bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of optimum window size for SAR image co‐registration with decomposition of auto‐correlation
Authors: Zou Weibao , Li Zhilin , Ding Xiaoli
Published: October 2007

Interferometric synthetic aperture radar (InSAR) is a promising recent technique for the generation of digital elevation models and/or the measurement of ground surface deformations. In InSAR data processing, the first step is the image co‐registration, achieved by using a set of tie points which are the conjugate image points on the master and slave images. Tie points are selected with the aim of finding the conjugate point automatically on the slave image for any given point on the master image, by the process known as image matching. To achieve reliable matching, a set of points within a window is used instead of a single point. The size of the window will affect the reliability of matching. Hitherto there have been no effective methods for the determination of optimum window size for this purpose. In practice, this parameter is determined by experience. In this paper, a pair of SAR images is used to test the effect of window size on the reliability of co‐registration. An optimum window size is selected on the basis of the experimental results. The determination of optimum window size for tie point matching is then examined theoretically, leading to a proposal for an automated method based on the auto‐correlation of the SAR images, which reflects the similarity between image pixels. The auto‐correlation function is decomposed into waves of various frequencies by a wavelet transform. By a combined analysis of the variations of wave amplitudes with frequency, the optimum window size for tie point matching can be determined. A procedure based on the use of Daubechies wavelet db1 is proposed in detail. An optimum window size could be determined in this way for any pair of SAR images.
Black Loyalists and Black Slaves in Maritime Canada
Authors: Whitfield Harvey Amani
Published: October 2007

We know a great deal about the Black Loyalists who achieved freedom during the Revolutionary War, settled in Maritime Canada, and those who eventually migrated to the coast of West Africa. However, what about black people who were slaves in the American colonies and remained slaves after migrating to Maritime Canada with their masters? This article examines the historiography of the Black Loyalists in Maritime Canada and attempts to address the experience of those who remained slaves. Indeed, to have a broader understanding of transnational black migration to Canada historians must look beyond the paradigm of from slavery in America to freedom in Canada and consider the experience of those who remained slaves.
Oil and the Origins of the Great War
Authors: Engdahl F. William
Published: October 2007

This article looks at the strategic if little‐known role of oil and construction of the Berlin to Baghdad railway link between the German Reich and the Persian Gulf through what is today Iraq, in igniting an economic, military, and diplomatic confrontation in Europe in the late nineteenth and early twentieth centuries, and how it ultimately contributed to the move to war in 1914. This article will set down the background to this contentious issue, and analyze the various interpretations that authors have set down in the past. It will argue that despite appearances, the British Empire was in decline after about 1873 while the new German economic colossus presented an entirely new challenge to British hegemony. To secure future domination of the seas, after 1882 leading British circles around Admiral Fischer and Winston Churchill pushed through the conversion of the Royal Navy from coal to oil. The article goes into how the Berlin‐Baghdad presented an unacceptable strategic threat to that vital strategy. The various phases in the buildup to the Great War will be examined, along with the role of oil within this broad framework. Finally, the author will posit his own conclusions to this debate.
Microtensile Bond Strength of Different Components of Core Veneered All‐Ceramic Restorations. Part 3: Double Veneer Technique
Authors: Aboushelib Moustafa N. , Kleverlaan Cornelis J. , Feilzer Albert J.
Published: October 2007

Purpose: The bond strength of zirconia veneer has been considered a weak link in the layered all‐ceramic restoration. In a previous study, this bond was improved using a new category of veneering ceramics adopting the pressing technique; however, the resulting esthetic quality lacked the individual characterization built using the layering technique. The aim of this work was to evaluate the effect of combining both press‐on and layering veneer ceramics in one restoration on the bond strength with zirconia frameworks.

Materials and Methods: Zirconia discs (19.4 mm in diameter, 3‐mm thick) were veneered with 3‐mm thick press‐on veneer ceramic or veneered with 1‐mm thick press‐on veneer ceramic and an additional 2‐mm thick of layering veneer ceramic. Two commercial layering veneer ceramics were tested. The specimens were sectioned into microbars, and the zirconia veneer microtensile bond strength (MTBS) was measured in a universal testing machine. Scanning electron microscopy (SEM) was used to examine core veneer interface quality and to assess failure type. Energy dispersive X‐ray microanalysis (EDAX) was used to analyze the chemical structure of the tested veneer ceramics, which may affect the structural integrity of the double veneered restoration. One‐way analysis of variance and Tukey HSD post hoc tests were selected to analyze the data (p < 0.05 was significant).

Results: The MTBS of zirconia and press‐on ceramic (34.4 ± 2.9 MPa) was not affected by the addition of a second layer of either veneer ceramic. SEM analysis revealed defect‐free zirconia press‐on veneer interface, while the interface between the press‐on and the layering veneer ceramics demonstrated a different crystal structure and glass matrix, which did not affect wetting and contact between the two materials. EDAX analysis revealed differences, which account for the observed structural differences, in the chemical composition between the tested veneers.

