bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliable p‐Hub Location Problems in Telecommunication Networks
Authors: Kim Hyun , O'Kelly Morton E.
Published: July 2009

Hubs are critical elements of telecommunication and transportation networks because they play a vital role in mass traffic movement. The design of more reliable networks in hub‐and‐spoke systems is a critical issue because current networks, particularly many commercial Internet backbones, are quite vulnerable. In hub‐and‐spoke‐type topologies, any malfunction at a hub may cause degradation of the entire network's ability to transfer flows. This article presents a new hub location problem, termed thereliable p‐hub location problem, which focuses on maximizing network performance in terms of reliability by locating hubs for delivering flows among city nodes. Two submodels, thep‐hub maximum reliabilitymodel and thep‐hub mandatory dispersionmodel, are formulated. Based on hypothetical and empirical analyses using telecommunication networks in the United States, the relationship between network performance and hub facility locations is explored. The results from these models could give useful insights into telecommunication network design.
Catastrophe Risk Financing in the United States and the European Union: A Comparative Analysis of Alternative Regulatory Approaches
Authors: Klein Robert W. , Wang Shaun
Published: July 2009

Abstract

The regulation of insurance companies in the United States and the European Union (EU) continues to evolve in response to market forces and the changing nature of risk but with somewhat different philosophies and at different rates. One important area where both economic realities and markets are changing is catastrophe risk and its financing. This article examines and compares regulatory and other government policies in the United States and the EU generally and their approaches to the financing of catastrophe risk specifically. It is important to understand the fundamental differences between the two systems to gain insights into their disparate treatment of catastrophe risk financing. Although policies could be improved in both jurisdictions, we argue that the much greater reform is needed in the United States relative to the EU regulatory policies that are being developed. We offer recommendations on how U.S. policies could be significantly improved as well as comment on issues facing the EU. We conclude with some observations on the needs for further progress in the U.S. and EU regulatory systems.
Modeling Mortality With Jumps: Applications to Mortality Securitization
Authors: Chen Hua , Cox Samuel H.
Published: July 2009

Abstract

In this article, we incorporate a jump process into the original Lee–Carter model, and use it to forecast mortality rates and analyze mortality securitization. We explore alternative models with transitory versus permanent jump effects and find that modeling mortality via transitory jump effects may be more appropriate in mortality securitization. We use the Swiss Re mortality bond in 2003 as an example to show how to apply our model together with the distortion measure approach to value mortality‐linked securities. Pricing the Swiss Re mortality bond is challenging because the mortality index is correlated across countries and over time. Cox, Lin, and Wang (2006) employ the normalized multivariate exponential tilting to take into account correlations across countries, but the problem of correlation over time remains unsolved. We show in this article how to account for the correlations of the mortality index over time by simulating the mortality index and changing the measure on paths.
Focal Atrial Fibrillation in Dextrocardia
Authors: Yamada Takumi , McElderry H. Thomas , Doppalapudi Harish , Platonov Michael , Epstein Andrew E. , Plumb Vance J. , Kay G. Neal
Published: July 2009

A 49‐year‐old woman with dextrocardia and situs inversus underwent catheter ablation of paroxysmal atrial fibrillation (AF). During the electrophysiologic study, AF triggered by frequent premature atrial contractions (PACs) with a short coupling interval exhibiting a “P on T” pattern occurred. Pulmonary vein mapping revealed that those PACs originated from right‐sided (anatomic left) or left‐sided (anatomic right) pulmonary veins. In this case with mirror‐image dextrocardia, the P‐wave morphologies in leads I and aVL and the II/III ratio of the P‐wave amplitude were helpful for predicting a right‐ or left‐sided pulmonary vein origin.
Correlation of Mechanical Dyssynchrony with QRS Duration Measured by Signal‐Averaged Electrocardiography
Authors: Andrikopoulos George K. , Tzeis Stylianos , Kolb Christof , Sakellariou Dimitrios , Avramides Dimosthenes , Alexopoulos Evangelos C. , Triantafyllou Konstantinos , Manolis Antonis S.
Published: July 2009

Background: Preimplantation left ventricular dyssynchrony is considered a prerequisite for a beneficial response to cardiac resynchronization therapy (CRT). However, electrical dyssynchrony estimated by QRS duration (QRSd) on ECG has not been proven to be an optimal surrogate of mechanical dyssynchrony. We evaluated the correlation of mechanical dyssynchrony with QRSd as measured by signal‐averaged electrocardiography (SAECG) in comparison with measurements based on conventional surface ECG and with onscreen measurements based on digital ECG.

Methods: We included 49 consecutive patients with decompensated heart failure (40 men, aged 66.8 ± 9.5 years), New York Heart Association (NYHA) class II–IV, and LVEF ≤ 40%. QRSd was calculated by manual measurement of 12‐lead ECG, on‐screen measurement of computer‐based ECG, and calculation of total ventricular activation time on SAECG.

Results: Only 60.4% of the studied patients had QRS ≥ 120 ms based on measurements derived by SAECG compared to 69.4% by using on‐screen measurement of computer‐based ECG and 73.5% based on surface ECG (P = 0.041). Interventricular but not intraventricular delay was correlated with QRSd. The correlation of interventricular dyssynchrony with QRSd was stronger when measured by SAECG than by surface ECG (r = 0.45, P = 0.001 vs r = 0.35, P < 0.01). Among patients with ischemic cardiomyopathy, no significant correlation was demonstrated between mechanical dyssynchrony and QRSd. In nonischemic patients, interventricular delay was significantly correlated with QRSd measured by surface ECG (r = 0.45, P < 0.05) and SAECG (r = 0.46, P < 0.05).

