jodi
Published: August 2006

In the face of the demise of socialism in Eastern Europe, the welfare state in Western Europe and the UK, and confidence in state or public approaches to social and economic problems in the USA, is democracy the primary signifier of the potential of emancipatory political struggle? And, if so, does this indicate a diminishment in political dreams, the loss, perhaps, of hopes for equity and social justice? This article takes up Slavoj Zizek's critical interrogation of democracy, defending Zizek's position as an alternative left politics, indeed, as that position most attuned to the loss of the political today. Whereas liberal and pragmatic approaches to politics and political theory accept the diminishment of political aspirations as realistic accommodation to the complexities of late capitalist societies as well as preferable to the dangers of totalitarianism accompanying Marxist and revolutionary theories, Zizek's psychoanalytic philosophy confronts directly the trap involved in acquiescence to a diminished political field, that is to say, to a political field constituted through the exclusion of the economy: within the ideological matrix of liberal democracy, any move against nationalism, fundamentalism, or ethnic violence ends up reinforcing Capital and guaranteeing democracy's failure. Arguing that formal democracy is irrevocably and necessarily ‘stained’ by a particular content that conditions and limits its universalizability, he challenges his readers to relinquish our attachment to democracy. I argue that critical Left theory should take up this challenge.
From the Posthumous Memoirs of Humanity: “Democracy to Come”
Authors: Ghetti Pablo S.
Published: August 2006

Taking Derrida's work as point of departure, this commentary aims to articulate the concept of the humanities with the postulation of a democracy to come. The humanities are thought through their constituent but posthumous humanism, and through their power within the university. The humanities have rewritten Humanity. Their autobiographical traces, unfindable traces of this writing, mean marks for a democracy to come. Following Derrida, this commentary asserts that no event of democracy is thinkable without the dissymmetry that comes from the humanities. Beyond Derrida, however, the productivity of fiction provides more elements for the untamed reactivation of the contemporary democratic discourse.
Bataille's Contestation
Authors: Minkkinen Panu
Published: August 2006

The aim of this essay is to clarify one of the central themes in Georges Bataille's post-war writings, namely sovereignty. At the same time, it attempts to bring to light the intellectual tradition from which Bataille's thinking arises and to which it contributes. Three specific themes are addressed: the so-called community debate (Jean-Luc Nancy and Maurice Blanchot), Bataille's Hegelian influences (especially Alexandre Kojeve's reading of Hegel's phenomenology), and the possible affinities between Bataille's understanding of sovereign enjoyment and Lacan's “other” jouissance. Through these admittedly brief and suggestive investigations, the essay can hopefully elucidate what Bataille understood as “contestation,” a rather specific form of critical thought and a confrontation with the Western traditions of knowledge and, further, examine the limitations and differences of this contestation in relation to what one could call “social criticism.”
The Vengeful Logic of Modern Criminal Restitution
Authors: Manaugh Sara
Published: August 2006

Restitution, a perpetual presence in the life of the law, dwells on the margins of our modern legal landscape, and invokes a pre-legal moment in which injured parties bore the responsibility-or the privilege of themselves remedying the harms committed against them. This article explores the criminal sanction of restitution, and particularly restitution's surprising relationship with revenge. Rather than regarding bloodlust and the desire to cause suffering in those who first made us suffer as revenge's sine qua non, I argue that just as essential to revenge is a nostalgia for a prehistorical and prelegal time in which being wronged was an occasion not for recourse to the law, but for action. The article examines two distinct but related sites of restitutive justice within the contemporary criminal justice system where this fantasy of agency plays out. First turning to the victims'rights movement, observing that the movement has become ossified in a punitive logic that belies its pretensions toward a victim centered paradigm, the article then looks at the kinder, gentler restorative justice movement, which values rehabilitation and reintegration but is motivated as well by a vengeful impulse. The place of restitution in these movements emerges as the instantiation of a doubled fantasy of return to a state of equilibrium: on a leveled playing field occupied by wrongdoer and wronged, liberated from law's domination, a struggle between equals can result in the natural justice of a wrong repaid. This fantasy is born of nostalgia for an economy of revenge that exists only as an illusory ideal of agency vis-a`-vis those who wrong us, forever (or at least for now) kept at arm's distance by virtue of its institutionalization within a state that seeks to preserve its monopoly on force.
Legal Realism, Common Courtesy, and Hypocrisy
Authors: Bybee Keith J.
Published: August 2006

