bluuebunny/crossref_metadata_2025 huggingface dataset:
Union Legitimacy and the Team Concept: A Case Study of Workers’ Attitudes*
Authors: Baugher John Eric
Published: April 2007

Unions are facing a crisis of legitimacy resulting in part from employer‐initiated workplace participation programs that seek to undermine labor militancy and attachment to unions. The overall trend among union leaders, however, is support for the team concept when implemented in unionized settings. This study examines the effect of union involvement in the team concept on pragmatic and moral union legitimacy at the first unionized team concept assembly plant in the automobile industry—the General Motors’ truck plant in Shreveport, Louisiana. The unique contribution of the study is that it systematically examines how workers who began their careers in the industry under different production regimes view the team concept and union legitimacy. The analysis is based on a random sample survey of workers and employs an original approach of comparing work attitudes and union legitimacy among different “political cohorts.” The results indicate that the team concept threatens pragmatic union legitimacy for veteran workers because it undermines seniority rights. Significant time working under the team concept may also weaken moral union legitimacy, even among workers socialized initially in nonteam concept environments.
Counselor Turnover in Substance Abuse Treatment Centers: An Organizational‐Level Analysis
Authors: McNulty Thomas L. , Oser Carrie B. , Aaron Johnson J. , Knudsen Hannah K. , Roman Paul M.
Published: April 2007

This article draws on institutional and ecological perspectives on work and organizations to develop a workplace level model of variation in voluntary counselor turnover rates across privately funded substance abuse treatment centers in the United States. Results show that participatory management structures reduce turnover rates principally by promoting organizational commitment. The analysis also tests hypotheses regarding the effects on turnover rates of other relevant theoretic domains of treatment center structure and organization. We discuss theoretical implications of the findings and suggest directions for future research.
Traditionalism or Low Self‐Control?: Explaining the Health‐Risk Behaviors of American Indian Youth
Authors: Morris Gregory D. , Wood Peter B. , Dunaway R. Gregory
Published: April 2007

Using a sample of American Indian high school students, we test self‐control and Native traditionalism as predictors of their health‐risk behaviors. Regression analyses found self‐control to be a significant influence on all seven health‐risk items as well as the health‐risk composite. Traditionalism by and large fails to influence these behaviors. However, the traditionalism measure serves a second purpose as a means of controlling for cultural variation while testing the influence of self‐control. In doing so, self‐control remains a robust predictor. By controlling for cultural variation and examining behaviors that transcend cultural definitions of deviance, we believe these results support the cultural invariance thesis of self‐control. Implications for refining traditionalism, testing the cultural invariance of self‐control, and considering new directions in understanding the health risks among American Indians are discussed.
Atoms for Peace, Atoms for War: Probing the Paradoxes of Modernity*
Authors: Alario Margarita V. , Freudenburg William R.
Published: April 2007

Macrostructural analyses have long dominated the field of social theories of modernity, with the work of Habermas, Giddens, and Beck providing influential cases in point. Empirical studies, however, have raised questions about the applicability and empirical soundness of macrostructural approaches to risks, technology, and nature, and U.S.‐based sociologists have offered alternative theories that have been identified in some studies as providing better predictions and explanations than the macrostructural analyses. Informed by all of the above theories, this article examines the “Atoms for Peace” program, which established the civilian uses of nuclear energy, providing one of the central scientific and technological achievements of modernity. Given the mixed results of nuclear technology development, the mid‐range, structurally informed perspectives of Short and other U.S.‐based sociologists do appear to provide the best interpretations, both for the “Atoms for Peace” program and for the broader legacy of the technological and environmental risks of modernity.
Heretical Social Movement Organizations and Their Framing Strategies*
Authors: Hipsher Patricia L.
Published: April 2007

This article is an exploratory study of heretical social movement organizations (HSMOs) and the challenges that they face in framing their issue positions. It examines how identity communities’ core issue positions serve to demarcate the boundaries of authentic group membership, making “heretics” out of community organizations that have contrary positions. It also analyzes how these organizations finesse their heretical status by utilizing specific framing strategies. It illustrates these processes using data on two social movement organizations involved in the American abortion controversy, Catholics for a Free Choice, a Catholic pro‐choice organization, and Feminists for Life of America, a feminist pro‐life organization, during the period between 1972 and 2000.

I begin by demonstrating the Catholic and feminist communities’ use of an abortion litmus test to maintain community boundaries. I, then, describe the two organizations’ use of value amplification and boundary framing to frame their “heretical” issue positions both within and against their identity communities, respectively. I conclude by discussing the trend toward orthodoxy in many identity communities and the role of heretical social movement organizations in challenging this trend.
Psychologists and the Use of Torture in Interrogations
Authors: Costanzo Mark , Gerrity Ellen , Lykes M. Brinton
Published: April 2007

