bluuebunny/crossref_metadata_2025 huggingface dataset:
Queueing performance estimation for general multifractal traffic
Authors: Dang Trang Dinh , Molnár Sándor , Maricza István
Published: March 2003

We present an approximation for the tail asymptotics in an infinite capacity single server queue serviced at a constant rate driven by generalmultifractalinput process. We show that in the special and important case of themonofractalfractional Brownian motion input traffic our result gives the well‐known Weibullian tail. We prove that the class of Gaussian processes with scaling properties is in the class of monofractal processes and we derive the related characterization functions. Our formula in the case of Gaussian input processes also gives a queueing result which is in good agreement with the theory of Gaussian processes. Applying the approximation we provide a new practical method for queueing performance estimation of general multifractal traffic. The validation of the method based on both analysis of simulations and measured network traffic have also been presented. Copyright © 2003 John Wiley & Sons, Ltd.
Performance issues of bandwidth management in ATM networks
Authors: Bouras Christos , Chantzi Chryssi , Kapoulas Vaggelis , Panagopoulos Alexandros , Sampraku Ioanna , Sevasti Afrodite
Published: March 2003

In our days, efficient management of the available network resources becomes a critical issue, both from a functional point of view (so that users can be provided with the bandwidth they need), and an economical point of view (so that carriers can satisfactorily and efficiently serve as many customers as possible and at the same time increase their revenue). In this paper we consider a bandwidth control scheme (i.e. managed bandwidth service) for an ATM network infrastructure which is applied to the Greek research and technology network (GRNET). We present some methods that we have tested (in a simulation setting) in order to increase the efficiency of the system and the utilization of the available bandwidth. More specifically, we consider a bandwidth‐resizing algorithm for virtual paths, in order to keep the allocated bandwidth very close to the bandwidth actually used. This leads to an increased number of accepted requests and better network utilization. We, also, use the simulation results in order to get an estimation of the effective bandwidth for VBR paths that can be used in call admission. Finally, we consider a semi‐offline scheme where requests are gathered and considered for acceptance in regular intervals. Simulation results show an increase in the utilization of resources. As a further improvement, we allow connections to be allocated a little before or after the time initially requested. This leads to further improvement in network utilization. All the improvement schemes were tested with the ATM‐TN simulator and the results look promising. Copyright © 2003 John Wiley & Sons, Ltd.
Packet level acknowledgement and Go‐Back‐N protocol performance in infrared wireless LANs
Authors: Vitsas V. , Boucouvalas A.
Published: March 2003

Infrared wireless LANs may employ repetition rate (RR) coding to increase the symbol capture probability at the receiver. This paper examines the effectiveness of RR coding to utilization for infrared LANs using the physical and link layer parameter values proposed in the Advanced Infrared (AIr) protocol standard, which is developed by the Infrared Data Association (IrDA). Infrared LANs employ a Go‐Back‐N (GBN) automatic repeat request (ARQ) retransmission scheme at the Link Control (LC) layer to ensure reliable information transfer. To efficiently implement RR coding, the receiver may return after every DATA packet a suggestion for the suitable RR value to be used by the transmitter and implement a Stop‐and‐Wait (SW) ARQ scheme at the medium access control (MAC) layer. The effectiveness of employing this optional SW ARQ scheme at the MAC layer is discussed. Analytical models for the ARQ retransmission schemes are developed and employed to compare protocol utilization for different link parameter values such as window size, packet length and LC time out periods. This analysis identifies the ARQ protocol that maximizes performance for the specific link quality and the implemented link layer parameters. The effectiveness of the proposed RR coding to LAN utilization for different ARQ scheme implementation is finally explored. This analysis identifies the link quality level at which RR should be adjusted for maximum performance. It is concluded that if the packet error rate is higher than 0.1–0.4 (depending on the implemented ARQ protocol), the receiver should advise the transmitter to double the implemented RR for maximum performance. These error rate values are high and can be effectively estimated by the transmitter based on packet retransmissions. Thus, the usefulness of the receiver indicating to the transmitter to adjust RR is questionable, as the transmitter can effectively implement the suitable RR value based on packet retransmissions. Copyright © 2003 John Wiley & Sons, Ltd.
Recovery of human postures using robust dynamic calibration
Authors: Hayashi Kentaro , Kuno Yoshinori , Shimada Nobutaka , Shirai Yoshiaki
Published: March 2003

It has been difficult to calibrate dynamically the movement of the human body by using a conventional method such as the 8‐point algorithm, since images have fewer feature points, and errors in the positions of corresponding points of images are large.

This paper proposes a method of robust and accurate reconstruction of postures of the human body by using sequential images taken with a camera (dynamic calibration). It is based on arbitrary corresponding points in a set of two images with simple knowledge of the human body. In this method, motion parameters (generally inaccurate due to noise) are estimated by one‐dimensional search with size data on the human body. This paper also proposes an additional method which obtains a robust dynamic calibration even during movement of the camera (assuming that the camera movement is linear in a short period). The method has been confirmed experimentally. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(4): 52–61, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10143
Statistical methods for the evaluation of health effects of prenatal mercury exposure
Authors: Budtz‐Jørgensen Esben , Keiding Niels , Grandjean Philippe , Weihe Pal , White Roberta F.
Published: March 2003