Conclusions: The use of SAECG results in different patient classification in wide QRS complex category as compared to surface ECG. Furthermore, QRSd measured by SAECG is correlated with interventricular but not intraventricular dyssynchrony in heart failure patients.
Correction for QT/RR Hysteresis in the Assessment of Drug‐Induced QTc Changes—Cardiac Safety of Gadobutrol
Authors: Malik Marek , Hnatkova Katerina , Schmidt Anna , Smetana Peter
Published: July 2009

Background: The so‐called thorough QT/QTc (TQT) studies required for every new pharmaceutical compound are negative if upper single‐sided 95% confidence interval (CI) of placebo and baseline corrected QTc prolongation is <10 ms. This tight requirement has many methodological implications. If the investigated drug has a fast action and ECGs cannot be obtained at stable heart rates, QT/RR hysteresis correction is needed.

Methods: This was used in a TQT study of gadobutrol. The TQT study was a randomized double‐blind five‐times crossover study of three doses of gadobutrol (0.1, 0.3, and 0.5 mmol/kg) that was placebo and positive effect controlled (moxifloxacin 400 mg). The study enrolled 50 healthy subjects with data of all periods. QT/RR hysteresis was assessed from prestudy exercise test ECGs. Among others, comparisons were made between population heart rate correction without hysteresis considerations and combined population heart rate and hysteresis correction.

Results: The highest heart rate increase (placebo and baseline controlled) of 13.1 beats per minute (90% CI 9.9–16.4) occurred 1 minute after the administration of the highest dose of gadobutrol. Without hysteresis consideration, the highest ΔΔQTc were 9.91 ms (90% CI 8.01–11.81) while with hysteresis correction, these values were 7.62 ms (90% CI 6.37–8.87), thus turning a marginally positive TQT study into a negative finding.

Conclusion: Hence, omitting hysteresis correction from episodes of fast heart rate changes may lead to incorrect conclusions. Despite substantial rate acceleration, accurate hysteresis correction confirms that gadobutrol does not have any effects on cardiac repolarization that would be within the limits of regulatory relevance.
Atrial Fibrillation in Patients with Constrictive Pericarditis: The Significance of Pericardial Calcification
Authors: Rezaian Gholam R. , Poor‐Moghaddas Masoud , Kojuri Javad , Rezaian Shahed , Liaghat Lida , Zare Najaf
Published: July 2009

Background: Although atrial fibrillation (AF) is commonly encountered in patients with constrictive pericarditis (CP), little has been done to clarify its associated predisposing factors. Our aim was to evaluate the association of age, gender, disease duration, and pericardial calcification with AF in these patients.

Methods: The medical records of 44 patients with CP were reviewed. There were 13 (29.5%) with AF and 31 (70.5%) with sinus rhythm. The two groups were compared for demographic variables, disease duration, and the presence of pericardial calcification.

Results: The male‐to‐female ratio was 3.4:1. Calcification was seen in 11 (25%) of the entire group. AF was much more common in those with calcification than those with sinus rhythm (odds ratio, 7.87 [95% CI, 1.73–35.78], P = 0.008). There was no association between the presence of AF and the age (P = 0.156) or gender (P ≈ 1.00). Logistic regression, however, showed that the chance of developing AF increased by 27% by each year of increase in disease duration (P = 0.025).

Conclusion: It seems that in patients with CP, the presence of pericardial calcification and the increasing disease duration are associated with a higher chance of developing AF.
T‐Wave Variability Detects Abnormalities in Ventricular Repolarization: A Prospective Study Comparing Healthy Persons and Olympic Athletes
Authors: Heinz Lara , Sax Anik , Robert Francois , Urhausen Axel , Balta Osman , Kreuz Jens , Nickenig Georg , Ocklenburg Rolf , Schwab Joerg O.
Published: July 2009

Background: Sudden cardiac death in athletes is more common than in the general population. Routine screening procedures are performed to identify competitors at risk. A new Holter‐based parameter analyzes variation of the ventricular repolarization (TVar). The aim of this study was to evaluate differences in electrocardiogram (ECG), Echo, and Holter (H) in competitive athletes compared to a healthy control group consisting of medical students (MS).

Methods: A total of 40 athletes (19 females, Olympic team, Luxembourg) and 40 MS (22 females) were examined by means of a resting ECG, treadmill exercise (TE), echocardiogram (Echo), as well as H recordings during a routine screening visit. To analyze TVar, a 20‐minute H recording at rest (sampling rate 1000 per second) was performed. Moreover, heart rate variability (HRV) as well as HR turbulence (HRT) was computed.

Results: No differences in demographic variables were detected. Quantification of HRV detected a significant increase in the vagal component of autonomic cardiac modulation. In contrast, no differences for HRT were found. Echo parameter demonstrated a thicker septal wall without differences of the posterior wall. TVar values were normal in range, but did differ significantly between the two groups. No correlation between TVar and echo as well as Holter parameters was detected.