This article argues that psychologists should not be involved in interrogations that make use of torture or other forms of cruel, inhumane, or degrading treatment. The use of torture is first evaluated in light of professional ethics codes and international law. Next, research on interrogations and false confessions is reviewed and its relevance for torture‐based interrogations is explored. Finally, research on the negative mental health consequences of torture for survivors and perpetrators is summarized. Based on our review, we conclude that psychologists' involvement in designing, assisting with, or participating in interrogations that make use of torture or other forms of cruel, inhumane, or degrading treatment is a violation of fundamental ethical principles, a violation of international and domestic law, and an ineffective means of extracting reliable information. Torture produces severe and lasting trauma as well as other negative consequences for individuals and for the societies that support it. The article concludes with several recommendations about how APA and other professional organizations should respond to the involvement of psychologists in interrogations that make use of torture or other forms of cruel, inhumane, or degrading treatment.
Stress Echocardiography: Abnormal Response of Tissue Doppler–Derived Indices to Dobutamine in the Absence of Obstructive Coronary Artery Disease in Patients with Chronic Renal Failure
Authors: Jassal Davinder S. , Neilan Tomas G. , Picard Michael H. , Wood Malissa J.
Published: April 2007

Background: Abnormal tissue Doppler (TD)–derived indices during dobutamine stress echocardiography (DSE) can predict the presence of coronary artery disease (CAD) in patients with normal renal function. These indices include a reduction in annular systolic velocity (S′), a decrease in early diastolic annular velocity (E′), and prolongation of the time to E′. However, the ability of these indices to detect or exclude CAD in patients with chronic renal failure (CRF) is unclear. Objective: To examine the ability of TD‐derived indices to detect or exclude the presence of CAD in patients with CRF. Methods: We evaluated a total of 30 patients (13 males, mean age 57 ± 15 years) using both DSE and coronary angiography. This cohort consisted of 12 control patients with normal renal function (mean creatinine 0.5 mg/dL) and 18 patient with CRF (mean creatinine 2.5 mg/dL). At each stage of the DSE, left ventricular (LV) diastolic function was assessed using conventional (peak early (E) and late (A) transmitral, E/A ratio, E‐wave deceleration time (DT), and isovolumic relaxation time (IVRT)) and TD‐derived indices (lateral annular systolic (S′), early diastolic (E′), and late atrial velocities (A′), time to E′ and E/E′). Results: All 30 patients had a normal DSE based on systolic regional function and a normal coronary angiogram. There was no difference in E, A, E/A, DT or IVRT between the two groups at each stage. Despite normal coronaries, patients with CRF demonstrated lower S′ and E′ velocities at peak stress compared to the control patients (8.0 ± 2.2 cm/sec vs 15.1 ± 2.6, P < 0.05 and 6.7 ± 1.6 cm/sec vs 13.3 ± 3.1, P < 0.05, respectively). During DSE, the time to E′ at peak stress in CRF patients was also prolonged compared to control (400 ± 44 ms vs 329 ± 51, P < 0.05). Patients with CRF also had increased filling pressures (as estimated by E/E′) as compared to controls at peak stress (14.7 ± 5.2 vs 7.4 ± 1.5, P < 0.05, respectively). Conclusion: In patients with CRF, a reduction in TD derived indices does not predict the presence of obstructive CAD.
Live/Real Time Three‐Dimensional Transthoracic Echocardiographic Identification of Quadricuspid Aortic Valve
Authors: Burri Manjula V. , Nanda Navin C. , Singh Anurag , Panwar Sadik R.
Published: April 2007

We describe an adult in whom live/real time three‐dimensional echocardiography was able to make a definite diagnosis of a quadricuspid aortic valve which was misdiagnosed as bicuspid by live two‐dimensional transthoracic echocardiography (2DTTE).
Oviposition behavior of orange wheat blossom midge on low‐ vs. high‐ranked grass seed heads
Authors: Ganehiarachchi G. A. S. M. , Harris M. O.
Published: May 2007

The discovery of Sm1, a highly effective resistance (R) gene that targets the first instar of the orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), has created concerns about wheat midge adaptation. Strategies for delaying adaptation to Sm1 include the simultaneous deployment of a resistance trait targeting a different life stage, i.e., the ovipositing adult female. Previous studies have shown that adult females distinguish between wheat genotypes and seed head developmental stages and are attracted by volatiles from young wheat heads. We focused on what happens after the female lands on the seed head, comparing in three tests a seed head of the high‐ranked pre‐anthesis ‘Roblin’ wheat, Triticum aestivum L. (Poaceae), and a head of one of three lower‐ranked types: post‐anthesis ‘Roblin’, pre‐anthesis ‘Key’ wheat (T. aestivum), and pre‐anthesis ‘Robust’ barley (Hordeum vulgare L.). Within each test, high‐ and low‐ranked heads were presented in choice and no‐choice assays, with the behavior of wheat midge females scored every 5 min from 20:30 to 23:00 hours, under mid‐summer natural light conditions and sunset occurring between 20:50 and 21:20 hours. Head type influenced both proportions of females observed on the head and proportions of females probing with the ovipositor. Head*assay interactions occurred only in the test comparing wheat to barley, with barley reducing females observed on the wheat head and wheat increasing females probing on barley. Results indicate that the wheat midge female detects plant cues while examining the seed head and that this detection contributes to differences in egg counts.
Parallel evolution in sympatric, hybridizing species: performance ofColiasbutterflies on their introduced host plants
Authors: Porter Adam H. , Levin Elena J.
Published: May 2007

