bluuebunny/crossref_metadata_2025 huggingface dataset:
Book‐to‐Market Components, Future Security Returns, and Errors in Expected Future Earnings
Authors: Billings Bruce K. , Morton Richard M.
Published: March 2003

This study investigates whether the ability of book‐to‐market to predict returns derives from systematic errors in the market’s expectation of future earnings. We extend Beaver and Ryan (1996, 2000) by decomposing book‐to‐market into a more persistent (bias) component and a delayed recognition (lag) component. We find that both components are related to analyst expectations of future earnings, but the lag component is the dominant factor across all forecast horizons. Similarly, we find that the lag component explains most of the inverse relation between book‐to‐market and future returns. Given that lag is constructed by regressing book‐to‐market ratios on lagged price changes, our results are consistent with the lag component capturing systematic stock price reversals. We find that the components have unique relations with subsequent earnings forecast revisions, and controlling for these relations substantially mitigates the components’ ability to predict returns. Our component‐level analysis provides insight into how expected future earnings, summarized in book‐to‐market ratios help to explain this market anomaly.
Economic Consequences of the Declining Relevance of Financial Reports
Authors: Sinha Nishi , Watts John
Published: March 2003

The proliferation of alternative information sources has reduced the relevance of corporate annual reports. This paper examines economic outcomes in an oligopolistic industry as investors become better informed but financial reports convey a smaller portion of the total information. Results show that an increase in alternate sources of information, and the resulting decline in relevance of financial reports, leads to a loss in economic efficiency despite the presence of additional information. Investors benefit, but at the expense of consumers and social welfare. Investors benefit not necessarily because the amount of information in the economy increases, but because there is a change in the channels through which the same information is communicated.
Diversification Benefits of iShares and Closed‐End Country Funds
Authors: Pennathur Anita K. , Delcoure Natalya , Anderson Dwight
Published: March 2003

We study the performance and diversification of iShares and their rival closed‐end country funds from April 1996 to December 1999. International iShares are country‐specific series of securities that track the price and yield of a specific Morgan Stanley Capital Internation (MSCI) country index and, presumably, should provide diversification benefits. Our single‐index model demonstrates that iShares replicate the home index, showing some potential for diversification. However, our two‐factor model, which isolates the “true” diversification virtues, documents that both iShares and closed‐end country fund market prices maintain considerable exposure to the U.S. market. Furthermore, the net asset value returns of the closed‐end funds demonstrate a strong home country exposure, suggesting there is no substitute for direct foreign investment.
Pricing Double‐Trigger Reinsurance Contracts: Financial Versus Actuarial Approach
Authors: Gründl Helmut , Schmeiser Hato
Published: March 2003

This article discusses various approaches to pricing double‐trigger reinsurance contracts—a new type of contract that has emerged in the area of ‘‘alternative risk transfer.’’ The potential coverage from this type of contract depends on both underwriting and financial risk. We determine the reinsurer's reservation price if it wants to retain the firm's same safety level after signing the contract, in which case the contract typically must be backed by large amounts of equity capital (if equity capital is the risk management measure to be taken). We contrast the financial insurance pricing models with an actuarial pricing model that has as its objective no lessening of the reinsurance company's expected profits and no worsening of its safety level. We show that actuarial pricing can lead the reinsurer into a trap that results in the failure to close reinsurance contracts that would have a positive net present value because typical actuarial pricing dictates the type of risk management measure that must be taken, namely, the insertion of additional capital. Additionally, this type of pricing structure forces the reinsurance buyer to provide this safety capital as a debtholder. Finally, we discuss conditions leading to a market for double‐trigger reinsurance contracts.
On (Not) “Coloring in the Outline”
Authors: Powell Linda C.
Published: March 2003

This article provides an overview and analysis of 10 studies on violence and injustice from the perspective of youth. These articles are contained in the issue of Journal of Social Issues entitled Youth Perspectives on Violence and Injustice and, in the articles, the authors offer a unique opportunity to go far beyond the current discursive terrains of youth and violence. Through a reinterpretation of what is conceptualized as normative, an expansion of the conceptualization of “youth” and an exploration of a broad range of topics, contexts and methods, the issue explores five provocative and significant critical themes. These themes are: methodology is critical; youth as subject, not object; gift and danger of a clinical approach; centrality of school? and at the intersection of social justice and development. The impact of popular culture on youth and violence and the importance of examining what adults value as “entertainment” are discussed also.
Internet Paradox Revisited
Authors: Kraut Robert , Kiesler Sara , Boneva Bonka , Cummings Jonathon , Helgeson Vicki , Crawford Anne
Published: March 2003

Kraut et al. (1998) reported negative effects of using the Internet on social involvement and psychological well‐being among new Internet users in 1995–96. We called the effects a “paradox” because participants used the Internet heavily for communication, which generally has positive effects. A 3‐year follow‐up of 208 of these respondents found that negative effects dissipated. We also report findings from a longitudinal survey in 1998–99 of 406 new computer and television purchasers. This sample generally experienced positive effects of using the Internet on communication, social involvement, and well‐being. However, consistent with a “rich get richer” model, using the Internet predicted better outcomes for extraverts and those with more social support but worse outcomes for introverts and those with less support.
The Costs of Seeking Self–Esteem
Authors: Crocker Jennifer
Published: March 2003

Americans are deeply engaged in the pursuit of self–esteem, attempting to satisfy contingencies or criteria for what makes a person worthwhile. In this article, I examine the costs of this pursuit of self–esteem for the self, in terms of competence, relatedness, and mental health, and for others. I hypothesize that external contingencies of self–worth require validation from others and are unreliable as a basis of self–esteem, and hence are associated with greater costs. Data from a longitudinal study of an ethnically diverse sample of 642 college freshman support the view that contingencies of self–worth shape how students spend their time, and the prediction that external contingencies of self–worth, especially appearance, have high costs for stress, aggression, drug and alcohol use, and symptoms of disordered eating.
MLJReviews
Authors: Liskin–Gasparro Judith E.
Published: March 2003

Books reviewed in this article:

American Association of Teachers of Spanish and Portuguese (AATSP), Spanish for Native Speakers.

