bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive predistortion of COFDM signals for a mobile satellite channel
Authors: Rodriguez Nibaldo , Soto Ismael , Carrasco Rolando
Published: March 2003

In this paper, we consider the optimization of the performance of QPSK and 16‐QAM coded orthogonal frequency division multiplexing (COFDM) signals over the non‐linear and mobile satellite channel. A high power amplifier and Rician flat fading channel produces non‐linear and linear distortions; an adaptive predistortion technique combined with turbo codes will reduce both types of distortion. The predistorter is based on a feedforward neural network, with the coefficients being derived using an extended Kalman filter (EKF). The conventional turbo code is used to mitigate Rician flat fading distortion and Gaussian noise. The performance over a non‐linear satellite channel indicates that QPSK COFDM followed by a predistorter provides a gain of about 1.7 dB at a BER of 3×10−3when compared to QPSK COFDM without the predistortion scheme and 16‐QAM COFDM provides a gain of 0.5 dB output back‐off and 1.2 dB signal to noise ratio at a BER of 3×10−5when compared with an adaptive predistorter based on the Harmmerstein model. We also investigate the influence of the guard time interval and Doppler frequency effect on the BER performance. When the guard interval increases from 0 to 0.125Tsamples and the normalized Doppler frequency is 0.001, there is a gain of 0.7 and 1 dB signal to noise ratio at a BER of 6×10−4for QPSK and 16‐QAM COFDM, respectively. Copyright © 2003 John Wiley & Sons, Ltd.
A switching function of a quantum dot surrounded by four tunnel junctions
Authors: Amemiya Katsuki , Ueta Tsuyoshi
Published: March 2003

The resonant tunneling effect is considered in a system consisting of a square quantum dot with quantum wires connected to each side via tunnel junctions. Due to resonance in the dot, it is possible to distinguish the case with forward transmission only for the incidence at a certain probe and the case in which transmission into the left and right probes appears. Further, by considering the asymmetry of the tunnel junctions, the possibility of using this structure as a switching element is explored. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(4): 10–17, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10102
A permanent magnet‐assisted synchronous reluctance motor
Authors: Murakami Hiroshi , Honda Yukio , Morimoto Shigeo , Takeda Yoji
Published: March 2003

Permanent magnet motors have attracted a lot of attention recently for their potential for saving energy. However, they are only used for certain applications because the magnets are expensive. This paper discusses the optimum design of the low‐cost, highly efficient magnet‐ assisted reluctance motors with a minimum amount of magnets. The motor considered in this study is a multi‐flux barrier reluctance motor. The configuration by which permanent magnets are embedded to the innermost side of the rotor to obtain maximum output with the minimum amount of magnets was evaluated through simulation and experiments with a prototype motor. As a result, we established a method for designing motors capable of realizing the same efficiency as permanent magnet motors with only one‐fourth the amount of magnets. In our experiments, we achieved a high efficiency of 94.5% with a 750‐W motor. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 142(4): 66–74, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10123
Differences in the recognition by CTL of peptides presented by the HLA‐B*4402 and the HLA‐B*4403 molecules which differ by a single amino acid
Authors: Herman J. , Jongeneel V. , Kuznetsov D. , Coulie P.G.
Published: March 2003

The HLA‐B*4402 and B*4403 molecules differ only at residue 156, which borders the peptide binding site. Strong in vivo allogeneic reactions mediated by cytolytic T lymphocytes (CTLs) were reported in patients who received a bone marrow graft mismatched for these B44 subtypes, indicating that HLA‐B*4402 and B*4403 molecules present distinct antigens. This could be due either to the presentation of different sets of antigenic peptides or to the recognition by CTLs of conformational epitopes formed by the MHC molecules alone or in association with antigenic peptides. To address this question, we compared the two B44 subtypes in their presentation to tumor‐specific CTLs of three peptides, encoded by genes MAGE‐3, MUM‐1 and Tyrosinase. The peptides bound with similar affinities to B*4402 or B*4403 molecules, as assessed by lytic competition assays. One HLA‐B*4402‐restricted and one HLA‐B*4403‐restricted CTL clone were derived against each peptide. When tested for lysis of B*4402 and B*4403 cells incubated with the antigenic peptides, most CTLs showed a marked preference for one of the two B44 subtypes. Using variant peptides incorporating single alanine substitutions, we compared a given CTLs’ recognition of its antigenic peptide presented by both B44 subtypes. Some substitutions, which had no effect on the binding of the peptide, affected its recognition by the same CTL differently on B*4402 and B*4403 molecules. These results imply that the conformations adopted by the same peptide on the two HLA‐B44 subtypes are different. We conclude that the B44 subtype specificity of T cells results mostly from distinct conformations adopted by the same peptides in the two B44 molecules. This does not exclude the possibility that in some cases the B44 subtype specificity results from the selective binding of a peptide to one subtype. We found several peptides, different from the three mentioned above, that contain the canonical HLA‐B44 binding motif and bind to B*4403 but not to B*4402 molecules.
Towards a molecular phototyping system for allelic variants of MICA, encoded by polymorphisms in exons 2, 3 and 4 of MHC class I chain‐related genes
Authors: Stephens H.A.F. , Vaughan R.W. , Collins R. , Kondeatis E. , Theron J. , Payne A.
Published: March 2003

In this study we have developed a polymerase chain reaction‐sequence‐specific primer (PCR‐SSP) or phototyping system to analyse the polymorphism of the human MICA gene locus. By scrutinising the reported MICA sequence variations in exons 2, 3 and 4 which encode the extracellular protein domains, we have selected and tested 20 MICA‐specific primer mixes that should discriminate between the majority of homozygous and heterozygous combinations of MICA alleles 001–016. We have tested this scheme on DNA prepared from a large number of well‐characterised tissue culture cell lines with previously reported MICA nucleotide sequences and found an excellent correlation with the observed PCR‐SSP phototypes. We believe that this scheme can also be modified to detect new MICA alleles when they are characterised, as well as be incorporated into standard phototyping protocols to generate allele and haplotype profiles of both classical and non‐classical HLA gene loci in test DNA samples.
Identification of HLA‐A*0224: Implications for PCR‐SSP HLA typing
Authors: Guttridge M.G. , Street J. , Thomas M. , Darke C.
Published: March 2003