Conclusions: TVar was able to demonstrate significant differences in terms of alterations of ventricular activation. This might indicate an early change of myocardial repolarization representing a substrate for life‐threatening arrhythmia. Larger studies on the predictive value of TVar including follow‐up are necessary to confirm this preliminary finding.
“It's not Really a Nickname, it's a Method”: Local Names, State Intimates, and Kinship Register in the IrishGaeltacht
Authors: Lele Veerendra
Published: July 2009

Naming systems inGaeltacht(Irish‐speaking) communities in western Ireland produce different sociolinguistic registers. I argue that the use of a person'sainm áitiúil(“local name”) establishes and enlists a generalized register of kinship and social intimacy in theGaeltacht.Local agents of the state (“state intimates”) articulate local names with official state‐recognized names, operating between the registers these names represent. The ways in which local names are used, the knowledge about persons they produce, and the social relations they represent draw together personal identity, spoken practice, and kinship values in this particular Gaeltacht community. [Ireland; Irish language; kinship; names; register]
Between love and property: Voice, sentiment, and subjectivity in the reform of daughter's inheritance in Nepal
Authors: KUNREUTHER LAURA
Published: July 2009

In this article, I trace the relation between the figure of voice and subjectivity by examining a Nepali reform movement that sought to give daughters a birth right to ancestral property. At its heart was a contest over emerging class and gender subjectivities that were repeatedly defined through the figure of the voice and related practices of address, hailing, and recognition. The competing formations of voice I discuss here entail shifting notions of intimacy. To challenge property relations thus meant to change existing practices of speech, sentiment, and the meaning of voice itself. [voice, sentiment, property, subjectivity, Nepal, gender, class distinction]
Chthonic science: Georges Niangoran‐Bouah and the anthropology of belonging in Côte d'Ivoire
Authors: ARNAUT KAREL , BLOMMAERT JAN
Published: July 2009

Georges Niangoran‐Bouah worked assiduously toward Africanizing national education, academia, and public culture in Côte d'Ivoire. As part of this venture, his research projects, including his study of “drummology,” can be regarded as a quest for “chthonic” science, that is, an anthropology that uncovers and implements the deep tenets of African–Ivorian culture. Properly situated in its academic, ideological, and political umwelt, we demonstrate, Niangoran‐Bouah's anthropology of belonging is not merely an instance of “closure” but must be seen as a multiform attempt to recover a “local” position as a way to participate in universal–global science. [Niangoran‐Bouah, chthonic science, postcolonial theory, autochthony, Côte d'Ivoire]
Synthesis, Structures, and Properties of Bulk Si(O)C Ceramics from Polycarbosilane
Authors: Li Ya‐Li , Fan Hua , Su Dong , Fasel Claudia , Riedel Ralf
Published: July 2009

Bulk Si(O)C ceramics are fabricated from polycarbosilane (PCS) by bulk pyrolysis along the route of cross linking, warm‐pressing, and pyrolysis. The PCS was thermally oxidized for cross linking at various temperatures as a critical step toward the bulk transformation of PCS into bulk Si(O)C ceramics. The degree of cross linking of PSC affects the densities and bonding qualities of the warm‐pressed powder compacts and, hence, the resultant ceramics. Under optimized processing conditions, crack‐free bulk Si(O)C ceramics are obtained with a bulk density attaining 2.2 g/cm3. Despite the existence of a considerable amount of oxygen in the ceramics (16.08 wt%), resulting from the thermal oxidation processing, the ceramics show the characteristics of structures and properties of SiC‐based ceramics. 29Si‐solid state nuclear magnetic resonance spectra (NMR) reveal that the as‐pyrolyzed X‐ray amorphous Si(O)C phase consists mainly of SiC4 coordination units in the ceramic network, with the remainder being silicon‐coordinated carbon and oxygen. Microhardness tests show that the as‐pyrolyzed amorphous Si(O)C ceramics have a high hardness, attaining 24.91 GPa at a load of 2 N, and 19.82 GPa at a load of 10 N. Upon annealing at 1300°C in argon, the amorphous ceramics crystallized into nanophase β‐SiC ceramics, and the ceramics kept the bulk nature of the amorphous ceramics with an increased density. The 29Si‐solid state NMR spectrum indicates that the nanophase β‐SiC ceramics consist of SiC4 units together with some mixed coordination units, namely SiO2C2 and SiOC3. The hardness of the crystallized nanophase Si(O)C ceramics attains 23.20 GPa at a load of 10 N. The present study demonstrates the possibility of fabricating bulk Si(O)C ceramics via the polymer‐processing route, resulting in ceramics with promising structural and mechanical properties.
Silicon Solar Cell with Nanoporous Structure Formed on a Textured Surface
Authors: Kim Bum Sung , Lee Don Hee , Kim Sun Hee , An Guk‐Hwan , Lee Kun‐Jae , Myung Nosang V. , Choa Yong‐Ho
Published: July 2009

A nanoporous silicon (Si) surface was formed on monocrystalline silicon solar cells by electrochemical etching. The galvanostatic mode was applied to conventional n–p–p+ solar cells, which were fabricated by pyramidal texturing, phosphorous diffusion, screen‐printing, rapid thermal firing, and laser isolation (effective area of 144.7 cm2). Without an additional antireflection layer such as SiNx, the anodic reaction of the Si wafer could provide uniform porous layers on a pyramidal surface (111) with relatively low reflectance, and it would improve the photovoltaic performance.
One‐year Outcomes Following Coronary Computerized Tomographic Angiography for Evaluation of Emergency Department Patients with Potential Acute Coronary Syndrome
Authors: Hollander Judd E. , Chang Anna Marie , Shofer Frances S. , Collin Mark J. , Walsh Kristy M. , McCusker Christine M. , Baxt William G. , Litt Harold I.
Published: July 2009

Objectives:  Coronary computerized tomographic angiography (CTA) has high correlation with cardiac catheterization and has been shown to be safe and cost‐effective when used for rapid evaluation of low‐risk chest pain patients from the emergency department (ED). The long‐term outcome of patients discharged from the ED with negative coronary CTA has not been well studied.