In the USA, courts are publicly defined by their distance from politics. Politics is said to be a matter of interest, competition, and compromise. Law, by contrast, is said to be a matter of principle and impartial reason. This distinction between courts and politics, though common, is also commonly doubted – and this raises difficult questions. How can the courts at once be in politics yet not be of politics? If the judiciary is mired in politics, how can one be sure that all the talk of law is not just mummery designed to disguise the pursuit of partisan interests? In one sense, an ambivalent public understanding of the courts and suspicions of judicial hypocrisy pose a threat to judicial and democratic legitimacy. Yet, in another sense, public ambivalence and suspected hypocrisy may actually open up space for the exercise of legal power. I illustrate and critique the enabling capacities of ambivalence and hypocrisy by drawing an analogy to common courtesy.
Law's Literature, Law's Body: The Aversion to Linguistic Ambiguity in Law and Literature
Authors: Dore Florence
Published: August 2006

In any kind of literary analysis, the critic must grapple with linguistic ambiguity, and the law cannot help but operate in a linguistic realm as well. Neither of these claims is terribly startling, yet studies of law and literature by literature scholars in particular remain strangely resistant to both. Literature scholars working in this field surprisingly tend to assert that the law grounds the ephemeral realm of the literary, and thus that the law corrects literature's linguistic quality. This unfortunate theoretical tendency is an effect of a broader problem in literary studies: an aversion to ambiguity that has seeped from studies of the novel into studies of law and literature.
Praxis: or the benefits of shedding hostility to theory
Authors: Pether Penelope
Published: August 2006

In this piece of critical, interdisciplinary and situated legal scholarship the author explores the implications of the material practices and institutional constraints that shape the place of Legal Writing and its professoriate in contemporary US legal education, and draws lessons from both the history of Rhetoric and Composition Studies and that of US legal education in seeking ways to address the gendered employment discrimination characteristically experienced by teachers of Legal Writing.
“No Truth Machine”: Law, Psychoanalysis, Uncertainty
Authors: Schmeiser Susan R.
Published: August 2006

Both law and psychoanalysis make certain truth claims. This essay considers instances in which each has evaluated the truth claims of the other and found them wanting. The essay begins by looking at legal materials and commentaries surrounding repressed memories of childhood sexual abuse and the therapies in which such memories come to light. Many of these materials contrast psychoanalytic knowledge to legal knowledge, locating speculation and potentially dangerous uncertainty in the former. Yet courts and others employ notable analogies between legal and psychoanalytic processes while simultaneously insisting on their incommensurability. Following an analysis of this tension, particularly as it plays out in one recent case, the essay turns to Freud's 1906 lecture on the usefulness of psychoanalytic techniques to legal proceedings and their search for facts. Freud, too, makes his case through a tenuous analogy between law and psychoanalysis. While courts and others may see the two as antagonistic, Freud imagines his own field as indispensable to law in enabling it to exploit the unconscious in the service of fact. Thus each field lays claim to truths that appear to elude the other, simultaneously perceiving in the other field a precarious likeness of itself.
Lear and Law's Doubles: Identity and Meaning in a Time of Crisis
Authors: Greenhouse Carol J.
Published: August 2006

Legal consciousness is vulnerable to sudden and profound change, even when there is no disruption to social or administrative routine. Such dilemmas pose problems that are at once hermeneutic, pragmatic and textual involving issues of recognition, decision making, agency, representation and discursive management, among other things. In this essay, I explore these issues by drawing on mixed media and genres comparative ethnography (from the margins of neoliberalism), current events (the Bush administration's case for war in Iraq and the campaign to ban same-sex marriage), and literary text (Shakespeare's King Lear). Reading across these sources, my purpose is to advance the case for taking the literariness of state power seriously as a register in which core propositions about the relationship between legitimacy and democratic accountability can be asserted and contested through the language of everyday life.
Effect of VIP on TLR2 and TLR4 Expression in Lymph Node Immune Cells During TNBS‐Induced Colitis
Authors: ARRANZ ALICIA , ABAD CATALINA , JUARRANZ YASMINA , TORROBA MARTA , ROSIGNOLI FLORENCIA , LECETA JAVIER , GOMARIZ ROSA PÉREZ , MARTÍNEZ CARMEN
Published: August 2006