Ascarrunz Gilman, Graciela, & K. Josubijuesca. Horizontes: Gramática y conversación

Rodney.Ball, Colloquial French Grammar: A Practical Guide

Carmen Benito–vessels, Horizontes: Cultura y literatura

Guiomar A. Borrás, Spanish for Business Worktext

Jeannette D. Bragger, & Donald B. Rice, Quant à moi . . .

M. Carol Brown & Kathleen C. Moore, Spanish for Life (with Atajo 3.0 CD–ROM)

Marianne Celce–Murcia & Elite Olshtain, Discourse and Context in Language Teaching.

Paul Davies & Eric Pearse, Success in English Teaching

Erika Diehl, Helen Christen, Sandra Leuenberger, Isabelle Pelvat, & Thérèse Studer, Grammatikunterricht: Alles für der Katz? Untersuchungen zum Zweitsprachenerwerb Deutsch. [Grammar Instruction: A Complete Waste of Time? Studies on the Acquisition of German as a Second Language.]

Jana Echevarria, Maryellen Vogt, & Deborah Short, Making Content Comprehensible for English Language Learners: The SIOP Model

Fe Maria De Varona Finch & Paul Summerlin, Spanish for Law Enforcement Worktext

Tammy Jandrey Hertel, Jennifer A. Zachman & Andrew Wolff, Spanish for LifeComputerized Test Bank CD.

Tammy Jandrey Hertel, Jennifer A. Zachman & Andrew Wolff, Spanish for Life Worktext

Richard Lambert & Elana Shohamy (Eds.), Language Policy and Pedagogy: Essays in Honor of A. Ronald Walton

Anne Leblans, Deborah Mcgee Mifflin, Margaret E. Mullens, Jacqueline Paskow, Yvonne Poser, & Gabriele L. Strauch, Was ist deutsch?

Nancy Levy–Konesky & Karen Daggett, Así es, 3rd ed

Nancy Levy–Konesky & Karen Daggett. Student Activities Manual

Ceil Lucas, Italia Contemporanea: Conversations with Native Speakers.

Brian MacWhinney, The CHILDES Project: Tools for Analyzing Talk. 3rd ed. Volume 1: Transcription Format and Programs

William McClure, Using Japanese: A Guide to Contemporary Usage

Shirley Melston, Margaret M. Spadinger & Sophie Knab, Spanish for Health Worktext

Howard Moss & Vanna Motta, Using Italian Synonyms

Joseph Mozur, An Advanced Russian Tabloid Reader

John Murray & Sarah Smyth, Intermediate Russian. A Grammar and Workbook

Paul Newman, The Hausa Language: An Encyclopedic Reference Grammar.

Amy Snyder Ohta, Second Language Acquisition Process in the Classroom: Learning Japanese

Robert Phillipson (Ed.), Rights to Language: Equity, Power, and Education

Kimberley Sallee, Horizontes Workbook/Lab Manual. 4th ed.

Terence Wade, A Comprehensive Russian Grammar. 2nd ed.
Perennial Budget Reform Proposals: Budget Staff versus Elected Officials
Authors: Rubin Irene S.
Published: March 2003

This article defines budget reform perennials at the national level as those that reoccur multiple times, with little chance of passage and little change from one iteration to the next. The literature has seldom examined proposals that do not pass or the staff effort that goes into keeping flawed proposals from passing. The article describes the sources of such proposals and what can conceivably be done to lessen the tension they cause. The research is based primarily on qualitative interviews and legislative testimony. Examples of reform perennials include biennial and capital budgeting.
The War on Terrorism and the Administration of the American State
Authors: Spicer Michael W.
Published: March 2003

Conditions of war lead to a style of teleocratic governance and administration that is at odds with the idea of civil association reflected in the American constitutional state. As a result, war can put our traditional notions of humanity, pluralism, and limited government at risk. In order to defend the values of civil association, public administrators should understand and appreciate the principles undergirding our constitutional system of governance and administration.
Whither Environmental Security in the Post–September 11th Era? Assessing the Legal, Organizational, and Policy Challenges for the National Security State
Authors: Durant Robert F.
Published: March 2003

What are the implications of the war on terrorism for the progress made to date and the likely future of environmental security efforts in the national security state? To put the evolving post–September 11th environmental security challenge facing the U.S. military in perspective, this article begins with a synopsis of the doctrinal, tactical, operational, and regulatory dilemmas faced by the U.S. military in the post–Cold War era. Next, the article reviews how and why the 1990s bequeathed a set of misaligned administrative systems that make existing and future progress in balancing national security with environmental and natural resources protection extremely vulnerable to shifts in the political economy surrounding this issue in the post–September 11th era. The article concludes with a review of how September 11th has affected the patterns of politics surrounding this issue since those tragic events. Despite recent increases in the defense budget, this analysis suggests that conflict over this issue will continue, rendering structural realignment a daunting challenge and further complicating the integration of national security and environmental and natural resources responsibilities in the post–September 11th era.
Optimal Valuation of Claims on Noisy Real Assets: Theory and an Application
Authors: Childs Paul D. , Ott Steven H. , Riddiough Timothy J.
Published: March 2003