Methods:  The authors prospectively evaluated consecutive low‐ to intermediate‐risk patients who received coronary CTA in the ED for evaluation of a potential acute coronary syndrome (ACS). Patients with cocaine use, known cancer, and significant comorbidity reducing life expectancy and those found to have significant disease (stenosis ≥ 50% or ejection fraction < 30%) were excluded. Demographics, medical and cardiac history, labs, and electrocardiogram (ECG) results were collected. Patients were followed by telephone contact and record review for 1 year. The main outcome was 1‐year cardiovascular death or nonfatal acute myocardial infarction (AMI).

Results:  Of 588 patients who received coronary CTA in the ED, 481 met study criteria. They had a mean (±SD) age of 46.1 (±8.8) years, 63% were black or African American, and 60% were female. There were 53 patients (11%) rehospitalized and 51 patients (11%) who received further diagnostic testing (stress or catheterization) over the subsequent year. There was one death (0.2%; 95% confidence interval [CI] = 0.01% to 1.15%) with unclear etiology, no AMI (0%; 95% CI = 0 to 0.76%), and no revascularization procedures (0%; 95% CI = 0 to 0.76%) during this time period.

Conclusions:  Low‐ to intermediate‐risk patients with a Thrombosis In Myocardial Infarction (TIMI) score of 0 to 2 who present to the ED with potential ACS and have a negative coronary CTA have a very low likelihood of cardiovascular events over the ensuing year.
Sequencing Negotiating Partners: Implications for the Two‐Level Game?
Authors: Enia Jason S.
Published: July 2009

In the late 1990s, Japan and South Korea concluded their first bilateral free trade agreements (FTAs) in completely opposite sequences despite similar domestic pressures. Japan concluded an “easier” FTA with Singapore first and then concluded a more “difficult” FTA with Mexico. South Korea concluded a more difficult FTA first with Chile and then moved on to negotiate with Singapore. In this article, I analyze these cases and review the literature on bargaining and two‐level games to develop a model of how these differences in sequence account in part for the relative differences in each country's bargaining strength in their more difficult negotiations. The preexistence of the Singapore FTA eased domestic pressures to reap the benefits of entry into the bilateral FTA game. Thus, Japan could approach the more difficult FTA negotiation knowing that a “no‐agreement” outcome would not fundamentally increase domestic pressure to get into the free trade “game.” This alternative to no agreement put the Japanese in a stronger international bargaining position. South Korea negotiated its harder case knowing that the relative domestic pressure to get in the FTA game would increase without an agreement. This relatively worse bargaining position created a context in which South Korea conceded more internationally at the expense of higher side payments domestically.
Teaching Mediation as Reflective Practice
Authors: Hardy Samantha
Published: July 2009

This article contributes to a growing body of research about how to effectively teach mediation by considering how best to use role‐plays in the mediation classroom to encourage reflective practice with a particular emphasis on the role of the teacher as a facilitator of reflective learning. The author suggests that the process of teaching mediation as reflective practice starts with teaching as reflective practice and emphasizes the importance of teachers' critical self‐reflection. The article provides some examples of how teachers can encourage students to engage in reflective learning and develop their skills as reflective practitioners for their continued professional development.
EORTC trial 11001: distribution of two 10B‐compounds in patients with squamous cell carcinoma of head and neck, a translational research/phase 1 trial
Authors: Wittig Andrea , Collette Laurence , Appelman Klaas , Bührmann Sandra , Jäckel Martin C. , Jöckel Karl‐Heinz , Schmid Kurt Werner , Ortmann Uta , Moss Raymond , Sauerwein Wolfgang A.G.
Published: July 2009

Boron neutron capture therapy (BNCT) provides highly targeted delivery of radiation through the limited spatial distribution of its effects. This translational research/phase I clinical trial investigates whether BNCT might be developed as a treatment option for squamous cell carcinoma of head and neck (SCCHN) relying upon preferential uptake of the two compounds, sodium mercaptoundecahydro‐closo‐dodecaborate (BSH) or L‐para‐boronophenylalanine (BPA) in the tumour. Before planned tumour resection, three patients received BSH and three patients received BPA. The 10B‐concentration in tissues and blood was measured with prompt gamma ray spectroscopy. Adverse effects from compounds did not occur. After BPA infusion the 10B‐concentration ratio of tumour/blood was 4.0 ± 1.7. 10B‐concentration ratios of tumour/normal tissue were 1.3 ± 0.5 for skin, 2.1 ± 1.2 for muscle and 1.4 ± 0.01 for mucosa. After BSH infusion the 10B‐concentration ratio of tumour/blood was 1.2 ± 0.4. 10B‐concentration ratios of tumour/normal tissue were 3.6 ± 0.6 for muscle, 2.5 ± 1.0 for lymph nodes, 1.4 ± 0.5 for skin and 1.0 ± 0.3 for mucosa. BPA and BSH deliver 10B to SCCHN to an extent that might allow effective BNCT treatment. Mucosa and skin are the most relevant organs at risk.
The effects of diet quality and quantity on plumage colour and growth of great tit Parus major nestlings: a food manipulation experiment along a pollution gradient
Authors: Eeva Tapio , Sillanpää Saila , Salminen Juha‐Pekka
Published: July 2009