Conclusion: The double veneer technique combines the high bond strength and superior interface quality achieved using press‐on ceramics with the superior esthetics and individual characterization obtained using layering ceramics. The technique promises superior function and performance of the double veneered restoration.
Prosthodontic Management of Sulcoplasty and Sialodochoplasty with a Conforming Surgical Stent
Authors: Berg Robert W. , Goldman Barry M. , Kurtz Kenneth , Schweitzer Kenneth , Kraut Richard A.
Published: October 2007

This clinical report describes the management of chronic, proliferative inflammatory epithelial and fibrous hyperplasia following loss of a mandibular implant‐retained prosthesis. A classic surgical technique was used. The patient was referred to the oral surgeon for sialodochoplasty and sulcoplasty. With a combination of surgery and prosthodontic management with a conforming surgical stent, a satisfactory denture foundation was created, allowing for fabrication of an implant‐retained definitive prosthesis.
A Survey of Deans: Trends, Challenges, and Mentoring in Prosthodontics. Part 2
Authors: Wright Robert F. , Dunlop Ryan A. , Kim Frances M. , Weber Hans Peter , Donoff R. Bruce
Published: October 2007

Purpose: This study consists of two parts. Part 1, a survey of program directors, was conducted to examine current trends in advanced education in prosthodontics in the United States. Part 2 reports on the findings of a survey distributed to the deans of US dental schools to evaluate their observations of trends in prosthodontic education.

Materials and Methods: A national, electronic survey of 55 dental school deans was distributed by e‐mail to evaluate an interest in specialty training, an interest in specialization in prosthodontics, faculty shortages, programs to address faculty shortages, predoctoral curriculum in prosthodontics, opinions regarding dental specialties, and the administrative position of prosthodontics within the schools.

Results: Of the 55 deans, 44 deans responded, an 80% response rate. Only five deans reported a decrease in the number of students seeking specialty training after dental school. The remaining 39 deans reported a large increase, slight increase, or no change in those seeking specialty training. In 29.6% of the deans' responses, an increased interest in prosthodontics was reported, whereas 16 deans reported no change in the level of interest. One or more open faculty positions in prosthodontics existed at 29 dental schools, and 28 schools offered at least one incentive or a variety of incentives to recruit faculty. The respondents to the deans' survey revealed predoctoral student exposure to prosthodontists was high, and exposure to postgraduate prosthodontics students was low. A survey of internal school programs that might have an impact on an increased interest in prosthodontics revealed the presence of a predoctoral mentoring program for prosthodontics in 80% of the institutions. The clinical curriculum included treatment of a variety of cases, including complex cases as defined by a diagnostic classification system. The response to whether dental specialties should be combined or remain individual provided some interesting data. Only 40.9% of the deans responded that prosthodontics was a separate department.

Conclusion: Dental school deans reported an increased interest in specialty training. Predoctoral student exposure to prosthodontics was high due to the nature of their clinical experience and due to the exposure to full‐time prosthodontics faculty. Many dental schools have programs, such as mentoring and new technology, which might have an impact on predoctoral students' increased interest in prosthodontics.
Optimization of Maxillary Obturator Thickness Using a Double‐Processing Technique
Authors: Oh Won‐suck , Roumanas Eleni D.
Published: October 2007

Preservation of remaining structures is a primary goal of prosthetic rehabilitation. Continuously applied stresses on the remaining tissues from a large, heavy obturator jeopardize the health of the tissues, compromise the function of the prosthesis, and affect patient comfort. Various techniques have been described for hollowing the bulb of an obturator after processing to reduce its weight; however, access to the inner aspects of the bulb is limited, preventing adequate control of thickness of the walls. This article describes a double‐processing technique for an obturator to optimize the weight and thickness of the bulb.
Masticatory dysfunction is associated with osteoporosis in older men
Authors: Laudisio Alice , Marzetti Emanuele , Antonica Livia , Settanni Silvana , Georgakakis Ioannis , Bernabei Roberto , Franceschi Claudio , Zuccalà Giuseppe
Published: October 2007

Aim: Thirty per cent of hip fractures occur in men. Nevertheless, the determinants of osteoporosis in men are unclear. Masticatory dysfunction is associated with malnutrition, and might represent an emergent cause of osteoporosis. The aim of this study was to assess the association of bone mineral density and self‐assessed masticatory dysfunction in a general older population.

Material and Methods: We assessed the association of masticatory dysfunction with standard parameters of bone mineral density (T‐score, Z‐score and the stiffness index) in all 310 subjects aged 75+ living in Tuscania (Italy).

Results: Among men, self‐assessed masticatory dysfunction was associated with T‐score [β=0.86, confidence intervals (CI)=0.15–1.57; p=0.019], Z‐score (β=0.86, CI=0.16–1.56; p=0.017) and the stiffness index (β=9.12, CI=0.47–17.77; p=0.039) in linear regression modeling, after adjusting. No significant associations were observed in women.