Shared ancestry and introgression can contribute to genetic similarity between hybridizing species, and it is generally difficult to disentangle these causes. However, shared ancestry plays a more limited role in traits that have recently undergone parallel directional selection in the two species, permitting the role of introgression to be better understood. The butterfliesColias eurytheme(Boisduval) andColias philodice(Godart) (Lepidoptera, Pieridae) are native to North America and have shifted their host ranges in parallel onto several introduced weedy and agricultural legumes. These butterflies hybridize at moderate rates throughout their range, and there is a strong possibility that they could be sharing host‐associated adaptations. We split families of each species among nine introduced, prospective hosts and measured survivorship, larval duration, pupal weight, and a new variable, effective daily growth rate (DGR), analogous to a compound daily interest rate in economics. We found strong effects of host, sex, and family (species), but negligible effects of the host*species interaction that would indicate species‐specific differences in performance on different hosts. We found species‐specific life‐history differences:C. eurythemematured significantly later and reached a significantly larger body size thanC. philodicewhile growing at the same DGR. Protandry was strong, and males, in addition to pupating sooner than females, grew significantly faster than females as measured by DGR. We measured broad‐sense heritabilities and genetic correlations for host‐associated performance variables. Most pairwise comparisons of performance among hosts and most pairwise comparisons between performance variables showed positive genetic correlations, except survivorship where little heritability was found. Nevertheless, a factorial multivariate analysis of variance of G‐matrices showed highly significant species, host, and host*species interactions, suggesting differentially evolving genetic architectures underlying host adaptation in these two species, despite the small differences in overall performance. At least some of the genes affecting host performance inColiasare likely to be in the small, species‐diagnostic regions and not shared via introgression between these hybridizing species. For biologists interested in the evolutionary ecology of their host associations, including applied biologists managing their agricultural pest potential,C. eurythemeandC. philodiceare most usefully studied as if they were a single polymorphic species wherever they co‐exist. In studying species that hybridize readily with a sympatric congener, it may often be necessary to include the second species in the experimental design.
Trade‐offs in oviposition choice? Food‐dependent performance and defence against predators of a herbivorous sawfly
Authors: Müller Caroline , Arand Katja
Published: May 2007

The sawfly Athalia rosae L. (Hymenoptera: Tenthredinidae) is a feeding specialist on plant species of the Brassicaceae, which are characterised by secondary metabolites, called glucosinolates. The larvae can take up the respective glucosinolates of their hosts and concentrate them in their haemolymph to protect themselves against predators. Oviposition preferences of naïve females were tested for three species, Sinapis alba L., Brassica nigra (L.) Koch, and Barbarea stricta Andrz., and were related to larval performance patterns. Larvae were reared on either one of these plants and it was investigated how host‐plant quality influences both the developmental times and growth of larvae (bottom‐up) and the defence efficiency against predators (top‐down). Innately, almost all adult females avoided B. stricta for oviposition and clearly preferred B. nigra over S. alba. On average, larvae developed best on B. nigra. Female larvae reached similar final body masses on all host‐plant species, but males reared on S. alba were slightly lighter. The developmental time of larvae reared on B. stricta was significantly longer than on the other two plants. However, larvae reared on B. stricta were best protected against the predatory wasp Polistes dominulus Christ (Hymenoptera: Vespidae). The wasps rejected these larvae most often, while they attacked larvae reared on S. alba most frequently. Thus, larvae feeding on B. stricta theoretically run a higher risk of predation due to a prolonged developmental time, but in practice they are better protected against predators. Overall, oviposition preferences of A. rosae seem to be more influenced by bottom‐up effects on larval performance than by top‐down effects.
Long Peace or Long War: A Conflict Resolution Perspective
Authors: Kriesberg Louis
Published: April 2007

Since the end of the 1980s, both the incidence and severity of violent conflicts and of domestic and international wars have declined globally. These declines are attributable to the convergence of many developments that help prevent, limit, and stop large‐scale violence, and the author suggests that those developments persist. Consequently, he suggests that the recent U.S. engagement in wars and recent surges in terrorist attacks are limited spikes in violence that can be overcome. The author discusses how the current violent events may be in part a consequence of behaviors of the U.S. government and other governmental and nongovernmental organizations that are contrary to the major developments that contribute to global peace and cooperation. Governments and peoples acting in concert with those ongoing changes can help reduce the current mass violence.
A Temporal Model of Negotiation Linkage Dynamics
Authors: Crump Larry
Published: April 2007

This article explores negotiation linkage dynamics (how one negotiation influences or determines the process or outcome of another) by examining three bilateral trade treaty negotiations conducted by the governments of Australia, Singapore, and the U.S. from 2000 to 2004. After developing a temporal framework of negotiation linkage, the study examines how one negotiation can influence another negotiation when time is treated as an independent variable and negotiation process and outcome are treated as dependent variables. The study's findings can be used to help negotiation scholars and practitioners strategically manage the opportunities and challenges inherent in negotiation linkage dynamics. The study concludes with a proposed research agenda and a temporal enhancement of the negotiation paradigm.
Structural organization of cornified cell envelopes and alterations in inherited skin disorders
Authors: Ishida‐Yamamoto Akemi , Iizuka Hajime
Published: May 2007

