_t0 CXT0242A _vn 4.0 _pd 20080519 _t1 CXT0242A 01973975 _jn Habitat International _cr Copyright (c) 2008 Elsevier Ltd _t2 CXT0242A 01973975 00320003 _vl 32 _is 3 _pr 283-410 _dt 200809 _t3 CXT0242A 01973975 00320003 08000301 _ii S0197-3975(08)00030-1 _ii [DOI] 10.1016/S0197-3975(08)00030-1 _ty EDB _li EN _ti Editorial Board/Publication Information _pg IFC _mf [XML Cit] 08000301 _t3 CXT0242A 01973975 00320003 07000574 _ii S0197-3975(07)00057-4 _ii [DOI] 10.1016/j.habitatint.2007.08.015 _ty FLA _li EN _ti Intergenerational discounting: A case from Hong Kong _au Wong, S.K. _au Chau, K.W. _au Yiu, C.Y. _au Yu, M.K.W. _ca S.K. Wong. Department of Real Estate and Construction, The University of Hong Kong, Hong Kong _ab In debating sustainable development issues such as climate changes and nuclear waste disposal, policymakers usually base their decisions on cost-and-benefit analysis (CBA), which evaluates tradeoffs between costs and benefits spanning over a century. Fundamental to this approach is the choice of an intergenerational discount rate for a society. Observable market rates, however, are mostly available up to 30 years only (e.g. US bonds), which do not necessarily reflect the long-term discount rate for a society to deal with sustainable development. A number of studies have demonstrated that a small change in the discount rate can drastically alter the CBA's outcome. This paper seeks to unveil the market's intergenerational discount rate by analyzing a very ''long-lived'' and inheritable asset-land property. By examining a mix of lease tenures (50, 75, 99, and 999 years) and their transactions, we found that 999-year property commands a significant premium of 5.74% over 99-year property from 1992 through 2006. The premium implies an intergenerational discount rate of 4.31% p.a. on average, which is significantly lower than the intragenerational discount rate. The discount rate so unveiled would contribute to a more informed intergenerational decision analysis, such as evaluating the cost-effectiveness of environmental legislation and assessing very long-term pollution damages in court. The result also has important implications for real estate valuation practices in China, as all land in Mainland China and Hong Kong is leasehold. _la EN _kw Sustainable development _kw Discount rate _kw Land value _kw Land tenure _pg 283-292 _mf [XML Cit] 07000574 _t3 CXT0242A 01973975 00320003 07000586 _ii S0197-3975(07)00058-6 _ii [DOI] 10.1016/j.habitatint.2007.09.001 _ty FLA _li EN _ti Strategies for urban conservation: A case example of George Town, Penang _au Lee, L.M. _au Lim, Y.M. _au Nor'Aini, Y. _ca Yoke Mui Lim. School of Housing, Building and Planning, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia _ab George Town, Penang has more than 200 years of urban history and the largest collection of heritage shophouses in Southeast Asia. These heritage buildings have remained unchanged since the 1800s in spite of the lack of conservation legislation. The objective of this paper is to determine which public policy instruments have been effective in protecting the urban heritage of George Town. In particular, the role played by the Control of Rent Act, 1966, is evaluated. Upon examination of records on property transaction, rent-control records, development applications and demographic trends, no conclusive evidence was found that this Act was instrumental in protecting heritage buildings. Instead it was the unintentional effects of various development policies that saved George Town's urban heritage. _la EN _kw Heritage conservation _kw Development policies _kw Rent control _kw Penang _pg 293-304 _mf [XML Cit] 07000586 _t3 CXT0242A 01973975 00320003 99999999 _ii S0197-3975(08)00030-1 _ii [DOI] 10.1016/S0197-3975(08)00030-1 _ty EDB _li EN _ti This item will terribly crash because 99999999.xml does not exist. _pg IFC _mf [XML Cit] 08000301 _t3 CXT0242A 01973975 00320003 07000677 _ii S0197-3975(07)00067-7 _ii [DOI] 10.1016/j.habitatint.2007.11.001 _ty FLA _li EN _ti Seeking urban sustainability on the world stage _au Holden, M. _au Roseland, M. _au Ferguson, K. _au Perl, A. _ca Meg Holden. Urban Studies Programme, Simon Fraser University, 3rd Floor, 515 West Hastings Street, Vancouver, BC, Canada V6B 5K3 _ab Nearly any introduction to the ideas and actions of sustainable development includes a mention of the role played in launching the global movement by the 1992 Earth Summit in Rio de Janeiro, Brazil. International forums have been a major vehicle for the pursuit of sustainability subsequent to 1992, as well, but little attention has been paid to the contribution that these global gatherings have made to the advancement of sustainability goals. This article takes up this question, with a focus on the role that major global gatherings may be playing in the pursuit of urban sustainability, specifically. To this end, we examine outcomes from the United Nations Habitat II Forum (1996, Istanbul), the World Summit on Sustainable Development (2002, Johannesburg), the World Social Forum (2001-present, Porto Alegre), and the World Urban Forum 3 (2006, Vancouver), based on reports in the scholarly literature and, in the latter case, based on our own experience as urbanists in the host city of the World Urban Forum 3. For comparative purposes, we include in our review reflections on the contribution made by a United Nations effort towards sustainability, the Millennium Development Goals (MDGs), made without an accompanying major global gathering. While we do not find evidence of 'Rio-scale' success among either the forums or in the case of the MDGs, we report on process and structural innovations made with each forum as well as common critiques of all of them. A primary contribution that all the forums have made to the advancement of urban sustainability has been more clearly differentiating among sustainability's very different types of proponents and charting the landscape of barriers and opportunities for paradigm change towards sustainable urban futures. _la EN _kw Sustainability movement _kw Urban sustainability _kw UN Habitat _kw Rio Earth Summit _kw World Urban Forum _kw Millennium Development Goals _kw Canada _kw Sustainable development _pg 305-317 _mf [XML Cit] 07000677 _t3 CXT0242A 01973975 00320003 07000689 _ii S0197-3975(07)00068-9 _ii [DOI] 10.1016/j.habitatint.2007.11.006 _ty FLA _li EN _ti Determinants of homeownership in Malaysia _au Tan, T.-H. _ca Teck-Hong Tan. Ara Damansara, 42A Jalan PJU 1A/1H, Petaling Jaya, Selangor, Malaysia _ab The housing industry is crucial to sustainable development in Malaysia. The efficiency and effectiveness of the housing delivery system require housing provision for all. The housing industry, which had grown rapidly in the 1980s, encountered property oversupply recently. The majority of these units remain unsold for reasons beyond the price factor, ranging from poor location to unattractive houses. The main objective of this paper is to tackle property oversupply in the country by examining a detailed knowledge of home owning determinants. Homeownership should be encouraged as positive externalities of homeownership can be found in many housing surveys. Homeownership is a complex issue that is the result of many determinants, including housing characteristics (house types and property types), employment and income trends, and socio-cultural and demographic descriptors. In addition to determinants, efforts are needed to reduce regulatory barriers in the housing delivery system, which can significantly increase the cost of building houses. The government should make home financing more available and affordable by providing subsidies to low-income families and by creating incentives to save for homeownership. Efforts are also needed to extend opportunities to enhance the affordability of homeownership by liberalizing rules and regulations of Employee Provident Fund (EPF) withdrawal. _la EN _kw Housing economics _kw Externalities _kw Motivation _kw Homeownership _pg 318-335 _mf [XML Cit] 07000689 _t3 CXT0242A 01973975 00320003 07000690 _ii S0197-3975(07)00069-0 _ii [DOI] 10.1016/j.habitatint.2007.11.004 _ty FLA _li EN _ti Private space, shared space and private housing prices in Hong Kong: An exploratory study _au Chan, E.H.-W. _au So, H.M. _au Tang, B.-S. _au Wong, W.-S. _ca Bo-Sin Tang. Department of Building and Real Estate, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong _ab This exploratory study examines the relationship between internal space, shared space and private housing prices. Housing floor area is an ambiguous concept in Hong Kong because it covers a possible exaggeration of the amount of 'private space' exclusively enjoyed by the owner and an unidentifiable portion of 'public space' shared with other owners within the development. Using hedonic pricing models, this study has found that different distributions between private and shared space command different values from the housing buyers. Shared communal space generally exerts a downward pressure on housing prices. The buyers are willing to pay more for the private space and some desirable forms of communal space. A higher willingness-to-pay for the desirable attributes such as clubhouse indicates that the Hong Kong people are increasingly concerned about the quality of living space in the built environment. This study suggests a need of further research into the exact measurement and the different forms of housing space rather than simply taking the stated floor space figures for granted. _la EN _kw Open space _kw Public space _kw Living space _kw Housing _kw Hong Kong _pg 336-348 _mf [XML Cit] 07000690 _t3 CXT0242A 01973975 00320003 07000707 _ii S0197-3975(07)00070-7 _ii [DOI] 10.1016/j.habitatint.2007.11.005 _ty FLA _li EN _ti Social housing estates and sustainable community development in South Korea _au Ha, S.