We describe a novel HLA‐A*02 allele, A*0224, that was identified after a comparison of DNA and serological typing revealed a discrepancy in the HLA‐A types: HLA‐A2 was defined by serology but was not detected by the polymerase chain reaction using sequence‐specific primers (PCR‐SSP). DNA sequencing indicated the presence of a variant HLA‐A*02 allele that differed from A*0201 by a single base (C/A) at position 453. This base substitution corresponded to the annealing site of a primer common to the two A*02‐amplifying PCR‐SSP mixtures used in the method. This provides an explanation for the results and highlights a limitation of PCR‐SSP methods even where two PCR mixtures are used to detect alleles. Serological titration studies suggested that A*0201, A*0205 and A*0224 Note are unlikely to be differentiated during routine serological typing.
Characterization of a new HLA‐B*38 allele (B*3803) in a Spanish Caucasian individual which is closely related to the Oriental B*38021 and B*39021 alleles
Authors: Balas A. , Santos S. , García‐Sánchez F. , Lillo R. , Merino J.L. , Vicario J.L.
Published: March 2003

The broad HLA‐B16 serologic specificity is divided into B38 and B39 splits associated to Bw4 and Bw6, respectively. Differential serologic variants have been defined for several molecular subtypes of B39 and for B38. We found a Spanish Caucasian individual carrying a B16 Bw4‐associated antigen which was not recognized by reagents against B16 splits. Sequencing analysis showed a new B16 subtype termed B*3803. HLA class I sequence‐based typing (SBT) analysis demonstrated that B*3803 co‐segregates with A*2608 and Cw*1203, forming a common Caucasian haplotype. Sequence comparison with B*38 and B*39 subtypes evidences that although B*3803 is close related to B*3802, it only differs from B*39021 by six clustered nucleotide position in the Bw4/Bw6 motif, and strongly suggests that B*3803 could have evolved from, or be the ancestral gene of the Oriental‐associated B*3802 and B*39021 alleles. However, more complex patterns of genetic events should be considered due to the Caucasian background of the B*3803 individual an its associated haplotype Note.
Sequence of HLA‐DRB1*0431 allele
Authors: Bettens F. , Kervaire B. , Tiercy J.‐M.
Published: March 2003

A novel HLA‐DR4 allele has been detected in a volunteer bone marrow donor using a reverse microtiter plate oligotyping assay. Exon 2 cloning and sequencing revealed the new HLA‐DRB1*0431 allele which differs from DRB1*0408 by two nucleotide changes at codon 74 leading to an Ala/Leu substitution. Although typical of DR8 alleles, Leu74 polymorphism was not sufficient to confer any serological reactivity with DR8 alloantisera. This rare DR4 subtype was identified in an individual of East European origin. The HLA typing of this donor is: A2,A31; B18,B51; Cw*0701,Cw*15; DRB1*1602,DRB1*0431; DRB4*01,DRB5*02; DQB1*0301,DQB1*0502 Note.
A null HLA‐A*68 allele in a bone marrow donor
Authors: Laforet M. , Froelich N. , Parissiadis A. , Schell A. , Pfeiffer B. , Cazenave J.‐P. , Tongio M.M.
Published: March 2003

The authors describe an A*68 allele present at the molecular level but not expressed at the cell surface. This non expression results from the deletion of one nucleotide in exon 1, which causes a shift of the reading frame leading to an early non‐sense codon in the same exon Note.
Relevance of individual CD5 extracellular domains on antibody recognition, glycosylation and co‐mitogenic signalling
Authors: Calvo J. , Padilla O. , Places L. , Vigorito E. , Vilà J.m. , Vilella R. , Milà J. , Vives J. , Bowen M.a. , Lozano F.
Published: March 2003

CD5 is a type I glycoprotein which modulates T‐ and B‐cell receptor‐mediated signals and is expressed by thymocytes, mature T cells and a subset of mature B cells. The extracellular region of CD5 is composed of three scavenger receptor cysteine‐rich domains (D1, D2, D3) for which only limited functional and structural data are available. Using cell transfectants expressing ectodomain‐deficient CD5 molecules or CD5 immunoglobulin fusion proteins, we analysed individual CD5 domains with respect to monoclonal antibody binding specificity, glycosylation, and co‐mitogenic signalling. Our results show the presence of N‐linked oligosaccharides on D1 and D2, but not on D3. D1, the most amino‐terminal domain, is predicted to be the most appropriately placed domain for an interaction with a ligand. This domain is recognised by a large panel of well characterised CD5 mAbs, reflecting its higher immunogenicity. In an attempt to develop mAbs with specificity for the more conserved membrane‐proximal domains, we generated a unique mAb, named 83‐C4, whose binding mapped to D3. Co‐stimulatory studies revealed no significant differences between anti‐D1 and anti‐D3 mAbs. The high interspecies conservation of D3 implies a conserved role of this domain in CD5 function and the 83‐C4 mAb promises to be a valuable tool in exploring this.
Analysis of tumor necrosis factor‐α promoter polymorphism in type 1 diabetes: HLA‐B and ‐DRB1 alleles are primarily associated with the disease in Japanese
Authors: Hamaguchi K. , Kimura A. , Seki N. , Higuchi T. , Yasunaga S. , Takahashi M. , Sasazuki T. , Kusuda Y. , Okeda T. , Itoh K. , Sakata T.
Published: March 2003