Abstract: The cornified cell envelope is a highly insoluble and extremely tough structure formed beneath the cell membrane during terminal differentiation of kerationcytes. Its main function is to provide human skin with a protective barrier against the environment. Sequential cross‐linking of several integral components catalyzed by transglutaminases leads to a gradual increase in the thickness of the envelope and underscores its rigidity. Key structural players in this cross‐linking process include involucrin, loricrin, SPRRs, elafin, cystatin A, S100 family proteins, and some desmosomal proteins. The recent identification of genetic skin diseases with mutations in the genes encoding some of these proteins, including transglutaminase 1 and loricrin, has disclosed that abnormal cornified cell envelope synthesis is significantly involved in the pathophysiology of certain inherited keratodermas and reflects perturbations in the complex yet highly orderly process of cornified cell envelope formation in normal skin biology.
Not all chronic urticaria is “idiopathic”
Authors: Greaves M. W. , O'Donnell B. F.
Published: May 2007

Abstract: The aetiology of chronic urticaria in the majority of patients is elusive. The cause of physical urticarias (dermographism, delayed pressure urticaria, cold urticaria) is unkonown. We have identified a subset of chronic “idiopathic” urticaria patients, representing approximately 30% of the total in which the disease is caused by the presence of IgG autoantibodies against the high affinity IgE receptor (FcœRIα). This functional autoantibody stimulates normal (albeit vicarious) activation of mast cells and basophils via FcœRI, causing whealing and angioedema. Anti‐FcœRI‐positive patients are recognized by a combination of autologous serum skin testing and evoked histamine release from basophils of normal human donors. Autoantibody‐positive and ‐negative patients are clinically indistinguishable and are treated routinely by combinations of H1 and occasionally H2‐antihistamines in both cases. However, severely affected patients who are anti‐FcœRI‐positive can also be treated by non‐specific immunotherapy (plasma pheresis, intravenous immunoglobulin, cyclosporin.
Increased activity of cathepsin B in fibroblasts isolated from primary melanoma in comparison to fibroblasts from normal skin
Authors: Ulmer Anja , Körber Valentine , Schmid Heide , Fierlbeck Gerhard
Published: May 2007

Abstract: We determined activity of cathepsin B in early‐passage fibroblasts isolated from primary melanoma and in fibroblasts from normal skin. Our results show an up to 5‐fold increase in activity of cathepsin B in the tumor‐derived fibroblasts in comparison to the fibroblasts from normal skin. We conclude that fibroblasts isolated from melanoma tissue are altered with regard to their specific activity of cathepsin B and preserve this elevated activity in early‐passage cell culture. The data support the idea that stromal cells are not passive elements of the peritumoral environment but actively participate in the production of proteolytic enzymes.
TNF‐α, RANTES, and MCP‐1 are major chemoattractants of murine Langerhans cells to the regional lymph nodes
Authors: Yamazaki S. , Yokozeki H. , Satoh T. , Katayama I. , Nishioka K.
Published: May 2007

We have previously reported that lymph node cells generated chemotactic factors for Langerhans cells (LCs) in the induction phase of contact dermatitis. In order to clarify the chemotactic factors involved in migration to the regional lymph nodes, we investigated the migratory activity of murine LCs toward several cytokines and chemokines in vitro. One‐day cultured LC‐enriched epidermal cells were added to the upper compartment of a modified Boyden chamber and cytokines were added to the lower compartment. We counted dendritic cells migrated to the lower chamber as LCs under phase contrast microscopy. About 99% of migrated dendritic cells were positively reacted with anti‐Iad and NLDC145 antibodies and considered to be LCs. We could detect LC migration more accurately by this direct examination than by counting the migrated cells in the filter membrane of a Boyden chamber. In our system, migration of murine epidermal LCs was stimulated by TNF‐β, RANTES and MCP‐1, but not by GM‐CSF, IL‐1β, IL‐4, and IL‐6. TNF‐α induced LC migration at concentrations from 4X103 U/ml to 5X104 U/ml. RANTES at concentrations from 10 to 100 ng/ml and MCP‐1 a concentration of 100 ng/ml induced LC migration in a dose‐dependent manner. These data confirmed that TNF‐α, RANTES, and MCP‐1 induced LC migration from epidermis during contact sensitization.
Expression of the anhidrotic ectodermal dysplasia gene is reduced in skin cancer coinciding with reduced E‐cadherin
Authors: Montonen O. , Ezer S. , Laurikkala J. , Karjalainen‐Lindsberg M.‐L. , Thesleff I. , Kere J. , Saarialho‐Kere U.
Published: May 2007