Environmental risk assessment based on epidemiological data puts stringent demands on the statistical procedures. First, convincing evidence has to be established that there is a risk at all. In practice this endeavor requires prudent use of the observational epidemiological information with delicate balancing between utilizing the information optimally but not over‐interpreting it. If a case for an environmental risk has been made, the second challenge is to provide useful input that regulatory authorities can use to set standards. This article surveys some of these issues in the concrete case of neurobehavioral effects in Faroese children prenatally exposed to methylmercury. A selection of modern, appropriate methods has been applied in the analysis of this material that may be considered typical of environmental epidemiology today. In particular we emphasize the potential of structural equation models for improving standard multiple regression analysis of complex environmental epidemiology data. Copyright © 2003 John Wiley & Sons, Ltd.
Structure–activity relationship information incorporation in health related environmental risk assessment
Authors: Sen Pranab K.
Published: March 2003

In the bioinformatics and environmetrics evolution, virology, molecular biology and toxicology, along with biostochastics, play the key role; the complex task is invaded by some statistical methodologic challenges. We need to identify the multitude of (often disguised) toxicants and virus working in synergism and slow progression, assess their absorption mode, as well as,in vivobiological activity and reaction, and then to formulate suitable stochastic models for statistical analysis. Lack of experimental control, difficulties with standard dose–response regression analysis, as well as limitations of usual dosimetric studies create impasses. Basically, chemical or viral structure andin vivobiological activity relationship information needs to be incorporated adequately to depict the causal cum stochastic relationship between environmental exposures (of toxins and virus) and specific health hazards. Limitations of conventional statistical analysis in health related environmental risk assessment are appraised; some Bayesian perspectives are also examined. Copyright © 2003 John Wiley & Sons, Ltd.
Economic integration and strategic change: the role of managers' mental models
Authors: Adamides E. D. , Stamboulis Y. , Kanellopoulos V.
Published: March 2003

Firms in emerging economies face new realities as far as markets and competition are concerned when their domestic economy joins an area of economic integration.

The management of these companies may choose to respond by either reinforcing their domestically successful strategic paradigm or by adopting a new one.

By considering the views of a sample of large Greek manufacturing companies with respect to the European integrated market (EMU), we discuss the role of managers belief systems in selecting incremental strategies within their successful domestic strategic paradigm.

Copyright © 2003 John Wiley & Sons, Ltd.
The validity of FFM personality dimensions and maladaptive traits to predict negative affects at work: a six month prospective study in a military sample
Authors: Rolland Jean‐Pierre , De Fruyt Filip
Published: March 2003

The present work explores what the domain of maladaptive traits has to offer to the industrial and organizational (I/O) field investigating the incremental validity of maladaptive traits from DSM Axis II to predict negative emotions experienced at work, beyond Five‐Factor Model dimensions. This study was designed to examine the validity of adaptive and maladaptive traits to predict four negative affects (Anger, Fear, Sadness, and Shame) experienced at work in military personnel. The design was longitudinal, including two measurement moments, i.e. prior to and immediately after returning from a peace mission in a foreign country. The four negative affects were largely stable across a six month interval. FFM dimensions substantially explained negative affects experienced six months later, although the variance accounted for varied strongly across affects. In line with previous research, emotional stability was a consistent negative predictor of negative affects at both measurement moments. Two maladaptive traits derived from DSM Axis II (i.e. Borderline and Avoidant) were consistently related to specific negative affects experienced at work. Finally, maladaptive traits did not predict negative affect variance beyond FFM traits. These results are in line with robust findings suggesting that maladaptive trait patterns could be integrated in the five‐factor space, and as a consequence have little or no incremental utility over FFM dimensions. Copyright © 2003 John Wiley & Sons, Ltd.
Personality and absenteeism: a meta‐analysis of integrity tests
Authors: Ones Deniz S. , Viswesvaran Chockalingam , Schmidt Frank L.
Published: March 2003

Until recently, research focus has been on a variety of demographic, attitudinal, and organizational variables in predicting and explaining absenteeism. If personality traits predict absenteeism, then it may be possible to use measures of these traits to identify and select job applicants and thereby reduce absenteeism rates. In this research, our goal was to examine whether integrity tests could be used to predict absenteeism. Meta‐analysis was applied to studies of the validity of pre‐employment integrity tests for predicting voluntary absenteeism. Twenty‐eight studies based on a total sample of 13 972 were meta‐analysed. The estimated mean predictive validity of personality‐based integrity tests was 0.33. This operational validity generalized across various predictor scales, organizations, settings, and jobs (SDρ = 0.00). Overt integrity tests, however, showed much lower predictive validity for absenteeism and greater variability than personality‐based tests (ρ = 0.09; SDρ = 0.16). The results indicate that a personnel selection approach to reducing absenteeism in organizations may be a useful strategy, particularly if personality‐based integrity tests are utilized. Potential explanations for differences between these results and those found for Big Five measures of personality are offered. Future research investigating models of absenteeism should incorporate the personality constructs assessed by integrity tests. Copyright © 2003 John Wiley & Sons, Ltd.
A new HLA‐Cw*15 allele, Cw*1508, identified in the Peruvian population
Authors: Sanz L. , Beraún Y. , Nieto A. , Martín J. , Vilches C. , De Pablo R.
Published: March 2003

A novel HLA‐Cw*15 allele , Cw*1508, has been found in the Peruvian population. This new allele, initially detected as a polymerase chain reaction with sequence‐specific primers (PCR‐SSP) variant, shows greatest similarity to Cw*1502. The nucleotide sequence of Cw*1508 only differs from that of Cw*1502 at position 539; this change determines the replacement of Leu by Arg 156 in Cw*1508 Note.
A novel HLA‐DR12 allele (DRB1*1206) found in a Korean B‐cell line
Authors: Maeng C.‐Y. , Kim K.H. , Kang J.H. , Han H. , Kim K.L.
Published: March 2003

