bluuebunny/crossref_metadata_2025 huggingface dataset:
The Equity Premium
Authors: Fama Eugene F. , French Kenneth R.
Published: March 2003

We estimate the equity premium using dividend and earnings growth rates to measure the expected rate of capital gain. Our estimates for 1951 to 2000, 2.55 percent and 4.32 percent, are much lower than the equity premium produced by the average stock return, 7.43 percent. Our evidence suggests that the high average return for 1951 to 2000 is due to a decline in discount rates that produces a large unexpected capital gain. Our main conclusion is that the average stock return of the last half‐century is a lot higher than expected.
Do Firms Hedge in Response to Tax Incentives?
Authors: Graham John R. , Rogers Daniel A.
Published: March 2003

There are two tax incentives for corporations to hedge: to increase debt capacity and interest tax deductions, and to reduce expected tax liability if the tax function is convex. We test whether these incentives affect the extent of corporate hedging with derivatives. Using an explicit measure of tax function convexity, we find no evidence that firms hedge in response to tax convexity. Our analysis does, however, indicate that firms hedge to increase debt capacity, with increased tax benefits averaging 1.1 percent of firm value. Our results also indicate that firms hedge because of expected financial distress costs and firm size.
New Evidence of the Impact of Dividend Taxation and on the Identity of the Marginal Investor
Authors: Bell Leonie , Jenkinson Tim
Published: March 2003

This paper examines the impact of a major change in dividend taxation introduced in the United Kingdom in July 1997. The reform was structured in such a way that the immediate impact fell almost entirely on the largest investor class in the United Kingdom, namely pension funds. We find significant changes in the valuation of dividend income after the reform, in particular for high‐yielding companies. These results provide strong support for the hypothesis that taxation affects the valuation of companies, and that pension funds were the effective marginal investors for high‐yielding companies.
Book‐to‐Market Equity, Distress Risk, and Stock Returns
Authors: Griffin John M. , Lemmon Michael L.
Published: March 2003

This paper examines the relationship between book‐to‐market equity, distress risk, and stock returns. Among firms with the highest distress risk as proxied by Ohlson's (1980) O‐score, the difference in returns between high and low book‐to market securities is more than twice as large as that in other firms. This large return differential cannot be explained by the three‐factor model or by differences in economic fundamentals. Consistent with mispricing arguments, firms with high distress risk exhibit the largest return reversals around earnings announcements, and the book‐to‐market effect is largest in small firms with low analyst coverage.
Rapid Localization of Gag/GagPol Complexes to Detergent-Resistant Membrane during the Assembly of Human Immunodeficiency Virus Type 1
Authors: Halwani Rabih , Khorchid Ahmad , Cen Shan , Kleiman Lawrence
Published: March 2003

During human immunodeficiency virus type 1 (HIV-1) assembly in HIV-1-transfected COS7 cells, almost all steady-state Gag/Gag and Gag/GagPol complexes are membrane bound. However, exposure to 1% Triton X-100 gives results indicating that while all Gag/GagPol complexes remain associated with the detergent-resistant membrane (DRM), only 30% of Gag/Gag complexes are associated with the DRM. Analysis of the localization of newly synthesized Gag/Gag and Gag/GagPol to the membrane indicates that after a 10-min pulse with radioactive [
35
S]Cys-[
35
S]Met, all newly synthesized Gag/GagPol is found at the DRM. Only 30% of newly synthesized Gag/Gag moves to the membrane, and at 0 min of chase, only 38% of this membrane-bound Gag/Gag is associated with the DRM. During the first 30 min of chase, most membrane-bound Gag/Gag moves to the DRM, while between 30 and 60 min of chase, there is a significant decrease in membrane-bound Gag/Gag and Gag/GagPol. Since the localization of newly synthesized Gag/Gag to the DRM and the interaction of GagPol with Gag both depend upon Gag multimerization, the rapid localization of GagPol to the DRM probably reflects the interaction of all newly synthesized GagPol with the first newly synthesized polymeric Gag to associate with the DRM.
Quantitative Analysis of Herpes Simplex Virus Reactivation In Vivo Demonstrates that Reactivation in the Nervous System Is Not Inhibited at Early Times Postinoculation
Authors: Sawtell N. M.
Published: March 2003