Conclusions: Masticatory dysfunction is independently associated with osteoporosis in elderly men. Evaluation of masticatory function should enter the routine assessment of older men with osteoporosis.
Using concept mapping principles in PowerPoint
Authors: Kinchin I. M. , Cabot L. B.
Published: October 2007

Abstract:  The use of linear PowerPoint templates to support lectures may inadvertently encourage dental students to adopt a passive approach to learning and a narrow appreciation of the field of study. Such presentations may support short‐term learning gains and validate assessment regimes that promote surface learning approaches at the expense of developing a wider appreciation of the field that is necessary for development of clinical expertise. Exploitation of concept mapping principles can provide a balance for the negative learning behaviour that is promoted by the unreflective use of PowerPoint. This increases the opportunities for students to access holistic knowledge structures that are indicators of expertise. We illustrate this using the example of partial denture design and show that undergraduates’ grasp of learning and teaching issues is sufficiently sophisticated for them to appreciate the implications of varying the mode of presentation. Our findings indicate that students understand the strategic value of bullet‐pointed presentations for short‐term assessment goals and the benefits of deep learning mediated by concept mapping that may support longer term professional development. Students are aware of the tension between these competing agendas.
Language background and OSCE performance: a study of potential bias
Authors: Schoonheim‐Klein M. , Hoogstraten J. , Habets L. , Aartman I. , Van der Vleuten C. , Manogue M. , Van der Velden U.
Published: October 2007

Aim:  To investigate whether Non‐Native dental students perceive drawbacks in their education and examination experience because of their lack of language proficiency and to test whether prolonging Objective Structured Clinical Examination (OSCE) test‐station duration improves their performance.

Materials and methods:  Dental students (n = 345) completed a questionnaire about their native country, their language background and the possible drawback they perceived in dental education and examination because of their language proficiency. Students were marked as ‘native’, when they were born in the Netherlands with Dutch as native language or ‘Non‐Native’ when they were born outside the Netherlands, raised with a non‐Dutch native language, or raised bilingually. A sample of 108 students was assessed by an OSCE testing a periodontal course with nine test‐stations. Test‐station topics were: (1) history taking, (2) measuring attachment level, (3) educating patients, (4) tracing a radiograph, (5) root‐planing, (6) writing a prescription, (7) diagnostics and prognostics, (8) differential diagnostics and (9) writing a referral letter. The first five test‐stations mentioned were of 5‐min duration. The other four test‐stations were provided in two modes: either with a short (5 min) or longer (10 min) version. Every student took at random two long and two short test‐stations.

Results:  In the group of 345 questionnaire responders, Non‐Native students (n = 116) perceived significantly more drawback in education and examination than Native students (n = 229) (P < 0.001). When Non‐Native students speak Dutch at home, around 38% of them reported perceived drawbacks in education, whereas when they speak their native language at home, around 60% reported perceived drawbacks in education (P = 0.005). In the periodontal OSCE (n = 108), the Native group (n = 70) had significantly higher total scores than the Non‐Native (n = 38), (P = 0.009, d = 0.53). The Non‐Native group had significantly lower mean scores in the communication station ‘educating patients’ (P = 0.034, d = 0.42). Prolonged test‐station duration from 5 to 10 min had no positive effect in all experimental test‐stations in the Native and Non‐Native group. Female students in the Native group out‐performed male in a communication test‐stations. Female students in Native and Non‐Native groups were found to be more successful in ‘tracing bone loss on radiographs’.

Conclusion:  Non‐Native students perceived a drawback in dental education and examination because of their language proficiency in Dutch, which is confirmed by their actual OSCE performance. Prolonging the time for a test‐station did not improve OSCE performance of Non‐Native students. It is recommended that students with problems in language ability need additional tuition and practice.
Dental education in Norway
Authors: Komabayashi Takashi , Åstrom Anne
Published: October 2007

Abstract:  Our review of dental education in Norway will address the following topics: the history of dental education, the dental school admission process, dental school curriculum, student evaluation, post‐graduation and the number of dentists in Norway relative to dental education.
Sponge eating: is it an obsessive compulsive disorder or an unusual form of pica?
Authors: Gupta A , Rajput S , Maduabuchi G , Kumar P
Published: October 2007

Association of pica, iron deficiency anaemia (IDA) and celiac disease (CD) have been reported in the literature. An unusual but completely reversible form of pica in the form obsessive compulsive sponge eating (pervasive disorder) was reported as an odd manifestation of IDA and CD.

Conclusion: The medical practice is full of challenges and complexity; and clinicians need to be vigilant all the time in their practice to appreciate unusual and rare manifestations of common clinical conditions like IDA and CD.
Severe child abuse: a study of cases reported to the police
Authors: Annerbäck E‐M , Lindell C , Svedin CG , Gustafsson PA
Published: October 2007

Aim: To investigate the characteristics of severe abuse of children and possible differences in comparison with less severe abuse.

Method: Cases of abuse reported to the police within a single police district (n = 142) in Sweden were studied. The severe cases were compared to all the remaining cases.

Results: Severe abuse constituted 14% of the total cases and was reported by agencies to a greater degree than minor cases. The suspected perpetrators were socially disadvantaged people in both groups. Half of the most serious cases led to conviction in the courts, compared to 8% in the reference group. The children who had been subjected to abuse were often already known to social services and reports of child abuse had frequently been made.