At least 6 HLA‐DRB1*12 alleles have been identified to date with nucleotide polymorphism occurring at codons 37, 57–58, 60, 67, 85 and 87. In this report, we describe the identification of another new HLA‐DRB1*12 allele: DRB1*1206. This novel allele was found in an Epstein‐Barr virus (EBV)‐transformed Korean B‐cell line “K‐KT” having the HLA‐phenotype A3, 24; B44, 61; Cw3; Bw4, 6; DR12, 13 during full‐length cDNA isolation for cell line characterization and for production of HLA‐DR recombinant proteins. The allele was identified initially by cycle sequencing of subcloned HLA‐DRB full‐length cDNA Note.
Sequence of HLA‐A*6808
Authors: Cox S.T. , Argüello J.R. , Marsh S.G.E. , Lau M. , Kwan P.L. , Madrigal J.A. , Little A.‐M.
Published: March 2003

A novel HLA‐A*68 allele was identified by reference strand conformation analysis of a DNA sample studied for the International Cell Exchange program. Direct sequencing of HLA‐A locus PCR products confirmed the presence of A*6602 and an A*68 allele which differed from A*68011 by two nucleotides at positions 538 and 539. The presence of this sequence motif in this allele which has been named A*6808 was verified by DNA sequencing of full‐length A*6808 clones. No other coding differences between A*68011 and A*6808 were identified. The two nucleotide substitutions found in A*6808 effect an amino acid difference in the encoded protein at residue 156 within the peptide binding site which may evoke allo‐reactive immune response after HLA‐A68 mismatched transplants Note.
No association with HLA‐DQB1 in European Caucasians with early‐onset periodontitis
Authors: Hodge P.J. , Riggio M.P. , Kinane D.F.
Published: March 2003

Periodontitis is a chronic inflammatory disease of the supporting tissues of the teeth that may ultimately result in tooth loss. The human leukocyte antigen (HLA) complex plays an important role in immune responsiveness and may be involved in antigen recognition of periodontal pathogens. A recent report of a Japanese population found an association between an atypical BamHI site in the HLA‐DQB1 gene and a severe form of early‐onset periodontitis (EOP). The aim of the present study was to test for the existence of the site in a European Caucasian EOP population using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) analysis. No statistically significant differences were found between the patients and controls with regard to the presence of the BamHI site. It was concluded that this lack of association could reflect racial genetic variation in HLA allelic frequencies.
Corneodesmosin gene polymorphism demonstrates strong linkage disequilibrium with HLA and association with psoriasis vulgaris
Authors: Jenisch S. , Koch S. , Henseler T. , Nair R.P. , Elder J.T. , Watts C.E. , Westphal E. , Voorhees J.J. , Christophers E. , Krönke M.
Published: March 2003

Corneodesmosin (CD) is thought to play a key role in corneocyte cohesion, and its proteolysis appears to be a major event in the process of desquamation. Recently it was shown that CD is encoded by the S‐gene, which is located approximately 160 kb telomeric of HLA‐C. In the present study, the role of CD in the genetics of psoriasis vulgaris was studied in greater detail. The second exon of the CD gene was sequenced in 86 HLA‐typed individuals from 13 psoriasis multiplex families. A total of 11 silent dimorphisms and 7 variants resulting in amino acid substitutions were found. Pedigree analysis showed that these variants could be grouped into 7 alleles, encoding 6 different amino acid sequences. These alleles are in strong linkage disequilibrium with HLA‐B and ‐C, indicating that the polymorphism of the CD gene is ancient and well conserved rather than sporadic. One allele at the CD locus, designated CD2, displayed strong linkage disequilibrium with HLA‐Cw6, the HLA allele most prominently associated with psoriasis. CD2 demonstrated a greater relative risk than Cw6 (3.4 vs. 2.5, not significant) and higher significant transmission disequilibrium with psoriasis than any of the investigated HLA‐alleles. Due to its biologic function, cellular location and disease association, the CD gene appears to be an excellent candidate gene for PSORS1, the HLA‐linked determinant of psoriasis vulgaris
Note.
Identification of a novel allele, B*15012, by polymerase chain reaction using sequence‐specific primers (PCR‐SSP) and sequence‐based typing
Authors: Day S. , Van Dam M. , Buckland E. , Dunn P.P.J. , Ross J.
Published: March 2003

We report here a new allele, B*15012, identified by polymerase chain reaction using sequence‐specific primers (PCR‐SSP) and sequence‐based typing (SBT). B*15012 differs to B*15011 (previously named B*1501) by a single nucleotide, at position 435 of codon 120. B*15011 encodes AAG and B*15012 encodes AAA at codon 120, this difference does not result in an amino acid change( Note).
New DRB1* alleles (HLA‐DRB1*1135, DRB1*1430 and DRB1*1433) and a confirmatory sequence (DRB1*1133)
Authors: Tréjaut J. , Hobart D. , Kennedy A. , Greville W.D. , Taverniti A. , Dunckley H.
Published: March 2003