Recent studies utilizing an ex vivo mouse model of herpes simplex virus (HSV) reactivation have led to the hypothesis that, under physiologic conditions inducing viral reactivation, the immune cells within the infected ganglion block the viral replication cycle and maintain the viral genome in a latent state. One prediction from the ex vivo study is that reactivation in ganglia in vivo would be inhibited at early times postinoculation, when the numbers of inflammatory cells in the ganglia are greatest. To distinguish between an effect of the immune infiltrates on (i) infectious virus produced and/or recovered in the ganglion and (ii) the number of neurons undergoing lytic transcriptional activity (reactivating), an assay to quantify the number of neurons expressing lytic viral protein in ganglia in vivo was developed. Infectious virus and HSV protein-positive neurons were quantified from days 9 through 240 postinoculation in latently infected trigeminal ganglia before and at 22 h after hyperthermic-stress-induced reactivation. Significant increases in the amount of virus and the number of positive neurons were detected poststress in ganglia at all times examined. Unexpectedly, the greatest levels of reactivation occurred at the times examined most proximal to inoculation. Acyclovir was utilized to stop residual acute-phase virus production, and this treatment did not reduce the level of reactivation on day 14. Thus, the virus measured after induction was a product of reactivation. These data indicate that, in contrast to observations in the ex vivo model, immune cells in the ganglia during the resolution of acute infection do not inhibit reactivation of the virus in ganglia in vivo.
Use of Transgenic HLA A*0201/Kb and HHD II Mice To Evaluate Frequency of Cytomegalovirus IE1-Derived Peptide Usage in Eliciting Human CD8 Cytokine Response
Authors: Gallez-Hawkins Ghislaine , Villacres Maria C. , Li Xiuli , Sanborn Margaret C. , Lomeli Norma A. , Zaia John A.
Published: March 2003

Unlike the pp65 protein of human cytomegalovirus (CMV), which has an immunodominant peptide, pp65495-503, recognized by human CD8+cells in the context of HLA A*0201, the fine peptide specificity for CMV IE1 has shown no such immunodominance. With the use of transgenic HLA A*0201/Kb and HHD II mice, a selected pool of IE1 peptides, including IE1p256-264, IE1p297-304, and IE1p316-324, were shown to stimulate cytolytic T-lymphocyte lysis in the context of HLA A*0201. Based on an intracellular gamma interferon response, IE1p297-304, a previously unrecognized CD8 epitope, triggered a prominent response to CMV IE1 in HLA A*0201 subjects.
CLUSTERING CATEGORICAL AND NUMERICAL DATA: A NEW PROCEDURE USING MULTIDIMENSIONAL SCALING
Authors: LEE SUNG-GI , YUN DEOK-KYUN
Published: March 2003

In this paper, we present a concept based on the similarity of categorical attribute values considering implicit relationships and propose a new and effective clustering procedure for mixed data. Our procedure obtains similarities between categorical values from careful analysis and maps the values in each categorical attribute into points in two-dimensional coordinate space using multidimensional scaling. These mapped values make it possible to interpret the relationships between attribute values and to directly apply categorical attributes to clustering algorithms using a Euclidean distance. After trivial modifications, our procedure for clustering mixed data uses the k-means algorithm, well known for its efficiency in clustering large data sets. We use the familiar soybean disease and adult data sets to demonstrate the performance of our clustering procedure. The satisfactory results that we have obtained demonstrate the effectiveness of our algorithm in discovering structure in data.
Combining environmental information via hierarchical modeling: an example using mutagenic potencies
Authors: Simmons Susan J. , Piegorsch Walter W. , Nitcheva Daniela , Zeiger Errol
Published: March 2003

Mutagenesis assays of toxic environmental agents often provide only a single snapshot of the agent's potential risk, leading to inferences on a possibly isolated phenomenon. Hierarchical models can enhance inferences on environmental agents and obtain more global perspectives on the potential risk. We investigate the use of such models to combine information across environmental studies. We emphasize combination of potency estimates from bioassays used for environmental hazard identification and risk assessment. The models and methods illustrate hierarchical Bayesian techniques to estimate the parameters and make inferences on the unknown potency values. Copyright © 2003 John Wiley & Sons, Ltd.
New serum‐free in vitro culture technique for midgestation mouse embryos
Authors: Moore‐Scott Billie A. , Gordon Julie , Blackburn C. Clare , Condie Brian G. , Manley Nancy R.
Published: March 2003

Summary: Current in vitro culture methods for mouse embryos are critically dependent on specially prepared rodent serum. Rodent serum requires careful preparation and stringent assessment of serum quality, while commercially available whole embryo culture serum is expensive and shows considerable lot variability. Thus, preparation and testing of suitable serum represents a considerable investment of time and resources, particularly for laboratories with only short‐term embryo culture requirements. In addition, serum supplementation of culture medium may introduce unknown serum components that could interfere with interpretation of experimental results, especially where the study is geared towards analysis of a specific growth factor. Here we describe the composition of a standardized serum free culture medium comprised of commercially available stem cell media supplements. With this method, we have successfully cultured midgestation stage mouse embryos and demonstrated, using both morphological and gene expression criteria, that these embryos exhibited proper developmental progression. We believe this method to be a significant advance in whole embryo culture technology that will be of particular use to laboratories needing to utilize whole embryo culture to study midgestation organogenesis. genesis 35:164–168, 2003. © 2003 Wiley‐Liss, Inc.
Incidence trends and familial risks in invasive and in situ cutaneous melanoma by sun‐exposed body sites
Authors: Hemminki Kari , Zhang Hong , Czene Kamila
Published: March 2003

