bluuebunny/crossref_metadata_2025 huggingface dataset:
Web‐Based Product Development Systems Integration and New Product Outcomes: A Conceptual Framework
Authors: Sethi Rajesh , Pant Somendra , Sethi Anju
Published: March 2003

In hopes of improving the effectiveness of their new product development (NPD) processes, many firms increasingly are eager to adopt integrated web‐based NPD systems for NPD. However, few would argue that the mere use of web‐based NPD systems substantially will improve the NPD process. But we know little about how and when these systems can be used for enhancing NPD.

An organization desiring to employ the web in its NPD process can use it at varying levels of functionality and sophistication, ranging from a tool for automating manual tasks and exchanging data to a means of integrating various intra‐ and interorganizational NPD functions and processes. At higher levels of technology sophistication or integration, an organization's NPD processes will get more integrated internally, i.e., between different stages of the NPD process and with the processes of its suppliers, technology providers, etc. Such integration of both internal and external NPD processes is considered important for successful innovation. Thus, on the surface, higher levels of web‐based systems integration may seem universally desirable. However, each increasing level of integration brings with it higher costs—not only the costs of expensive technology but also costs of implementing a complicated system, redesigning intra‐ and interorganizational processes, disrupting the status quo, and spending management time and energy during implementation. Therefore, it may not be wise for firms to jump blindly on the web‐based NPD bandwagon. High levels of web‐based NPD systems integration may be created when low levels of integration may not deliver the desired results. Further, if such systems are installed without appropriate conditions within and outside the firm, it may not be possible to exploit their full potential. As such, it is important to know how much web‐based NPD systems integration is suitable for different conditions.

In this article, we develop a conceptual framework that focuses on how web‐based NPD systems integration can influence the outcome of NPD and how the relationship between systems integration and outcomes can be affected by various contextual factors. For this purpose, we draw on research in areas such as NPD, web‐based information systems, and organization theory and on many discussions we had with professionals and software vendors who deal with NPD and web‐based NPD systems. The contextual factors of interest in this framework are strategic orientation of the firm, product‐related factors, business environment, organizational factors, information technology factors, and partner‐characteristics. Managerial and research implications of the framework are discussed.
Cooperation and the Ability to Minimize the Time and Cost of New Product Development within the Spanish Automotive Supplier Industry
Authors: Martínez Sánchez Angel , Pérez Pérez Manuela
Published: March 2003

New product development (NPD) cycle time has become a strategic competitive weapon for corporations and a focus for research on product development management. Reducing NPD cycle time may create relative advantages in market share, profit, and long‐term competitiveness. This article follows recent research that already has moved beyond anecdotes and case studies to test factors empirically and variables that are associated with the company's NPD time and cost minimization abilities. One emerging research area is the impact of comprehensive lists or sets of firm variables (not project variables) on the ability to speed up NPD.

At the same time, several authors' findings suggest a contingency approach to speeding up innovation. Contingency theory argues that there is not one “best answer” to a particular problem: Instead, the appropriateness of managerial interventions is dependent on the prevailing conditions that surround that problem. On the issue of NPD, several scholars point out that cooperation accelerates learning and product development: Firms that combine resources can gain a competitive advantage over firms that are unable to do so, and this is viewed as one of the key benefits of interfirm cooperation. A firm's network of cooperations represent a valuable resource that can yield differential returns in the same way as other tangible and intangible assets such as product brands or R&D capabilities. Combining both lines of research, this study seeks to add to the growing literature and further to inform practicing managers in speeding up NPD by analyzing the relationship between cooperation and the use of some NPD firm practices.

This article shows the results of a survey of 63 Spanish automotive suppliers to test the moderation effect of cooperation in the relationship between the use of NPD firm practices and the company's NPD time and cost minimization abilities. Factor and regression analyses were used to test the article's hypotheses. It was found that high‐cooperation companies used more intensively sets of firm practices than low‐cooperation companies. It also was found that two out of four identified factors of NPD firm practices—Design‐Manufacturing Interface and Cross‐Functional Design—were related positively to the company's NPD time and cost minimization abilities in the subsample of high‐cooperation companies but not in the low‐cooperation companies. These results support late research in the area of speeding up NPD. The article discusses some implications for managers.
Government Shekels without Government Shackles? The Administrative Challenges of Charitable Choice
Authors: Kennedy Sheila Suess , Bielefeld Wolfgang
Published: March 2003

As President Bush plans to expand “Charitable Choice,” civil libertarians worry that the legislation is part of a new assault on separation of church and state. Religious Right activists demand assurances that funds will not flow to groups like the Nation of Islam or Scientologists. African American pastors in urban areas—arguably the main targets of the initiative—are concerned that “government shekels” will be accompanied by “government shackles,” that the costs and regulatory burdens accompanying collaborations with government will divert resources from client services and mute their prophetic voice.