Three new DRB1 alleles (DRB1*1135, DRB1*1430 and DRB1*1433) and a confirmatory sequence (DRB1*1133) have been identified after following up unusual or novel polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) patterns during routine typing of the DRB1*03,*08,*11,*12,*13 and *14 allele groups. Of the new alleles found and described in this paper, two alleles were initially detected by the PCR‐RFLP method which produced unexpected restriction polymorphism (DRB1*1133 and DRB1*1135) while the remaining two were found after following up rare allele typings from this technique (DRB1*1430 and DRB1*1433).
Detection of four novel alleles: DRB1*1130, DRB1*13072, DRB1*1315 and DRB1*1331
Authors: Lin Y.‐S. , Hoyer R.J. , Tang T.F. , Ng J. , Hartzman R.J. , Hurley C.K.
Published: March 2003

Four new DR52‐associated DRB1 alleles are described. One allele, DRB1*1130, is a hybrid between a DRB3*02 allele and a DRB1*11011 allele. The other alleles, DRB1*13072, DRB1*1315, and DRB1*1331, are simple reshufflings of known polymorphic motifs.
An unusual insertion in intron 2 of apparently functional MHC class I alleles in rhesus macaques
Authors: Urvater J.A. , Steffen S.R. , Rehrauer, W. , Watkins D.I.
Published: March 2003

Here we describe a nucleotide insertion in intron 2 of two rhesus major histocompatibility complex (MHC) class I alleles, Mamu‐A*05 and Mamu‐A*07 . This resulted in an intron 2 that was nearly twice the length of any other intron 2 of primate MHC class I genes sequenced to date. This insertion was most similar (93% identity) to the beginning of intron 3 of HLA‐A alleles. It was also similar to intron 3 of several human MHC class I pseudogenes and MHC class I pseduogenes from cotton top tamarin and cat. The finding of this insertion in two rhesus MHC class I genes is surprising given the uniformity in length and sequence of introns of functional HLA‐A, ‐B and ‐C genes.
Multiple mechanisms underlie HLA dysregulation in cervical cancer
Authors: Brady C.S. , Bartholomew J.S. , Burt D.J. , Duggan‐Keen M.F. , Glenville S. , Telford N. , Little A‐M. , Davidson J.A. , Jimenez P. , Ruiz‐Cabello F. , Garrido F. , Stern P.L.
Published: March 2003

The consistent dysregulation of HLA expression in cervical neoplasia is likely to influence the natural history of the disease and prospects for cell‐mediated vaccine therapies. We have studied the underlying mechanisms in eight new cervical cancer cell lines derived from primary tumour biopsies. At least five independent mechanisms leading to changes in HLA expression were seen: HLA class I allelic transcription but no protein; abnormal HLA class I allelic transcription; no HLA‐B locus transcription; loss of heterozygosity (LOH); no γIFN‐mediated upregulation of HLA class I expression, and/or no interferon‐gamma (γIFN)‐mediated HLA class II induction. These were evident in different combinations in 7/8 cell lines showing that multiple, mostly irreversible mechanisms not overridden by γIFN, are responsible for HLA dysregulation in cervical neoplasia. Point mutations were responsible for lack of HLA‐A2 expression in two cases. In cell line 808, the mutation encodes a stop codon in exon 3; in cell line 778, mutation of the first intron acceptor site leads to use of an alternative AG site in exon 2, resulting in a frameshift and a stop codon after the translation of only 38 amino acids. Tumour cells showing specific HLA class I loss may have selective advantage in the face of tumour‐specific cytotoxic T cells (CTL). Such immune escape mechanisms present a major obstacle for the success of CTL‐mediated therapies in cervical cancer.
Novel HLA‐B*15 alleles identified in potential marrow donors
Authors: Williams T.M. , Wu J. , Bassinger S. , Montoya G.D. , Yee J. , Griffith B.B. , Kearns J. , McKeen M. , Birkos S. , Gourley I.S. , Kamoun M.
Published: March 2003

Several methods for low‐resolution class I typing of potential bone marrow donors are available. The National Marrow Donor Program® (NMDP) has initiated pilot projects for large‐scale DNA‐based class I typing to initially characterize donors. Sequence‐specific oligonucleotide probe hybridization and sequence‐specific primer polymerase chain reaction (PCR) screening of 3,500 NMDP potential donors suggested the presence of variants of known HLA‐B*15 variants in 3 donors. PCR products encompassing HLA‐B locus exons 1 through 3 were prepared and subcloned. Sequencing revealed 3 alleles differing from known HLA‐B*15 alleles by nucleotide substitutions resulting in predicted novel HLA‐B antigens. The new alleles occur in distinct ethnic groups. These findings further illustrate the substantial genetic variation present at the HLA‐B locus within human populations ( Note).
Molecular cloning and characterization of major histocompatibility complex class I cDNAs from woodchuck (Marmota monax)
Authors: Yang D.‐L. , Lu M. , Hao L.‐J. , Roggendorf M.
Published: March 2003