A theory for valuing claims on noisy real assets is developed and applied. Central to the theory is determination of the dynamics for the best estimate of real asset value. The dynamics of the value estimate are shown to differ from the dynamics of the true asset value only in the arrival rate of information. The rate of information arrival in the value estimate can be faster or slower than information arrival in the true asset value, which can lead to unexpected outcomes in the valuation and exercise of options on noisy real assets. The theory we develop is illustrated through an application. An imperfectly competitive market for real estate development is examined, in which agents compete over the timing of lead investment. Information spillover and free–rider incentives are shown to cause significant delay in lead investment. Delay together with a competitive response once lead investment has occurred explain observed patterns of development in gentrified urban land markets and multistage development projects.
Market Timing and Capital Structure
Authors: Baker Malcolm , Wurgler Jeffrey
Published: March 2003

It is well known that firms are more likely to issue equity when their market values are high, relative to book and past market values, and to repurchase equity when their market values are low. We document that the resulting effects on capital structure are very persistent. As a consequence, current capital structure is strongly related to historical market values. The results suggest the theory that capital structure is the cumulative outcome of past attempts to time the equity market.
Investor Protection and Corporate Valuation
Authors: La Porta Rafael , Lopez‐De‐Silanes Florencio , Shleifer Andrei , Vishny Robert
Published: March 2003

We present a model of the effects of legal protection of minority shareholders and of cash‐flow ownership by a controlling shareholder on the valuation of firms. We then test this model using a sample of 539 large firms from 27 wealthy economies. Consistent with the model, we find evidence of higher valuation of firms in countries with better protection of minority shareholders and in firms with higher cash‐flow ownership by the controlling shareholder.
Interleukin-7-Dependent Production of RANTES That Correlates with Human Immunodeficiency Virus Disease Progression
Authors: Llano Anuska , Barretina Jordi , Gutiérrez Arantxa , Clotet Bonaventura , Esté José A.
Published: March 2003

There is a relationship between CD4-T-cell number and circulating interleukin 7 (IL-7) levels in human immunodeficiency virus (HIV)-positive individuals. Here, we show that IL-7 induced a dose-dependent production of CCL3 (MIP-1α), CCL4 (MIP-1β), and CCL5 (RANTES) in peripheral blood mononuclear cells (PBMC), ex vivo tonsil lymphoid tissue of HIV
−
individuals, and PBMC from HIV
+
individuals, suggesting that IL-7 may regulate β-chemokine production in vivo. In a cross-sectional study of HIV
+
individuals (
n
= 130), a weak but significant correlation between IL-7 and RANTES was noted (
r
= 0.379;
P
< 0.001). Remarkably, the correlation between IL-7 and RANTES increased to an
r
value of 0.798 (
P
< 0.001) if individuals with low CD4 cell counts (<200 cells/μl) were excluded from the analysis. Our results suggest that there is a relationship between IL-7 and the production of RANTES both in vitro and in vivo that is lost in immune-compromised patients (CD4 count of <200 cells/μl) but that could be restored by antiretroviral therapy. Unlike the case for IL-7, high levels of RANTES suggest an intermediate stage of HIV disease progression.
AN ALGORITHM FOR SCORE CALIBRATION BASED ON CUMULATIVE BAD RATES
Authors: SCHWALB OTTO , LEE TIMOTHY H. , ZHENG SHEN
Published: March 2003

In credit scoring, it is sometimes desirable to implement a new score in place of an existing score. Let Y denote the existing score and let X denote the new score. It is almost always the case that the score ranges for X and Y are different. For example, the score range for X might be 0 to 100, while the score range for Y might be 300 to 600. It follows from this difference in score ranges that a major difficulty in implementing any new score will be in training those who use the existing score to use the new score.

Score calibration is the process of constructing a calibration function g (·) in such a way that the calibrated score, g (X), is a score which mimics the behavior of Y. In applications, it is commonly found that problems in the distribution of g (X) arise as the result of the calibration process. There is a great need in production for an agorithm which automates the task of discovering these problems and correcting them. In this paper, we propose such a fully automatic algorithm. This algorithm has been successfully tested in many applications.
AGENT-BASED SYSTEM ARCHITECTURE FOR DYNAMIC AND OPEN ENVIRONMENTS
Authors: SHAKSHUKI ELHADI , GHENNIWA HAMADA , KAMEL MAHAMED
Published: March 2003

The rapid growth of the network-centered (Internet and Intranet) computing environments requires new architectures for information gathering systems. Typically, in these environments, the information resources are dynamic, heterogeneous and distributed. In addition, these computing environments are open, where information resources may be connected or disconnected at any time. This paper presents an architecture for a multi-agent information gathering system. The architecture includes three types of agents: interface, broker and resource agents. The interface agents interact with the users to fulfill their interests and preferences. The resource agents access and capture the content of the information resources. The broker agents facilitate cooperation among the information and the resource agents to achieve their desired goals. This paper provides the agents' architecture, design and implementations that enable them to cooperate, coordinate and communicate with each other to gather information in an open and dynamic environment.
Defining and evaluating impact in environmental toxicology
Authors: Bailer A. John , Oris James T. , See Kyoungah , Hughes Michael R. , Schaefer Robert
Published: March 2003