The yellow carotenoid‐based plumage coloration of great tit Parus major nestlings is found to be paler in polluted and urban environments. Because carotenoid pigmentation is often considered to be a condition dependent trait in birds we wanted to find out whether food‐limitation and poor nestling condition could explain the pale plumage colour in a polluted area. P. major nestlings were supplemented with variable diets along a well known heavy metal pollution gradient around a copper smelter: two food treatments with carotenoids, one food treatment with little carotenoid and one unsupplemented control. Our field experiment showed that nestlings in the polluted area grew better with carotenoid rich diets, while such effect was not found in the unpolluted area. Nestlings showed higher plasma carotenoid (lutein) levels and higher plumage carotenoid chroma values in the unpolluted area than in the polluted area. However, plasma lutein levels or plumage colour were not associated with heavy metal levels in nestling faeces (a proxy for dietary exposure). Our results provide only weak evidence for carotenoid‐based colouration to be condition‐dependent in great tit nestlings as we found a positive relationship between body mass and carotenoid chroma in the non‐supplemented control group only. The positive relationship between body mass and plumage colour intensity is more likely to be produced by the fact that good availability of caterpillars, an important food source for P. major, also means a good availability of carotenoids to nestlings. Our results suggest that main reason for pale nestling plumage in the polluted area is lower quality invertebrate food, and not nutrition‐related oxidative stress.
Nodal blue nevus: a pitfall in lymph node biopsies
Authors: Dohse Lindsey , Ferringer Tammie
Published: July 2009

The sentinel lymph node from a 72‐year‐old female with melanoma revealed a pigmented and spindled melanocytic proliferation in the capsule that extended into the trabeculae. Benign nodal nevi are uncommon but have been reported in lymph nodes of melanoma patients and less often in lymph nodes removed for other reasons. Nodal blue nevi are particularly rare. These melanocytic proliferations can be distinguished from metastatic melanoma by evaluation of the distribution in the node, morphologic characteristics and the assistance of immunohistochemistry.
CD4/CD8 double negative pagetoid reticulosis: a case report and literature review
Authors: Mourtzinos Nikki , Puri Puja K. , Wang Guanghua , Liu Min‐Ling
Published: July 2009

Pagetoid reticulosis is an indolent primary cutaneous T‐cell lymphoma. It typically presents as a solitary and slowly growing patch or plaque on the extremity, histologically characterized by an acanthotic epidermis infiltrated with atypical lymphocytes. Here, we present histological, immunophenotypical and molecular findings of a 29‐year‐old Jamaican man with bilateral wrist plaques. Histology showed marked acanthosis, hyperkeratosis and an intraepidermal infiltration consisting of large atypical lymphocytes. Immunohistochemical stains showed CD3 and CD5 positive T cells with significant loss of CD7, double negative CD4 and CD8 and strong positive CD30. Molecular analysis showed a monoclonal T‐cell receptor (TCR) gamma gene rearrangement. Review of the literature confirms that the immunophenotype of pagetoid reticulosis is variable with decreasing frequency of CD8+ cytotoxic/suppressor T cell, CD4+ helper T cell and least commonly CD4/CD8 double negative phenotypes. Although CD4/CD8 double negative phenotype appears to be associated with higher proliferation index, it does not appear to confer prognostic significance.

Mourtzinos N, Puri PK, Guanghua W, Liu M‐L. CD4/CD8 double negative pagetoid reticulosis: a case report and literature review.
Intralymphatic atypical T‐cell proliferation in a cutaneous hemangioma
Authors: Ardighieri Laura , Lonardi Silvia , Vermi William , Medicina Daniela , Cerroni Lorenzo , Facchetti Fabio
Published: July 2009

We report an unusual case of atypical T‐cell proliferation involving the lymphatic vessels within a cutaneous hemangioma from an elderly woman. Despite the blastic morphology, the CD4 restricted phenotype and the very high proliferation index, the clinical presentation (single skin lesion in a healthy woman), the benign clinical course and the absence of T‐cell receptor (TCR) clonal rearrangement favored a reactive nature of the process. Since the atypical cells showed an effector/memory‐like regulatory T‐phenotype (CD45RO+, CD25+ and FOXp3+), expressed the migration‐associated molecule CCR7 and were exclusively located within podoplanin+ lymphatic vessels, we speculate that the process might reflect an unusual local immune response, with migration of T‐cells to draining lymph nodes.

Ardighieri L, Lonardi S, Vermi W, Medicina D, Cerroni L, Facchetti F. Intralymphatic atypical T‐cell proliferation arising in a cutaneous hemangioma.
Benign mixed tumor of the skin, hypercellular variant: a case report
Authors: Hafezi‐Bakhtiari Sara , Al‐Habeeb Ayman , Ghazarian Danny
Published: July 2009

A 71‐year‐old man presented with a slowly growing 2.0×2.0×1.0 cm scalp lesion that was surgically removed. Microscopic examination showed a well‐circumscribed dermally located tumor composed of ductal elements lined by double to multiple cell layers of bland cuboidal inner cells and elongated spindled outer cells with areas showing cribriform and solid growth patterns. Some cells showed prominent cytoplasmic clearing. A few mitotic figures are noted ranging from 1‐2 mitotic figure/10 hpf. There are also foci of squamous differentiation as well as occasional mature adipocytes. The background stroma was predominantly sclerotic with only small area of myxoid background (confirmed by Hale's colloidal iron).

Immunohistochemical studies revealed positive immunoreactivity for EMA, CEA, CD117, HWMK, LWMK, CK7, Androgen receptor and S100 in the ductal (epithelial) cells and positive immunereactivity for calponin, SMA, CK 5/6 and p63 in the myoepithelial component. No immunoreactivity for Brst‐2, ER, PR and CK20 was noted. MIB‐1 showed mildly increased proliferrative index highlighting 5% of the nuclei. The overall morphology and immunohistochemical profile are that of a benign cutanoues mixed tumor (chondroid syringoma). Given the unusual striking celluarlity, we suggest to subclassify this as a hyper‐cellular variant.