The full‐length cDNAs of woodchuck major histocompatibility complex (MHC) class I (MhcMamo‐I or Mamo‐I) genes were cloned by using cellular mRNA isolated from the peripheral blood mononuclear cells and liver tissues of woodchucks. DNA sequence analysis of Mamo‐I cDNAs revealed that the coding regions of Mamo‐I genes were about 1080 bp long, encoding 359 amino acid residues. The deduced amino acid sequences of Mamo‐I showed structural features like leader, α1, α2, α3, transmembrane and cytoplasmic domains, similar to their homologues in human and other mammals. Analysis of five full‐length clones from unrelated woodchucks indicated a polymorphism within the α1 and α2 domains of Mamo‐I heavy chain and a high conservation within the α3 and the transmembrane/cytoplasmic domains. Amino acid residues of the α2 and α3 domains that are supposed to be involved in the binding of MHC class I to CD8 molecule, were largely conserved in Mamo‐I genes. Phylogenetic comparison of MHC class I genes of woodchuck and other mammals indicated a close evolutionary relationship between woodchuck and squirrel MHC class I. We tentatively named this region the locus A of Mamo‐I genes (Mamo‐A). Sequence analysis of 101 clones of α1 and α2 regions derived from 14 woodchucks revealed that at least 14 different alleles within Mamo‐A exist. Among these 14 alleles identified so far, Mamo‐A*01 and Mamo‐A*09 were of the highest frequency of about 21.5% and 14.5%, respectively. Our results indicate that Mamo‐I genes are of a similar molecular structure to those of human and other mammals.
Bypassing hybridoma technology: HLA‐C reactive human single‐chain antibody fragments (scFv) derived from a synthetic phage display library (HuCAL) and their potential to discriminate HLA class I specificities
Authors: Marget M. , Sharma B.B. , Tesar M. , Kretzschmar T. , Jenisch S. , Westphal E. , Davarnia P. , Weiss E. , Ulbrecht M. , Kabelitz D. , Krönke M.
Published: March 2003

The generation of discriminative, monospecific anti‐HLA antibodies used to be a difficult endeavor. Phage display technology, using single‐chain antibody fragments (scFv) offers a powerful alternative obtaining target‐specific, genetically stable reagents. Most of scFv obtained to date have been enriched by panning phage libraries to solid‐phase coupled antigens. In the present study, HLA‐C‐specific scFv were isolated using a synthetic phage library in combination with a Cw*0602 overexpressing cell line. ScFv from this procedure precipitated HLA‐Cw*0602 heavy chains from whole cell lysates. Flow cytometry analysis revealed that scFv stained HLA‐Cw*0602‐positive cells, but not cells expressing HLA alleles Cw*0302, Cw*0802, A*0201, B*2705, or Gm1*01011, indicating the specificity of scFv. Similarly they showed an ability to discriminate Cw*0602‐positive from Cw*0602‐negative peripheral blood lymphocytes (PBL). The rsults of our study demonstrate the feasibility to genetically engineer single‐chain HLA‐class I‐specific antibodies, by phage display technology. This approach might be a valuable tool to develop a broad range of novel monospecific antibodies against HLA‐class I specificities.
HLA‐B44 subtyping in the Catalan population using reference strand mediated conformation analysis. Implications for the selection of unrelated bone marrow donors
Authors: Gallardo D. , Aróstegui J.I. , Rodríguez‐Luaces M. , Querol S. , González J.R. , García‐López J. , Grañena A.
Published: March 2003

Cytotoxic T lymphocytes (CTLs) reactive against the disparity between HLA‐B*4402 and HLA‐B*4403 have been reported after unrelated donor bone marrow transplantation. These CTLs have been associated with acute graft‐versus‐host disease and graft rejection. This study describes the HLA‐B44‐subtyping in the Catalan population using reference‐strand mediated conformation analysis. It has been performed on 297 unrelated HLA‐B44+ cord blood units from the Barcelona Cord Blood Bank (Barcelona, Spain). We have found a predominance of HLA‐B*4403 (66.04%) over HLA‐B*4402 (33.02%), whereas the predominant HLA‐B44 allele in Northern Europe and the United States is HLA‐B*4402. This inverted proportion between HLA‐B44 subtypes in Mediterranean populations compared with other Caucasian populations suggests that HLA‐B44 subtyping should be performed when an HLA‐B44+ unrelated donor marrow is identified.
Serological and nucleotide sequence analysis of HLA‐A*6812
Authors: Faé I. , Gleißner B. , Kriks D. , Leitner D. , Fischer G.F.
Published: March 2003

We describe a novel HLA‐A allele, HLA‐A*6812. HLA‐typing of a patient was performed by serology and by DNA‐based analyses. Cloning and sequencing of exons 2 and 3 revealed that the genotype consisted of a common HLA‐A*0101 allele and the novel HLA‐A*6812 allele. HLA*6812 is identical to HLA‐A*68012 except for a single non‐synonymous nucleotide substitution leading to an exchange of a threonine to an isoleucine residue at position 142 of the HLA‐class I alpha chain. The allele was also found in the patient’s mother. The novel HLA‐A68 molecule is recognised by some but not all of our HLA‐A28‐specific sera. These results confirm that position 142 is important for the serological properties of the HLA‐A molecule ( Note).
Soluble HLA‐DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease‐associated epitopes
Authors: Verbruggen L.A. , Dumarey N. , Van de Velde H. , Rebmann V. , Flament J. , Van Wayenberge C. , Grosse‐Wilde H. , Demanet C.
Published: March 2003

Acknowledgments:

This study was supported by a grant from the Belgian Red Cross. The authors thank Prof. W. Duquet for valuable help with the statistical analysis of the results.

We investigated correlations between soluble HLA‐DR (sHLA‐DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA‐DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti‐human HLA‐DR antibodies. The mean sHLA‐DR serum level in RA patients was significantly increased with 277±19 ng/ml compared to 142±13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA‐DR and EULAR swelling and pain scores, Waaler‐Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA‐DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty‐seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA‐DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease‐associated epitope (Q)R/KRAA within the HLA‐DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA‐DR was respectively 169±17 (no disease associated epitope), 324±34 (heterozygous) and 442±69 ng/ml (homozygous for the disease‐associated epitope on HLA‐DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA‐DR levels and RA disease activity parameters, as well as increased sHLA‐DR in patients with disease‐associated epitope on HLA‐DRB1 alleles.
Sequence of a new class I null allele within the HLA‐B44 specificity
Authors: Bettens F. , Tiercy J.‐M.
Published: March 2003

Acknowledgments:

We thank the blood donor ALBA and her mother for their cooperation to this study. We also thank B. Kervaire and R. Zanone for expert technical assistance. This work was supported by the Swiss National Science Foundation (grant no. 32–52061.97 and no. 31–57557.99).