-K. _ca Seong-Kyu Ha. Department of Urban and Regional Planning, Chung-Ang University, 304 Shingu Villa, 551-19 Banpo 4 Dong, Seochogu, Seoul 137-807, Republic of Korea _ab The purpose of this paper is to examine the characteristics and problems of social housing estates in South Korea, and to explore sustainable community development issues. In order to examine the social housing situation, a survey of the three social housing communities in Seoul was conducted. The survey evidence demonstrates that there is a growing stigma against the poor and social exclusion. This kind of social bias is likely to escalate the construction of social housing estates, which the poor concentrates in. Residents recognized that mixing public and private housing would be an issue and problematic. Public housing was thought to have a negative impact on the neighborhood. It is important to examine why these kinds of social problems arise. Applying the concept of social sustainability to low-income communities in urban Korea requires mobilizing residents and their governments to strengthen all forms of community capital. _la EN _kw Social housing _kw Low-income communities _kw Social mix _kw Sustainable development _kw South Korea _pg 349-363 _mf [XML Cit] 07000707 _t3 CXT0242A 01973975 00320003 07000719 _ii S0197-3975(07)00071-9 _ii [DOI] 10.1016/j.habitatint.2007.11.003 _ty FLA _li EN _ti Local planning and global implementation: Foreign investment and urban development of Pudong, Shanghai _au Wu, J. _au Barnes, T. _ca Jiaping Wu. School for Social and Policy Research, Charles Darwin University, Darwin, NT 0909, Australia _ab Competitive planning programmes for global integration have been created in cities throughout developed and developing countries during the past 2 decades. In China, global aspiration planning has been characterised by the establishment of Pudong New Area of Shanghai in 1990, with a group of foreign direct investment (FDI)-oriented themed zones targeting different types of global flows. Pudong very rapidly became a focus of FDI in the city, which extended to China as a whole in the 1990s, and now is further extended to playing a global role. However, spatial planning for the themed zones in Pudong has been limited in its scope to the physical design, land use, and the pattern of transport routes. This limited role of land use planning has been inadequate to coordinate the mutual engagement between global and local factors; however, an improved mechanism for coordinating planning has not yet emerged to replace it. The competitive and entrepreneurial approach of land management in conjunction with the imperatives of global firms has effectively diminished the original plan's intention that each zone should focus on particular industries, with each of them complementing the others. _la EN _kw Global competition _kw Urban planning _kw Foreign direct investment _kw Urban development _kw Shanghai _pg 364-374 _mf [XML Cit] 07000719 _t3 CXT0242A 01973975 00320003 07000720 _ii S0197-3975(07)00072-0 _ii [DOI] 10.1016/j.habitatint.2007.11.002 _ty FLA _li EN _ti The myths and politics of housing in Hong Kong: The controversy over the demolition of the Hunghom Estate _au Chu, C. _ca Cecilia Chu. Department of Architecture, 370 Wurster Hall, University of California, Berkeley, CA 94720-1800, USA _ab This paper explores the post-handover surge of civic activism in Hong Kong by examining the controversy over the demolition of the Hunghom Estate-a government subsidized housing project that was sold to private developers during a recession in early 2004. In a departure from ''business as usual,'' the high-profile demolition was stopped 10 months later after a series of protests mobilized by environmental activists. This result was widely hailed as a triumph of corporate responsibility and environmental consciousness. By tracing the competing narratives over the course of the controversy, this paper attempts to elucidate this ''success'' story by revealing the inherent conflicts between different stakeholders, and how these narratives nevertheless share and sustain a number of long-held myths about Hong Kong's economy and housing market. It argues that these myths obscure the ongoing political choices of an interventionist administration, which maintains legitimacy by tightly controlling urban development and securing support from powerful economic actors. By connecting the various claims of the present case with historic discourses of the territory, the paper aims to shed light on the power relations embedded in the development policies that characterized Hong Kong over the colonial period, and which continues to shape the practices of housing in the present. _la EN _kw Housing policy _kw Homeownership _kw Privatization _kw Activism _kw Hong Kong _pg 375-383 _mf [XML Cit] 07000720 _t3 CXT0242A 01973975 00320003 07000732 _ii S0197-3975(07)00073-2 _ii [DOI] 10.1016/j.habitatint.2007.11.009 _ty FLA _li EN _ti Application of human development index to measurement of deprivations among urban households in Minna, Nigeria _au Sanusi, Y.A. _ca Yekeen A. Sanusi. Department of Urban and Regional Planning, School of Environmental Technology, Federal University of Technology, Minna, Nigeria _ab The human development index (HDI) as a measure of human well-being became popular with the publication of the first report on human development in 1990 by the United Nations Development Programme (UNDP). Not only has the index been accepted