Caught in the middle are public managers, who must make the legislation work in the face of significant administrative challenges. Those challenges occur in three areas: contracting procedures, contract administration, and evaluation. In each of these categories, political realities and constitutional constraints will significantly complicate the manager's job.
The Securities and Exchange Commission: A Small Regulatory Agency with a Gargantuan Challenge
Authors: Khademian Anne M.
Published: March 2003

Multibillion–dollar accounting scandals have brought down Enron and WorldCom, while other corporations continue to revise and restate earnings. The gradual stock market tumble has played havoc with investment portfolios of retirees, parents saving for education, small business owners, and corporate America. All eyes are on the Securities and Exchange Commission (SEC), a small, independent regulator of the securities markets with a gargantuan challenge. On the one hand, it faces great public expectations for rigorous reform of Wall Street. Politicians have mandated rules and sanctions for cleaning up the practice of outside audits and for improving the veracity of financial disclosures. Yet the public’s expectations for a vigorous market recovery are even greater. If sanctions and rules are too severe, though, reform efforts could slow capital accumulation. This special report examines the SEC’s regulatory past in order to understand the task it faces today. Management challenges posed by recent legislation are discussed, and recommendations for strengthening the SEC are presented.
Assessing the Effectiveness of Executive Order 12898: Environmental Justice for All?
Authors: Murphy–Greene Celeste , Leip Leslie A.
Published: March 2003

This article examines several federal and state laws, such as the Worker Protection Standards and the Florida Pesticide Law, to determine whether the goals of these laws are being achieved in the State of Florida. A survey based on questions pertaining to various laws was used to gather data on farm workers in three South Florida counties. Face–to–face interviews were conducted with farm workers in Palm Beach and Indian River counties, Florida, in 1997 and in Collier County, Florida, in 1999.

Overall, the findings indicate that farm workers in South Florida have been exposed to pesticides through direct or indirect spraying. The findings of the study reveal that federal and state laws—currently in place to protect the workers from pesticide exposure—are not effectively implemented, and farm workers are uninformed of the laws that exist to protect them from pesticide exposure.

The study concludes with policy recommendations that will improve the implementation and enforcement of the current laws, which are designed to protect farm workers from pesticide exposure.
The Professional Researcher as Change Agent in the Government–Performance Movement
Authors: Coplin William D. , Merget Astrid E. , Bourdeaux Carolyn
Published: March 2003

Although academic and professional publications give the impression that performance measurement is a growing government practice, in actuality the use of this technology is not as deep or as widespread as it may appear. Even when performance measures are used, governments rarely integrate them into planning, budget, personnel, and other management processes. Most professional researchers located primarily in academic institutions, but also in research and government organizations, approach performance measurement as though governmental officials, elected or otherwise, are already sold on its usefulness. Instead, they need to function as “change agents,” using a variety of strategies to gain acceptance and understanding of the strengths and limitations of performance measurement. This article draws on the authors’ experiences with the Community Benchmarks Program of the Maxwell School in Onondaga County and a review of the current literature. It suggests guidelines for professional researchers who want to increase the use of performance measures by governments at all levels.
Breaking up Is Hard to Do: The Dissolution of Judicial Supervision of Public Services
Authors: Wise Charles R. , O'Leary Rosemary
Published: March 2003

Public services in many states have been placed under federal court supervision. In our 1991 PAR article, we examined the implications of the federal judicial decisions in supervising the Kansas City Metropolitan School District for the “new triumviate” governing public services—public officials, legislators, and judges. In this article, we examine judicial decisions affecting the same school district a decade later to reveal the impact of judicial supervision on the school district and to discern the implications for policy termination. We find that, once begun, judicially mandated federal court supervision of public institutions is not readily terminated, even pursuant to the wishes of the United States Supreme Court.
Playing with Fire: The Civil Liberties Implications of September 11th
Authors: Gould Jon B.
Published: March 2003

The aftermath of September 11th has seen a worrisome rise in invasive surveillance measures. Both adopted by statute and initiated by agencies, these provisions provide unprecedented powers for government agents to investigate suspects and search individuals, whether they are directly involved in terrorism or not. The prevailing wisdom has been that the American people will accept these restrictions as the natural cost of heightened security, and initial evidence suggests the public has been willing to tolerate greater limits on civil liberties. However, over time such support will erode, leaving in place permanent restrictions on civil liberties that not only will concern Americans, but also may turn them against government officials and civic participation. Thus, contrary to many interpretations of September 11th, this article argues that the policy response has only sown the seeds for greater detachment from and dissatisfaction with government as the public becomes increasingly separated from the workings and operations of public policy.
Renegotiation of Troubled Debt: The Choice between Discounted Payoff and Maturity Extension
Authors: Harding John P. , Sirmans C.F.
Published: March 2003

Renegotiation of securitized debt contracts is generally a more efficient solution to default than foreclosure when there are significant deadweight costs associated with the enforcement of security rights. Recent literature shows that when renegotiation takes the form of discounted loan payoffs, it eliminates deadweight costs associated with the liquidation or transfer of assets. There is evidence, however, that, in practice, renegotiation of other contract terms such as maturity is a more common form of loan workout. This observation is puzzling because, in general, maturity renegotiation does not eliminate deadweight costs. We provide a partial answer to this puzzle by showing that maturity renegotiation better aligns the incentives of borrowers and lenders than does renegotiation of principal. Specifically, we find that borrowers who expect that lenders will renegotiate maturity in the event of default have less incentive to divert cash flow from the collateral during the term of the loan and less incentive to take on additional risk. If the lender’s cost of managing these standard agency problems is positively related to the magnitude of the borrower’s incentive, then maturity renegotiation will result in lower monitoring and enforcement costs.
Does Homeownership Affect Child Outcomes?
Authors: Haurin Donald R. , Parcel Toby L. , Haurin R. Jean
Published: March 2003