A new HLA class I null allele has been identified within the B44 group by combined serological and molecular typing of a blood donor. Based on full‐length cDNA sequencing, this novel HLA‐B*4419N allele was found to differ from B*4402 by one single base pair deletion at position 7 of exon 1 which results in a stop at codon 19. This mutation was confirmed by polymerace chain reaction‐sequence‐specific oligonucleotide probe (PCR‐SSOP) hybridization on genomic DNA. Based on family typing, this new allele segregates with the haplotype A*01‐B*4419N‐Cw*0501‐DRB1*1301‐DRB3*0101. Since nonsense codons are generally associated with increased mRNA decay, we investigated B*4419N mRNA by semi‐quantitative reverse transcriptase (RT)‐PCR and by cDNA cloning efficiency. Comparison of B*4419N cDNA to B*4402 control cDNA and to B35 cDNA levels in the same donor, as well as the analysis of cloned inserts, revealed that the exon 1 mutation did not significantly influence B*4419N steady‐state mRNA.
Rapid identification of minor histocompatibility antigen HA‐1 subtypes H and R using fluorescence‐labeled oligonucleotides
Authors: Kreiter S. , Wehler T. , Landt O. , Huber C. , Derigs H.‐G. , Heß G.
Published: March 2003

Acknowledgments:

We thank Brigitte Schuch and Karola Schmidt for excellent technical assistance. This work was supported by a grant of the Deutsche Krebshilfe (Nr. 70‐2427 and Nr. 70‐2428).

Donor‐recipient disparitiy of the minor histocompatibility antigen HA‐1 is relevant for the development of graft‐versus‐host disease after HLA‐matched sibling allogeneic bone marrow transplantation in HLA‐A*0201‐positive individuals. Two different alleles of HA‐1 with a single amino acid polymorphism have been identified. Here we describe a time‐ and cost‐efficient method for HA‐1 typing of genomic DNA, using site‐specific hybridization probes with the LightCycler. This method was compared with standard techniques as sequencing or allele‐specific polymerase chain reaction (PCR) and proved to be specific, reliable and reproducible. We conclude that HA–1‐subtyping using fluorescent‐labeled oligonucleotides represents a attractive method for the screening of samples before allogeneic transplantation in HLA‐A*0201‐positive individuals.
Identification of a new DQB1 allele that appears to have been generated by an interallelic sequence exchange
Authors: Perrier P. , Reveillere C. , Andre‐Botte C. , Schuhmacher A.
Published: March 2003

The study reports the molecular characterization of a new DQB1 variant initially detected by unusual sequence‐specific oligonucleotide (SSO) hybridization patterns in one Caucasoid individual. This new allele is identical to DQB1*0501 except for two silent nucleotide substitutions at codons 49 (GCA→GCG) and 77 (AGG→AGA). Compared with DQB1*0502 it differs in three nucleotides at codon 57 changing AGC (encoding Ser) to GTT (encoding Val). Considering the paternal genotype, it appears this new allele might have been generated by an interallelic sequence exchange between the two paternal DQB1 alleles ( 1).
Further diversity at HLA‐A and ‐B loci identified in Afro‐Caribbean potential bone marrow donors
Authors: Cox S.T. , McWhinnie A.J. , Koester R.P. , Heine U. , Holman R. , Madrigal J.A. , Little A.‐M.
Published: March 2003

Two novel HLA‐A and three novel HLA‐B alleles were identified within a group of Afro‐Caribbean individuals who were recruited as potential donors for the Anthony Nolan Bone Marrow Trust Register. HLA typing was performed on DNA extracted from peripheral blood mononuclear cells using sequence‐specific oligonucleotide (SSO) probes for HLA‐A and ‐B loci. Eight individuals analysed exhibited hybridisation patterns for which a type could not be assigned. DNA from these individuals was further typed by two methodologies: direct sequencing of PCR products and reference strand conformation analysis (RSCA). The direct sequencing results allowed the identification of new alleles but did not allow confirmation of the cis/trans orientation of the new sequence motifs identified. RSCA analysis confirmed the results obtained by SSO and direct sequencing and in addition confirmed the cis/trans orientation of the new sequences. One individual possesses a new A*30 allele – A*3008 and two individuals possess an identical new A*74 allele – A*7404. The three novel HLA‐B alleles were identified in three individuals: B*0812, B*1554 and B*4503 respectively. For the remaining two samples, A*2612 was identified. At present Caucasoid individuals, and therefore Caucasoid phenotypes, are predominantly represented on the various different volunteer bone marrow donor registries. The examples presented here highlight the potential for identification of further polymorphisms within the HLA system as more individuals from the much‐needed ethnic minorities are recruited onto bone marrow donor registers.
A novel HLA allele, B*4104, identified in a cord blood donor
Authors: Turner D.M. , Vlachos G. , Cavanna S.L. , Brown J. , Brown C. , Navarrete C.V.
Published: March 2003