Conclusion: In comparison between cases of severe and minor child abuse reported to the police, the results did not show any crucial differences except the pattern of reporting and a higher occurrence of prosecution/conviction in the severe cases. This finding places a responsibility on agencies outside of the justice system to consider all cases of reported abuse as serious warning signals and to make independent evaluations to identify risks and the possible need for child protection.
Kikuchi‐Fujimoto disease manifesting as recurrent thrombocytopenia and Mobitz type II atrioventricular block in a 7‐year‐old girl: a case report and analysis of 138 Chinese childhood Kikuchi‐Fujimoto cases with 10 years of follow‐up in 97 patients
Authors: Jun‐Fen Fu , Chun‐Lin Wang , Li Liang , Dayan Colin , Guan‐Ping Dong , Fang Hong
Published: October 2007

Background: The diagnosis of Kikuchi‐Fujimoto disease (KFD) is challenging for a paediatrician. Recognizing unusual clinical presentations and features of KFD is essential for doctors to obtain a thorough understanding of this clinical entity.

Method: We reported a case recently diagnosed in our ward with manifestation of recurrent thrombocytopenia and Mobitz type II atrioventricular block, which is very unusual in childhood KFD. We also used three powerful Chinese Journal Search Engines (Cqvip.com, Wanfang.data and ScienceChina) to search the cases reported in China from 1989 to 2006.

Results: One hundred seventy‐three patients younger than 16 years old with pathologic proof of KFD were identified. Among them, 138 cases with detailed clinical records from eight different provinces and cities were analyzed, and of which 97 patients were followed‐up for average of 10 years and the outcomes are discussed.

Conclusions: KFD is characterized by a spectrum of distinctive features, but also a variety of systemic manifestations. A hyperimmune reaction to unidentified agents as well as an autoimmune component may play an important role in this disease. Early corticosteroid therapy may improve the long‐term prognosis of KFD in children.
Secular trends of pedometer‐determined physical activity in Swedish school children
Authors: Raustorp Anders , Ludvigsson Johnny
Published: October 2007

Aim: To explore the secular trends (time change) of pedometer‐determined physical activity (steps per day) in Swedish schoolchildren 7–9 years of age from 2000 to 2006. It was an additional aim to examine the secular trends in body mass index.

Methods: The study was analyzed between two cross‐sectional cohorts on children 7–9 years of age carried out in October 2000 (336 children, 153 girls) and March/April 2006 (168 children, 83 girls) in the same five schools in south eastern Sweden, using identical procedures at the two occasions. Data of mean steps per day were collected during four consecutive weekdays (sealed pedometer Yamax SW‐200 Tokyo, Japan) and in addition height and weight were measured.

Results: Physical activity (mean steps per day) was significantly higher in 2006 than in 2000 among girls (13788 vs. 15141 steps per day) and boys (15991 vs. 16973 steps per day). The share of girls and boys to meet the preliminary weight control recommendations of 12000 and 15000 steps per day respectively was higher in 2006 than in 2000: 90% versus 75% (girls) and 67% versus 60% (boys).

Conclusion: The level of physical activity (steps per day) during school weekdays was higher in 2006 than in 2000. Enhanced focus on physical activity in society and at school might have influenced the result.
‘Thair is Richt Litill Play at My Hungrie Hart’: Politics and Play in David Lyndsay's Ane Satyre of the Thrie Estaitis
Authors: Martin Joanna
Published: October 2007

Ane Satyre of the Thrie Estaitis is the only extant play by the prolific poet Sir David Lyndsay of the Mount, and the only surviving dramatic text from pre‐Reformation Scotland. Acknowledged to be controversial in its own time, the play was devised in c.1540, and reworked for performances in Cupar and Edinburgh in the 1550s. Its composition thus spans a particularly troubled period in Scottish history, and in its action Lyndsay examines the possibilities of political and religious reform with great contemporaneity. The play also explores the meta‐theatrical question of the ability of dramatic performance to facilitate social and governmental reform, and the capacity of theatre to influence the personal ethics of its audience. In order to explore these theatrical and moral issues Lyndsay creates a rich and sophisticated drama which draws on the tradition of the medieval morality play, contemporary European dramatic forms and his native Scots literary tradition.
Knowledge and Subjunctive Conditionals
Authors: Comesaña Juan
Published: October 2007

What relation must hold between a fact p and the corresponding belief that p for the belief to amount to knowledge? Many authors have recently proposed that the relation can be captured by subjunctive conditionals. In this paper I critically evaluate the main proposals along those lines.
Cultural Shaping of Self, Emotion, and Well‐Being: How Does It Work?
Authors: Kitayama Shinobu , Park Hyekyung
Published: October 2007

In this paper, we review the existent literature to propose that (i) different cultures have distinct views of self, which are instrumental in organizing daily routines, practices, and public meanings, (ii) the resulting behavioral environment shapes personal motivational propensities, (iii) the behavioral environment also carries information about normative expectations about what it is to be a ‘good’ person, and, as a consequence, (iv) culture has substantive influences on emotion, well‐being, and health. In making this proposal, we highlight the distinction between personal motivational propensities and the society's normative expectations. The consequences of the cultural views of self on personal motivational propensities and those on the society's normative expectations may typically be concordant and, yet, the concordance can be disrupted especially at times of rapid social change. Directions for future research on culture, emotion, and well‐being are discussed.
Toward a Social Psychology of Culture and Globalization: Some Social Cognitive Consequences of Activating Two Cultures Simultaneously
Authors: Chiu Chi‐Yue , Cheng Shirley Y. Y.
Published: October 2007