Legal mandates exist for the protection of wildlife and human health from the impacts of toxins released into the environment. To accomplish this objective, numeric environmental quality criteria are set. Toxicity test data are often analyzed in the development of such criteria. Regression‐based estimators are frequently employed to calculate the concentration associated with a specified decrement/inhibition in response relative to control conditions. Non‐monotonic concentration response patterns, often characterized as ‘hormesis’, may lead to alternative definitions of baseline responses for inhibition concentration calculations. In particular, the presence of hormesis may suggest that the definition of an impact measure is not always clear. In other cases, the impact measure may be clearly defined; however, adequate statistical study of such measures may not have been conducted. The bioconcentration factor, an index of how a toxicant accumulates within an aquatic organism relative to water, is an example where point estimates are often reported; however, reports of precision or confidence intervals are rare. A second example is the use of a no‐observed‐effect concentration, the highest concentration with responses that do not statistically differ from responses in the control group. Finally, multiple lines of evidence (e.g. toxicological, ecological, chemical, etc.) might be available to evaluate the degree of contamination at a particular site. The combination of this information to obtain overall site contamination assessment is a continuing challenge. These three issues provide a framework for discussing impact in environmental toxicology. Copyright © 2003 John Wiley & Sons, Ltd.
Suppression of EGFRvIII‐mediated proliferation and tumorigenesis of breast cancer cells by ribozyme
Authors: Luo Xunyi , Gong Xiaoqi , Tang Careen K.
Published: March 2003

EGFRvIII is a tumor specific, ligand‐independent, constitutively active variant of the epidermal growth factor receptor. Its expression has been detected in many human malignancies including breast cancer. No detectable level of EGFRvIII has, however, been observed in adult tissues, including normal breast tissues. These unique features of the EGFRvIII make it an excellent target for biologically based therapies. We have designed and generated a tumor specific ribozyme targeted to EGFRvIII. This specific EGFRvIII ribozyme is able to effectively cleave EGFRvIII mRNA under physiological conditions in a cell‐free system, but does not cleave wild‐type EGFR and other EGF‐family receptors. While expressing this EGFRvIII‐ribozyme in breast cancer cells, EGFRvIII‐ribozyme is capable of downregulating endogenous EGFRvIII expression at the mRNA and protein levels. Inhibition of proliferation was observed in EGFRvIII‐ribozyme transfectants. In addition, downregulation of EGFRvIII in breast cancer cells significantly inhibited tumor growth in athymic nude mice. Furthermore, this ribozyme has no effect on EGF‐family receptor expression or the proliferation of breast cancer cells, which do not express EGFRvIII but express wild‐type EGFR and other EGF‐family receptors. These results suggest that we have generated a tumor‐specific, biologically functional ribozyme and further demonstrate that EGFRvIII plays a significant role in breast cancer cell proliferation. The ultimate goal of this approach is to provide a potential treatment for breast cancer by specifically targeting this receptor. © 2003 Wiley‐Liss, Inc.
A novel platinum compound inhibits telomerase activity in vitro and reduces telomere length in a human hepatoma cell line
Authors: Furuta Miho , Nozawa Katsura , Takemura Masaharu , Izuta Shunji , Murate Takashi , Tsuchiya Masayuki , Yoshida Kenji , Taka Naoki , Nimura Yuji , Yoshida Shonen
Published: March 2003

Telomerase activity is detectable in most human tumors but not in most normal somatic cells or tissues. Telomerase inhibition has, therefore, been proposed as a novel and potentially selective strategy for antitumor therapy. In the present study, we found that platinum compounds, including cisplatin [cis‐diamminedichloro‐platinum (II)], strongly inhibited the activity of partially purified rat telomerase. Among the agents tested, 2,3‐dibromosuccinato [2‐(methylaminomethyl)pyridine]platinum (II) (compound E) exhibited the strongest inhibition, with an median inhibitory concentration (IC50) of 0.8 μM. The mode of inhibition was noncompetitive with either dNTPs or TS (first) primer, with Ki values estimated to be 2.3 or 3.9 μM for varied TS primer or dNTPs, respectively. Notably, cisplatin also inhibited the telomerase activity, with an IC50 of 2.0 μM. Again, the mode of inhibition was noncompetitive, with Ki values estimated as 7.3 or 8.1 μM. Preincubation of TS primer with compound E did not affect the telomerase inhibition, whereas preincubation with cisplatin caused remarkable enhancement. Treatment of a human hepatoma cell line HepG2 with a low concentration of compound E gradually reduced the telomere length, indicating that this compound was able to inhibit telomerase in living cells as well as in vitro. © 2003 Wiley‐Liss, Inc.
Tissue distribution of the mRNA for a rhesus monkey major histocompatibility class Ib molecule, Mamu‐AG
Authors: Slukvin I.I. , Watkins D.I. , Golos T.G.
Published: March 2003