Abstract: X‐linked anhidrotic ectodermal dysplasia (EDA) is characterized by defects in the development of hair, teeth, and sweat glands. We have recently cloned the gene for EDA by positional cloning. The EDA gene encodes a transmembrane protein with a putative role in epithelial‐mesenchymal interactions. Since EDA could play a role in cell‐cell or cell‐matrix adhesion, acantholytic skin diseases and several types of non‐invasive and invasive skin cancers were studied using in situ hybridization. Because of the observation that the promoter region of the EDA gene contains a binding site for LEF‐1, which is involved in the signaling through E‐cadherin/beta catenin complex, we compared the expression of EDA with immunolocalization for E‐cadherin (E‐CD). EDA expression during hair growth cycle, in benign adnexal tumors, and neuroectodermderived nevus cells was also examined. Our findings indicate that EDA expression is less abundant in malignant tumors, including basal and squamous cell carcinomas and melanoma, and in acantholytic keratinocytes compared to normal epidermis. The reduction in expression also coincides with diminished E‐CD staining in all malignant cell types and in acantholytic cells. Our results suggest that EDA protein functions in the regulation of epithelial cell contacts and that it may be associated with the E‐CD signaling pathway.
CD24 expression on human keratinocytes
Authors: Redondo Pedro , García‐Foncillas Jesús , Okroujnov Iouri , de Felipe Iñigo , Quintanilla Emilio
Published: May 2007

Abstract: CD24 or Nectadrin is a cell surface glycoprotein expressed in pre‐B lymphocytes, T lymphocytes, neurons, muscle cells and carcinoma cells. Its function is not completely known, but it has been suggested that it is involved in cell adhesion and signalling. CD24 has recently been identified as the human molecule homologous to the murine heat‐stable antigen (HSA). HSA is expressed by murine keratinocytes and delivers costimulatory signals in T‐cell activation. Long‐term cultures of normal human keratinocytes (HKC) were obtained from skin of human female breast sections and either left untreated or were treated with phorbol‐12‐myristate‐13‐acetate (PMA) at 10–100 ng/ml, calcium 0.5–2 mM or IFN‐γ 100–1000 U/ml, for 24–48 h. Using RT‐PCR and flow cytometry we showed that HKC express low levels of CD24 even under basal conditions, and the treatment with calcium, PMA or IFN‐γ increased levels of CD24 mRNA and protein. To the best of our knowledge, this is the first report to measure CD24 expression and production by cultured HKC in basal conditions and after stimulation. Further studies are needed to determine biological and therapeutical relevance of these findings.
Immunohistochemical investigation of evolving inflammation in lesions of acne vulgaris
Authors: Layton A. M. , Morris C. , Cunliffe W. J. , Ingham E.
Published: May 2007

Abstract: The mechanisms involved in the development of inflammation in acne vulgaris have yet to be elucidated. Previous studies have shown that the initial cellular infiltrate in early inflammatory lesions is mononuclear, predominantly CD4 positive T cells. The aims of this study were to investigate the pattern of expression of adhesion molecules and HLA‐DR in evolving acne lesions. Forty‐nine patients with moderate to severe acne were biopsied following lesion mapping. Lesions were classified according to their duration of inflammation as up to 6 h, from 6 to 24 h, from 24 to 48 h and from 24 to 48 h and from 48 to 72 h. The cellular infiltrate was determined using monoclonal antibodies to CD1, CD3, CD4 and CD8. The expression of ICAM‐1, E‐selectin, VCAM‐1 and HLA‐DR was determined. Early (6 h) lesions had perivascular CD3 positive T‐cell infiltrates which were predominantly CD4 positive. This was associated with vascular expression of ICAM‐1, E‐selectin, VCAM‐1 and HLA‐DR. Periductal infiltrates were present in 70% of the early lesions (up to 6 h). The cells were predominantly CD4 positive and associated with a high level of HLA‐DR and ICAM‐1 expression. Periductal infiltration increased with time and persisted to 72 h. ICAM‐1 and HLA‐DR were expressed epidermally in early and late lesions. CD1 positive cells were a minor, but consistent element in the perivascular and periductal infiltrates of early and late lesions. There was no statistically significant difference in the levels of expression of E‐selectin, VCAM‐1, ICAM‐1 or HLA‐DR for lesions of different duration. The pattern of HLA‐DR and adhesion molecule expression plus the nature of the cellular infiltrate supports the hypothesis that inflammation in acne is mediated by CD4 positive T cells.
Cytokines and cutaneous T‐cell lymphomas
Authors: Asadullah K. , Döcke W. D. , Volk H. D. , Sterry W.
Published: May 2007

Abstract: Cytokines are considered to be of major importance for the pathogenesis of cutaneous T‐cell lymphomas (CTCL). Their impact may result from autocrine, paracrine or endocrine effects. Several investigations demonstrated the overexpression of different cytokines in different CTCL entities. Interestingly, stage‐dependent shifts in the cytokine pattern have been observed in mycosis fungoides (MF). There is evidence that the abnormal cytokine expression in CTCL might be responsible for tumor progression, resulting from an enhanced proliferation of the malignant cells and/or the depression of the anti‐tumor immune response. Moreover, cytokine loops might explain phenomena like the epidermotropism of malignant cells or eosinophilia and increased plasma levels of IgE, which are present in advanced stages of CTCL. Analysis of the cytokine pattern in CTCL might give the basis for direct therapeutic intervention into the cytokine network as a new therapeutic approach. In this review, the current knowledge regarding cytokines in CTCL is summarized.
Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo
Authors: Yawalkar N. , Aebischer M. C. , Hunger R. , Brand C. U. , Braathen L. R.
Published: May 2007