by academics, policy makers, governments and development agencies, it has become a means of ranking countries annually. While the HDI offers a composite index that summarises basic choices available to people, it has been criticized on many grounds. For example, it is argued that it does not capture the totality of issues that affect human well-being. Hence, efforts are being made to widen the scope of issues covered by the index. This work contributes to these efforts. The study examines housing facilities, housing adequacy, housing space and solid waste disposal as part of issues that affect human development. While the possession of these amenities by households within their dwelling units contribute to human development, their absence will constitute some form of deprivation. _la EN _kw Poverty _kw Deprivation _kw Household _kw Human development _kw Human development index _kw Composite index _pg 384-398 _mf [XML Cit] 07000732 _t3 CXT0242A 01973975 00320003 08000027 _ii S0197-3975(08)00002-7 _ii [DOI] 10.1016/j.habitatint.2008.01.004 _ty FLA _li EN _ti Making places: The role of attachment in creating the sense of place for traditional streets in Malaysia _au Shamsuddin, S. _au Ujang, N. _ca Norsidah Ujang. Faculty of Design and Architecture, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia _ab Sense of place definition includes the point where the physical element, activity and meaning are intertwined in the people experience of place. In urban design and place quality research, much has been discussed on the significance of the physical elements and activities in creating the sense of place; however, the role of place attachment as a component that gives places meaning(s) has not been adequately explored. This article is based on the main findings of a doctoral research examining attachment to traditional shopping streets in the city centre of Kuala Lumpur. Surveys and face-to-face interviews were conducted with users of the streets to investigate place attachment and its influence on place identity. The finding demonstrates that attachment to the traditional streets is strong and it influences the users' perception on the identity of the places. The streets were regarded as very important in sustaining the economic activities and meaningful in accentuating cultural diversity and self and group identity. The historical significance of the area as the earliest shopping locations in the city evoked personal and shared meanings to the long-term users who developed stronger place attachment. The paper concludes by establishing that place attachment has a significant contribution to the sense of place therefore should be considered in the design of urban places especially when redevelopment is one of the options. _la EN _kw Place attachment _kw Sense of place _kw Traditional shopping street _pg 399-409 _mf [XML Cit] 08000027 _t1 CXT0242A 01988859 _jn Human Immunology _cr Copyright (c) 2008 American Society for Histocompatibility and Immunogenetics _t2 CXT0242A 01988859 00690004 _vl 69 _is 4-5 _pr 227-320 _dt 200804/05 _t3 CXT0242A 01988859 00690004 08000608 _ii S0198-8859(08)00060-8 _ii [DOI] 10.1016/j.humimm.2008.03.004 _ty FLA _li EN _ti Strategies and technical challenges in allele level Class II typing in 2578 bone marrow transplantation donor-recipient pairs _au Williams, T.M. _au Winden, T. _au Setterholm, M. _au Vierra-Green, C.A. _au Spellman, S. _au Flesch, S. _au Awdeh, Z. _au Baxter-Lowe, L.A. _au Begovich, A.B. _au Fernandez-Vina, M. _au Hegland, J. _au Hurley, C.K. _au Johnson, D. _au Noreen, H. _au Salazar, M. _au Schmeckpeper, B. _au Yunis, E.J. _ca T.M. Williams. University of New Mexico, Albuquerque, NM, USA _ab Human leukocyte antigen typing of 2578 donor-recipient pairs whose transplantation was facilitated by the National Marrow Donor Program allowed for an in-depth analysis of the accuracy of high-volume allele level testing data. The methods employed provided allele level typing at DRB1/3/5, DQA1, DQB1, DPA1, and DPB1 using sequence-specific oligonucleotide probe hybridization (SSOPH), polymerase chain reaction (PCR) restriction fragment length polymorphism analysis, sequence specific PCR, and direct sequence-based typing (SBT). Each typing was independently tested by two laboratories in Phase 1, and in subsequent phases targeted samples were typed in duplicate by SBT to monitor typing quality. Comparison with prior transplant center typing was also evaluated. SSOPH detected discrepancies ranged from 0.6% at DPB1 to 5.1% at DQB1 in Phase 1. The majority of discrepancies, 62%, resulted from human error such as sample handling, result interpretation, or clerical errors. Alleles that are frequently discrepant have been identified in this predominantly white population. _la EN _kw Bone marrow transplantation _kw Histocompatibility antigens class II _kw HLA antigens _pg 227-234 _mf [XML Cit] 08000608 _t3 CXT0242A 01988859 00690004 08000323 _ii S0198-8859(08)00032-3 _ii [DOI] 10.1016/j.humimm.2008.01.021 _ty SCO _li EN _ti Soluble MHC class I chain-related protein B serum levels correlate with disease activity in