Polymorphisms in the 5′‐flanking region of the tumor necrosis factor (TNF)‐α gene were examined to study the genetic background of type 1 diabetes in Japanese. Five different biallelic polymorphisms were examined in 136 type 1 diabetic patients and 300 control subjects. The frequencies of individuals carrying TNF‐α–857T allele (designated as TNFP‐D allele) or −863A/−1,031C allele (designated as TNFP‐B allele) were significantly increased in the patients as compared with the controls. Since these TNF‐α alleles are in linkage disequilibria with certain DRB1 and HLA‐B alleles, two‐locus analyses were carried out. The TNFP‐D allele did not increase the risk in either the presence or absence of the DRB1*0405 or HLA‐B54 allele, while the DRB1*0405 and HLA‐B54 alleles per se could confer susceptibility in both the TNFP‐D allele‐positive and ‐negative populations. Moreover, an odds ratio was remarkably elevated in the population carrying both DRB1*0405 and HLA‐B54. Similarly, the TNFP‐B allele did not show significant association with the disease in either the HLA‐B61‐positive or ‐negative population, while the HLA‐B61 allele could significantly increase the risk in the TNFP‐B allele‐positive population. These data suggest that the associations of TNFP‐D and ‐B alleles may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles. Because HLA‐B and DRB1 genes were independently associated, both of these genes may be contributed primarily to the pathogenesis of type 1 diabetes in Japanese.
An HLA‐B null allele (B*0808N) caused by a nucleotide deletion in exon 3, found in the family of a bone marrow transplant recipient
Authors: Carter V. , Dunn P.P.J. , Cavanagh G. , Day S. , Ross J. , Chapman C.
Published: March 2003

We have identified a variant HLA‐B allele, B*0808N, segregating through two generations of healthy individuals, whilst HLA typing the family of a bone marrow patient. Serological typing identified a disparity between the father (A1, A3 B7 DR7) and the brother (A1, A2 B56 DR1, DR7) of the patient. Low/medium resolution polymerase chain reaction using sequence‐specific primers (PCR‐SSP) revealed a B*08 allele undetectable by serological methods. High resolution DNA typing by polymerase chain reaction‐sequencing based typing (PCR‐SBT), revealed a nucleotide deletion at position 131 (C) in exon 3, the only difference between the new allele and B*0801. The deletion results in a frame shift in the protein coding sequence, introducing a premature termination codon (TGA) in exon 4. Although a B*08 allele is present in these individuals, the deletion prevents correct expression of the antigen on the cell surface ( Note).
Complete sequence analysis of the A*1103 allele
Authors: Tijssen H.J. , Sistermans E.A. , Van Den Beucken M. , Krausa P. , Joosten I.
Published: March 2003

Here we report the full‐length sequence of a novel A*11 variant. The variant was identified by ARMS‐PCR and serology, the sequence was confirmed by cloning and subsequent sequencing. This variant, A*1103, found in a family of oriental origin, resembles the A*1101 sequence in exon 2 but differs in exon 3 with regard to codons 151 and 152.

The polymorphism’s result in two amino acid substitutions (one conserved (His‐>Arg), one introducing a negative charge (Ala‐>Glu)) located in the α2 helical region. The arginine at amino acid position 151 is rare amongst A‐locus alleles and is besides A*1103 only observed in A*29 variants, the glutamine at amino acid position 152 is shared with A*0301, A*25, *26, *34 variants and the A*02 subtypes A*0203, *0213 and *0226. In fact, the amino acid motif comprising codons 151 and 152 is unique to A*1103 among A‐locus alleles, but is common to C‐locus alleles ( Note).
Identification of an HLA‐B7 serological variant and its characterization by sequencing based typing
Authors: Dunn P.P.J. , Carter V. , Dunn A. , Day S. , Fuggle S.V. , Ross J. , Cavanagh G.
Published: March 2003

We have identified an HLA‐B*07 variant allele, B*0716, in a Caucasoid cadaver kidney donor. The HLA class I type by polymerase chain reaction using sequence‐specific primers (PCR‐SSP) was A*01, 32; B*07, 08; Cw*07. Serological typing, using monoclonal and polyclonal anti‐HLA antisera, gave disparate results for the B antigens. Monoclonal antibodies identified B7 and B8 antigens but polyclonal antisera recognised only the B8 antigen. PCR using sequencing based typing (PCR‐SBT) confirmed the presence of both B*0703 and B*0801 alleles but with a mutation in one of the alleles. The HLA‐B*07 allele was isolated by allele‐specific PCR and was shown to have a mutation, G→T, at 292 in exon 2. This mutation changes codon 74, which encodes aspartic acid (GAC) present in all previously identified B*07 alleles, to tyrosine (TAC) in the variant. The serological results suggest that codon 74 is a crucial part of a B7 antigen‐specific epitope recognised by tissue typing polyclonal antisera ( Note).
Identification of a novel HLA‐Cw*O7 variant (Cw*0714) in a German Caucasian family
Authors: Lozano F. , Arias M.‐T. , Vilà J.‐M. , Gimferrer I. , Places L. , Hummler A. , Ehninger G. , Martorell J. , Vives J.
Published: March 2003

We report herein the identification of a new HLA‐Cw*07 allele in two members of a German Caucasian family. This novel allele, designated as Cw*0714, differs from Cw*07011 and Cw*0706 by two nucleotide changes: one at codon 66 (AAC→AAG) in the exon 2, leading to an amino acid change from Asn to Lys; and another silent substitution at codon 99 (TAT→TAC) in the exon 3. The latest substitution (T→C at the third position of codon 99) was not seen in any of the HLA‐Cw*07 alleles reported so far, thus being characteristic to the new HLA‐Cw*0714 allele ( Note).
Identification of the immunoreactive peptide sequence for AgSK1, an adenocarcinoma‐restricted antigen
Authors: Yasutomi J. , Koda K. , Saito N. , Nakajima N. , Nasoff M. , McKnight M. , Mukerjee S. , Gaskins C. , Chau P.C. , Glassy M.C.
Published: March 2003

Acknowledgments:

We would like to thank Jose Galindo and David Larocca for help during the initial phases of this work and to Minyi Gu, Soujan Wang and Janessa Molinari for expert technical assistance.