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV‐A and UV‐B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CDla, CD4, CD8, CD28, CD54, CD80, CD86 and HLA‐DR on migrating lymph cells and cytokine levels (IL‐1α, IL‐1β, IL‐2, IL‐6, IL‐8, IL‐10, IL‐13, TNF‐α and IFN‐γ) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CDla, CD4, CD8, CD28, CD54, CD80, CD86 and HLA‐DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL‐8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL‐8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL‐8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL‐8 in the afferent lymph.
Hepatitis C virus (HCV) in cryoglobulinaemic leukocytoclastic vasculitis (LCV): could the presence of HCV in skin lesions be related to T CD8+ lymphocytes, HLA‐DR and ICAM‐1 expression?
Authors: Bernacchi E. , Civita L. L. , Caproni M. , Zignego A. L. , Bianchi B. , Monti M. , Fabbri P. , Pasero G. , Ferri C.
Published: May 2007

An association between mixed cryoglobulinaemia (MC) and hepatotropic viruses, chiefly hepatitis C virus (HCV), has been widely reported. The presence of HCV genomic sequences or HCV‐related viral proteins in the serum, purified cryoglobulins, peripheral blood mononuclear cells and into several tissues has suggested an important triggering role for HCV in MC patients. However, only few reports investigated the presence of HCV in cutaneous vasculitis and its potential pathogenetic role. Biopsies of cutaneous purpuric lesions from 5 MC female patient (aged from 40 to 80 years) were carried out for virological and histopathological evaluation. A leukocytoclastic vasculitis pattern was found in 4/5 subjects, while the presence of HCV RNA was detected in 3/5. In only 3 cases biopsy specimens were sufficient for immunohistochemical and direct immunofluorescence (DIF) studies. Immunohistochemical evaluation was performed by means of alkaline phosphatase and monoclonal anti‐alkaline phosphatase (APAAP) immune‐complexes. In the same skin specimen APAAP and DIF findings were compared with the presence/absence of HCV genomic sequences (PCR technique). In 1 MC patient, the detection of HCV‐RNA was associated to a prevalent CD8+ T suppressor pattern with a perivascular and subjunctional distribution as well as an intense expresion of second class (HLA‐DR) and intercellular adhesion (ICAM‐1) molecules on basal keratinocytes, endothelial cells and perivascular infiltrate. These findings suggest a marked inflammatory activation that spreads from endothelial cells to keratinocytes and Langerhans cells. In the 2 HCV‐RNA negative specimens the scanty immuopathological staining could indicate a residual activity due to the previous inflammatory event triggered by cryoglobulins. The deposition of circulating HCV‐containing immune complexes (CIC) in the skin could be the initial pathogenic event for cryoglobulinemic vasculits; subsequently CIC could spread from vacular bed to the perivascular tissue and then could be very rapidly eliminated. If confirmed in larger patients' series these finding could definitely demonstrate a direct role of HCV in the pathogenesis of cryoglobulinemic vasculitis.
Mast cells and their mediators in cutaneous wound healing – active participants or innocent bystanders?
Authors: Artuc M. , Hermes B. , Stckelings U. M. , Grützkau A. , Henz B. M.
Published: May 2007

Abstract: Mast cells are traditionally viewed as effector cells of immediate type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. We here present our own data and those from the literature elucidating the possible role of mast cells during wound healing. Studies on the fate of mast cells in scars of varying ages suggest that these cells degranulate during wounding, with a marked decrease of chymase‐positive cells, although the total number of cells does not decrease, based on SCF‐receptor staining. Mast cells contain a plethora of preformed mediators like heparin, histamine, tryptase, chymase, VEGF and TNF‐α which, on release during the initial stages of wound healing, affect bleeding and subsequent coagulation and acute inflammation. Various additional vasoactive and chemotactic, rapidly generated mediators (C3a, C5a, LTB4, LTC4, PAF) will contribute to these processes, whereas mast cell‐derived proinflammatory and growth promoting peptide mediators (VEGF, FGF‐2, PDGF, TGF‐β, NGF, IL‐4, IL‐8) contribute to neoangiogenesis, fibrinogenesis or re‐epithelization during the repair process. The increasing number of tryptase‐positive mast cells in older scars suggest that these cells continue to be exposed to specific chemotactic, growth‐ and differentiation‐promoting factors throughout the process of tissue remodelling. All these data indicate that mast cells contribute in a major way to wound healing, their role as potential initiators of or as contributors to this process, compared to other cell types, will however have to be further elucidated.
Enzymatic dissociation of keratinocytes from human skin biopsies for in vitro cell propagation
Authors: Hybbinette S. , Boström M. , Lindberg K.
Published: May 2007