Abstract:  Toll‐like receptors (TLRs) are a family of pattern recognition receptors (PRRs), which recognize numerous molecules collectively named pathogen‐associated molecular patterns, with an essential role in inflammatory conditions and connecting innate and acquired immune responses. Moreover, a new function of TLRs in the intestinal mucosa has been described. Under homeostatic conditions, TLRs act to protect the intestinal epithelium; but when homeostasis is disrupted, TLRs appear deregulated. Disruption of intestinal homeostasis occurs in disorders, such as Crohn's disease (CD). Trinitrobenzene sulfonic acid (TNBS)‐induced colitis is a murine model of human CD and vasoactive intestinal polypeptide (VIP) exerts a beneficial effect, by decreasing both inflammatory and autoimmune components of the disease. Recently, we have demonstrated the constitutive expression of TLR2 and TLR4 at mRNA and protein levels in colon extracts and their upregulation in TNBS‐treated mice as well as the effect of VIP treatment, approaching control levels. However, the systemic effect is little known. The present results demonstrate a beneficial role of VIP, restoring homeostatic conditions through the regulation of both lymphoid cell traffic and TLR2/4 expression on macrophages (MØ), dendritic cells (DCs), and CD4 and CD8 T lymphocytes.
Search for the Optimal Monosodium Glutamate Treatment Schedule to Study the Neuroprotective Effects of PACAP in the Retina
Authors: BABAI NORBERT , ATLASZ TAMAS , TAMÁS ANDREA , REGL?DI DORA , TÓTH GABOR , KISS PETER , GÁBRIEL ROBERT
Published: August 2006

Abstract:  We have previously shown the protective effects of pituitary adenylate cyclaseactivating polypeptide (PACAP) in monosodium glutamate (MSG)‐induced retinal degeneration. In the present article, we have investigated the optimal model for examining this neuroprotective effect. One MSG treatment on postnatal (P) days 1 or 5, in spite of leading to same ultrastructural changes, does not cause enough damage to study neuroprotection. When retinas were treated three times with MSG, the entire inner retina degenerated. Neuroprotection with PACAP was achieved with at least two treatments. Evidence suggests that PACAP provides protection against excitotoxicity, therefore, it may be a useful agent in reducing excitotoxic damage in the retina.
The Delayed Rectifier Channel Current IKPlays a Key Role in the Control of Programmed Cell Death by PACAP and Ethanol in Cerebellar Granule Neurons
Authors: CASTEL HÉLÈNE , VAUDRY DAVID , MEI YAN‐AI , LEFEBVRE THOMAS , BASILLE MAGALI , DESRUES LAURENCE , FOURNIER ALAIN , VAUDRY HUBERT , TONON MARIE‐CHRISTINE , GONZALEZ BRUNO J.
Published: August 2006

Abstract: Alcohol exposure during development causes severe brain malformations, and thus, identification of molecules that can counteract the neurotoxicity of ethanol deserves high priority. Since activation of potassium (K+) currents has been shown to play a critical role in the control of programmed cell death, we have investigated the effects of ethanol and PACAP on K+currents in cultured cerebellar granule cells using the patch‐clamp technique in the whole cell configuration. In the presence of the fast‐inactivating IAcurrent blocker 4‐AP, a focal application of ethanol (200 mM) in the vicinity of granule cells provoked a robust hyperpolarization and a marked increase of the delayed rectifier IKcurrent. Addition of PACAP (0.1 μM) in the bath solution prevented ethanol‐induced membrane hyperpolarization and suppressed the stimulatory effect of ethanol on IKcurrent. These data suggest that ethanol alters neuronal survival, at least in part, through activation of IK, and that PACAP abolishes ethanol‐induced cerebellar granule cell death via inhibition of IK.
Spatial Approximation between the C‐Terminus of VIP and the N‐Terminal Ectodomain of the VPAC1 Receptor
Authors: CERAUDO E. , TAN Y.‐V. , COUVINEAU A. , LACAPERE J.‐J. , LABURTHE MARK
Published: August 2006