Results from a number of HLA typing methods prompted the DNA sequencing (SBT) of a cord blood sample at the HLA‐B locus. A novel HLA‐B allele, B*4104, was identified. This was confirmed by sequencing the mother of the cord blood unit for HLA‐B (Note).
Identification of HLA‐B*0722
Authors: Little A.‐M. , Cox S.T. , Hoddinott M.A. , Ogilvie H. , Bohan E.M. , Mufti G.J. , Madrigal J.A.
Published: March 2003

Abstract: A novel polymorphism was identified in a B*07 allele. B*0722 possesses a unique nucleotide substitution at nucleotide 481. This polymorphism encodes an amino acid difference from aspartic acid in B*07021 to asparagine in B*0722. The functional significance of this polymorphism on peptide binding and/or T‐cell recognition is unknown (Note).
Allele frequency of HLA‐B39 in the Japanese population and identification of a novel B39 allele, B*3923
Authors: Akesaka T. , Kashiwase K. , Ishikawa Y. , Tanaka H. , Shimizu M. , Kawai S. , Akaza T. , Takahashi T. , Juji T.
Published: March 2003

Abstract: A new HLA‐B39 allele, B*3923, was found in the Japanese population. Compared with B*39022, the new allele had a single point mutation at position 503 in exon 3 with an amino acid substitution, Gln144Arg. To determine B39 allele frequency in Japanese, 275 B39‐positive samples from 3277 Japanese individuals were examined by polymerase chain reaction using microtitre plate hydribization (PCR‐MPH) and single‐strand conformation polymorphism (PCR‐SSCP). The frequency of B*3923 was estimated to be 0.4% in B39 alleles of the Japanese population. B*3923 was found in samples from four Japanese individuals, all of whom have DRB1*1406 (Note).
The origin of Minnan and Hakka, the so‐called “Taiwanese”, inferred by HLA study
Authors: Lin M. , Chu C.‐C. , Chang S.‐L. , Lee H.‐L. , Loo J.‐H. , Akaza T. , Juji T. , Ohashi J. , Tokunaga K.
Published: March 2003

Abstract: The Minnan and Hakka people groups, the so‐called “Taiwanese”, are the descendants of early settlers from the southeast coast of China during the last few centuries. Genetically they showed affinities to southern Asian populations, as determined by phylogenetic trees and correspondence analysis calculated from HLA allele frequencies. This corresponds historically with the fact that they are the descendants of the southeast coastal indigenous population (Yueh) of China and should therefore not be considered as descendants of “pure” northern Han Chinese. A33‐B58‐DRB1*03 (A33‐Cw10‐B58‐DRB1*03‐DQB1*02), the most common HLA haplotype among “Taiwanese”, with a haplotype frequency of 6.3%, has also been found to be the most common haplotype among Thai‐Chinese and Singapore Chinese, two other populations also originating from the southeast coast of China. These observations suggests that this haplotype is the most well‐conserved ancient haplotype of the Yueh.
Description of a new HLA‐DRB1 allele, DRB1*1139
Authors: Longhi E. , Frison S. , Poli F. , Scalamogna M. , Sirchia G.
Published: March 2003

Abstract: We report the identification of a novel DRB1*11 using sequence‐based typing. This new allele, officially named DRB1*1139, was detected while performing HLA‐DRB1 high‐resolution typing of a volunteer bone marrow donor. DRB1*1139 is identical to DRB1*11011 except at codon 51 (ACG→AGG) changing the encoded Threonine to Arginine. The triplet AGG has never been found in any other DRB1 allele. In fact, with standard polymerase chain reaction (PCR) amplification with sequence specific primers, the presented allele would have been interpreted as DRB1*1101 (Note).
Heat shock protein 70 gene polymorphism in Japanese patients with multiple sclerosis
Authors: Niino M. , Kikuchi S. , Fukazawa T. , Yabe I. , Sasaki H. , Tashiro K.
Published: March 2003

Abstract: Despite the strength of the association of multiple sclerosis (MS) and human leukocyte antigen (HLA)‐DR2, other genetic elements could have a role in the pathophysiology of MS. We investigated possible associations with polymorphic susceptibility genes located within the HLA complex, i.e., heat‐shock protein (HSP)70‐1, HSP70‐2, and HSP70‐hom in Japanese patients with MS. Furthermore, we analyzed the influence of HSP70 gene polymorphisms on the severity of the disease, clinical course, magnetic resonance imaging findings, and oligoclonal bands in the cerebrospinal fluid, and HLA in MS patients. The results of the present study indicated that there were no significant differences in the distribution of all HSP70 genotypes and allele frequencies between Japanese MS patients and controls. In MS patients, there were no associations between HSP70 gene polymorphisms and the clinical data. Moreover, there were no significant differences in HSP70 genotype or allele frequencies between MS patients positive for HLA‐DRB1*1501 alleles and matched controls. Our data indicate that HSP70 gene polymorphisms are not relevant in the susceptibility to or the severity of Japanese MS patients.
HLA‐DQA1 and ‐DQB1 genes and Helicobacter pylori infection in Italian patients with gastric adenocarcinoma
Authors: Perri F. , Piepoli A. , Quitadamo M. , Quarticelli M. , Merla A. , Bisceglia M.
Published: March 2003