Abstract: Four techniques for dissociation of skin biopsies were compared to identify the method of choice for optimal expansion of isolated keratinocytes. Equivalent biopsies were obtained from 4 healthy human subjects and each divided into four parts. One part was minced and placed in a trypsinizing flask containing 0.05% trypsin and 0.01% ethylenediamine‐tetraacetic acid (EDTA). Released cells were harvested hourly. With the other parts, the epidermis was separated from the dermis after treatment with 0.5 mg/ml thermolysin, 2.5 mg/ml Dispase, or 0.17% trypsin and the epidermal portions were minced and incubated for 1 h in trypsin:EDTA. The cells were cocultivated with irradiated 3T3 fibroblasts to study the keratinocytes' proliferative capacity. Freshly isolated cells were immunostained with anti‐vimentin antibodies or grown in fibroblast‐supportive conditions to detect the presence of human dermal fibroblasts. The mean number of cells dissociated per cm2 biopsy was higher after trypsin:EDTA digestion of a dermis‐containing biopsy using a trypsinizing flask (4.0x106 cells/cm2) compared to a biopsy where dermis‐epidermis had been separated by thermolysin (2.8x106 cells/cm2), Dispase (2.3x106 cells/cm2) or trypsin (1.1x106 cells/cm2). Between 0.5% and 4% of the cells dissociated from a dermis‐containing biopsy were human fibroblasts. This comprised more than twice the number of fibroblasts obtained by using epidermal/dermal split techniques. The proliferative capacity in primary and secondary culture was higher in cells isolated by trypsin:EDTA incubation in the trypsinizing flask or after epidermal‐dermal separation using thermolysin, suggesting that Dispase or trypsin may have a more detrimental effect on the isolated keratinocytes. Our results show that dissociating the cells by trypsin:EDTA incubation in a trypsinizing flask or after epidermal‐dermal separation using thermolysin, are preferable methods for isolating keratinocytes from human skin.
Evidence that apoptosis and terminal differentiation of epidermal keratinocytes are distinct processes
Authors: Gandarillas A. , Goldsmith L. A. , Gschmeissner S. , Leigh I. M. , Watt F. M.
Published: May 2007

Abstract: Although there are clear parallels between apoptosis and epidermal terminal differentiation it is unclear whether terminal differentiation of keratinocytes is a form of apoptosis. We found that apoptosis was rare in adherent cultures of normal keratinocytes, even when growth factors were removed. When keratinocytes were placed in suspension for 24‐96 h the majority of cells were induced to undergo terminal differentiation, as assessed by involucrin expression and cornified envelope assembly, but few cells underwent apoptosis, as assessed by morphological examination, TUNEL labelling and by DNA laddering. Withdrawal of serum and growth factors stimulated apoptosis of suspended keratinocytes but led to some reduction in the number of cells that underwent terminal differentiation. At 96 h the majority of cells retained their nuclei in the presence or absence of serum and growth factors. In normal epidermis only occasional cells within the granular layer had apoptotic nuclei, determined by TUNEL labelling and light and electron microscopy. In affected epidermis of psoriasis, Darier's disease and pityriasis rubra pilaris, diseases characterized by perturbation of growth, differentiation or adhesion, light microscopy revealed no higher proportion of apoptotic nuclei than in normal epidermis. However, the majority of viable epidermal layers in diseased skin were positive by TUNEL labelling, suggesting that TUNEL is not always a specific marker of apoptosis in keratinocytes. We conclude that in vivo and in culture keratinocyte terminal differentiation and apoptosis are distinct cellular events, subject to different stimuli.
A mutation detection strategy for the human keratin 6A gene and novel missense mutations in two cases of pachyonychia congenita type 1
Authors: Smith F. J. D. , McKenna K. E. , Irvine A. D. , Bingham E. A. , Coleman C. M. , Uitto J. , McLean W. H. I.
Published: May 2007

Abstract: Pachyonychia congenita type 1 (PC‐1) is an autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy, focal non‐epidermolytic palmoplantar keratoderma and variable features of oral leukokeratosis and follicular keratosis. Previously, we have shown that this disease can be caused by mutations in type I keratin K16 and one mutation has been reported in its type II keratin expression partner, K6a. Mutation analysis for K6a has been hampered by the presence of multiple copies of the K6 gene in the human genome, of which some are expressed and others are pseudogenes. Here, we describe a mutation detection strategy where the entire KRT6A gene, 17 kb, is specifically amplified by long‐range PCR. Using this technique, we have detected two novel mutations in the 1A domain of the K6a polypeptide, N171K and F174S. Mutations were confirmed in the affected individuals and were excluded from 50 unaffected unrelated individuals by restriction enzyme analysis of KRT6A PCR products. Additionally, mutation N171K was confirmed by RT‐PCR in mRNA derived from lesional palmoplantar epidermis of an affected individual, confirming the specificity of the genomic PCR for the functional K6a gene. This, together with a similar strategy which we have developed for the K16 gene, provide a robust system for mutation detection and prenatal diagnosis for patients with PC‐1.
Identification of PTEN mutations in five families with Bannayan‐Zonana syndrome
Authors: Çelebi J. Tok , Chen F. F. , Zhang H. , Ping X. L. , Tsou H. C. , Peacocke M.
Published: May 2007