We identified recently a novel major histocompatibility complex (MHC) class I locus in the rhesus monkey, Mamu‐AG , which is expressed in the placenta and encodes molecules that share unique characteristics of human HLA‐G. We established locus‐specific reverse transcription‐polymerase chain reaction (RT‐PCR) and ribonuclease protection assays to determine whether Mamu‐AG is expressed in other rhesus monkey tissues. With an RT‐PCR assay, Mamu‐AG mRNA was detected in placenta, amniotic membranes, kidney, spleen, eye, brain, lung, spinal cord, liver and occasionally heart, but was undetectable in lymph nodes, salivary glands, peripheral blood lymphocytes (PBL), large and small intestine, skeletal muscle or skin. Examination of endocrine organs demonstrated the presence of Mamu‐AG transcripts in pituitary, testes, ovary and adrenal glands but not in pancreas or thyroid. Quantitative analysis using a ribonuclease protection assay demonstrated that the highest level of Mamu‐AG mRNA expression was consistently in the placenta and amniotic membranes, while expression was moderate in a few tissues (testis, adrenal) and low to undetectable in all other tissues. These results suggest that the Mamu‐AG mRNA, like the mRNA for the human MHC class Ib gene HLA‐G, is expressed at high levels in the placenta, but also has restricted low‐level expression in other tissues.
Biotinylation of class I MHC molecules abrogates recognition by W6/32 antibody
Authors: Malik P. , Baba E. , Strominger J.L.
Published: March 2003

W6/32 is one of the most common monoclonal antibodies (mAb) used to characterize human class I major histocompatibility complex (MHC) molecules. It recognizes a conformational epitope on the intact MHC molecule containing both β2‐microglobulin (β2‐m) and the heavy chain. Labelling proteins by biotinylation is a very useful technique of for their detection, purification and analysis. A common method for biotinylating proteins is through the use of N‐hydroxysuccinimide (NHS) biotin or Sulfo‐NHS‐biotin where the free amino groups on the protein are used for coupling the biotin moiety. However, W6/32 was unable to effectively immunoprecipitate biotinylated human class I MHC molecules including the human non‐classical HLA‐G molecule. FACScan analysis confirmed that biotinylating human class I MHC and HLA‐G molecules prevents the recognition of these molecule by W6/32. In contrast, the recognition by another conformation‐dependent monoclonal antibody, ME1, specific to HLA‐B27 molecules, remained totally unaffected.
An allelic non‐histocompatibility antigen with wide tissue distribution as a marker for chimerism in pigs
Authors: Fuchimoto Y. , Huang C. , Shimizu A. , Seebach J. , Arn S. , Sachs D.h.
Published: March 2003

It is frequently useful in studies of transplantation to have available an antibody to a cell surface antigen, which is not itself responsible for transplant rejection. In this paper, we identify and describe such an antibody/antigen system in miniature swine. The monoclonal antibody, 1038H‐10‐9, was found to react to a pig allelic antigen (called PAA), found on a variety of pig cells and tissues, including peripheral blood mononuclear cells (PBMC), thymocytes, lymph node, bone marrow, and skin. Analysis for recipient sensitization against PAA was performed by in vitro cell‐mediated lympholysis (CML) assay, mixed lymphocyte reaction (MLR) assay, antibody binding studies, and skin graft rejection patterns were examined. No evidence was found to indicate detection of PAA by any of these assays of alloreactivity. We therefore conclude that PAA is an allelic swine cell surface antigen, with wide tissue distribution, and that it is not a histocompatibility antigen. It should provide a powerful tool for studies of transplantation biology in miniature swine, such as identification and quantification of chimerism following organ transplantation.
The relative frequencies of HLA‐DRB1*01 alleles in the major US populations
Authors: Collins M.M. , Tang T. , Slack R. , Sintasath D. , Hartzman R.J. , Ng J. , Hurley C.K.
Published: March 2003

The frequencies of alleles in the HLA‐DRB1*01 family were determined in each of five US populations from a database of 82,979 individuals. Individuals typed as DR1 (or DRB1*01) comprised between 7.6%–21.3% of the individuals in each population group. Fifty‐nine DR1 individuals were randomly selected from each group and subjected to high‐resolution DNA typing by polymerase chain reaction using sequence‐specific oligonucleotide probes. DRB1*0101 was the most common allele in the Caucasian, Asian/Pacific Islander, and Native American groups while the DRB1*0102 allele was found in the majority of African Americans and Hispanics. DRB1*0103 was present at a similar frequency in all populations. DRB1*0104, DRB1*0105, and DRB1*0106 alleles were not observed.
A new MICA allele with ten alanine residues in the exon 5 microsatellite
Authors: Pérez‐Rodríguez M. , Corell A. , Argüello J.R. , Cox S.T. , McWhinnie A. , Marsh S.G.E. , Madrigal J.A.
Published: March 2003

Acknowledgments:

This work is funded by the Anthony Nolan Bone Marrow Trust. We thank Dr. Gaby Fischer for technical support and critical reading of this manuscript.

The MICA and MICB genes code for protein products that have structural similarities to major histocompatibility complex (MHC) class I genes. These genes are upregulated by heat stress. They have been shown to interact with a common receptor (NKG2D/DAP10) on γδ T cells, CD8+ T cells and natural killer (NK) cells. The MICA gene has an expressed microsatellite, GCT, within the exon 5 which encodes for alanine. So far, four different repetitions of this short tandem have been reported. Also one non‐synonymous, one synonymous substitution and a 1‐bp insertion within this region have also been described. An association of Behçet’s disease with the microsatellite A9 has been reported. Here we report a novel allele with 10 GCT repetitions (A10) which was detected by reference strand mediated conformation analysis and confirmed by DNA sequencing.
The isolation and characterisation of human monoclonal HLA‐A2 antibodies from an immune V gene phage display library
Authors: Watkins N.A. , Brown C. , Hurd C. , Navarrete C. , Ouwehand W.H.
Published: March 2003