Abstract: Both HLA‐DQA1 and ‐DQB1 genes and Helicobacter pylori infection have been linked to gastric cancer. The aim of this work was to determine if HLA‐DQA1 and ‐DQB1 alleles are presented at altered frequency in Italian patients with gastric adenocarcinoma and H. pylori infection. Oligotyping for HLA‐DQA1 and ‐DQB1 and H. pylori serology was performed for 50 patients with gastric adenocarcinoma and compared with 80 patients with colonic adenocarcinoma and 179 healthy subjects. H. pylori infection was present in 76% of gastric cancer patients, 77.5% of colonic cancer patients, and 72% of controls. The prevalence of infection was not significantly different in the three groups of subjects sorted according to their HLA‐DQA1 or ‐DQB1 status. Apart from HLA‐DQA1* 0201, which was less common in patients with colonic carcinoma than controls, no other HLA‐DQA1 and no HLA‐DQB1 allele were present at altered frequency in patients with gastric or colonic cancer. Neither anatomical location and histological type of cancer nor the presence of lymph node or distant metastases were significantly associated with specific HLA‐DQA1 or ‐DQB1 alleles or H. pylori infection. Both HLA‐DQA1 and ‐DQB1 genes have a minor, if any, role in H. pylori infection and gastric carcinogenesis.
Molecular cloning and sequencing of feline melanoma antigen 2 (fMAGE‐2) obtained from a lymphoma cell line
Authors: Ma Z. , Khatlani T.S. , Sasaki K. , Okuda M. , Inokuma H. , Onishi T.
Published: March 2003

Abstract:Melanoma antigens (MAGE), thought to induce tumor‐specific immune responses, are used as potential therapeutical targets for cancer immunotherapy. We hereby report the cloning and sequencing of MAGE cDNA clone, called feline MAGE‐2 (fMAGE‐2), obtained from a lymphoma cell line. fMAGE‐2 cDNA is 1535 base pairs (bp) in length and contains an open reading frame (ORF) of 1131 bp encoding a protein of 376 amino acids. The predicted amino acid sequence shows 45%, 32–42%, 44–47%, and 33% homology with feline MAGE‐1, human MAGE‐A, human MAGE‐B, and human MAGE‐C proteins, respectively. mRNA transcripts of fMAGE‐2 were detected by RT‐PCR in some feline tumors, as well as in testis of adult cat, but not in other normal tissues, indicating that the expression pattern of fMAGE‐2 is similar to that of the human MAGE family genes in tumors and normal tissues.
Distribution of HLA‐B alleles in nasopharyngeal carcinoma patients and normal controls in Thailand
Authors: Pimtanothai N. , Charoenwongse P. , Mutirangura A. , Hurley C.K.
Published: March 2003

Abstract:HLA‐B frequencies in 54 unrelated nasopharyngeal carcinoma (NPC) patients and 49 healthy random controls in Thailand were investigated by direct DNA sequencing. Similar to previous reports in Chinese NPC patients, HLA‐B*4601 was observed at a greater frequency in patients (21/54 (40%)) compared to controls (7/49 (14%). An increase in HLA‐B*51012 was also demonstrated. B*51012 was present in 6/54 (11%) NPC patients but was not observed (0%) in controls. B*44032 was associated with a decreased risk. Five out of 54 (9%) NPC patients had B*44032 compared to 14/49 (29%) in the control group.
Six new HLA Class I alleles detected by PCR‐SSO genotyping
Authors: Kennedy C.T. , Greville W.D. , Dodd R. , Le T. , Taverniti A. , Chapman G. , Wallace R. , Kennedy A. , Strickland J. , Dunckley H.
Published: March 2003

Abstract: This paper describes six new alleles; A*0240, A*2614, B*3924, B*4425, Cw*0807 and Cw*12023, which were discovered during routine genotyping with sequence specific oligonucleotides (SSO's). Five of the new alleles have changes in residues which belong to the antigen binding site of the HLA protein. These new variants may have altered antigen binding properties and may cause differential immunological responses that could affect transplantation outcome1.
HLA‐A*3306, a novel variant in the Indian population
Authors: Rozemuller E. H. , Mehra N. , Van Der Zwan A.‐W. , Jaini R. , Tilanus M. G. J.
Published: March 2003

Abstract: We describe a new HLA‐A allele, A*3306, which was identified by sequencing based typing (SBT) in an individual of Indian origin. A*3306 is similar to A*3303, with a difference at position 228 (A to G). This difference leads to an amino‐acid change at codon 52 from Ile (ATA) to Met (ATG). Until now this position has been considered conserved.
Efficient cloning and expression of HLAclass I cDNA in human B‐lymphoblastoidcell lines
Authors: Akatsuka Y. , Goldberg T.A. , Kondo E. , Martin E.G. , Obata Y. , Morishima Y. , Takahashi T. , Hansen J.A.
Published: March 2003

Abstract: Analysis of HLA restriction specificity is one of the important steps in characterizing T cell clones. This usually requires either a panel of HLA‐typed cells or HLA cDNA transfectants. Although preparation of HLA cDNA transfectants is laborious, utilization of transfectants is advantageous when a suitable panel is not available due to linkage disequilibrium or rarity of the HLA allele of interest. In this report, we describe an efficient and rapid HLA cloning and expression system. Three sets of PCR primers specific for HLA‐A, B and C loci were designed by extensively sequencing 5′‐ and 3′‐ untranslated regions of HLA class I genes. The PCR‐amplified products were introduced into modified Phoenix retrovirus vectors containing a puromycin resistant gene under the control of a LTR promotor. Gibbon ape leukemia virus (GALV)‐pseudotyped retrovirus was produced and infected into B‐lymphoid cell lines. Following expansion in selection media, more than 80% of cells expressed transduced HLA at a comparable level to that normally expressed. These results indicate that locus‐specific PCR cloning and utilization of GALV‐pseudotyped retroviral vector can be an effective and relatively efficient tool for constructing a panel of different HLA transfectants.