We study the impact of homeowning on the cognitive and behavioral outcomes of children. Using four waves of a comprehensive national panel data set, we control for many social, demographic and economic variables previously found to influence child outcomes. The data are a panel, allowing us to control for unobserved household– and child–specific factors. We use a treatment effects model to address the issue of possible sample selection bias caused by unobserved variables that influence both the parent’s choice of whether to own or rent and whether to invest in their children. We find that owning a home compared with renting leads to a 13 to 23% higher quality home environment, greater cognitive ability and fewer child behavior problems. For children living in owned homes, math achievement is up to 9% higher, reading achievement is up to 7% higher, and children’s behavioral problems are 1 to 3% lower.
Stress at Home, Peace at Work: A Test of the Time Bind Hypothesis
Authors: Brown Susan L. , Booth Alan
Published: March 2003

Objective. We test the central thesis of Hochschild’s (1997) The Time Bind: people who are unsatisfied with housework, parenting, or their marriage work more hours, or at a minimum prefer to work more hours, especially if satisfaction with work is high. Methods. Using the data from the 1987–1988 National Survey of Families and Households, we analyzed the influence of work and home satisfaction on the actual and desired work hours of 1,533 respondents who were employed, married to an employed spouse, and had one or more resident children under age 18. Results. We found that people who were more satisfied with work than home or who were dissatisfied with home life in general did not work more hours or even desire to do so. Conclusions. Contrary to Hochschild’s assertions, there was little evidence that working parents dissatisfied with home life worked more hours or desired to spend more time at work.
Momentum Trading by Institutions
Authors: Badrinath S.G. , Wahal Sunil
Published: March 2003

We document the equity trading practices of approximately 1,200 institutions from the third quarter of 1987 through the third quarter of 1995. We decompose trading by institutions into the initiation of new positions (entry), the termination of previous positions (exit), and adjustments to ongoing holdings. Institutions act as momentum traders when they enter stocks but as contrarian traders when they exit or make adjustments to ongoing holdings. We find significant differences in trading practices among different types of institutions.
Modeling Sovereign Yield Spreads: A Case Study of Russian Debt
Authors: Duffie Darrell , Pedersen Lasse Heje , Singleton Kenneth J.
Published: March 2003

We construct a model for pricing sovereign debt that accounts for the risks of both default and restructuring, and allows for compensation for illiquidity. Using a new and relatively efficient method, we estimate the model using Russian dollar‐denominated bonds. We consider the determinants of the Russian yield spread, the yield differential across different Russian bonds, and the implications for market integration, relative liquidity, relative expected recovery rates, and implied expectations of different default scenarios.
Capital Gains, Dividend Yields, and Expected Inflation
Authors: Pilotte Eugene A.
Published: March 2003

One explanation for the negative relationship between short‐horizon stock returns and inflation is that inflation proxies (inversely) for expected future real output. In this paper, I examine the possibility that inflation also proxies for variation in real price/dividend ratios (excess returns). I show that when the covariance between real price/dividend ratios and inflation is nonzero, the relationship between returns and expected inflation differs for the two components of returns: dividend yields and capital gains returns. My empirical evidence demonstrates that dividend yields and capital gains are related differently to expected inflation in U.S. and foreign markets.
APPLICATION OF SU(3) IN MESON DECAYS
Authors: Peters Klaus
Published: March 2003

The isoscalar SU(3) factors can be used to derive relations between different decay modes of one meson as well as relations between decays of different mesons of the same nonet. These relations are derived assuming the OZI rule.
INVARIANT HYDRODYNAMIC PATTERN FORMATION: FAST ROTATING DISK ELECTRODE UNDER DISSOLUTION CONDITIONS
Authors: BAUNE M. , BREUNIG-LYRITI V. , PLATH P. J.
Published: March 2003

During the dissolution of stainless steel in a highly concentrated iron(III) chloride (3.5 M) solution, patterns in the micrometer range can be observed on the surface of the rotating disk. These patterns are formed by convection vortices in the direction of hydrodynamic flow. At fast rotational speeds (2000–6000 rpm), the etched patterns are spiral in shape. By digitizing the observed patterns, the mathematical equation for the spirals can be determined and a description obtained for their invariant logarithmic shape, with an aspect ratio of [Formula: see text] for the radial and tangential velocity. A comparison with classical hydrodynamic equations for the rotating disk electrode and the analysis of previous investigations of patterns formed on slowly rotating disk electrodes provides an explanation for chemically induced invariant hydrodynamic pattern formation.
G10.3 monoclonal antibody identifies novel functional cell surface structures expressed by normal B lymphocytes and various malignant cell lines
Authors: Schiavon V. , Elhabazi A. , Agrawal S. , Tawab A. , Nikolova M. , Boumsell L. , Bensussan A.
Published: March 2003

G10.3, a unique monoclonal antibody (mAb), was produced to better characterize lymphocyte subsets. In the present study, we show that this mAb identifies 118, 83 and 51 kDa cell surface sialylated glycoproteins on the immunizing cell line YTindi. The reactivity of G10.3 mAb is restricted in normal cells to B lymphocytes, whereas within tumoral cell lines various lymphoid and non‐lymphoid cells were found positive. Interestingly, functional studies revealed that triggering G10.3 mAb reactive molecules with soluble antibody led to an inhibition of growth and to an induction of programmed cell death in tumor cell lines expressing high levels of reactive molecules.
Impaired binding of a DQ2 and DQ8‐binding HSV VP16 peptide to a DQA1*0501/DQB1*0302 trans class II heterodimer
Authors: Reichstetter S. , Kwok W.W. , Nepom G.T.
Published: March 2003