Molecular cloning techniques and V gene phage display have revolutionised the production of human monoclonal antibodies. Antibodies of a defined specificity can be obtained by selecting phage display libraries on antigen in a process known as panning. We have applied these techniques to the isolation of three HLA‐A2‐specific single chain variable domain fragments (scFv) from a patient alloimmunised by blood transfusion. Analysis of specificity with cells of HLA genotyped donors revealed the following: i) in addition to the major reactivity with HLA‐A2, cross‐reactivity with the HLA‐A28 epitope; and ii) inhibition of scFv binding to the antigen by the patients’ antibodies. The heavy chain variable genes of all three were derived from the germline gene Cos‐3, carry the hallmarks of somatic hypermutation, and are most likely derived from clonally related B cells. The light chain variable domains were encoded by DPK1 and DPK8 from the VκI family. These data show that phage display can be used to clone HLA‐specific alloantibodies that recognise the native antigen from alloimmunised patients.
Cloning and sequencing of canine MAGE cDNA
Authors: Ma Z. , Khatlani T.S. , Ohno K. , Sasaki K. , Inokuma H. , Onishi T.
Published: March 2003

Melanoma antigens (MAGE) are regarded to induce tumour‐specific immune response and thought to be potential therapeutical agents for cancer immunotherapy. We hereby report the canine MAGE cDNA cloned from the testis of a beagle dog. Canine MAGE cDNA is 1455 base pair (bp) nucleotides in length, and contains an open reading frame (ORF) of 1137 bp nucleotides encoding a protein of 378 amino acids. The predicted amino acid sequence has 22–49% of homology with other MAGE proteins. mRNA transcripts of canine MAGE were detected only in the melanoma and testis and not in other normal tissues of adult dog by reverse transcriptase‐polymerase chain reaction (RT‐PCR), indicating that the expression pattern of canine MAGE mRNA is similar to that of the MAGE family genes in tumor and normal tissues.
Identification of a new HLA‐B*39 allele: HLA‐B*3924
Authors: Cook J.T. , Day S. , Dunn P.P.J. , Welsh K.I. , Bunce M.
Published: March 2003

We have identified a new HLA‐B*39 allele through polymerase chain reaction (PCR) using sequence‐specific primers (SSP) and sequence‐based typing of exons 2 and 3. This novel allele was identified in three HLA‐identical siblings of Turkish origin. This allele only differs from HLA‐B*3903 at a unique single nucleotide substitution (T for C) at position 365 in exon 3 which results in an amino acid change in codon 98 of methionine (ATG) to threonine (ACG). The sequencing enabled the development of a monospecific PCR‐SSP reaction which can be used to discriminate between HLA‐B*3924 and other B*39 alleles.
Incomplete penetrance of MHC susceptibility genes: prospective analysis of polygenic MHC‐determined traits
Authors: Alper C.A. , Awdeh Z.
Published: March 2003

We propose an approach to understanding incomplete penetrance of disease susceptibility genes as a method of studying the underlying mechanisms of polygenic diseases. Incomplete penetrance is the failure of genetically susceptible individuals to exhibit a trait. We define as baseline penetrance that which occurs in genetically identical (monozygotic) twins of an index subject with a major histocompatibility complex (MHC)‐associated disease or trait. We consider two mechanisms for incomplete baseline penetrance: an extrinsic (environmental) trigger and an intrinsic stochastic, gene‐associated process. The latter can be detected for dominant expression because susceptibility genes in homozygotes (with their two intrinsic triggers) will be up to twice as frequently penetrant as those in heterozygotes. The extent of MHC and non‐MHC gene contribution determines differences between baseline penetrance and apparent penetrance in MHC‐identical sib pairs, sib pairs in general and MHC‐identical unrelated individuals. Inheritance patterns in families do not reveal modes of inheritance of incompletely penetrant polygenic MHC‐determined traits. A method is proposed to study such traits prospectively in persons presumed to be homozygous, heterozygous or non‐carrying for susceptibility genes by determining trait expression in homozygotes, heterozygotes or non‐carriers of trait‐associated conserved extended MHC haplotypes. The method provides direct estimates of apparent penetrance rates, modes of genetic determination, and, if the trait is dominant, the origin of penetrance. When applied to dominant MHC susceptibility gene‐determined immunoglobulin deficiencies in two populations, the ratios of affected haplotype homozygotes to heterozygotes near 2.0 were consistent with an intrinsic mechanism for baseline penetrance acting on the MHC susceptibility genes.
Wide distribution of the MICA‐MICB null haplotype in East Asians
Authors: Komatsu‐Wakui M. , Tokunaga K. , Ishikawa Y. , Leelayuwat C. , Kashiwase K. , Tanaka H. , Moriyama S. , Nakajima F. , Park M.H. , Jia G.J. , Chimge N.‐O. , Sideltseva E.W. , Juji T.
Published: March 2003

Stress‐inducible MICA (MHC class I chain‐related A) is known to bind to NKG2D, which is one of the natural killer (NK) cell receptors, and plays a role in immune surveillance. We have reported that a MICA‐MICB null haplotype is in linkage disequilibrium with HLA‐B*4801 in the Japanese population. In the haplotype, an approximately 100‐kb deletion, including the entire MICA gene, was observed and MICB possessed a premature stop codon. In this study, a multiplex polymerase chain reaction (PCR) method was developed for detecting the MICA deletion. MICB alleles were typed by PCR‐single‐strand conformation polymorphism (SSCP) method and direct sequencing. The frequency of the MICA‐MICB null haplotype was 3.7% on the average, and was strongly associated with HLA‐B48 in seven East Asian populations. It was presumed that the stop codon of MICB gene generated after the large‐scale deletion. The wide distribution of the null haplotype at polymorphic frequencies suggests that the haplotype has been conservatively maintained because of some selective advantage.
Identification of HLA‐A*2306
Authors: Cox S.T. , McWhinnie A.J. , Baker F.A. , Stubbins M.J. , Allen C.J. , Holman R. , Madrigal J.A. , Little A.‐M.
Published: March 2003