relapsing-remitting multiple sclerosis _au Fernandez-Morera, J.L. _au Rodriguez-Rodero, S. _au Lahoz, C. _au Tunon, A. _au Astudillo, A. _au Garcia-Suarez, O. _au Martinez-Borra, J. _au Lopez-Vazquez, A. _au Rodrigo, L. _au Gonzalez, S. _au Lopez-Larrea, C. _ca Carlos Lopez-Larrea. Unidad de Histocompatibilidad y Transplantes, Hospital Universitario Central de Asturias, Oviedo, Spain _ab Recent studies demonstrated that dysregulation of NKG2D and its ligands, leading to activation of autoreactive effector cells, can trigger autoimmune diseases, but soluble forms of these ligands can downmodulate NKG2D expression in T effector cells. We investigated the presence of soluble major histocompatibility complex class I chain-related A or B (MICA or MICB) molecules in sera of multiple sclerosis (MS) patients and whether they play a role in the progression of the disease. Although soluble MICA serum levels did not differ, soluble MICB serum levels were higher in MS patients compared with controls. Moreover, the highest MICB levels were in MS patients during relapses. Using immunohistochemistry techniques, it was possible to locate MIC expression in neurons of MS demyelinating plaques that were intracellularly accumulated. Elevated soluble MICB levels exist in serum of multiple sclerosis patients related with disease activity. This may contribute to the modulation of immune response activity during relapses. _la EN _kw MICB _kw MICA _kw Multiple sclerosis _kw HLA _kw Relapsing-remitting _pg 235-240 _mf [XML Cit] 08000323 _t3 CXT0242A 01988859 00690004 08000372 _ii S0198-8859(08)00037-2 _ii [DOI] 10.1016/j.humimm.2008.02.005 _ty REV _li EN _ti Tumor-specific regulatory T cells in cancer patients _au Piersma, S.J. _au Welters, M.J.P. _au van der Burg, S.H. _ca Sjoerd H. van der Burg. Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands _ab A large body of evidence indicates that the presence of regulatory T cells (Tregs) in tumors is associated with a dampened tumor-specific immune response and a clear negative impact on survival. Many different subsets of Tregs have been identified, which all act through similar or distinct pathways to suppress tumor-specific effector cells. The observation that tumor-infiltrating Tregs are able to recognize tumor-derived antigens and can be expanded by vaccines that primarily aim at reinforcing the effector arm of the antitumor response stresses the need to study Tregs for each type of cancer targeted by immunotherapy. Current protocols enable us to isolate and culture tumor-infiltrating Tregs. Ultimately, this will not only lead to a full comprehension of the specificity and working mechanisms of Tregs but also facilitate the development of successful interventions strategies for the immunotherapy of cancer. _la EN _kw Tumor _kw Immune suppression _kw Regulatory T cell _kw Generation _kw Culture _pg 241-249 _mf [XML Cit] 08000372 _t3 CXT0242A 01988859 00690004 08000384 _ii S0198-8859(08)00038-4 _ii [DOI] 10.1016/j.humimm.2008.02.006 _ty FLA _li EN _ti Induction of immune response and anti-tumor activities in mice with a DNA vaccine encoding human mucin 1 variable-number tandem repeats _au Zhang, S. _au Zhang, H. _au Shi, H. _au Yu, X. _au Kong, W. _au Li, W. _ca Wei Kong. Vaccine Research Center, College of Life Science, Jilin University, Changchun, People's Republic of China _ab Mucin 1 (MUC1) is a tumor-associated antigen that carries the important variable-number tandem repeat (VNTR) epitopes for inducing cytotoxic T lymphocytes. Such a property makes MUC1 VNTR potentially attractive for immunotherapy. This study explored the possibility of developing an efficient anti-tumor vaccine strategy using the specific antitumor immunity induced by the MUC1 VNTR DNA vaccine combined with the adjuvant effect of a plasmid expressing murine interleukin-2 (IL-2). The results showed that the MUC1 VNTR DNA vaccine successfully induced both humoral and cellular immune responses against MUC1 VNTR in mice. The effect could be obviously enhanced by increasing the number of tandem repeats, the number of immunizations, and by co-administration of the cytokine plasmid. The growth of MUC1-expressing (MUC1^+) tumors was significantly inhibited in mice immunized with the MUC1 VNTR DNA vaccine combined with the IL-2 plasmid, both before and after tumor challenge. A much larger percentage of the immunized mice survived tumor challenge than the non-immunized mice. The combination of the MUC1 VNTR DNA vaccine and the IL-2 adjuvant plasmid provides an attractive alternative for prophylactic and therapeutic vaccinations against MUC1^+ tumors. _la EN _kw DNA vaccine _kw Tumor immunity _kw Cytotoxic T lymphocyte _kw MUC1 VNTR _kw Tumor-associated antigen _pg 250-258 _mf [XML Cit] 08000384 _t3 CXT0242A 01988859 00690004 08000098 _ii S0198-8859(08)00009-8 _ii [DOI] 10.1016/j.humimm.2008.01.020 _ty FLA _li EN _ti Overexpression of the PDCD2-like gene results in Inhibited TNF-@a production in activated Daudi cells _au Chen, Q. _au Yan, C.Q. _au Liu, F.J. _au Tong, J. _au Miao, S.L. _au Chen, J.P. _ca J.-P. Chen. Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, People's Republic of China _ab Both PDCD2 and PDCD2-like proteins have PDCD2_C terminal domains, but their functions are still unclear. After analysis of their expression in Gene Expression Omnibus, we hypothesized that they played a role in inflammation. In Daudi cells exposed to lipopolysaccharides, PDCD2-like RNA was upregulated, whereas PDCD2 was downregulated. Overexpression of PDCD2-like gene effectively attenuated tumor necrosis factor (TNF)-@a release but elevated interleukin (IL)-6 and PDCD2 expression induced by lipopolysaccharide (LPS). It is possible that both proteins have anti-inflammatory effects like IL-6. The results have implications for understanding the function of PDCD2/PDCD2-like proteins and may help in the development of novel anti-inflammatory drugs. _la EN _kw PDCD2-like _kw TNF-@a _kw PDCD2 _kw Anti-inflammation _pg 259-265 _mf [XML Cit] 08000098 _t3 CXT0242A 01988859 00690004 08000347 _ii S0198-8859(08)00034-7 _ii [DOI] 10.1016/j.humimm.2008.02.007 _ty FLA _li EN _ti Characterization of a single peptide derived from cytochrome P450 1B1 that elicits spontaneous human leukocyte antigen (HLA)-A1 as well as HLA-B35 restricted CD8 T-cell responses in cancer patients _au Kvistborg, P. _au Hadrup, S.R. _au Svane, I.M. _au Andersen, M.H. _au Straten, P.t. _ca Per thor Straten. Center for Cancer Immune Therapy, Department of Hematology, University Hospital Herlev, Herlev Ringvej 75, Denmark _ab Cytochrome P450 1B1 (CYP1B1) is widely expressed in human malignancies, but silent in most normal tissues. Importantly, the protein is believed to play an important role in the survival and growth of cancer cells in a stressed environment, e.g., as a result of hypoxia or chemotherapy. Thus, targeting of CYP1B1 represents a potentially successful strategy in the treatment of metastatic cancer, e.g., by therapeutic vaccination. Herein, we describe the characterization of a novel peptide from the CYP1B1 protein (CYP240), which is spontaneously recognized by CD8 T cells in cancer patients. Interestingly, the peptide binds to both human leukocyte antigen (HLA)-A1 and HLA-B35. Hence, peripheral blood lymphocytes from a total of 49 cancer patients (25 melanoma, 13 RCC, and 11 breast cancer; 41 HLA-A1 positive, 8 HLA-B35 positive) were analyzed for reactivity taking advantage of the EliSpot assay. Rare but strong responses were detected in HLA-A1-positive patients, and more frequent responses were detected in HLA-B35-positive patients. No reactivity against the peptide could be detected in healthy donors. Furthermore, we demonstrated that peptide-specific T cells were able to lyze target cells presenting the peptide on the surface. The characterized CYP240 peptide presented herein opens the avenue for more broader recruitment of patients in vaccination trials targeting CYB1B1. _la EN _kw Tumor associated antigen (TAA) _kw CD8 T cell _kw Cytochrome P450 1B1 _kw Cancer _kw HLA-A1 _kw HLA-B35 _pg 266-272 _mf [XML Cit] 08000347 _t3 CXT0242A 01988859 00690004 08000505 _ii S0198-8859(08)00050-5 _ii [DOI] 10.1016/j.humimm.2008.03.002 _ty SCO _li EN _ti Association between MBL2 gene functional polymorphisms and high-risk human papillomavirus infection in Brazilian women _au Guimaraes, V. _au Guimaraes, R. _au Brandao, L. _au Baldez da Silva, M.F.P.T. _au Milanese, M. _au Segat, L. _au Castelletti, H. _au Bruneska, D. _au de Lima Filho, J.L. _au de Freitas, A.C. _au Arraes, L.C. _au Rocha, C. _au Crovella, S. _ca Ludovica Segat. Instituto Materno Infantil Prof. Fernando Figueira, Recife, Brazil _ab We studied the association between high-risk human papillomavirus (HPV) infection and MBL2 functional polymorphisms in a group of 180 high-risk HPV-infected women and 180 healthy control subjects. The most frequent high-risk HPV genotypes were 16 (47.2%), 31 (11.7%), 33 (5%), and 18 (2.2%), respectively. Of the 180 HPV-infected women, 99 presented with uterine cervical cancer and 81 did not. No differences in MBL2 genotype or in allelic or haplotype frequencies were found between HPV patients who developed cervical uterine cancer and those who did not. When considering combined genotypes grouped according to MBL production (designated as high, low, and deficient producers), we detected a significant difference between healthy controls and high-risk HPV-positive patients, the latter group showing increased frequencies of deficient-producer genotypes (14.4% vs 9.4% in the healthy control group, corrected p = 0.04). In conclusion, a correlation between MBL2 polymorphisms and high-risk HPV infection was found in this study. _la EN _kw MBL2 _kw High- and low-risk HPV genotypes _kw Genetic polymorphisms _kw Cervical uterine cancer _kw Brazilian women _kw Innate immunity _pg 273-278 _mf [XML Cit] 08000505 _t3 CXT0242A 01988859 00690004 08000414 _ii S0198-8859(08)00041-4 _ii [DOI] 10.1016/j.humimm.2008.03.001 _ty FLA _li EN _ti Intron 4 a/b polymorphism of the endothelial nitric oxide synthase gene is associated with both type 1 and type 2 diabetes in a genetically homogeneous population _au Galanakis, E. _au Kofteridis, D. _au Stratigi, K. _au