Hafezi‐Bakhtiari S, Al Habeeb A, Ghazarian D. Benign mixed tumor of the skin, hypercellular variant: a case report.
Cytokeratin 75 expression in central, centrifugal, cicatricial alopecia – new observations in normal and diseased hair follicles
Authors: Sperling Leonard C. , Hussey Sean , Sorrells Timothy , Wang Ji‐an , Darling Thomas
Published: July 2009

Background: Premature desquamation of the inner root sheath (IRS) is an important histological marker for central, centrifugal, cicatricial alopecia (CCCA), and an inherently defective IRS may be responsible. Cytokeratin 75 (K75; formerly K6hf) is an appealing candidate for study because K75 is specifically expressed in the companion layer of the hair follicle, the interface for IRS desquamation. Also, K75 abnormalities have been found in other hair diseases bearing similarities to CCCA.

Methods: We used a commercially available antibody to K75 on formalin‐fixed, paraffin‐embedded tissue from clinically and histologically “normal” scalp (n=9); clinically diseased scalp from patients with CCCA (n=15); and clinically “normal” scalp from patients with CCCA (n=6).

Results: K75 expression disappears during the process of IRS desquamation, and loss of expression begins even when IRS desquamation is in its incipient phase. Also, K75 has a characteristic pattern of expression in telogen follicles.

Conclusions: K75 expression is closely associated with the process of desquamation of the IRS. This process occurs prematurely (below the isthmus) in many follicles from patients with, but not without, CCCA. K75 expression highlights premature desquamation of the IRS in CCCA, but may not be directly involved in disease pathogenesis.

Sperling LC, Hussey S, Sorrells T, Wang J‐A, Darling T. Cytokeratin 75 expression in central, centrifugal, cicatricial alopecia – new observations in normal and diseased hair follicles.
Leptin and the skin: a new frontier
Authors: Poeggeler Burkhard , Schulz Carla , Pappolla Miguel A. , Bodó Enikő , Tiede Stephan , Lehnert Hendrik , Paus Ralf
Published: July 2009

Abstract:  Here, we examine the currently available information which supports that the adipokine, leptin, is a major player in the biology and pathology of mammalian skin and its appendages. Specifically, the potent metabolic effects of leptin and its mimetics may be utilized to improve, preserve and restore skin regeneration and hair cycle progression, and may halt or even partially reverse some aspects of skin ageing. Since leptin can enhance mitochondrial activity and biogenesis, this may contribute to the wound healing‐promoting and hair growth‐modulatory effects of leptin. Leptin dependent intracellular signalling by the Janus kinase 2 dependent signal transducer and activator of transcription 3, adenosine monophosphate kinase, and peroxisome proliferator‐activated receptor (PPAR) gamma coactivator/PPAR converges to mediate mitochondrial metabolic activation and enhanced cell proliferation which may orchestrate the potent developmental, trophic and protective effects of leptin. Since leptin and leptin mimetics have already been clinically tested, investigative dermatology is well‐advised to place greater emphasis on the systematic exploration of the cutaneous dimensions and dermatological potential of this pleiotropic hormone.
Effects of small interfering RNAs targeting Fascin on gene expression in oral cancer cells
Authors: Chen Su‐Feng , Lin Chi‐Yu , Chang Yun‐Ching , Li Jhy‐Wei , Fu Earl , Chang Fei‐Ni , Lin Yu‐Lu , Nieh Shin
Published: July 2009

Background:  Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. The prognosis of OSCC is usually poor because of extensive local invasion at initial diagnosis. In the literature, Fascin has been reported responsible for cell motility and over‐expression of Fascin contributes to an unfavorable clinical course. Nevertheless, the roles of Fascin protein playing in aggressiveness of OSCC and their potential mechanisms need to be elucidated.

Methods:  Two cell lines of OSCC (OECM‐1 and SCC‐25) via the vector‐based small interfering RNA (siRNA) to suppress the expression of the Fascin gene were used. Subsequent analyses and observation regarding the expression of Fascin protein and cyto‐morphological alterations were detected by Western blot and immunofluorescent microscopy. Boyden chamber invasion assay, cell migration assay and adhesion assay were also applied to investigate the functional changes of OSCC.

Results:  There were statistically significant differences (P < 0.05) of Fascin expression before and after silencing. Down‐regulation of Fascin protein directly led to changes of cell surface protrusions under immunofluorescent microscopy and resulted in suppression of migration, invasion and increase of adhesion in both cell lines (P < 0.05). Furthermore, down‐regulation of Fascin expression also resulted in alterations of E‐cadherin, β‐catenin and TWIST at certain level, implicative of an association with epithelial‐mesenchymal transition (EMT).

Conclusions:  Our results suggest that expression of Fascin protein may play an essential role in regulation of progression of OSCC and contributes to the event of EMT in the early aggressiveness of OSCC.
Inhibition of ameloblastoma invasion in vitro and in vivo by inhibitor of metalloproteinase‐2 activity
Authors: Zhang Bin , Zhang Jin , Huang Hong‐Zhang , Chen Wei‐Liang , Tao Qian , Zeng Dong‐Lin , Zhang Lei‐Tao , Xu Jian‐Hui
Published: July 2009

Background:  Ameloblastoma is an odontogenic benign tumor characterized by local invasiveness and most of its local recurrences clinically result from local invasion. This study used matrix metalloproteinase‐2 (MMP‐2) inhibitor I (MMP‐2I) to investigate the role played by MMP‐2 activity in the local invasiveness of ameloblastoma.