DQα and DQβtrans heterodimeric HLA‐DQ molecules form in individuals heterozygous for the DQ2 and DQ8 specificities. Unique functions and disease associations have been postulated for such trans‐dimers, which may be different from cis‐encoded DQ molecules encoded by the corresponding haplotypes. We analyzed the ability of the trans‐dimer encoded by HLA‐DQA1*0501/DQB1*0302 to bind a peptide antigen which interacts with DQ molecules encoded by both parental haplotypes. Markedly impaired binding was observed, consistent with both the use of different anchor residues and with changes in levels of DQ cis‐dimer availability for peptide binding interactions.
Human dendritic cells express a 95 kDa activation/differentiation antigen defined by CMRF‐56
Authors: Hock B.D. , Fearnley D.B. , Boyce A. , McLellan A.D. , Sorg R.V. , Summers K.L. , Hart D.N.J.
Published: March 2003

Despite the unique functions of dendritic cells (DC), only two cell surface antigens (CMRF‐44 and CD83) with relatively restricted expression on human DC have been described to date. We describe a third mAb, CMRF‐56, which recognizes another DC early activation/differentiation antigen with limited expression on other haemopoietic cell populations. Circulating blood leukocytes did not express the CMRF‐56 antigen and, following either in vitro culture or activation of PBMC populations, CMRF‐56 antigen expression was detected only on DC and a subpopulation of CD19+ lymphocytes. Circulating blood DC were CMRF‐56− but induced expression within 6 h of in vitro culture. This, together with the finding that tonsil and synovial fluid DC upregulate the antigen following short‐term in vitro culture, confirmed that CMRF‐56 recognizes an early activation antigen on DC. Isolated Langerhan’s cells, dermal DC, migratory dermal DC and monocyte derived DC (GM‐CSF/IL‐4/TNFα) also express the CMRF‐56 antigen. Antigen modulation studies demonstrated that the amount of cell surface bound CMRF‐56 and CMRF‐44 (but not CD83) mAb was dramatically reduced by short‐term incubation at 37°C. This effect was not due to internalization and the reduction in CMRF‐56 binding was a reversible, temperature‐dependent process. In contrast, the decrease in CMRF‐44 binding was irreversible, suggesting that following ligation the CMRF‐44 antigen undergoes an irreversible conformational change or shedding at 37°C. Western blotting confirmed that CMRF‐56 recognizes a previously undescribed 95 kDa activation antigen whose cellular distribution and expression kinetics overlaps with, but is clearly distinguishable from, that of the CD83 and CMRF‐44 antigens. CMRF‐56 therefore provides a useful additional marker for studies on human DC.
Limited polymorphism in the HLA‐DOA gene
Authors: Naruse T.K. , Kawata H. , Anzai T. , Takashige N. , Kagiya M. , Nose Y. , Nabeya N. , Isshiki G. , Tatsumi N. , Inoko H.
Published: March 2003

The HLA‐DO molecule, a heterodimer consisting of two novel members of the class II gene family, DOA and DOB, has recently been suggested to function as an important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA‐DM molecule. In this study, we have analyzed genetic polymorphism and allelic variation of the HLA‐DOA gene in 37 HLA class II homozygous typing cells using the direct DNA sequencing technique. As a result, we recognized at least eight allelic variations, DOA*01011, *0101201, *0101202, *0101203, *01013, *0101401, *0101402 and *01015. None of them, however, result in amino acid substitution. The HLA‐DOA gene has been identified in other mammals as well, and the nucleotide sequences were well conserved among these species. These results suggest that the DOA molecule has undergone strong selective pressure to preserve functional structure and conformation required for interaction with the DM molecule, preventing non‐synonymous amino acid substituiton Note.
Novel HLA‐A and HLA‐B alleles in South American Indians
Authors: Marcos C.Y. , Fernández‐Viña M.A. , Lázaro A.M. , Moraes M.E. , Moraes J.R. , Stastny P.
Published: March 2003

The human leukocyte antigen (HLA) complex includes the most polymorphic genes in humans. More than 600 allelic variants have been described in different populations. The HLA‐B locus has contributed the largest number of alleles. Although Native American populations display a restricted number of HLA‐alleles, many novel HLA class I alleles have been identified in indigenous communities of Central and South America. We have studied 248 unrelated individuals from three tribes of North‐East Argentina and one from South‐West Brazil, as well as 80 related individuals from the Brazilian tribe. In the course of this work, we found 8 new B‐locus alleles and 2 novel A‐locus alleles in these populations. Here we report the nucleotide sequences of A*0219, A*0222, B*3519, B*3520, B*3521, B*3912, B*4009 and B*4803 and we show their relationship with similar alleles. The new alleles B*35092 and B*3518 have been described by us in a previous paper. The possible mechanisms that may have produced these alleles over evolutionary time are discussed Note.
Identification of a new variant, HLA‐Cw*1507, differing from Cw*1502 only at the KIR‐related dimorphism of codons 77 and 80
Authors: Day S. , Van Dam M. , Buckland E. , Dunn P.P.J. , Ross J.
Published: March 2003