Petraki, E. _au Vazgiourakis, V. _au Fragouli, E. _au Mamoulakis, D. _au Boumpas, D.T. _au Goulielmos, G.N. _ca George N. Goulielmos. Laboratory of Internal Medicine, Medical School, University of Crete, Heraklion, Crete, Greece _ab Current classifications of diabetes distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D), however recent evidence highlights overlap between T1D and T2D. Earlier studies have suggested altered nitric oxide (NO) metabolism in both T1D and T2D. In the present case-control study, we investigated whether the endothelial NO synthase gene intron 4 a/b polymorphism is associated with T1D and T2D in the island of Crete, a well-defined area with genetically homogeneous population. Mutated allele ''a'' was more common in individuals with both T1D and T2D than in controls (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.06-2.77, p = 0.013; and OR = 1.50, 95% CI = 0.930-2.42, p = 0.047, respectively). Mutated genotype (a/a or a/b) was more common in individuals with T1D than in nondiabetic individuals (OR = 1.93, 95% CI = 1.12-3.32, p = 0.008); this increased frequency was also observed for T2D, although not at a significant level (OR = 1.38, 95% CI = 0.802-2.37). No difference was found in the frequency of mutated allele a or mutated genotype (a/a or a/b) between T1D and T2D populations. In conclusion, our results indicate that allele a of the intron 4 endothelial NO synthase gene is associated with susceptibility to both T1D and T2D and may represent a common genetic factor for diabetes. _la EN _kw Endothelial nitric oxide synthase gene _kw Type 1 diabetes _kw Type 2 diabetes _kw Gene polymorphisms _kw Genetic background _pg 279-283 _mf [XML Cit] 08000414 _t3 CXT0242A 01988859 00690004 08000402 _ii S0198-8859(08)00040-2 _ii [DOI] 10.1016/j.humimm.2008.02.004 _ty SCO _li EN _ti Polymorphism and linkage disequilibrium of immunoglobulin-like transcript 3 gene _au Chang, C.C. _au Silvia, E.A. _au Ho, E.K. _au Vlad, G. _au Suciu-Foca, N. _au Vasilescu, E.R. _ca Chih-Chao Chang. Department of Pathology, Columbia University, New York, NY, USA _ab Immunoglobulin-like transcript 3 (ILT3) is an inhibitory receptor molecule expressed by dendritic cells, monocytes, and endothelial cells. Upon upregulation of ILT3 expression, antigen presenting cells (APCs) become tolerogenic, triggering the differentiation of antigen-specific CD8^+ and CD4^+ regulatory T cells. To analyze the polymorphism of ILT3, we screened DNA from a panel of 150 healthy subjects for single nucleotide polymorphisms (SNPs) within genomic region encoding the extracellular domain (exons 1-8). Here we report the identification of 15 SNPs, including nine nonsynonymous, three synonymous base-pair substitutions, and three intronic, including one deletion polymorphism within 3.6 kb of the ILT3 genomic region. Analysis of three physically linked SNP in healthy individuals indicates that c.356-41-46del, a 6-base-pair (bp) deletion located in intron 3/4, is predominantly associated with c.678A allele, a nonsynonymous SNP located in exon 5. Linkage studies in five nuclear families showed that these two minor alleles co-segregate. Our results demonstrate that ILT3 is highly polymorphic and may be associated with susceptibility to immune disorders. _la EN _kw Polymorphism _kw Linkage disequilibrium _kw Immunoglobulin-like transcript 3 _kw Genotype _kw Haplotype _pg 284-290 _mf [XML Cit] 08000402 _t3 CXT0242A 01988859 00690004 08000396 _ii S0198-8859(08)00039-6 _ii [DOI] 10.1016/j.humimm.2008.02.003 _ty FLA _li EN _ti Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on genotypic context: Association of DPB1 and HLA class I loci among DR3- and DR4-matched Italian patients and controls _au Noble, J.A. _au Martin, A. _au Valdes, A.M. _au Lane, J.A. _au Galgani, A. _au Petrone, A. _au Lorini, R. _au Pozzilli, P. _au Buzzetti, R. _au Erlich, H.A. _ca Janelle A. Noble. Childrens Hospital Oakland Research Institute, Oakland, CA, USA _ab Patients with high-risk human leukocyte antigen (HLA)-DR-DQ genotypes for type 1 diabetes (T1D) were compared with HLA-matched controls to evaluate T1D risk for other HLA loci, including HLA-A, -B, -Cw, and DPB1. Patients (n = 133) with high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio (Rome) region of Italy. Screening of more than 9000 patients from the Lazio region and northern Italy yielded 162 controls with high-T1D-risk haplotypes. Although the overall distributions did not differ significantly, allele frequency differences were discovered between the controls from Lazio and controls from northern Italy for some alleles previously determined to affect T1D risk, such as A*3002, DPB1*0301, and DPB1*0402. Therefore, Lazio patient data were compared both with the Lazio subset of controls (n = 53) and with the entire group of controls for association analyses. Significant allele frequency differences between patients and DR-DQ-matched controls existed for specific alleles at all loci. Data for the DR3/DR3 subset of patients and controls demonstrated an increase of Cw*0702 in patients. Compared with controls, reduced patient