Methods:  The cells and xenografts of ameloblastoma were treated with MMP‐2I and treatment group were compared with the control group. In vitro, the invasive activity of tumor cells was assayed in transwell cell culture chamber. Gelatinolytic activity of gelatinases and MMP‐2/tissue inhibitor of matrix metalloproteinase (TIMP‐2) protein expression was detected using gelatin zymography and flow cytometry. The cell viability and adhesion were evaluated using methyl thiazol tetrazolium. In vivo, bilateral subrenal capsule xenograft transplantation of ameloblastoma was performed in 10 nude mice and the invasion of ameloblastoma into the renal parenchyma was observed.

Results:  Active‐MMP‐2 of conditioned media was significantly lower in treatment group than in the control group. Accordingly, potential of in vitro cell invasion, adhesion and in vivo tumor invasion were also significantly lower in the treatment group than in the control group.

Conclusions:  Inhibitor of MMP‐2 activity suppressed the local invasive capability of ameloblastoma by decreasing MMP‐2 activity. MMP‐2 activity is in relation with invasive capacity of ameloblastoma.
Degenerative and protective reactions of the rat trigeminal motor nucleus after removal of the masseter and temporal muscles
Authors: Seki Yoshihiro , Suzuki Satoshi O. , Nakamura Seiji , Iwaki Toru
Published: July 2009

Background:  Microsurgical reconstruction techniques have allowed treatment of advanced head and neck carcinomas; however, it remains difficult to achieve long‐term, functional reconstruction of the faciocervical muscles. To address this issue, in this we developed a rat trigeminal nerve denervation model that closely simulates the effects of oral surgery.

Methods:  The rat trigeminal nerve denervation model was developed by removing the masseter and temporal muscles, and degeneration process of the trigeminal motor nucleus was investigated by immunohistochemistry with particular focus on microglial/astrocytic reactions and motoneuron degeneration.

Results:  Atrophy of the trigeminal motor nucleus was observed at 8 weeks after denervation. A microglial reaction peaked at 3 days post‐operation, while an astrocytic reaction was evident within 2 weeks, and peaked around 4 weeks post‐operation. Expression of the stress protein HSP27 and an autophagy marker Rab24 was also upregulated in the injured trigeminal motor nucleus.

Conclusions:  The results from this study suggest that this model is a practical and useful tool help to develop a further understanding of the pathology of the trigeminal motor nucleus after surgical denervation.
The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI‐1 and bcl‐2 is similar to ameloblastoma but different from odontogenic cysts
Authors: Vered M. , Peleg O. , Taicher S. , Buchner A.
Published: July 2009

Background:  The aggressive biological behavior of odontogenic keratocysts (OKCs), unlike that of other odontogenic cysts, has argued for its recent re‐classification as a neoplasm, ‘keratocystic odontogenic tumor’. Identification of mutations in the PTCH gene in some of the OKCs that were expected to produce truncated proteins, resulting in loss of control of the cell cycle, provided additional support for OKCs having a neoplastic nature.

Methods:  We investigated the immunohistochemical expression of the sonic hedgehog (SHH) signaling pathway‐related proteins, PTCH, smoothened (SMO) and GLI‐1, and of the SHH–induced bcl‐2 oncoprotein in a series of primary OKC (pOKC), recurrent OKC (rOKC) and nevoid basal cell carcinoma syndrome‐associated OKCs (NBCCS‐OKCs), and compared them to solid ameloblastomas (SAMs), unicystic ameloblastomas (UAMs), ‘orthokeratinized’ OKCs (oOKCs), dentigerous cysts (DCs) and radicular cysts (RCs).

Results:  All studied lesions expressed the SHH pathway‐related proteins in a similar pattern. The expression of bcl‐2 in OKCs (pOKCs and NBCCS‐OKCs) and SAMs was significantly higher than in oOKCs, DCs and RCs (P < 0.001).

Conclusions:  The present results of the immunoprofile of OKCs (that includes the expression of the SHH‐related proteins and the SHH‐induced bcl‐2 oncoprotein) further support the notion of OKC having a neoplastic nature. As OKCs vary considerably in their biologic behavior, it is suggested that the quality and quantity of interactions between the SHH and other cell cycle regulatory pathways are likely to work synergistically to define the individual phenotype and corresponding biological behavior of this lesion.
MYC gene amplification reveals clinical association with head and neck squamous cell carcinoma in Indian patients
Authors: Bhattacharya N. , Roy A. , Roy B. , Roychoudhury S. , Panda C. K.
Published: July 2009

Background:  Amplification of the MYC gene is reported to be associated with the development of head and neck squamous cell carcinoma (HNSCC). This study is focused to analyze the correlation between MYC gene amplification and various clinicopathological features and outcome in a cohort of 49 dysplastic and 187 primary head and neck lesions.

Methods:  MYC gene amplification was assessed by differential polymerase chain reaction using primer sets from the MYC gene as target locus and DRD2 gene as the control locus.

Result:  The MYC gene amplification was detected in a total of 23.7% (56/236) head and neck lesions comprising 14.2% (7/49) dysplastic lesions and 26% (49/187) HNSCC samples. The clinicopathological association study between MYC gene amplification with the different clinical parameters like sex, tumor stage, tumor differentiation, lymph node status, tobacco habit and HPV 16/18 status determined significant association of MYC amplification with tumor progression (P = 0.009). Kaplan Meier analysis revealed MYC gene has no prognostic significance on survival in HNSCC.