We studied incidence trends, age‐incidence relationships and familial risks in invasive and in situ cutaneous melanoma, based on the Swedish Family‐Cancer Database of more than 10 million individuals. Offspring were 0–66 years of age. Cancers were obtained from the Swedish Cancer Registry from years 1961–98. The study was based on 9,771 offspring and 22,888 parents with invasive melanoma and 2,446 offspring and 5,017 parents with in situ melanoma. Incidence rates increased markedly for invasive melanoma in the trunk. For in situ melanoma, trunk and head and neck were affected, and, in addition, legs for women. The maximal incidence was around age 80 years, independent of the type or site in men; in women early onset superficially spreading melanoma shifted the age for maximal incidence to about 60 years. For in situ melanoma, lentigo maligna was the main histogenetic type in the head and neck but in the trunk and legs superficially spreading melanoma was somewhat more common. Standardized incidence ratios (SIR) were calculated for familial risk at exposed and covered sites. The combined familial risks for invasive and in situ melanoma were higher at covered (SIR 3.56 from parents) than sun‐exposed (1.92 from parents) sites and they agreed when familiality was defined between parents and offspring or between siblings; the sibling SIRs were 3.90 at covered and 2.53 at exposed sites. The data suggest that the higher melanoma density at exposed sites masks familial effects. Furthermore, sun exposure does not appear to reinforce the familial effect. © 2003 Wiley‐Liss, Inc.
Management accounting in the twenty‐first‐century firm: a strategic view
Authors: Yazdifar Hassan
Published: March 2003

This paper proposes that conventional management accounting needs to be changed to assist management in strategic decision making.

The deficiencies of conventional management accounting systems are discussed and some suggestions are made to improve their role in new organizational settings.

Copyright © 2003 John Wiley & Sons, Ltd.
Detection of soluble HLA‐G molecules in plasma and amniotic fluid
Authors: Rebmann V. , Pfeiffer K. , Päßler M. , Ferrone S. , Maier S. , Weiss E. , Grosse‐Wilde H.
Published: March 2003

Although the cDNA sequence of HLA‐G antigens is compatible with their expression as soluble molecules (sHLA‐G), the determination of native sHLA‐G levels in body fluids has not yet been described. The lack of this information is likely to reflect the difficulties in developing an assay suitable to measure sHLA‐G antigens in the presence of soluble HLA‐A, ‐B and ‐C (sHLA‐I) antigens, since most of the available anti‐HLA‐G mAb do not detect soluble β2‐m associated HLA‐G antigens or crossreact with sHLA‐I antigens. Therefore, we have developed a two‐step assay which eliminates the interference of classical HLA class I antigens. In the first step, the sample is depleted of sHLA‐I antigens and of HLA‐E antigens with mAb TP25.99. Then, HLA‐G antigens are captured with mAb W6/32 and detected with anti‐β2‐m mAb in ELISA. Utilizing this assay, sHLA‐G antigen levels were measured in EDTA plasma from 92 controls with known HLA types, 28 women at delivery and the corresponding cord bloods and in 50 amniotic fluids. Mean sHLA‐G plasma levels did not differ between males (24.9±3.0 SEM ng/ml; n=42) and females (20.1±2.1 SEM ng/ml; n=50). However, sHLA‐G levels in HLA‐A11 positive probands (mean: 13.0±4.4 SEM ng/ml; n=12) were significantly (P<0.05) lower than in HLA‐A11 negative ones (mean: 24.5±2.0 SEM ng/ml; n=80). sHLA‐G levels in women at delivery (mean: 22.9±2.2 SEM ng/ml; n=28) were in the range of controls but were significantly (P<0.001) reduced in the corresponding cord bloods (mean: 13.8±1.5 SEM ng/ml; n=28). sHLA‐G levels in amniotic fluids (mean: 15.5+1.0 SEM ng/ml; n=50) were significantly (P<0.001) lower than in plasma. sHLA‐G levels were 5 and 11% of those of sHLA‐I antigens in plasmas and amniotic fluids, respectively. Individual sHLA‐G levels were not correlated with sHLA‐I levels. SDS‐PAGE analysis of plasma sHLA‐G antigens revealed two molecular variants with a 35 kD and a 27 kD MW corresponding to the sizes of sHLA‐G1 and ‐G2 isoforms. In conclusion, our study has shown that the two‐step assay we have developed is reliable in measuring sHLA‐G antigen levels. This assay will facilitate the analysis of the biological and clinical significance of sHLA‐G antigens in plasma.
HLA‐A, ‐B, ‐DRB1 allele and haplotype frequencies in 510 Koreans
Authors: Park M.H. , Kim H.S. , Kang S.J.
Published: March 2003