We describe a novel allele encoding HLA‐A23: A*2306, discovered in an African‐American individual, whose DNA was HLA typed as part of a quality control exercise. Direct sequencing typing identified A*2301 and A*6601 with an unexpected heterozygous peak at position 331. As position 331 is at the end of exon 2, near the priming site for the B3.6 anti‐sense sequencing primer, the sequencing data is not optimal in this region and sequencing from the sense primer is relied on. In addition the new polymorphism was not at an expected polymorphic position and could easily have been missed, leading to the assignment of A*2301. However, data from reference strand mediated conformation analysis showed distinct new mobilities from those expected for A*2301 with two different fluorescent‐labelled references, leading to the conclusion that the heterozygous peak seen at position 331 was a true variant of the A*2301 allele. A*2306 is most similar to A*2301 with 1 nucleotide difference at position 331 in exon 2 which was previously a conserved position. This mutation results in an amino acid substitution of glutamine for glutamate at residue 87 (Note).
Identification of a novel DRB1 allele, DRB1*1112, by sequence‐based DRB typing
Authors: Luo M. , Blanchard J. , Maclean I. , Brunham R.
Published: March 2003

We report here a novel DRB1 allele (DRB1*1112) identified during sequence‐based HLA‐DRB typing. Polymerase chain reaction with generic DRB primers and group‐specific primers and subsequent sequencing yielded identical results. Molecular cloning and sequencing confirmed that the new DRB1 allele is identical to DRB1*11011 and 1129 at exon 2 except for a single nucleotide substitution at codon 37, changing the codon from Tyr (DRB1*11011) or Ser (DRB1*1129) to Phe (Note).
Identification of a novel HLA‐B allele – HLA‐B*4902
Authors: Poli F. , Longhi E. , Frison S. , Scalamogna M. , Crespiatico L. , Bianchi P. , Sirchia G.
Published: March 2003

Abstract: We report herein the identification of HLA‐B*4902. This new allele was identified in a Caucasian individual serologically typed as B49. The allele codifying for this antigen was not clearly detectable with polymerase chain reaction using sequence‐specific primers (PCR‐SSP) because of an atypical amplification pattern. DNA sequencing demonstrated the presence of a new variant due to two nucleotide substitutions (from G to C and from T to C) in exon 2 at nucleotides 309 and 311 respectively. These substitutions would result in a silent mutation and in one amino acid substitution from Ile to Thr, respectively (Note).
Novel HLA‐B alleles associated with antigens in the 8C CREG
Authors: Steiner N.K. , Gans C.P. , Kosman C. , Baldassarre L.A. , Edson S. , Jones P.F. , Rizzuto G. , Pimtanothai N. , Koester R. , Mitton W. , Ng J. , Hartzman R.J. , Hurley C.K.
Published: March 2003

Abstract: This paper describes 13 novel HLA‐B locus alleles, B*0809, B*0812, B*0813, B*0814, B*14062, B*3804, B*3806, B*3914, B*3915, B*3918, B*3919, B*3920, and B*3922 which represent new patterns of known polymorphic residues.
The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations
Authors: Sánchez‐Velasco P. , Leyva‐Cobián F.
Published: March 2003

Abstract:The Caucasus and the Iberian peninsula have been connected from a linguistic (Basque and Kvartelian languages), toponimic and historic perspectives. They also represent places (e.g. Dmanisi in Georgia and Atapuerca in Northern Spain) where the oldest hominoid remains in Europe are being discovered and studied. These circumstances prompted us to study the genetic background of the Svans (living on the southern slopes of the Greater Caucasus in the Republic of Georgia) in comparison with Basques from the semi‐isolated Arratia valley as well with other Northern Spanish and Western European populations. DRB1*1101‐DQA1*0501‐DQB1*0301 and DRB1*1301‐DQA1*0103‐DQB1*0603 haplotypes were found in Svans at the highest frequency. The second most frequent three‐locus haplotypes in this population were DRB1*0701‐DQA1*0201‐DQB1*0201 and DRB1*1301‐DQA1*0103‐DQB1*0602. Furthermore, the following 5‐locus extended haplotypes were not found in other populations: A3‐B8‐DRB1*11‐DQA1*0501‐DQB1*0301, A2‐B8‐DRB1*13‐DQA1*0103‐DQB1*0603, A2‐B40‐DRB1*14‐DQA1*0104‐DQB1*0501, A2‐B51‐DRB1*08‐DQA1*0401‐DQB1*0402, A3‐B7‐DRB1*03‐DQA1*0501‐DQB1*0201 and A24‐B39‐DRB1*08‐DQA1*0401‐DQB1*0402. Other haplotypes present in Svans were also frequently observed in Northern Spain and in other Western European countries. However, haplotypes reported as characteristic for Basques were not found in the Svans. A dendrogram using HLA class II alleles places the closest genetic distance observed between Svans and Czechs, whereas Slovenes and other Mediterranean populations (Jews, Hungarians, Frenchmen, Sardinians and Greeks) have the greatest genetic distance. When both HLA class I and class II alleles from 17 populations were compared, the smallest genetic distances were with Rumanians, Czechs and Armenians. Northern Spanish populations were placed closer to each other and clearly separated from Svans. In conclusion, the Svan population shows considerable polymorphism. These observations suggest a mixture of alleles in Svans from geographically distinct areas, and probably do not support a common ancestor for these Caucasian inhabitants and people from Northern Spain.
MICA, MICB and C1_4_1 polymorphism in Crohn’s disease and ulcerative colitis
Authors: Glas J. , Martin K. , Brünnler G. , Kopp R. , Folwaczny C. , Weiss E.H. , Albert E.D.
Published: March 2003