We describe here a novel allele, HLA‐Cw*1507, identified by polymerase chain reaction using sequence‐specific primers (PCR‐SSP) and sequence‐based typing (SBT). Cw*1507 is similar to Cw*1502 with differences at nucleotide positions 302 (A to G) and 312 (A to C) in exon 2. The substitutions observed in Cw*1507, change codon 77 from AAC (asparagine) to AGC (serine) and codon 80 from AAA (lysine) to AAC (asparagine), compared to Cw*1502. Residues 77 and 80 of HLA‐C alleles are located in the alpha 1 domain, where they can influence interaction between antigenic peptides and the T‐cell receptor. Also, the dimorphism at these residues from asparagine and lysine to serine and asparagine, respectively, are known to modulate interaction with the natural killer (NK) cell killer inhibitory receptor (KIR). The new HLA‐Cw*1507, together with Cw*1502, represents the fourth pair of HLA‐C alleles differing only at the KIR‐related dimorphic codons 77 and 80 Note.
HLA‐B*4703: sequence confirmation, serology and distribution
Authors: Darke C. , Guttridge M.G. , Street J. , Thompson J. , Thomas M.
Published: March 2003

This study has confirmed the nucleotide sequence of exons 2 and 3 of the B*4703 allele, discovered by an unusual HLA‐B47 and Bw6 serological pattern, in two subjects of Black/Japanese and Caribbean Black descent. Titration studies on 25 HLA‐B47 cross‐reactive sera, stimulated by B13, B27, B44 and B60, and nine Bw6 antisera/monoclonal antibodies, showed that the B*4703 product can be distinguished from the established HLA‐B47 specificity. The phenotypes of these donors and an International Cell Exchange donor suggests an association between B*4703 and Cw*0701/06 in Black subjects. No examples of B*4703 (or B*4702) were found in 10,194 PCR‐SSP HLA‐A,B typed Welsh Bone Marrow Donor Registry panel members indicating a phenotype frequency of <0.0098% in this primarily Northern European Caucasoid population Note.
Identification of an HLA‐A11 serological variant and its characterization by sequencing based typing
Authors: Morrell G. , Whalley J. , Stewart A. , Day S. , Lewis L. , Makar Y. , Fuggle S.V. , Ross J. , Dunn P.P.J.
Published: March 2003

We have identified an HLA‐A11 variant allele, A*1105, segregating in a Caucasoid family. The variant antigen expressed by this allele failed to cross‐react with most Caucasoid anti‐HLA‐A11 antisera tested. Sequencing based typing has been used to characterize this new allele and this showed that it has a novel mutation at a polymorphic position (502) in exon 3. In comparison with A*1101, the mutation (A→G) results in an amino acid change from positively‐charged lysine to negative glutamate and this may explain the altered HLA‐A11 serological profile exhibited by this antigen. The new allele was found in a patient with acute lymphoid leukaemia (ALL), her father and two siblings Note.
Histocompatibility antigens and alleles in Japanese haemophilia A patients with or without factor VIII antibodies
Authors: Ohta H. , Takahashi I. , Kojima T. , Takamatsu J. , Shima M. , Yoshioka A. , Saito H. , Kamiya T.
Published: March 2003

We carried out human leukocyte antigen (HLA)‐A, B, Cw, DR and DQ serological typing and HLA‐DQA1, DQB1, DRB1 and DPB1 genetic typing for 46 Japanese haemophilia A patients, including 20 who had developed an antibody to factor VIII. It appears that anti FVIII inhibitor formation is associated with the major histocompatibility complex in Japanese haemophilia A patients. Absence of HLA‐A24 is a principal risk factor for inhibitor formation in Japanese haemophilia A patients. As supplemental risk factors, HLA‐DR4.1, DQ4 and DQA1*0301=2 are positively associated with patients exhibiting inhibitor compared with normal subjects. This and previous studies show that the association between HLA antigens and the formation of inhibitor depends on race. Data of HLA typing may be useful for the recognition of groups at high risk for the possible formation of inhibitor among Japanese haemophilia A patients.
Augmentation of immune response by altered peptide ligands of the antigenic peptide in a human CD4+ T‐cell clone reacting to TEL/AML1 fusion protein
Authors: Yun C. , Senju S. , Fujita H. , Tsuji Y. , Irie A. , Matsushita S. , Nishimura Y.
Published: March 2003

The 12;21 chromosomal translocation occurs in leukemic cells from 20–30% of patients with B‐lineage childhood acute lymphoblastic leukemia, the result being the TEL/AML1 fusion gene carrying a sequence different from TEL or AML1. Because the protein newly formed by TEL/AML1 fusion is probably not tolerated by human immune system, the fusion region is a good candidate for tumor antigen expressed only in TEL/AML1‐positive leukemic cells. We established two human CD4+αβ T‐cell clones (T31.1 and Y41.2) reacting to the TEL/AML1 fusion region, from two unrelated healthy donors. In order to do this, we stimulated peripheral blood mononuclear cells with synthetic peptides corresponding to the TEL/AML1 fusion region. Both T31.1 and Y41.2 proliferated in response to TEL/AML1 fusion protein as well as to a peptide IGRIAECILGMNPSR, in the context of HLA‐DP5 and DP17, respectively, and killed B lymphoblastoid cells pulsed with the peptide. Furthermore, these T‐cell clones proliferated in response to several altered peptide ligands carrying a single residue substitution in the TEL/AML1 peptide, and some induced augmentation of proliferation and production of Th1‐type cytokines. These superagonistic altered peptide ligands can be given consideration for anti‐leukemic immunotherapy.
The relative frequencies of HLA‐A*10 alleles in five major United States ethnic populations
Authors: Bei M. , Ng J. , Slack R. , Ellis J. , Hartzman R.J. , Hurley C.K.
Published: March 2003