Abstract:  Vasoactive intestinal peptide (VIP) exerts many biological functions through interaction with the VPAC1 receptor, a class II G protein–coupled receptor. Photoaffinity labeling studies associated with receptor mapping and three‐dimensional molecular modeling demonstrated that the central part of VIP (6–24) interacts with the N‐terminal ectodomain of VPAC1 receptor.
However, the domain of the VPAC1 receptor interacting with the C‐terminus of VIP is still unknown. A photoaffinity probe, Bpa28‐VIP, was synthetized by substitution of amidated Asn28 of VIP by amidated photoreactive para‐benzoyl‐L‐Phe (Bpa). Bpa28‐VIP was shown to be a hVPAC1 receptor agonist in CHO cells expressing the recombinant VPAC1 receptor. After obtaining a covalent 125I‐[Bpa28‐VIP]/hVPAC1 complex, it was cleaved by CNBr, PNGase F, and endopeptidase Glu‐C and the cleavage products were analyzed by electrophoresis. The data demonstrated that 125I‐[Bpa28‐VIP] was covalently bonded to the 121–133 fragment within the N‐terminal ectodomain of the receptor. This fragment is adjacent to those covalently attached to the central part (6–24) of VIP.
Secretin: A Pleiotrophic Hormone
Authors: CHU J.Y.S. , YUNG W.H. , CHOW B.K.C.
Published: August 2006

Abstract:  Secretin holds a unique place in the history of endocrinology and gastrointestinal physiology, as it is the first peptide designated as a hormone. During the last century since its first discovery, the hormonal effects of secretin in the gastrointestinal tract were extensively studied, and its principal role in the periphery was found to stimulate exocrine secretion from the pancreas. Recently, a functional role of secretin in the brain has also been substantiated, with evidence suggesting a possible role of secretin in embryonic brain development. Given that secretin and its receptors are widely expressed in multiple tissues, this peptide should therefore exhibit pleiotrophic functions throughout the body. The present article reviews the current knowledge on the central and peripheral effects of secretin as well as its therapeutic uses.
The Human VPAC1 Receptor
Authors: COUVINEAU ALAIN , TAN YOSSAN‐VAR , CERAUDO EMILLE , LACAPÈRE JEAN‐JACQUES , MURAIL SAMUEL , NEUMANN JEAN‐MICHEL , LABURTHE MARC
Published: August 2006

Abstract:  The human VPAC1 receptor for VIP and PACAP is a class II Gprotein–coupled receptor (GPCR).The N‐terminal ectodomain of the VPAC1 receptor plays a crucial role in VIP binding. Photoaffinity experiments clearly indicated that the 6–28 part of VIP physically interacts with the N‐terminal ectodomain. Construction of a 3D model of the N‐terminal ectodomain of VPAC1 receptor based on the NMR structure of the mouse CRF receptor 2 indicated the presence of short consensus repeat/Sushi domain. Docking of VIP in the N‐terminal ectodomain structural model was performed taking into account the severe constraints provided by photoaffinity. A VIP‐binding site was identified on the side of the structured core of the N‐terminal ectodomain of the receptor.
VPAC2 Receptor Activation Mediates VIP Enhancement of Population Spikes in the CA1 Area of the Hippocampus
Authors: CUNHA‐REIS DIANA , RIBEIRO JOAQUIM ALEXANDRE , SEBASTIÃO ANA M.
Published: August 2006

Abstract:  The receptors mediating vasoactive intestinal polypeptide (VIP) enhancement of synaptic transmission to pyramidal cell bodies were investigated. RO 25–1553 (VPAC2 agonist) mimicked the excitatory effect of VIP on population spike (PS) amplitude. [K15, R16, L27] VIP (1–7)/GRF (8–27) (VPAC1 agonist) caused only a small increase in PS amplitude. The effect of VPAC2 agonist (but not of the VPAC1 agonist) persisted upon blockade of GABAergic transmission and was strongly attenuated upon inhibition of PKA. In conclusion, VPAC2 receptor activation mediates VIP enhancement of PS amplitude in the hippocampus essentially through a PKA‐dependent mechanism.
Vasoactive Intestinal Polypeptide Induces Regulatory Dendritic Cells That Prevent Acute Graft Versus Host Disease and Leukemia Relapse after Bone Marrow Transplantation
Authors: DELGADO MARIO , CHORNY ALEJO , GANEA DOINA , GONZALEZ‐REY ELENA
Published: August 2006