SK1, a human immunoglobulin M (IgM) monoclonal antibody was derived from regional nodal lymphocytes of a Dukes B colon carcinoma patient. The antigen recognized by the human monoclonal antibody (HuMab) SK1, termed AgSK1, was shown to be a two‐chain glycoprotein with an apparent molecular weight range of 42–46 kDa and preferentially expressed by human adenocarcinomas, particularly human gastrointestinal malignancies. To identify the gene encoding the AgSK1 antigenic epitope, a cDNA expression library constructed in λgt22A using mRNA from the colon carcinoma cell line HT29 was screened and one of the isolated clones encoding a 1.5‐kb cDNA, which showed strong immunoreactivity with HuMab SK1, was selected for further analysis. This clone consisted of an amino terminal open reading frame of 54 amino acids and the carboxyl terminal 20 amino acids of this protein coding region contained the antigenic epitope recognized by HuMab SK1.
Susceptible locus for obese type 2 diabetes mellitus in the 5′‐flanking region of the tumor necrosis factor‐α gene
Authors: Kamizono S. , Yamada K. , Seki N. , Higuchi T. , Kimura A. , Nonaka K. , Itoh K.
Published: March 2003

We have identified three novel polymorphisms in the promoter/enhancer region of the tumor necrosis factor (TNF)‐α gene. In this study we investigated the role of the polymorphisms in predisposition to Type 2 diabetes. The allele frequency of C→T substitution at −857 tended to be higher in obese patients with diabetes than in lean subjects with normal glucose tolerance (0.280 vs. 0.190). This tendency was due to a significantly higher ratio of −857T homozygotes in the obese patients with diabetes (15%) than in lean subjects with normal glucose tolerance (4%). There was no significant association between polymorphisms at positions −863 or −1,013, and diabetes. The homozygous −857T allele may be associated with genetic susceptibility to type 2 diabetes in obese subjects.
HLA‐DR51 expression failure caused by a two‐base deletion at exon 2 of a DRB5 null allele (DRB5*0110N) in a Spanish gypsy family
Authors: Balas A. , Ocon P. , Vicario J.L. , Alonso A.
Published: March 2003

Here we describe a new HLA class II null allele at the DRB5 gene. Serologic HLA typing of a Spanish gypsy family rendered the following paternal haplotype: A2‐Cblk‐B52‐Bw4‐DR15‐DQ5. However, DNA typing demonstrated the presence of a DRB5 gene in the haplotype DRB1*1502‐DRB5*0102‐DQB1*05031. Complete DRB5 cDNA sequencing revealed a DRB5*0102 allele with a deletion of two nucleotides at exon 2 (239–240) in codon 80. This change generates a frame shift leading to a stop codon at position 86, and could explain the lack of DR51 protein at the cell surface. This is the second DRB5 null allele described together with DRB5*0108N, raising the number of HLA alleles with an expression disorder ( Note).
A PCR‐SSP method to specifically select HLA‐A*0201 individuals for immunotherapeutic studies
Authors: Gatz S.A. , Pohla H. , Schendel D.J.
Published: March 2003

HLA‐A*0201 is an important restriction element for peptide presentation to T cells in disease and cancer. Mutation studies and analyses using cytotoxic T lymphocytes have shown the functional relevance of subtype‐specific differences in HLA‐A2 molecules for peptide binding and T‐cell receptor recognition. Therefore, many immunotherapeutic studies need to accurately select HLA‐A*0201‐positive individuals. We designed an easy, robust approach based on the polymerase chain reaction using sequence‐specific primers (PCR‐SSP) to specifically distinguish A*0201‐positive individuals from other HLA‐A2 subtypes described to date. The first step includes reactions that give information whether the sample donor is HLA‐A2 and, if so, whether the individual is homozygous or heterozygous for HLA‐A2. Further, it is determined whether the sample has an HLA‐A*0209 or an HLA‐A*0201 sequence at the corresponding position in exon 4. Samples that may contain an HLA‐A*0201 allele according to the results of this first step are subtyped in a second step nested PCR. Here the strategy is focussed on the discrimination of HLA‐A*0201 from the other subtypes by considering divergent nucleotide positions in two ways. One SSP combination amplifies the HLA‐A*0201 sequence while a corresponding SSP combination specifically amplifies the subtype or group of subtypes differing from HLA‐A*0201 at this position. Thus, at relevant polymorphic nucleotide positions the HLA‐A*0201 sequence is both directly and indirectly confirmed. This strategy strongly enhances the reliability of the subtyping and allows better verification of HLA‐A*0201‐positive patient selection for clinical studies ( Note).
HLA‐B*8202 identified in a Caucasoid potential bone marrow donor
Authors: Cox S.T. , Hossain E. , McWhinnie A. , Prokupek B. , Madrigal J.A. , Little A.‐M.
Published: March 2003