The frequency of each A*10 allele was determined in 5 major United States ethnic populations randomly selected from a pool containing 82,979 unrelated individuals. The phenotype frequency of A10 was 10.5% in Caucasians, 14.0% in African‐Americans, 21.1% in Asians/Pacific Islanders, 10.6% in Hispanics, and 9.8% in Native Americans. Fifty‐nine individuals who had at least one A10 antigen were randomly chosen from each ethnic group for polymerase chain reaction using sequence‐specific oligonucleotide probes (PCR‐SSOP) typing. Thirteen of sixteen known A10 alleles were identified in this pool. The most common alleles observed were: A*2601 in Caucasians (55%), Hispanics (58%), and Native Americans (45%); A*3402 in African‐Americans (34%); and A*3401 in Asians/Pacific Islanders (61%). The African‐American and Asian/Pacific Islander populations differ from all other populations in the distribution of A*10 alleles, particularly, A*2601, A*3401, and A*3402.
Virtual DNA analysis as a platform for interlaboratory data exchange of HLA DNA typing results
Authors: Helmberg W. , Zahn R. , Keller E. , Weinmair B. , Lanzer G. , Albert E.
Published: March 2003

In 1998, the German DNA Exchange offered the possibility to report typing data as virtual DNA. Participating labs have been equipped with software based on the principle of Virtual DNA Analysis (VDA). This approach allows the combination of sequence‐specific oligonucleotide (SSO), sequence‐specific primer (SSP) and sequence‐based typing (SBT) results. The use of all types of test kits has been allowed without any limitations, as long as basic sequence information on SSOs or SSPs was available, at least the sequence and the position of the detected motif on the sample DNA. Typing raw data of the actual SSO‐SSP and, if performed, SBT information was collected. Participating labs received 20 DNA samples to type. Fourteen labs returned data on 1,250 single‐locus testings. Reported data consisted of 317 SBT data, 452 SSO kits and 1,795 SSP kits with 43,312 single SSO/SSP reactivities. One hundred and twenty‐six different typing kits (unique laboratory‐specific kits, commercial kits from 7 companies) have been used. In 30 (2.4%) single‐locus testings, at least one single SSO/SSP reactivity has been false‐positive or ‐negative, thus not leading to a valid result on primary evaluation. Eight of these 30 cases were due to the presence of a new DRB1*14 allele in sample no. 2. Thirty‐five tests (2.8%) showed wrong allele assignments. This first attempt to collect raw typing data instead of typing interpretation on a larger scale shows the advantages of Virtual DNA Analysis like interlaboratory data exchange without loss of information, transparency of typing interpretation and reinterpretation of typing data with an updated allele database. The VDA format is a useful tool for workshops and bone marrow donor registries.
Lack of a strong association of CTLA‐4 exon 1 polymorphism with the susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese: an association study using a novel variation screening method
Authors: Matsushita M. , Tsuchiya N. , Shiota M. , Komata T. , Matsuta K. , Zama K. , Oka T. , Juji T. , Yamane A. , Tokunaga K.
Published: March 2003

CTLA‐4 is considered to be one of the attractive candidates for the susceptibility genes to rheumatic diseases. In the present study, the association of CTLA‐4 polymorphism with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was examined in the Japanese population using the case‐control association analysis. Polymerase chain reaction‐preferential homoduplex formation assay (PCR‐PHFA) was applied for the screening of genetic variations and for the genotyping of a large number of samples. A greater proportion of Japanese patients with RA (44%) and SLE (44%) compared with healthy individuals (37%) had exon 1 49 G/G genotype, but the difference did not reach statistical significance. However, when the patients with RA and healthy individuals were stratified according to HLA‐DRB1 alleles, a weakly significant increase of the positivity of CTLA‐4 49G allele was observed in HLA‐DRB1*0405‐positive patients (87%) compared with DRB1*0405‐positive healthy individuals (71%) (P=0.014, odds ratio=2.77). These results indicate that CTLA‐4 exon 1 polymorphism does not contribute greatly to the susceptibility to RA and SLE, at least in Japanese, although the presence of CTLA‐4 49G allele could be a minor predisposing factor for RA in HLA‐DRB1*0405‐positive individuals. In addition, PCR‐PHFA was shown to be useful for a mass screening of gene variations.
Immunogenicity of P/Q‐type calcium channel in small cell lung cancer: investigation of α1 subunit polyglutamine expansion
Authors: Black J.L. , Nelson T.R. , Snow K. , Lennon V.A.
Published: March 2003

The ectopic expression of neuronal P/Q‐type voltage‐gated calcium channels in small cell lung carcinoma (SCLC) is thought to induce anti‐synaptic autoimmunity in the paraneoplastic Lambert‐Eaton myasthenic syndrome. The gene CACNL1A4, encoding the principal (α1A) subunit of this calcium channel, is mutated in several inherited neurological disorders. One of these disorders (spinocerebellar ataxia, type 6, or SCA‐6) involves the expansion of a trinucleotide (CAG) repeat unit. We hypothesized that a somatic CAG repeat instability of this gene in neoplastic cells might generate a non‐self epitope capable of initiating autoimmunity to P/Q‐type calcium channels. We therefore analyzed the CACNL1A4 gene in SCLC lines established from metastases derived from seven individual patients (four associated with Lambert‐Eaton myasthenic syndrome, one associated with myasthenia gravis, and two not associated with neurological autoimmunity). We compared their CAG repeat numbers (determined by polymerase chain reaction (PCR) amplification followed by separation of products on a 6% polyacrylamide/8M urea gel) to published norms and to DNA from a patient with SCA‐6. The number of CAG repeats in SCLC DNA fell within a normal range whether or not the neoplasm was complicated by neurological autoimmunity. Therefore, it is unlikely that somatically unstable CAG repeat units in the gene encoding the P/Q‐type voltage‐gated calcium channel account for this tumor protein’s immunogenicity in the Lambert‐Eaton myasthenic syndrome.
A novel HLA‐B*51 allele (B*5116) identified by nucleotide sequencing
Authors: Tamouza R. , Carbonnelle E. , Schaeffer V. , Sadki K. , Abed Y. , Marzais F. , Poirier J.C. , Fortier C. , Toubert A. , Raffoux C. , Charron D.
Published: March 2003

Acknowledgments:

This work was supported by Grants from EFG and LNCC.