Conclusion:   In conclusion, our results suggest that MYC gene amplification is associated with tumor progression in HNSCC.
Production of proinflammatory and immunoregulatory cytokines by inflammatory cells from periapical lesions in culture
Authors: Gazivoda Dragan , Dzopalic Tanja , Bozic Biljana , Tatomirovic Zeljka , Brkic Zlata , Colic Miodrag
Published: July 2009

Background:  The role of cytokines in pathogenesis of periapical lesions is not well understood. The aim of this study was to study the correlation between proinflammatory and immunoregulatory cytokines in periapical lesions and their relationship with cellular composition and clinical presentation.

Methods:  Inflammatory cells were isolated from 67 human periapical lesions and cultivated for 24 h. The levels of proinflammatory cytokines: interleukin‐1 beta (IL‐1β), IL‐6, IL‐8 and tumour necrosis factor alpha (TNF‐α) and immunoregulatory cytokines: transforming growth factor‐beta (TGF‐β) and IL‐10 were determined in culture supernatants using a fluorescent bead immunoassay or ELISA. The phenotype of cells was analysed by immunocytochemistry.

Results:  Inflammatory cells from symptomatic lesions which contained higher proportion of granulocytes, secreted higher levels of IL‐1, IL‐6 and IL‐8 compared with asymptomatic lesions. Large‐size lesions contained lower percentages of mononuclear phagocytes, higher percentages of CD8+ T cells and produced higher levels of TNF‐α, IL‐6 and IL‐10 compared with small‐size lesions. There were negative correlations between the concentrations of TGF‐β and proinflammatory cytokines. TGF‐β, added to cultures, downregulated the levels of proinflammatory cytokines more strongly than IL‐10, independently of clinical presentation of the lesions. By contrast, exogenous IL‐10 was mainly immunosuppressive in cultures of asymptomatic lesions.

Conclusion:  Symptomatic lesions are characterized by higher production of proinflammatory cytokines. Immunoregulatory cytokines are more important for suppression of inflammation in asymptomatic lesions and in this context the effect of TGF‐β is more potent and different from IL‐10.
The efficacy of topical intralesional BCG‐PSN injection in the treatment of erosive oral lichen planus: a randomized controlled trial
Authors: Xiong C. , Li Q. , Lin M. , Li X. , Meng W. , Wu Y. , Zeng X. , Zhou H. , Zhou G.
Published: July 2009

Background:  Nowadays, it has been widely accepted that the local cell‐mediated immunologic disorders may play an important role in the pathogenesis of oral lichen planus (OLP). Therefore, we sieved out polysaccharide nucleic acid fraction of bacillus Calmette‐Guerin (BCG‐PSN) from various immunomodulators to evaluate the short‐term therapeutic efficacy and clinical safety of intralesional BCG‐PSN injection for erosive OLP.

Methods:  A total of 56 OLP patients were randomly assigned to receive either intralesional injection of 0.5 ml BCG‐PSN every other day (31 of 56) or 10 mg triamcinolone acetonide (TA, a positive‐controlled group, 25 of 56) every week for 2 weeks. After the cessation of treatment, those cured from erosion were followed up for 3 months. Another two researchers measured erosive areas and recorded visual analog scale (VAS) scores both at the start and the end of the treatment. We also registered adverse reactions and the recurrence intervals.

Results:  After 2‐week treatment, 27 of 31 BCG‐PSN‐treated patients (87.1%) and 22 of 25 TA‐treated patients (88.0%) healed. There were no statistical differences between the two groups in erosive areas (27.86 ± 27.97 vs. 25.68 ± 34.65, P = 0.801) and VAS scores (2.45 ± 1.64 vs. 2.40 ± 1.38, P = 0.946). Three of 31 BCG‐PSN‐treated patients (9.7%) vs. 2 of 25 TA‐treated patients (8.0%) experienced the swelling or burning sensation (P = 0.827). A total of 49 of 56 patients were followed up. There were no statistical differences in the recurrence rates (33.3% vs. 45.5%, P = 0.386) and intervals (80.89 ± 26.83 vs. 73.48 ± 28.11, P = 0.419).

Conclusions:  Topical intralesional BCG‐PSN injection is as effective as TA for erosive OLP, which suggests that topical intralesional BCG‐PSN injection can be a promising therapeutic alternative for erosive OLP, especially for those insensitive, or even resistant, to glucocorticoids.
Distribution and quantity of label‐retaining cells in rat oral epithelia
Authors: Huang Yu‐Lei , Tao Xiaoan , Xia Juan , Li Chun‐Yang , Cheng Bin
Published: July 2009

Background:  Label‐retaining cells (LRCs), the presumptive stem cells, have been detected in the mouse and hamster oral epithelia, but the data on LRCs in rat oral epithelia have not been available yet. The aim of this study was to identify LRCs in oral squamous epithelia of rat.

Methods:  Fifty‐four two‐week‐old Sprague‐Dawley rats were injected intraperitoneally with BrdU twice daily for four consecutive days. The BrdU‐labeled rats were sacrificed at 2 h, week 2, 4, 6, 8, 10, 12, 14 and 16 after the last BrdU injection. The tissues of cheek, tongue and palate were analyzed by techniques of fluorescence‐activated cell sorting (FACS) and immunohistochemistry.

Results:  The number of BrdU‐labeled cells quantified by FACS increased within 2 weeks after labeling, then, decreased gradually until week 10. After week 10, the BrdU‐labeled cells were found to locate mainly in basal layer and their number kept consistent at 3–7% of total oral epithelial cells. The number of BrdU‐labeled epithelial cells in palate was statistically higher than that in cheek or tongue at the same time point.

Conclusions:  This study showed that the number and the distribution of BrdU‐labeled epithelial cells stabilized from 10 weeks after labeling. Therefore, these BrdU‐labeled cells after a 10‐week chase were considered oral epithelial LRCs.