Sequence analysis of HLA class I alleles has continued to reveal the true extent of polymorphism, particularly for B‐locus alleles. This diversity can arise through reshuffling of polymorphic sequences generated by point mutation, resulting in interallelic recombination or intergenic recombination ( 1). Here we describe a new B‐locus allele, B*8202, which is structurally most similar to B*8201, having only one nucleotide difference in exon 3 at nucleotide 557, resulting in an amino acid change of aspartic acid to glycine at residue 162. Glycine is the consensus amino acid for B‐locus alleles, which suggests that B*8202 is older than B*8201 in evolutionary terms. B*8201 was found to be a hybrid of B*4501 and B*5602 that may have arisen through recombination events, explaining the serological patterns observed with these allotypes. The importance of high‐resolution typing is emphasised here as routine typing suggested the presence of B*8201 and the new variant allele may have been missed had it not been typed further by sequence‐based typing ( Note).
Identification by sequencing based typing and complete coding region analysis of three new HLA class II alleles: DRB3*0210, DRB3*0211 and DQB1*0310
Authors: Balas A. , Santos S. , Aviles M.J. , Garcia‐Sanchez F. , Lillo R. , Vicario J.L.
Published: March 2003

The study of HLA class II polymorphism by direct exon 2 DNA sequencing analysis has been established to be a reliable and accurate high‐resolution typing procedure. This approach shows some advantages in relation to previous methods, polymerase chain reaction using sequence‐specific oligonucleotides (PCR‐SSO) and sequence‐specific primers (PCR‐SSP), basically due to the capability of analysis for the complete sequenced genomic region, including non‐polymorphic motifs. DRB3 and DQB1 sequencing based typing (SBT) in unrelated bone marrow donor searching allowed us to detect three new alleles. The complete coding region sequences were characterised from cDNA. Two new DRB3 alleles, DRB3*0210 and DRB3*0211, were described in two Caucasian bone marrow donors. Both sequences showed single point mutations regarding DRB3*0202, producing amino acid replacements at positions 51 (Asp to Thr) and 67 (Leu to Ile), respectively. These two point mutations can be found in other DRB alleles, and suggest that gene conversion would be involved in the origin of both alleles. A new DQB1 sequence was found in a Spanish patient that showed two nucleotide differences, positions 134 and 141, with regard to its close similar DQB1*03011 allele. Only substitution at position 134 provoked amino acid replacement at residue 45, Glu to Gly. This single amino acid change would be involved in the lack of serologic recognition of this new molecule by DQ7‐specific reagents ( Note).
HLA‐B*0811: another example of a single point substitution of the HLA‐B*0801 allele
Authors: Magira E. , Beznik‐Cizman B. , Monos D.
Published: March 2003

Acknowledgments:

This work was supported in part by office of Naval Research cooperative agreement # N‐00014‐96‐2‐0016 to the National Marrow Donor Program and by funding from the E.B. Foerderer Fund of the Children’s Hospital of Philadelphia to D.M.

The described alle HLA‐B*0811 is of Caucasoid origin. Most likely it derived from a point mutation of the B*0801 allele at position 559, where an adenine was converted to guanine. This position corresponds to codon 163 and resulted in an amino acid change from threonine to alanine. This substitution may influence both, T‐cell interactions and/or peptide binding ( Note).
No association between IL‐10 promoter gene polymorphism and heart failure or rejection following cardiac transplantation
Authors: Bijlsma F.J. , Bruggink A.H. , Hartman M. , Gmelig‐Meyling F.H.J. , Tilanus M.G.J. , De Jonge N. , De Weger R.A.
Published: March 2003

Abstract: Expression of interleukin (IL)‐10 influences the frequency of rejection events after organ transplantation. Therefore, 70 heart transplant patients were genotyped for three single nucleotide polymorphisms and a microsatellite polymorphism in the promotor region of the IL‐10 gene. The promoter region was amplified by polymerase chain reaction and genotyped by a colorometric oligo ligation assay and gene scan analysis, respectively. Patient groups consisted of patients suffering from dilated cardiomyopathy or ischaemic heart disease. Cardiac donors served as control group. No correlation was found between genotypes and heart failure or rejection after heart transplantation. This may indicate that in heart transplantation, the total balance of cytokine production is more important for post‐transplant rejection activities than the levels of IL‐10 as such.
Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA‐Cw*0602‐B*5701 in German families
Authors: Schmitt‐Egenolf M. , Windemuth C. , Hennies H.C. , Albis‐Camps M. , Von Engelhardt B. , Wienker T. , Reis A. , Traupe H. , Blasczyk R.
Published: March 2003

Abstract: HLA antigens are associated with psoriasis vulgaris across populations with different ethnic background. We have previously shown that in Caucasians this association is primarily based on the class I alleles of the extended HLA haplotype 57.1 (EH57.1/I), HLA‐Cw6‐HLA‐B57. However, it remained unclear whether HLA‐Cw6 itself or a closely linked locus predisposes to the disease. An interesting candidate for this presumed locus is corneodesmosin, which is exclusively synthesized in keratinocytes. The corneodesmosin gene locus (CDSN) is only 160 kb telomeric to HLA‐C and tightly associated with psoriasis. In order to find out whether EH57.1/I or a corneodesmosin variant are the susceptibility determinants on 6p, HLA class I alleles and single‐nucleotide polymorphisms (SNPs) of corneodesmosin were investigated at the sequence level and analyzed by comparative association tests. Transmission disequilibrium tests (TDT) were performed in 52 nuclear families, of which 36 were fully informative for a joint comparison of HLA and CDSN with regard to association to psoriasis. The extended TDT according to Wilson was employed to test for locus interaction. Using the HLA haplotype EH57.1/I and the CDSN haplotype formed by three intragenic variant sites at nt=619 (T), 1236 (T), and 1243 (C), we obtained the best resolution of parental transmission to index cases in the trio families. On direct comparison of the contributions of the HLA and the CDSN haplotypes, there was a markedly stronger association of the corneodesmosin TTC haplotype, which is not apparent in single locus analysis. We show furthermore that there is no higher order interaction between psoriasis, HLA, and CDSN. This lack of three‐locus interaction is suggestive of two independent genetic contributions to psoriasis within the major histocompatibility complex (MHC).
Analysis of HLA class I expression in different metastases from two melanoma patients undergoing peptide immunotherapy
Authors: Mendez R. , Serrano A. , Jäger E. , Maleno I. , Ruiz‐Cabello F. , Knuth A. , Garrido F.
Published: March 2003