We report here an additional HLA‐B*51 variant designated HLA‐B*5116. Detected by an abnormal serological reactivity pattern, this variant was identified as a B*51 allele by polymerase chain reaction using sequence‐specific primers (PCR‐SSP) and characterized by nucleotide sequencing. The new variant sequence match closely with the classical HLA‐B*5101 excepted two adjacent nucleotide substitutions at positions 216 and 217 of the third exon and the subsequent Leucine to Glutamic acid change at codon 163 of the α2 domain (CTG→GAG). This new variant was not detected in three different ethnic groups (French, Algerian and Lebanese) suggesting a very rare frequency ( Note).
Dog class I gene DLA‐88 histocompatibility typing by PCR‐SSCP and sequencing
Authors: Wagner J.L. , Creer S.A. , Storb R.
Published: March 2003

The dog has been an important model for solid organ and hematopoietic stem cell transplantation, as well as for studying autoimmune diseases, the growth of malignant tumors and the immunology of vaccines. Fundamental to the continuing usage of the canine model for research is the development of molecular‐based histocompatibility typing. Previous histocompatibility methods have focused on class II genes. This study was undertaken to develop a molecular‐based histocompatibility typing method for the most polymorphic class I gene, DLA‐88. In this study, polymerase chain reaction single‐stranded conformational polymorphism was used to separate alleles, thereby allowing sequenced‐based typing.
Identification of a new DRB3*02 allelic variant (DRB3*0209) by high‐resolution sequence‐based typing
Authors: Morabito A. , Pera C. , Longo A. , Delfino L. , Ferrara G.B.
Published: March 2003

The HLA‐DRB3/B4/B5 sequence‐based typing method developed in this study in combination with PCR‐SSP, enabled us to identify a new DRB3*02 allele, that was named as DRB3*0209 (GenBank accession number AF148518). This name has been officially assigned by the WHO Nomenclature Committee in May 1999. The new allele differs from DRB3*0207 by one substitution in codon 51 from AGG to ACG and another in codon 60 from TAC to TCC, resulting in aminoacid changes from Arg→Thr (codon 51) and from Tyr→Ser (codon 60). The DRB3*0209 allele was discovered in two related North Italian families. The fact that it was present in an hemizygous situation in three members of the paternal family and in one member of the secondary related family enabled us to isolate and sequence the new DRB3 allele without cloning, to identify its association with the DRB1 locus, and to generate an Epstein‐Barr virus (EBV)‐transformed cell line, now present in our ECBR (European Collection for Biomedical Research) Cell Line Bank (
Note).
HNA‐1a, HNA‐1b, and HNA‐1c (NA1, NA2, SH) frequencies in African and American Blacks and in Chinese
Authors: Kissel K. , Hofmann C. , Gittinger F.S. , Daniels G. , Bux J.
Published: March 2003

The granulocyte antigens HNA‐1a, ‐1b, and ‐1c (formerly named NA1, NA2 and SH) which reside on the neutrophil FcγReceptor IIIb (FcγRIIIb) play a major role in immune neutropenias and pulmonary transfusion reactions. In an attempt to shed some light on the origin and history of these antigens we typed the DNA of Blacks from South Africa (n=99), and Ghana (n=27), of 56 African Americans, and of 138 Chinese from Taiwan for HNA‐1a,‐1b, and ‐1c antigens using polymerase chain reaction with sequence‐specific primers (PCR‐SSP). In African and American Blacks, the HNA‐1b antigen was more frequent than HNA‐1a (77 vs. 67% and 77 vs. 59%, respectively). In contrast, in Chinese HNA‐1a was more frequent than HNA‐1b (91 vs. 54%). We observed 3 individuals with FcγRIIIB deficiency among the 126 tested African Blacks indicating a higher frequency of FcγRIIIB deficiency in Blacks than the reported 0.1% in Europeans. In addition, the frequency of HNA‐1c in African and American Blacks (38 and 23%, respectively) was higher than the reported 5% in Europeans. Among the 57 HNA‐1c (+) Blacks, all were HNA‐1b (+) but only 26 were HNA‐1a (+) supporting the idea that the HNA‐1c antigen is the result of an additional point mutation in the allele coding for HNA‐1b. Recently, HNA‐1a, ‐1b, and ‐1c (+) Europeans have been reported to have three distinct FcγRIIIB genes. Among 26 Blacks who had been typed HNA‐1a,b,c (+) by PCR‐SSP we identified only 7 having three FcγRIIIB genes by DNA sequencing. When we sequenced the DNA of 6 HNA‐1a,b,c (+) Europeans we found 4 of the individuals had three FcγRIIIB genes. Therefore, we assume that in Africa the point mutation occurred first in the HNA‐1b allele resulting in the HNA‐1c allele and the FcγRIIIB gene duplication took place later.
Characterization of the novel allele HLA‐B*4417: implications for bone marrow transplantation
Authors: Elsner H.‐A. , Schmitz G. , Ballas M. , Lenhard V. , Blasczyk R.
Published: March 2003

Acknowledgments:

We would like to thank Sandra Reuter for excellent technical assistance. This study was in part supported by the Wilhelm Sander‐Foundation.