Abstract:MICA and MICB belong to a multicopy gene family located in the major histocompatibility complex (MHC) class I region near the HLA‐B gene. They encode for MHC class I molecules, which are induced by stress factors like infection, heat shock or neoplastic transformation and which are mainly expressed on gastrointestinal epithelium. They are recognized by γδ T lymphocytes and natural killer (NK) cells. Additionally they are located within a linkage region on chromosome 6p around HLA‐B and TNFα. Thus the polymorphic MICA and MICB genes are excellent candidate genes for providing the genetic background of inflammatory bowel disease. A strong association of allele A6 of the MICA exon 5 trinucleotide microsatellite polymorphism with ulcerative colitis has been found in Japanese patients. Therefore, we have analysed the MICA exon 5 polymorphism, the MICB intron 1 dinucleotide polymorphism and in addition the tetranucleotide polymorphism C1_4_1, which is located between the MICA gene and the HLA‐B gene, in patients of Caucasoid origin with Crohn’s disease (n=94) and ulcerative colitis (n=94). In this study we could not find any associations of particular alleles of the MICA, MICB and C1_4_1 polymorphisms with Crohn’s disease or ulcerative colitis. We could also not discover any associations of specific two‐point or three‐point haplotypes with these diseases. Thus it is unlikely that the MICA and MICB genes are involved in causing susceptibility for inflammatory bowel disease, although it cannot be excluded that a weak association could be identified in a larger patient sample.
Combination of HLA‐A and HLA class II alleles controls the susceptibility to rheumatoid arthritis
Authors: Tsuchiya K. , Kimura A. , Kondo M. , Nishimura Y. , Sasazuki T.
Published: March 2003

Abstract:Two hundred and four unrelated Japanese patients with rheumatoid arthritis (RA) were typed for HLA by serological typing and DNA typing. The serological typing revealed that frequencies of HLA‐A11, DR4, DR53 and DQ4 were increased and those of DR8 and DQ1 were decreased in the patients. The DNA typing has precisely defined the disease‐associated HLA class II alleles; DRBl*0405, DQAl*03 and DQBl*0401 showed positive associations, while negative associations were found with DRBl*0803, DQAl*0103 and DQBl*0601. The risk for RA was found to be closely associated with particular amino acid sequences of DR‐beta chain, including glycine residue at the 86th position in addition to those between 70 and 74, which are known to confer binding specificity and affinity to antigenic peptides. The observation that the frequency of HLA‐A11 was increased in the DRBl*0405‐positive patients suggested the interaction of these two alleles in the susceptibility to RA. On the other hand, the frequency of DPB1*0201 was increased in the DRBl*0405‐negative patients and the frequency of HLA‐A2 was increased in the DPBl*0201‐positive patients, especially in the younger onset group. These findings suggested that the combination of HLA‐A2 and DPBl*0201 may confer the susceptibility in the DRBl*0405‐negative patients. Our results suggested the possibility that the susceptibility to RA is controlled by the interaction of HLA‐A and DRBl genes or by that of HLA‐A and DPBl genes in different patient subgroups.
EFFECTS OF HLA MISMATCHING ON GRAFT SURVIVAL IN LIVING DONOR‐KIDNEY TRANSPLANTATION
Authors: Haberal M , Emiroğlu R , Başaran Ö , Tezel E , Karakayalý H , Bilgin N
Published: March 2003

To investigate the influence of HLA match on graft survival, we evaluated 878 live‐donor and 183 cadaver‐donor kidney transplantations performed at our hospital between October 1985 and November 2001. In the 878 live‐donor cases, 273 of the donors were mothers, 131 were fathers, 281 were siblings, 28 were offspring, 89 were second‐degree relatives, and 76 were unrelated (68 spouses and eight emotionally attached friends).

The 1‐, 3‐, and 5‐year graft survival rates in the first‐degree living‐related transplantation group were 90%, 76%, and 66%, respectively. The corresponding rates in the second‐degree living‐related group were 90%, 75%, and 70%, respectively; and in the living‐unrelated group were 80%, 70%, and 60%, respectively. The 1‐, 3‐, and 5‐ year graft survival rates for the cadaveric kidney transplantations carried out at our center during this same time period were 78%, 60%, and 48%, respectively. These rates were significantly lower than those for each of the live‐donor transplantations. We analyzed graft survival in relation to HLA mismatch, and a comparison of the findings showed that 0‐mismatched cases had a statistically significant graft survival advantage over those with 1, 2, 3,4 and 5 mismatches; however, there were no significant differences between the groups with 1, 2, 3, 4 and 5 mismatches. In conclusion, even kidneys from live donors in transplantations with suboptimal donor‐recipient HLA matching show better 5‐year survival than cadaveric grafts in transplantations. These results from a single centre suggest that immunological as well as nonimmunological factors are associated with the pathogenesis of late graft loss.