Abstract:  Acute graft‐versus‐host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for the treatment of leukemia and other immunogenetic disorders. The use of tolerogenic dendritic cells (DCs) with potent immunoregulatory properties by inducing the generation/activation of regulatory T cells (Tr) for the treatment of acute GVHD following allogeneic BMT has been recently established.
Here we report the use of the known immunosuppressive neuropeptide, vasoactive intestinal polypeptide (VIP), as a new approach to inducing tolerogenic DCs with the capacity to prevent acute GVHD. DCs differentiated with VIP impair allogeneic haplotype‐specific responses of donor CD4+ T cells in transplanted mice by inducing the generation of Tr in the graft. Importantly, VIP‐induced tolerogenic DCs did not abrogate the graft versus leukemia response, probably because they do not abrogate cytotoxicity of transplanted T cells against the leukemic cells. Therefore, the inclusion of VIP‐induced tolerogenic DC in future therapeutic regimens may facilitate the successful transplantation from mismatched donors, reducing the deleterious consequences of acute GVHD, extending the applicability of BMT.
VIP and PACAP Receptor Pharmacology
Authors: DICKSON LOUISE , ARAMORI ICHIRO , SHARKEY JOHN , FINLAYSON KEITH
Published: August 2006

Abstract:  VIP/PACAP receptor activation stimulates the production of [cAMP]i and [Ca2+]i by coupling to independent G‐protein subunits, although agonist potencies for the different transduction pathways appear to differ. Using CHO‐K1 cells stably expressing the human VIP/PACAP receptors (hVPAC1R, hVPAC2R, and hPAC1R), functional assays ([cAMP]i and [Ca2+]i) were established and the receptor pharmacology was characterized with five peptide agonists (VIP, PACAP‐27, PACAP‐38, [Ala11,22,28]VIP, and R3P65). The rank order of potency (ROP) was consistent between assays for the individual receptor subtypes, however, higher agonist concentrations (∼100‐fold) were required for stimulating [Ca2+]i when compared to [cAMP]i.
Use of Photoaffinity Labeling to Understand the Molecular Basis of Ligand Binding to the Secretin Receptor
Authors: DONG MAOQING , MILLER LAURENCE J.
Published: August 2006

Abstract:  The secretin receptor was the first member of the Class B family of G protein–coupled receptors that was identified in 1991, 89 years after secretin action was first recognized. That report resulted in the introduction of the term hormone and in the birth of the field of endocrinology. The secretin receptor has become prototypic of this receptor family, binding a moderately long linear peptide with a diffuse pharmacophoric domain. Here, we provide a detailed account of the contributions of photoaffinity labeling to establish the molecular basis of natural ligand binding to this receptor, as well as to provide insights into possible mechanisms for receptor activation and initiation of signaling. Each of the themes discussed are also relevant to other members of this physiologically and pharmacologically important receptor family.
PACAP and Ceramides Exert Opposite Effects on Migration, Neurite Outgrowth, and Cytoskeleton Remodeling
Authors: FALLUEL‐MOREL ANTHONY , VAUDRY DAVID , AUBERT NICOLAS , GALAS LUDOVIC , BENARD MAGALIE , BASILLE MAGALI , FONTAINE MARC , FOURNIER ALAIN , VAUDRY HUBERT , GONZALEZ BRUNO J.
Published: August 2006

Abstract:  During brain development, cells that fail to reach their final destination or to establish proper connections are eliminated. It has been shown that the proinflammatory cytokine second messenger ceramides and the neuropeptide pituitary adenylate cyclase‐activating polypeptide (PACAP) play pivotal roles in the histogenesis of the cerebellum. However, little is known regarding the effects of these two factors on cerebellar granule cell migration. We have found that PACAP prevents the effects of C2‐ceramide on granule cell motility and neurite outgrowth. These actions are attributable to opposite effects on actin distribution, tubulin polymerization, and Tau phosphorylation. These data suggest that PACAP and factors inducing ceramide production may control granule cell migration during cerebellar development.
VIP Prevents Experimental Multiple Sclerosis by Downregulating Both Inflammatory and Autoimmune Components of the Disease
Authors: FERNANDEZ‐MARTIN AMELIA , GONZALEZ‐REY ELENA , CHORNY ALEJO , MARTIN JAVIER , POZO DAVID , GANEA DOINA , DELGADO MARIO
Published: August 2006

Abstract:  Multiple sclerosis (MS) is a disabling inflammatory, autoimmune demyelinating disease of the central nervous system (CNS). Despite intensive investigation, the mechanisms of disease pathogenesis remain unclear, and curative therapies are unavailable for MS. The current study describes a new possible strategy for the treatment of MS, based on the administration of the vasoactive intestinal peptide (VIP). Treatment with VIP significantly reduced incidence and severity of experimental autoimmune encephalomyelitis (EAE), an MS‐related rodent model. VIP suppressed EAE neuropathology by reducing CNS inflammation and by selective blocking encephalitogenic T‐cell reactivity, emerging as an attractive candidate for the treatment of human MS.
Aromatase Gene Expression and Regulation in the Female Rat Pituitary
Authors: GALMICHE GUILLAUME , CORVAISIER SOPHIE , KOTTLER MARIE‐LAURE
Published: August 2006