Abstract: We characterized the HLA class I alterations in five metastases obtained from two patients with melanoma immunized with Melan A/MART‐1, tyrosinase and gp100 tumor peptides. All three metastases analyzed in the first patient (NW145) showed a similar HLA class I alteration with a dual population of melanoma cells. One population was HLA class I antigen positive and the other had loss of heterozygosity (LOH) in the short arm of chromosome 6 leading to an HLA haplotype loss (A02011, B4007, Cw1). The absence of HLA‐A2 antigen may explain why this patient did not develop HLA‐A2 restricted, Melan A/MART‐1 specificity immunization, since this HLA molecule is the restriction element for the tumor peptides used. However, this HLA‐deficient population was not selected after peptide immunotherapy. The primary tumor in this patient presented LOH in region 6q, but only in the vertical growth phase of the lesion, whereas LOH at 6p was observed only in DNA from metastatic material. The second patient (NW16) also presented two metastatic lesions with an identical HLA molecular defect, i.e. HLA B locus downregulation (HLA B51011: serological B51; B1503: serological B70). One lesion expressed the tumor antigen (Melan A/ MART‐1), but the other did not. Interestingly, the antigen‐positive metastasis regressed after peptide immunotherapy, whereas the other progressed rapidly. These findings provide the first indication that multiple metastases generated in the same host can have identically altered HLA class I phenotypes.
The distribution of DQ genes in the Saharawi population provides only a partial explanation for the high celiac disease prevalence
Authors: Catassi C. , Doloretta Macis M. , Rätsch I.‐M. , De Virgiliis S. , Cucca F.
Published: March 2003

Abstract: Celiac disease (CD) is a multifactorial disorder of the small intestine caused by a permanent dietary intolerance to gluten. The combined presence of the HLA class II DQA1*0501 and DQB1*0201 alleles represents the major genetic component for disease predisposition. It has been shown that the Saharawi refugees living in northern Africa have a very high frequency of CD. In the present study we analysed this population to evaluate the degree of association with CD of the haplotypes and genotypes at the main HLA‐DQB1 and DQA1 disease loci. We found a strong association of the DR3, DQB1*0201‐DQA1*0501‐positive haplotypes and genotypes. A very high frequency of DR3, DQB1*0201‐DQA1*0501 was also observed in the general Saharawi population. These results indicate that there is a good correlation between disease prevalence and frequency of the main predisposing haplotype in the background population. However, the correlation is incomplete because similar frequencies of DR3 are also observed in populations such as the Sardinians showing a much lower prevalence of CD. We can conclude that the distribution of DQ genes in the Saharawi population only provides a partial explanation for the high prevalence of CD. Other factors, such as rapidly changing dietary habits and/or non‐DQ genes, may also play some role.
Association of HLA‐DRB1*1502–DQB1*0501 haplotype with susceptibility to systemic lupus erythematosus in Thais
Authors: Sirikong M. , Tsuchiya N. , Chandanayingyong D. , Bejrachandra S. , Suthipinittharm P. , Luangtrakool K. , Srinak D. , Thongpradit R. , Siriboonrit U. , Tokunaga K.
Published: March 2003

Abstract: In this study, we investigated the association of HLA‐DRB1 and DQB1 with Thai patients with SLE. A highly significant increase in the frequency of DRB1*1502 and DQB1*0501 was found in SLE patients compared with normal controls. DRB1*1501 and DRB1*1602 were also slightly increased. In contrast, DRB1*1202 and DQB1*0301 were decreased, and DRB1*0406 and DRB1*1401 were not found in the patients' group. The haplotype analysis revealed that DRB1*1502 – DQB1*0501 was most strongly associated with SLE, and also suggested a primary role for DRB1 rather than DQB1. Taken together with the previous report which demonstrated the association of the same haplotype in Taiwan, our present observations strongly suggested that DRB1*1502 – DQB1*0501 is the major HLA haplotype that confers susceptibility to SLE in the South‐east Asian populations.
IMPORTANCE OF A3 ALLELE OF HLA CLASS I IN RESPONSE TO HEPATITIS B VACCINE IN END‐STAGE RENAL DISEASE PATIENTS
Authors: Turan M , Özdemir FN , Micozkadıoğlu H , Arat Z , Gülmüş S , Haberal M
Published: March 2003

Vaccination against hepatitis B virus (HBV) infection is very important for hemodialysis (HD) patients, as these individuals are at high risk because of intravenous interventions and therapies. The aim of this study was to examine how genetic factors may be related to the response of HD patients to the HBV vaccination. This was carried out by investigating the frequencies of HLA class I and II alleles in responders and nonresponders. The study included 256 (171 male and 85 female) HD patients who tested negative for antibodies to the hepatitis B surface antigen in pretransplantation evaluations performed at our center between 1986 and 1999. Each patient received four doses of 40 μg DNA‐recombinant hepatitis B vaccine at 0, 1, 2 and 6 months. Group I consisted of the 166 patients who responded to the vaccination (anti‐HBsAg >10 SI U/l) and Group II consisted of the 90 nonresponders (anti‐HBsAg <10 SI U/l). The frequency of the HLA‐A3 allele was significantly higher in Group I than in Group II (P=0.02). One hundred and seven of the 256 patients underwent renal allograft transplantation, and 14 recipients lost their grafts at a mean of 1326±1394 days. There was no significant difference in graft outcome between the responders and the nonresponders (P>0.05). In conclusion, this was a preliminary study showing that HLA alleles may have immunomodulatory effects in end‐stage renal failure patients. The response to hepatitis B vaccination is affected multifactorially and HLA‐A3 may be a genetic predictor for responders, but further studies and larger series are required.
HLA‐B*5130, a new HLA‐B allele carrying a rare nucleotide substitution in exon 4
Authors: Gimferrer I. , Arias M. T. , Fabregat V. , Martorell J. , Vives J. , Lozano F.
Published: March 2003