The identification of the novel allele HLA‐B*4417, which was found in a blood donor of Caucasian origin, is described. In the sequence analysis the new allele differs from B*4402 by three nucleotides in exon 3. At the protein level, the new allele has two residue differences compared to B*4402. Due to substantial differences with other B*44 variants a possible mismatch may impair clinical outcome of bone marrow transplantation ( Note).
Identification of six novel polymorphisms in the human corneodesmosin gene
Authors: Guerrin M. , Vincent C. , Simon M. , Ahnini R. Tazi , Fort M. , Serre G.
Published: March 2003

Psoriatic epidermis is characterised by a defective differentiation program leading to an abnormal permeability barrier and impaired desquamation. The corneodesmosin gene (CDSN) or “S” gene is a strong candidate in psoriasis susceptibility, due first to its genomic position (“S” gene, 160 kb telomeric to HLA‐C) and second to its expression and function in the epidermis. Moreover, an association between CDSN and psoriasis vulgaris was recently shown in Caucasian populations. In order to pursue the CDSN polymorphism analysis, we determined the sequence of its alleles in 14 HLA‐Cw6‐positive individuals. A 4.6 kb genomic fragment encompassing the first exon, the unique intron and the coding sequence of the second exon was amplified from 8 psoriatic patients and 6 controls. Allelic discrimination was performed by restriction fragment length polymorphism analysis. The entire coding sequence and the intron boundaries of 27 alleles were sequenced. A total of 26 dimorphic sites were found, 23 consisting in single nucleotide polymorphisms (SNPs) and 3 in triplet modifications. Five out of the 23 SNPs have not been previously reported, and among them, one causes amino‐acid exchange leading to the suppression of a potential chymotrypsin site. Among the triplet modifications, one leads to deletion of one out of five consecutive valines in the protein. The high polymorphism of the gene allowed the identification of 13 different alleles. These haplotypes will permit additional family‐based studies that could provide new genetic support for the involvement of CDSN in psoriasis susceptibility. Moreover, the establishment of an extensive catalogue of CDSN alleles will allow functional analyses of the different protein isoforms.
Platelet‐specific alloantigens in cadaveric renal transplantation. A prospective study. Effect of HPA‐5b mismatch in acute vascular rejection of renal allografts
Authors: Kekomäki S. , Kyllönen L. , Salmela K. , Koskimies S. , Kekomäki R.
Published: March 2003

Abstract:This prospective study comprised 166 renal allograft‐recipient pairs that were studied for human platelet alloantigens (HPA) 1–3 and 5, which have been shown to be expressed by adhesion molecules of the vascular endothelium. Four of the five (80%) HPA‐5a5a regraft recipients developing acute vascular rejection (AVR) had received an HPA‐5b‐incompatible graft in contrast to one of the 32 (3%) regraft recipients without rejection. The occurrence of AVR was not explained by the degree of HLA mismatches. All four regraft recipients of an HPA‐5b‐mismatched graft with AVR were HLA‐A3,B7, and the combination of HLA‐A3 and/or B7 match and an HPA‐5b‐mismatched graft was associated with AVR. No antibodies against HPA‐5b were detected in the patients with AVR of an HPA‐5b‐mismatched graft. These preliminary findings suggest that HPA‐5b is a minor histocompatibility antigen involved in the development of AVR.
Ligation of major histocompatibility complex class I antigens (MHC‐I) prevents apoptosis induced by Fas or SAPK/JNK activation in T‐lymphoma cells
Authors: Lamberth K. , Claesson M.H.
Published: March 2003

Abstract: Early apoptosis in Jurkat T‐lymphoma cells was induced by agonistic anti‐Fas Ab or by anisomycin which activates the stress kinases SAPK/JNK. Apoptosis was inhibited by ligation of major histocompatibility complex class I antigens (MHC‐I). MHC‐I ligation induced upregulation of the anti‐apoptotic Bcl‐2 protein and stabilized the mitochondrial membrane potential (Δψm). MHC‐I ligation also prevented downregulation of Bcl‐2 and destabilization of Δψm induced by anti‐Fas Ab treatment or anisomycin exposure. Studies on three different Jurkat cell mutants deficient for src p56lck, ZAP‐70 kinase, or TCR/CD3 γ‐chain showed that the cells undergo apoptosis after Fas ligation. Anisomycin exposure induced apoptosis in the src p56lck‐deficient cell line but not in the two other mutant cell lines. Simultaneous cross‐linking of MHC‐I and Fas ligation inhibited apoptosis in the ZAP‐70 kinase and the TCR/CD3 γ‐chain mutants, but did not protect the src p56lck‐deficient cells. Similarly, MHC‐I ligation did not protect anisomycin‐treated src p56lck‐deficient cells against apoptosis. These data suggest that MHC‐I‐induced inhibition of apoptosis depends on intact src p56lck activity, but not on major secondary messenger molecules associated with TCR signaling. Overall the results support the idea that signal transduction by MHC‐I molecules is involved in homeostatic processes of importance for T‐cell survival and death.