Despite the increased attention given to cultural phenomena in social psychology, the field has neglected issues related to globalization's cultural impacts. Meanwhile, opinions in the debates over these issues are divided, polarized, and often motivated by political and ideological commitments. Globalization has brought symbols of diverse cultures together and provided ample opportunities for the simultaneous activation of two or more cultural representations. Using our research on the social cognitive consequences of activating two cultural representations simultaneously as an example, we argue for constructing a social psychology of globalization that offers nuanced understandings of people's psychological responses to globalization. Although simultaneous activation of cultural representations does not determine an individual's cultural identity, it enlarges the felt distinctions between different identity options and magnifies the effects of identity choice. Furthermore, in situations that emphasize appropriating intellectual resources from diverse cultures to foster creativity, simultaneous activation of cultural representations may facilitate creative performance.
Mindful Relating: Exploring Mindfulness and Emotion Repertoires in Intimate Relationships
Authors: Wachs Karen , Cordova James V.
Published: October 2007

This study tested the theory that mindfulness contributes to greater intimate relationship satisfaction by fostering more relationally skillful emotion repertoires. A sample of married couples was administered measures of mindful awareness, emotion skills, and marital quality. We hypothesized that mindfulness would be associated with both marital quality and partners’ emotion skills and that the association between mindfulness and marital quality would be mediated by emotion repertoire skill. Findings suggested that emotion skills and mindfulness are both related to marital adjustment, and that skilled emotion repertoires, specifically those associated with identifying and communicating emotions, as well as the regulation of anger expression, fully mediate the association between mindfulness and marital quality. Theoretical implications are discussed.
The role of mindfulness in romantic relationship satisfaction and responses to relationship stress
Authors: Barnes Sean , Brown Kirk Warren , Krusemark Elizabeth , Campbell W. Keith , Rogge Ronald D.
Published: October 2007

Two studies examined the role of mindfulness in romantic relationship satisfaction and in responses to relationship stress. Using a longitudinal design, Study 1 found that higher trait mindfulness predicted higher relationship satisfaction and greater capacities to respond constructively to relationship stress. Study 2 replicated and extended these findings. Mindfulness was again shown to relate to relationship satisfaction; then, using a conflict discussion paradigm, trait mindfulness was found to predict lower emotional stress responses and positive pre‐ and postconflict change in perception of the relationship. State mindfulness was related to better communication quality during the discussion. Both studies indicated that mindfulness may play an influential role in romantic relationship well‐being. Discussion highlights future research directions for this new area of inquiry.
Self‐expansion as a mediator of relationship improvements in a mindfulness intervention
Authors: Carson James W. , Carson Kimberly M. , Gil Karen M. , Baucom Donald H.
Published: October 2007

In a recent randomized controlled trial, couples participating in a mindfulness‐based relationship enhancement program demonstrated significant improvements in relationship satisfaction and relationship distress (Carson, Carson, Gil, & Baucom, 2004). Here we report on a multiple mediation analysis of these couples’ improvements. Potential mediators included measures of couples’ engagement in exciting self‐expanding activities, couples’ ability to accept one another’s difficult characteristics, and individual partners’ ability to relax. Results indicate that to a large extent, the mindfulness‐related relationship improvements can be attributed to partners’ sense that they were participating in exciting self‐expanding activities together during the course of the intervention. The implications of these findings for future mindfulness research are discussed.
Characteristics and Clinical Practices of Rural Marriage and Family Therapists
Authors: Morris James
Published: October 2007

This report presents a subset of data collected from the American Association for Marriage and Family Therapy (AAMFT) Practice Research Network project conducted in 2002. A sample of 47 clinical members of AAMFT who indicated they practiced in a rural community provided descriptive information on demographic characteristics, training, clinical practices, and treatment of substance abuse disorders. Similarities and differences with the demographic characteristics and practice patterns of the overall sample of 285 are discussed.
A Careful Balance: Multinational Perspectives on Culture, Gender, and Power in Marriage and Family Therapy Practice
Authors: Keeling Margaret L. , Piercy Fred P.
Published: October 2007

In this study, we examined how marriage and family therapists from various countries and diverse cultural backgrounds address the intersection of gender, power, and culture in therapy. Twenty participants from 15 countries responded to an Internet survey that included several hypothetical, clinical vignettes not associated with any one particular culture or nationality. Participants selected a vignette based on its similarity to clinical situations they face in practice within their cultural contexts, and provided information about their conceptualizations of gender, culture, and power, along with treatment recommendations. We analyzed data using analytic induction and constant comparison methods. Results indicate the careful balance with which the participants work to engage clients in therapy, respect cultural values and practices, and promote equitable gender relationships.
Regulatory T cells in hepatitis C virus infection
Authors: Chang Kyong‐Mi
Published: October 2007