Abstract: We report herein the identification of a new HLA‐B*51 allele in a Spanish Caucasoid organ donor. The novel allele, designated B*5130, differs from B*51011 by one nucleotide change at position 787 (A to G) in exon 4, leading to an amino acid change from Arg (AGA) to Gly (GGA) at codon 239 in the α3 domain. This substitution is present in most classical and nonclassical HLA class I loci (A, C, E, and G) but not in any of the HLA‐B alleles reported so far, except for B*7301. Although the frequency of the new variant seems to be low, its existence makes mandatory the analysis of exon 4 before assigning a B*5101 type.
Design of peptides withα,β‐dehydro‐residues: synthesis, and crystal and molecular structure of a310‐helical tetrapeptide Boc‐l‐Val‐ΔPhe‐ΔPhe‐l‐Ile‐OCH3
Authors: Bhatia S. , Kumar P. , Kaur P. , Singh T.P.
Published: March 2003

Abstract: The peptide Boc‐l‐Val‐ΔPhe‐ΔPhe‐l‐Ile‐OCH3 was synthesized using the azlactone method in the solution phase, and its crystal and molecular structures were determined by X‐ray diffraction. Single crystals were grown by slow evaporation from solution in methanol at 25°C. The crystals belong to an orthorhombic space group P212121 with a = 12.882(7) Å, b = 15.430(5) Å, c = 18.330(5) Å and Z = 4. The structure was determined by direct methods and refined by a least‐squares procedure to an R‐value of 0.073. The peptide adopts a right‐handed 310‐helical conformation with backbone torsion angles: φ1 = 56.0(6)°, ψ1 = –38.0(6)°, φ2 = –53.8(6)°, ψ2 = 23.6(6)°, φ3 = –82.9(6)°, ψ3 = –10.6(7)°, φ4 = 124.9(5)°. All the peptide bonds are trans. The conformation is stabilized by intramolecular 4→1 hydrogen bonds involving Boc carbonyl oxygen and NH of ΔPhe3 and CO of Val1 and NH of Ile4. It is noteworthy that the two other chemically very similar peptides: Boc‐Val‐ΔPhe‐ΔPhe‐Ala‐OCH3 (i) and Boc‐Val‐ΔPhe‐ΔPhe‐Val‐OCH3 (ii) with differences only at the fourth position have been found to adopt folded conformations with two overlapping β‐turns of types II and III′, respectively, whereas the present peptide adopts two overlapping β‐turns of type III. Thus the introduction of Ile at fourth position in a sequence Val‐ΔPhe‐ΔPhe‐X results in the formation of a 310‐helix. The crystal structure is stabilized by intermolecular hydrogen bonds involving NH of Val1 and carbonyl oxygen of a symmetry related (–x, y – 1/2, 1/2 + z) ΔPhe2 and NH of ΔPhe2 with carbonyl oxygen of a symmetry related (x, y1/2, 1/2 + z) Ile4. This gives rise to long columns of helical molecules linked head to tail running along [010] direction.
Solution structures of the cytoplasmic linkers between segments S4 and S5 (S4−S5) in domains III and IV of human brain sodium channels in SDS micelles
Authors: Miyamoto K. , Nakagawa T. , Kuroda Y.
Published: March 2003

Abstract: The two cytoplasmic linkers connecting segment S4 and segment S5 (S4−S5 linker) of both domain III (III/S4−S5) and IV (IV/S4−S5) of the sodium channel α‐subunit are considered to work as a hydrophobic receptor for the inactivation particle because of the three hydrophobic amino acids of Ile‐Phe‐Met (IFM motif) in the III−IV linker of the sodium channel α‐subunit. To date, the solution structures of the peptides related to III/S4−S5 (MP‐D3: A1325−M1338) and IV/S4−S5 (MP‐D4: T1648−L1666) of human brain sodium channels have been investigated using CD and 1H NMR spectroscopies. SDS micelles were employed as a solvent. The micelles mimic either biological membranes or the interior of a protein and can be a relevant environment at the inactivated state of the channels. It was found that the secondary structures of both MP‐D3 and MP‐D4 assume α‐helical conformations around the N‐terminal half‐side of the sequences, i.e. the residues between V1326 and L1331 in MP‐D3 and between L1650 and S1656 in MP‐D4. Residue A1329 in MP‐D3, which is considered to interact with F1489 of the IFM motif, was found to be located within the α‐helix. Residues F1651, M1654, M1655, L1657 and A1669 in MP‐D4, which also play an important role in inactivation, formed a hydrophobic cluster on one side of the helix. This cluster was concluded to interact with the hydrophobic cluster due to the III−IV linker before the inactivation gate closes.
Effect of asymmetric modification on the conformation of ascidiacyclamide analogs
Authors: Asano A. , Minoura K. , Yamada T. , Numata A. , Ishida T. , Doi M. , Katsuya Y. , Mezaki Y. , Sasaki M. , Taniguchi T. , Nakai M. , Hasegawa H. , Terashima A.
Published: March 2003