frequencies were seen for several alleles, including A*0101, B*0801, and Cw*0701, all on the highly conserved, extended DR3 haplotype known as 8.1 in DR3/DR3, but not DR3/DR4, subgroup. DPB1*0101, often reported on 8.1 haplotypes, was also less frequent in DR3/DR3 patients than controls. Analysis of family-based data from the HBDI repository was consistent with the observed results from the Italian patients, indicating the presence of a T1D-protective locus at or near A*0101 and a second T1D-protective locus at or near DPB1*0101. These data indicate that T1D risk conferred by the 8.1 haplotype is genotype dependent. _la EN _kw HLA class I _kw DPB1 _kw Type 1 diabetes DR3 haplotype _kw Disease association _pg 291-300 _mf [XML Cit] 08000396 _t3 CXT0242A 01988859 00690004 08000360 _ii S0198-8859(08)00036-0 _ii [DOI] 10.1016/j.humimm.2008.02.002 _ty FLA _li EN _ti Interleukin-6 gene variation in Spanish patients with immunoglobulin-A deficiency _au Lopez-Mejias, R. _au Martinez, A. _au del Pozo, N. _au Fernandez-Arquero, M. _au Ferreira, A. _au Urcelay, E. _au Fontan, G. _au de la Concha, E.G. _au Nunez, C. _ca Concepcion Nunez. Department of Clinical Immunology, Hospital Clinico San Carlos, Madrid, Spain _ab Selective immunoglobulin-A deficiency (IgAD) is the most common immunodeficiency in Caucasian populations. Genetic factors are important in its etiology; however human leukocyte antigen (HLA) genes, which explain 40% of the genetic risk for IgAD, are the only susceptibility factors commonly agreed upon at this time. Because interleukin-6 (IL-6) plays an important role in B-lymphocyte differentiation from plasma cells, we aimed to address the IL-6 genetic influence on IgAD susceptibility. We performed a case-control study that included 305 Caucasian Spanish IgAD patients and 529 ethnically matched healthy control subjects, as well as a familial study with 128 IgAD trios. We genotyped the functional promoter polymorphism -174G>C and nine additional single nucleotide polymorphisms. For the case-control analyses the @g^2 test or Fisher's exact test were used, and for the family study the transmission disequilibrium test was used. We observed an increased frequency of the -174C allele in IgAD patients (p = 0.005, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.12-2.04) and a protective effect of the rs2069849_C allele (p = 0.007, odds ratio = 0.29, 95% CI = 0.09-0.76). In conclusion, we described for the first time an association between IL6 polymorphisms and IgAD. Although it is not clear which genetic variants are causing susceptibility/protection, this intriguing finding is remarkable because of the role of IL-6 in antibody production. _la EN _kw Interleukin-6 _kw Selective IgA deficiency _kw Disease susceptibility _kw Polymorphism _pg 301-305 _mf [XML Cit] 08000360 _t3 CXT0242A 01988859 00690004 08000591 _ii S0198-8859(08)00059-1 _ii [DOI] 10.1016/j.humimm.2008.03.003 _ty FLA _li EN _ti Haplotype analysis of the endothelial nitric oxide synthase gene in asthma _au Holla, L.I. _au Jurajda, M. _au Pohunek, P. _au Znojil, V. _ca Lydie Izakovicova Holla. Department of Pathophysiology, Medical Faculty, Masaryk University Brno, Brno, Czech Republic _ab Nitric oxide (NO) is an important mediator of physiologic processes in the airways. Evidence exists that genetic factors affect NO formation and contribute to the pathophysiology of asthma. The aims of this study were to determine the endothelial NO synthase (eNOS) haplotypes in Czech asthmatics and control subjects and examine their relation to asthma. We analyzed a total of six polymorphisms. Two SNPs in the promoter (C-786T and C-691T), two variants in the introns (27-bp repeat in intron 4 and G11T in intron 23), and two others in the exons (C774T in exon 6 and G894T in exon 7) were genotyped in 610 subjects (asthma, n = 294; healthy controls, n = 316), and a case-control association study was conducted. No significant differences in allele or genotype frequencies for individual polymorphisms were observed between patients with asthma and controls after correction for multiple comparisons. Nevertheless, a G to T exchange in intron 23 was related with specific sensitization for feather (p = 0.008, p"c"o"r"r < 0.05). However, the common haplotype -786T/-691C/27-bp 5 repeat variant/774C/894G/11T was associated with lower risk of asthma (p = 0.001, p"c"o"r"r < 0.05, odds ratio = 0.58, 95% confidence interval = 0.46-0.73). These findings suggest that endothelial NOS variants may be one of the factors participating in protection or susceptibility to asthma in our population. _la EN _kw Asthma _kw Gene _kw Nitric oxide synthase _kw NOS3 _kw Polymorphisms _pg 306-313 _mf [XML Cit] 08000591 _t3 CXT0242A 01988859 00690004 0800061X _ii S0198-8859(08)00061-X _ii [DOI] 10.1016/j.humimm.2008.04.001 _ty SCO _li EN _ti Nomenclature for Factors of the HLA System, Update January 2008 _au WHO Nomenclature Committee for Factors of the HLA System _au Marsh, S.G.E. _ca Steven G.E. Marsh. Anthony Nolan Research Institute, Royal Free Hospital, Pond Street, London NW3 3QG, United Kingdom _pg 314-316 _mf [XML Cit] 0800061X