Hepatitis C virus (HCV) is a highly mutable RNA virus with a high propensity for chronic infection, affecting over 3% of the world's population. Persistent infection is associated with chronic hepatitis that may progress to cirrhosis and hepatocellular carcinoma over many years of infection. While cellular immune response plays a key role in viral infection, HCV persistence is associated with antiviral effector T‐cell dysfunction with increased CD4+ CD25+ Tregs and interleukin‐10+ Tr1cells, raising the possibility that the balance between antiviral effector and regulatory T‐cell subsets contributes to the outcome of HCV infection.
Clinical immune characterization of hepatitis B virus infection and implications for immune intervention: Progress and challenges
Authors: Wang Fu‐Sheng
Published: October 2007

The host immune response plays an important role in mediating hepatitis B virus (HBV) control and induction of liver damage, which determines the outcome of infection. However, interactions between HBV, the immune system, and the liver microenvironment, remain poorly understood. This review briefly outlines what we know about innate and adaptive immune responses to HBV, as well as the liver immunology in infected patients. It addresses how our knowledge of the anti‐HBV immune response might aid the development of adoptive immune therapeutic strategies against HBV. This review also highlights the challenges we are facing in understanding the cellular and molecular mechanisms bywhich the innate, adaptive and liver immune responses exert a synergistic antiviral function and influence disease progression. It concludes by addressing future directions and unanswered questions regarding the use of clinical immunotherapy. We hope this review will help hepatologists and gastroenterologists to understand the anti‐HBV immune response, as well as current challenges and potential immunotherapeutic strategies against this disease.
Role of X chromosome defects in primary biliary cirrhosis
Authors: Invernizzi Pietro
Published: October 2007

Similar to the majority of autoimmune conditions, primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by a striking female predominance; it is characterized by high titer serum autoantibodies to mitochondrial antigens, elevated serum immunoglobulin M, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. Familiarity and high concordance rates for the disease among monozygotic twins strongly support the role of genetics in the disease. Experimental efforts have been dedicated by our and other research groups to investigate the role of X chromosome abnormalities (i.e. monosomyrates and inactivation patterns) in autoimmunity. Our recent work has demonstrated enhanced X monosomy in women with PBC as well as two other female‐predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. We will review herein the most recent evidence on the role of the X chromosome in PBC onset and discuss the potential implications. Future developments of these findings will be discussed.
Environmental factors in primary biliary cirrhosis
Authors: Selmi Carlo
Published: October 2007

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease more commonly found in women (with most cases being diagnosed in the fourth to fifth decades of life) that share peculiar features. Among these, serum antimitochondrial autoantibodies (AMA), serum hyper‐immunoglobulin M, and progressive destruction of intrahepatic bile ducts are the most common clinical findings. The pathogenesis of the selective destruction of small‐duct biliary epithelial cells is still unknown, although an autoimmune mechanism appears likely due to the detection of autoreactive T and B cells. Genetic background is critical in determining susceptibility to the disease, despite the limited associations with alleles within the major histocompatibility complex. However, among other observations, incomplete concordance of the disease in monozygotic twins and epidemiology strongly support a role for environmental factors in PBC onset. Molecular mimicry by either infectious agents or chemicals has been proposed to induce breakdown of immune tolerance in genetically predisposed individuals. This hypothesis is further supported by clinical (risk factors) and experimental evidence obtained also in animal models.
Murine models of primary biliary cirrhosis: Comparisons and contrasts
Authors: Oertelt Sabine , Ridgway William M. , Ansari Aftab A. , Coppel Ross L. , Gershwin M. Eric
Published: October 2007

The absence of suitable mouse models has represented a major drawback in our understanding of early events leading to the development of primary biliary cirrhosis (PBC). The recent report of not one, but three mouse models, each with distinctive features resembling PBC, represents a major advance in PBC research and generates novel experimental perspectives. The dnTGFβRII mouse, the IL‐2Rα–/– mouse and the NOD.c3c4 mouse are all characterized by different genetic backgrounds and modifications, nonetheless all develop characteristic lymphocytic biliary infiltrates and specific antimitochondrial antibody response. Each model reflects characteristics of PBC in association with unique phenotypic differences. These three distinct models will allow a better understanding of the specific genetics involved in breaking of tolerance and progression of disease, in association with the possible definition of novel therapeutic approaches.
Nuclear envelope protein autoantigens in primary biliary cirrhosis
Authors: Worman Howard J.
Published: October 2007