Abstract: Germline mutations in PTEN, a putative tumor suppressor gene, has been identified in 2 autosomal dominant inherited hamartoma syndromes, Cowden syndrome (CS) and Bannayan‐Zonana syndrome (BZS). While both diseases exhibit distinct phenotypic features. there seems to be a partial clinical overlap between the 2 diseases. To date, 9 families with BZS have been screened for PTEN mutations, of which 5 were found to exhibit mutations in this gene. We report 5 novel germline mutations in the PTEN coding sequence from 5 unrelated families with the BZS phenotype. While all the mutations we identified are novel in BZS, 1003C‐T (nonsense mutation) and 209+5G‐A (putative splice site mutation) have been previously reported in unrelated families with CS and Lhermitte‐Duclos disease. Interestingly, 1 of the families has an individual with BZS and 1 with CS phenotype, associated with a single PTEN mutation, 885insA. These data support the notion that CS and BZS may be within the spectrum of the same primary disorder.
Neopterin: a review
Authors: Hamerlinck F. F. V.
Published: May 2007

Abstract: Neopterin was discovered in bee larvae, in worker bees and in royal jelly. The compound was termed “neopterin” to denote that it might start a new (Greek, neo) epoch in pteridine research. Increased concentrations of neopterin were reported in patients with viral infections, suggesting that increased neopterin may originate from the immune response of patients to the infections. In vitro studies revealed that human monocytes/macrophages produce neopterin when stimulated by interferon‐ γ. Neopterin can easily be detected in serum and urine. The most important clinical applications for the determination of neopterin are prognostic indicator of malignant diseases, follow‐up control of chronic infections, monitoring of immune‐stimulatory therapy, differential diagnosis of acute viral and bacterial infections, prognostic indicator in HIV infections and early indications of complications in allograft recipients. In recent years new physiological functions of neopterin have been discovered such as inducing or enhancing cytotoxicity, inducing apoptosis and the role of a chain breaking antioxidant. This review will focus on the immunological and physiological properties of neopterin.
Fine genetic mapping of diffuse non‐epidermolytic palmoplantar keratoderma to chromosome 12q11‐q13: exclusion of the mapped type II keratins
Authors: Kelsell D. P. , Stevens H. P. , Purkis P. E. , Talas U. , Rustin M. H. A. , Leigh I. M.
Published: May 2007

Abstract: Diffuse non‐epidermolytic palmoplantar keratoderma (NEPPK) belongs to the heterogeneous group of skin diseases characterized by thickening of the stratum corneum of the palms and soles (1). This autosomal dominant PPK is characterized by a diffuse pattern of palmar and plantar hyperkeratosis giving the affected areas a thickened yellowish appearance with a marked erythematous edge. Linkage of diffuse NEPPK to chromosome 12q11‐q13 has been demonstrated in two independent reports (2, 3). In this study, we describe detailed haplotyping with microsatellite markers mapping to this chromosomal region in three diffuse NEPPK pedigrees from the south of England. Fine mapping of a previously identified recombination event and the identification of a common disease haplotype segregating in the three pedigrees places the diffuse NEPPK locus proximal to the type II keratin gene cluster.
Antigen retrieval of loricrin epitopes at desmosomal areas of cornified cell envelopes: an immunoelectron microscopic analysis
Authors: Ishida‐Yamamoto A. , Tanaka H. , Nakane H. , Takahashi H. , Iizuka H.
Published: May 2007

Abstract: Cell envelopes (CEs) are insoluble, chemically and mechanically tough structures formed during terminal differentiation of keratinocytes, providing skin with a protective barrier against the environment. They are 15 to 20 nm thick structures beneath the plasma membrane and continuous with desmosomal attachment plaques. Sequential deposition of several proteins including involucrin and loricrin leads to a gradual increase in envelope thickness and rigidity. Cross‐linking of demosomal components to other CE‐proteins has been demonstrated and desmosomes in the cornified cells have been demonstrated and desmosomes in the cornified cells have been regarded as a part of CEs. Our previous immunoelectron microscopy studies showed that desmosomal areas of granular cells were loricrin‐positive, but those in cornified cells were negative. We asked whether this is due to epitope masking and applied trypsin digestion of the electron microscopy sections to retrieve the possibly masked epitopes. Since this treatment made desmosomal structures obscure, one side of the sections was stained with anti‐desmoglein antibody as an indicator of desmosomes. Trypsin was applied on the other side followed by immunolabeling with anti‐loricrin antibody. Trypsin digestion indeed unmasked the loricrin epitopes in the desmoglein‐positive desmosomal areas of CEs. It seems therefore that loricrin is first accumulated at the desmosomes before the CE‐assembly and cross‐linking of loricrin occurs at the desmosomal areas of CEs as well as at the non‐desmosomal areas.
Rhetoric of Atrocities: The Place of Horrific Human Rights Abuses in Presidential Persuasion Efforts
Authors: BEN‐PORATH ERAN N.
Published: April 2007

An analysis of presidential rhetoric in the post‐Cold War era finds that in building the case for imminent war, presidents turn to narrative descriptions of specific atrocities, namely rape, torture, and victimization of children. By the same token, presidents wishing to avoid American involvement in war use abstract terms and statistical information concerning human rights crises, but refrain from detailing personalized stories of abuse. This study expands on the theory of savagery as a necessary component in enemy construction and on the literature concerning the changing rhetorical landscape of the post‐Cold War era. The analysis finds the rhetoric of atrocities employed and avoided, in similar fashion, by three presidents and across several different settings. The implications are discussed in the article.