Abstract:  Aromatase cytochrome P450, the key enzyme of estrogen biosynthesis from androgens, is encoded by CYP19. Its structure shows some peculiarities: exons II to X encode the protein, while multiple alternative exons I encode unique 5'‐untranslated regions of the aromatase mRNA transcripts. Immunohistochemistry studies in the rat have shown that pituitary aromatase expression is sex‐dependent and varies across the estrous cycle, suggesting that estrogens might be involved in the regulation of aromatase activity and might act locally as a paracrine or autocrine factor in the pituitary. In the present study, we used RT‐PCR to characterize aromatase transcripts and real‐time PCR to quantify the expression of the total aromatase mRNA at the different stages of the estrous cycle and from an ovariectomy and estradiol replacement model. We identified the two previously described aromatase transcripts with a specific 5'untranslated region of the brain 1f and the gonadal PII transcripts. Total aromatase mRNA expression in the pituitary varied significantly during the estrous cycle, with the highest level occurring on the day of metestrus. After ovariectomy, we observed an increase of aromatase mRNA levels, and this effect was completely prevented by estradiol administration. These results suggest that pituitary aromatase mRNA expression is downregulated by estrogens.
PACAP Inhibits Oxidative Stress‐Induced Activation of MAP Kinase‐Dependent Apoptotic Pathway in Cultured Cardiomyocytes
Authors: GASZ BALAZS , RÁCZ BOGLARKA , RÖTH ERZSEBET , BORSICZKY BALAZS , TAMÁS ANDREA , BORONKAI ARPAD , GALLYAS FERENC , TÓTH GABOR , REGL?DI DORA
Published: August 2006

Abstract:  The present article investigated the effect of pituitary adenylate cyclase‐activating polypeptide (PACAP) on oxidative stress‐induced apoptosis in neonatal rat cardiomyocytes. Our results show that PACAP decreased the ratio of apoptotic cells following H2O2 treatment. PACAP also diminished the activity of apoptosis signal‐regulating kinase. These effects of PACAP were counteracted by the PACAP antagonist PACAP6‐38. In summary, our results show that PACAP is able to attenuate oxidative stress‐induced cardiomyocyte apoptosis and suggest that its cardioprotective effect is mediated through inhibition of the MAP kinase‐dependent apoptotic pathway.
PACAP Stimulates the Release of the Secretogranin II‐Derived Peptide EM66 from Chromaffin Cells
Authors: GUILLEMOT JOHANN , AIT‐ALI DJIDA , TURQUIER VALERIE , MONTERO‐HADJADJE MAITE , FOURNIER ALAIN , VAUDRY HUBERT , ANOUAR YOUSSEF , YON LAURENT
Published: August 2006

Abstract:  The aim of the present article was to examine the effect of PACAP on the release of the SgII‐derived peptide EM66 from primary cultures of bovine chromaffin cells. PACAP dose dependently stimulated EM66 release from cultured chromaffin cells. A significant response was observed after 6 h of treatment with PACAP and increased to reach a 3.6‐fold stimulation at 72 h. The stimulatory effect of PACAP was mediated through multiple signaling pathways, including calcium influx through L‐type channels, PKA, PKC, and MAP‐kinase cascades, to regulate EM66 release from chromaffin cells. These data suggest that EM66 may act downstream of the trans‐synaptic stimulation of the adrenal medulla by neurocrine factors.
Clues to VIP Function from Knockout Mice
Authors: HAMIDI S.A. , SZEMA A.M. , LYUBSKY S. , DICKMAN K.G. , DEGENE A. , MATHEW S.M. , WASCHEK J.A. , SAID S.I.
Published: August 2006

Abstract:  We have taken advantage of the availability of vasoactive intestinal polypeptide (VIP) knockout (KO) mice to examine the possible influence of deletion of the VIP gene on: (a) airway reactivity and airway inflammation, as indicators of bronchial asthma; (b) mortality from endotoxemia, a model of septic shock; and (c) the pulmonary circulation. VIP KO mice showed: (a) airway hyperresponsiveness to the cholinergic agonist methacholine, as well as peribronchial and perivascular inflammation; (b) a greater susceptibility to death from endotoxemia; and (c) evidence suggestive of pulmonary hypertension.