Antinuclear antibodies are detectable in approximately 50% of subjects with primary biliary cirrhosis (PBC). Most clinical laboratories use indirect immunofluorescence microscopy to detect antinuclear antibodies and two labeling patterns that predominate in PBC are nuclear rim and multiple nuclear dots. Antibodies giving these patterns most often recognize nuclear envelope protein gp210 and nuclear body protein sp100, respectively. Fewer subjects with PBC have autoantibodies giving nuclear rim labeling that recognize nucleoporin p62 and LBR. Gp210 is an integral protein localized to the nuclear pore membranes. Approximately 25% of subjects with PBC have detectable serum anti‐gp210 antibodies. The vast majority of anti‐gp210 antibodies from patients with PBC recognize a stretch of only 15 amino acids in the carboxyl‐terminal tail that faces the nuclear pore complex. Enzyme‐linked immunosorbent assays using either recombinant protein expressed in bacteria or chemically synthesized polypeptides have been established to reliably detect these autoantibodies. Although initial studies did not find a correlation between the presence of anti‐gp210 antibodies and prognosis in PBC, recent data suggest that the presence of antinuclear envelope protein antibodies correlate with an unfavorable disease course and more rapid progression.
Autoimmune diseases of the liver, autoimmune hepatitis and primary biliary cirrhosis: Unfinished business
Authors: Mackay Ian R.
Published: October 2007

Autoimmune liver diseases (AILD) including autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) have attracted much attention since their discovery 50 years ago, but there remain items of unfinished business. These relate to disease susceptibility including genetic influences (HLA and non‐HLA genes, genes associated with female predisposition, and others) and environmental influences (infections, chemicals, xenobiotics and medications). Also needed is better characterization of autoantigenic molecules, particularly the anti‐F‐actin specificity characteristic of AIH, shown here to have functional effects in vitro. Deeper analysis of T‐lymphocyte function in AILD should reveal relative contributions of eachof the multiple subsets of T cells now being defined in studies on laboratory animals, CD4+, CD8+, Th1, Th2, Th17, memory subsets and regulatory subsets. Diagnostic immunology providers now offer high‐performance assay formats that call for systematic clinical assessments to achieve standardization, calibration and optimal information.
Use of hepatitis B vaccine for the treatment of chronic hepatitis B
Authors: Ishikawa Tetsuya , Kakumu Shinichi
Published: October 2007

Current therapeutic approaches to control chronic hepatitis B (CH‐B), such as administrations of interferon or nucleoside analogs, are still unsatisfactory. Vaccination with conventional hepatitis B (HB) vaccine is another therapeutic approach with lower cost and potentially long‐lasting beneficial effect. However, a response rate to vaccination therapy is not necessarily high. Therefore, combination therapy of interferon, nucleoside analogs and vaccination, would be the promising therapeutic approach that improves therapeutic effect and solves the problems of individual therapies. Herein, we report the results of the clinical trial, the combination therapy of lamivudine (LAM) and HB vaccine in patientswith B‐CH as one of the candidates for the combination therapies. The results indicate that the combination therapy of LAM and HB vaccine was more effective in regulating viral replication than the LAM monotherapy was. In addition, no adverse effect was observed in the patients given HB vaccine. This novel therapy should be further examined for the improvement of its efficacy and achievement of continuous suppression of HB virus replication.
Pathology of autoimmune liver diseases in children
Authors: Kage Masayoshi
Published: October 2007

Liver disorders are more diverse in children than in adults, and autoimmune liver diseases also develop in childhood, although rarely. The autoimmune diseases in children comprise autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). The pathology of AIH and PSC is described. Although AIH in children is rare, it occurs in early childhood, and some elementary school students have been reported to develop cirrhosis. The histology of AIH in children is essentially the same as that in adults. We analyzed eight patients with childhood AIH. Four of these patients had a high AIH score, with typical histological features of AIH, that is, interface hepatitis with infiltration of lymphocytes and plasma cells, a severe necroinflammatory reaction and rosette formation of hepatocytes. Multinucleated hepatocytes were observed in three patients. This finding seems characteristic of childhood AIH, although rarely observed in adult AIH. Clinically, the distinction between AIH and PSC is often difficult in childhood, and the overlapping of both has also been reported. PSC‐like histological features may be observed in some pediatric patients with AIH. In patients with acute onset of AIH, they show a pronounced necroinflammatory reaction in zone 3 (central area). Because an autoimmune phenomenon may occur in the early stage of childhood PSC, it is difficult to differentiate it from AIH in some patients. Some patients are diagnosed with AIH in the early stage, but with PSC during long‐term follow up. The histopathological findings of childhood PSC are the same as those of adult PSC, and are characterized by biliary‐type portal fibrosis and onion‐like periductal fibrosis in medium‐sized portal tracts.
Sclerosing cholangitis associated with autoimmune pancreatitis
Authors: Kawa Shigeyuki , Hamano Hideaki , Umemura Takeji , Kiyosawa Kendo , Uehara Takeshi
Published: October 2007

Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by irregular narrowing of the pancreatic duct, pancreatic swelling, and a favorable response to corticosteroids, in which the autoimmune mechanism is postulated in the pathogenesis. High serum immunoglobulin (Ig)G4 concentrations and various types of extrapancreatic involvement are prominent features of this disease. Sclerosing cholangitis is a major extrapancreatic lesion of autoimmune pancreatitis that has been regarded as primary sclerosing cholangitis (PSC) complicating chronic pancreatitis. Because sclerosing cholangitis associated with autoimmune pancreatitis (SC‐AIP) also favorably responds to corticosteroid therapy, it should be differentiated from PSC. Useful points regarding the differentiation between SC‐AIP and PSC are as follows: (i) PSC occurs in younger and SC‐AIP in older individuals; (ii) obstructive jaundice is more frequently seen in SC‐AIP; (iii) PSC is complicated with inflammatory bowel disease, whereas SC‐AIP is complicated with so called extrapancreatic lesions of AIP; (iv) high serum IgG4 concentrations are frequently seen in SC‐AIP; (v) a cholangiogram may differentiate the two conditions to some extent; (vi) abundant IgG4‐bearing plasma cell infiltration is seen in SC‐AIP; and (vii) steroid therapy is effective for SC‐AIP. IgG4‐related sclerosing cholangitis without pancreatic lesion may be a metachronous phenotype of SC‐AIP, and also should be differentiated from PSC. The pathogenesis of AIP and SC‐AIP remains unclear. The complement activation system of the classical pathway may be contributing in some cases.
Innate immunity in hepatitis C virus infection: Interplay among dendritic cells, natural killer cells and natural killer T cells
Authors: Kanto Tatsuya , Hayashi Norio
Published: October 2007

Sequential activation of innate and adaptive immune response is crucial for virus elimination. We thus sought to clarify the role of innate immune system in the pathogenesis of hepatitis C virus (HCV) infection. Dendritic cells (DC) sense virus infection via toll‐like receptors (TLR) or retinoic acid inducible gene‐I (RIG‐I), resulting in the secretion of type‐I interferons (IFN) and inflammatory cytokines. Blood DC consist of two subsets; myeloid DC (MDC) and plasmacytoid DC (PDC). In MDC from HCV‐infected patients, regardless of higher expression of TLR2, TLR4 and RIG‐I compared to the controls, the levels of TLR/RIG‐I‐mediated IFN‐β or TNF‐α induction are lower than those in uninfected donors. These results suggest that the signal transduction in the downstream of TLR/RIG‐I in MDC is profoundly impaired in HCV infection. In response to IFN‐α, DC are able to express MHC class‐I related chain A/B (MICA/B) and activate natural killer (NK) cells following ligation of NKG2D. Interestingly, DC from HCV‐infected patients are unresponsive to exogenous IFN‐α to enhance MICA/B expression and fail to activate NK cells. Alternatively, NK cells from HCV‐infected patients downregulate DC functions in the presence of human leukocyte antigen E‐expressing hepatocytes by secreting interleukin (IL)‐10 and transforming growth factor‐β1. Such functional alteration of NK cells in HCV infection is ascribed to the enhanced expression of inhibitory receptor NKG2A/CD94 compared to the healthy counterparts. Invariant NKT cells activated by CD1d‐positive DC secrete both T‐helper (Th)1 and Th2 cytokines, serving as immune regulators. The frequency of NKT cells in chronic HCV infection does not differ from those in healthy donors. Activated NKT cells produce higher levels of IL‐13 but comparable levels of IFN‐γ with those from healthy subjects, showing that NKT cells are biased to Th2‐type in chronic HCV infection. In conclusion, cross‐talks among DC, NK cells and NKT cells are critical in shaping subsequent adaptive immune response against HCV.
Human intrahepatic biliary epithelial cell as a possible modulator of hepatic regeneration: Potential role of biliary epithelial cell for hepatic remodeling in vivo
Authors: Komori Atsumasa , Nakamura Minoru , Fujiwara Shinsuke , Yano Koji , Fujioka Hikaru , Migita Kiyoshi , Yatsuhashi Hiroshi , Ishibashi Hiromi
Published: October 2007

Background:  During liver regeneration, the process of hepatic wound healing, a complex cascade of inflammatory signals, recruit inflammatory cells, stimulate hepatobiliary cell proliferation, direct cell migration and induce vascularization to restore tissue integrity, irrespective of its etiology. This might also be the case in cholangiopathies, in which the initial target is the branch of the intrahepatic biliary tree; that is, primary biliary cirrhosis. Previous studies about biliary wound healing focused mainly on the inducers of compensatory biliary proliferation following bile duct insult. Nevertheless, the microenvironment around biliary wound healing responses, which in turn might affect hepatic remodeling, possibly by biliary epithelial cells themselves via paracrine manner, is still less known.

Methods:  In this study, we defined the humoral factors that are released from human intrahepatic biliary epithelial cell lines (HIBEC) with human cytokine array, and reviewed their relevance according to the previous published work.

Results:  Conditioned medium of HIBEC were revealed to be rich in multiple cytokines and chemokines, including ELR+CXC chemokines, such as interleukin‐8/CXCL8, growth‐related oncoprotein (GRO), epithelial neutrophil chemoattractant (ENA‐78), known chemoattractants with a wide range of non‐leukocytic activities. Subsequent enzyme‐linked immunosorbent assay analyses confirmed that the secretion was commonly observed in various culture conditions and in both an apical and basolateral direction.

Conclusions:  Considering that some of these factors had been already reported to have direct autocrine mitogenic influence on HIBEC, these findings could further strengthen an active role of HIBEC as a modulator of hepatic regeneration, through its biological reactivity on inflamed milieu.