Abstract: Ascidiacyclamide (ASC), cyclo(‐Ile1‐Oxz2‐d‐Val3‐Thz4‐)2 (Oxz=oxazoline and Thz=thiazole) has a C2‐symmetric sequence, and the relationships between its conformation and symmetry have been studied. In a previous study, we performed asymmetric modifications in which an Ile residue was replaced by Gly, Leu or Phe to disturb the symmetry [Doi et al. (1999) Biopolymers49, 459–469]. In this study, the modifications were extended. The Ile1 residue was replaced by Gly, Ala, aminoisobutyric acid (Aib), Val, Leu, Phe or d‐Ile, and the d‐Val3 residue was replaced by Val. The structures of these analogs were analyzed by X‐ray diffraction, 1H NMR and CD techniques. X‐Ray diffraction analyses revealed that the [Ala1], [Aib1] and [Phe1]ASC analogs are folded, whereas [Val1]ASC has a square form. These structures are the first examples of folded structures for ASC analogs in the crystal state and are similar to the previously reported structures of [Gly1] and [Phe1]ASC in solution. The resonances of amide NH and Thz CH protons linearly shift with temperature changes; in particular, those of [Aib1], [d‐Ile1] and [Val3]ASCs exhibited a large temperature dependence. DMSO titration caused nonlinear shifts of proton resonances for all analogs and largely affected [d‐Ile1] and [Val3]ASCs. A similar tendency was observed upon the addition of acetone to peptide solutions. Regarding peptide concentration changes, amide NH and Thz CH protons of [Gly1]ASC showed a relatively large dependence. CD spectra of these analogs indicated approximately two patterns in MeCN solution, which were related to the crystal structures. However, all spectra showed a similar positive Cotton effect in TFE solution, except that of [Val3]ASC. In the cytotoxicity test using P388 cells, [Val1]ASC exhibited the strongest activity, whereas the epimers of ASC ([d‐Ile1] and [Val3]ASCs), showed fairly moderate activities.
Prediction of β‐turns from amino acid sequences using the residue‐coupled model
Authors: Guruprasad K. , Shukla S.
Published: March 2003

Abstract: We evaluated the prediction of β‐turns from amino acid sequences using the residue‐coupled model with an enlarged representative protein data set selected from the Protein Data Bank. Our results show that the probability values derived from a data set comprising 425 protein chains yielded an overall β‐turn prediction accuracy 68.74%, compared with 94.7% reported earlier on a data set of 30 proteins using the same method. However, we noted that the overall β‐turn prediction accuracy using probability values derived from the 30‐protein data set reduces to 40.74% when tested on the data set comprising 425 protein chains. In contrast, using probability values derived from the 425 data set used in this analysis, the overall β‐turn prediction accuracy yielded consistent results when tested on either the 30‐protein data set (64.62%) used earlier or a more recent representative data set comprising 619 protein chains (64.66%) or on a jackknife data set comprising 476 representative protein chains (63.38%). We therefore recommend the use of probability values derived from the 425 representative protein chains data set reported here, which gives more realistic and consistent predictions of β‐turns from amino acid sequences.
Insights into the determinants of β‐sheet stability: 1H and 13C NMR conformational investigation of three‐stranded antiparallel β‐sheet‐forming peptides
Authors: Santiveri C.M. , Rico M. , Jiménez M.A. , Pastor M.T. , Pérez‐Payá E.
Published: March 2003

Abstract: In a previous study we designed a 20‐residue peptide able to adopt a significant population of a three‐stranded antiparallel β‐sheet in aqueous solution (de Alba et al. [1999]Protein Sci.8, 854–865). In order to better understand the factors contributing to β‐sheet folding and stability we designed and prepared nine variants of the parent peptide by substituting residues at selected positions in its strands. The ability of these peptides to form the target motif was assessed on the basis of NMR parameters, in particular NOE data and 13Cα conformational shifts. The populations of the target β‐sheet motif were lower in the variants than in the parent peptide. Comparative analysis of the conformational behavior of the peptides showed that, as expected, strand residues with low intrinsic β‐sheet propensities greatly disfavor β‐sheet folding and that, as already found in other β‐sheet models, specific cross‐strand side chain–side chain interactions contribute to β‐sheet stability. More interestingly, the performed analysis indicated that the destabilization effect of the unfavorable strand residues depends on their location at inner or edge strands, being larger at the latter. Moreover, in all the cases examined, favorable cross‐strand side chain–side chain interactions were not strong enough to counterbalance the disfavoring effect of a poor β‐sheet‐forming residue, such as Gly.
Dipole interaction model predicted π−π* circular dichroism of cyclo(l‐Pro)3 using structures created by semi‐empirical, ab initio, and molecular mechanics methods
Authors: Lowe S.L. , Pandey R.R. , Czlapinski J. , Kie‐Adams G. , Hoffmann M.R. , Thomasson K.A. , Pierce Ken S.
Published: March 2003

Abstract: Cyclo(l‐Pro)3 (CP3) is a synthetic peptide created to model cis and torsionally strained peptide bonds that also exhibits a strong distinctive UV circular dichroic (CD) spectrum. Circular dichroic spectra were computed for the amide π − π* transition using the dipole interaction model for various conformations of the peptide. Conformations of CP3 were created initially from crystal data, and followed by energy minimizations via molecular mechanics using the cvff force field; the effects of additional geometric optimizations by semi‐empirical and ab initio quantum mechanics were investigated. The CD spectra for each conformation were calculated using a variety of different parameters, and each result was compared with the published experimental spectrum [Deber, C.M., Scatturin, A., Vaidya, V.M. & Blout, E.R. (1970) Small cyclic proline peptides: UV absorption and CD. In: Peptides: Chemistry and Biochemistry, Proceedings of the First American Peptide Symposium (Weinstein, B., ed.), Marcel Dekker, New York pp. 163–173]. Herein, two distinct conformations, a C3 symmetric and an asymmetric form, gave CD predictions that separately did not resemble the experimental spectrum. Energy differences were predicted at various theoretical levels, including MP2 and density functional theory. When the predicted CD spectra for each conformation were multiplied by Boltzmann weighting factors created using heats of formation determined by the AM1 optimizations, the weighted composite CD spectrum created did resemble experiment for the π − π* transition indicating that both conformations may exist simultaneously in solution.