The frequencies of HLA‐A, ‐B, and ‐DRB1 alleles and A‐B‐DRB1 haplotypes were studied in 510 healthy unrelated Koreans, using serological (for A, B) and polymerase chain reaction (PCR)‐single strand conformation polymorphism (for DRB1) methods. A total of 35 DRB1 alleles were detected and the most frequent alleles were DRB1*1302 (10.9%), *0901 (9.5%), *1501 (8.2%), *0803 (7.3%), *0405 (7.3%), *0101 (6.4%), *0406 (6.0%), and *0701 (6.0%). HLA‐DR4 and DR14 groups were most polymorphic, each group composed of eight DRB1 alleles. Two‐locus associations between HLA‐DRB1 and ‐B loci were analyzed. There were 16 A‐B‐DRB1 haplotypes occurring at frequencies of ≥1%, and the five most common haplotypes were A33‐B44‐DRB1*1302 (5.4%), A33‐B58‐DRB1*1302 (3.7%), A33‐B44‐DRB1*0701 (2.9%), A24‐B7‐DRB1*0101 (2.2%), and A24‐B52‐DRB1*1502 (2.0%). Comparison of the distribution of A‐B‐DRB1 haplotypes among East Asian populations revealed that Koreans are closest to Japanese, but show a higher degree of polymorphism compared with Japanese.
HLA class II molecular polymorphisms in healthy Slavic individuals from North‐Western Russia
Authors: Kapustin S. , Lyshchov A. , Alexandrova J. , Imyanitov E. , Blinov M.
Published: March 2003

Polymerase chain reaction (PCR)‐based genotyping was used to characterize the features of HLA class II molecular polymorphisms in a Slavic population of North‐Western Russia. Two hundred individuals were analyzed for the DRB1 gene, and 100 persons randomly selected from this cohort were additionally typed for DQA1, DQB1 and DPB1 genes. Allele and haplotype frequencies were found to be similar to those observed in other Caucasian populations, with the exception of considerably high prevalence of the DPB1*0301 allele (16.0%) in the group studied. The high rate of diversity was observed within DRB1*04 and DRB1*14 specificities, as well as for extended DR‐DQ haplotypes. In addition, significant number of “unusual” DR‐DQ linkage patterns have been detected. The data seem to reflect the complexity of ethnic background of “European” Russians and may be helpful for the development of international network between donor registries.
Hardy‐Weinberg testing for HLA class II (DRB1, DQA1, DQB1, AND DPB1) loci in 26 human ethnic groups
Authors: Chen J.J. , Hollenbach J.A. , Trachtenberg E.A. , Just J.J. , Carrington M. , Rønningen K.S. , Begovich A. , King M.‐C. , McWeeney S. , Mack S.J. , Erlich H.A. , Thomson G.
Published: March 2003

Testing the fit of population data to Hardy‐Weinberg proportions is crucial in the validation of many current approaches in population genetic studies. In this paper, we tested fit to Hardy‐Weinberg proportions using exact approaches for both the overall and individual heterozygote genotype data of four HLA Class II loci: DRB1, DQA1, DQB1, and DPB1, from 26 human populations. Eighty of 99 overall tests fit the Hardy‐Weinberg expectation (73% for DRB1, 89% for DQA1, 81% for DQB1 and 81% for DPB1). Deviations from Hardy‐Weinberg proportions were both locus and group specific. Although we could not rule out other mechanisms at work, the individual test results indicated that the departure was possibly partly due to recent admixture. Evidence for selection and other sources of deviation are also discussed.
Poor correspondence between predicted and experimental binding of peptides to class I MHC molecules
Authors: Andersen M.H. , Tan L. , Søndergaard I. , Zeuthen J. , Elliott T. , Haurum J.S.
Published: March 2003

Naturally processed peptides presented by class I major histocompatibility complex (MHC) molecules display a characteristic allele specific motif of two or more essential amino acid side chains, the so‐called peptide anchor residues, in the context of an 8–10 amino acid long peptide. Knowledge of the peptide binding motif of individual class I MHC molecules permits the selection of potential peptide antigens from proteins of infectious organisms that could induce protective T‐cell‐mediated immunity. Several methods have been developed for the prediction of potential class I MHC binding peptides. One is based on a simple scanning for the presence of primary peptide anchor residues in the sequence of interest. A more sophisticated technology is the utilization of predictive computer algorithms. Here, we have analyzed the experimental binding of 84 peptides selected on the basis of the presence of peptide binding motifs for individual class I MHC molecules. The actual binding was compared with the results obtained when analyzing the same peptides by two well‐known, publicly available computer algorithms. We conclude that there is no strong correlation between actual and predicted binding when using predictive computer algorithms. Furthermore, we found a high number of false‐negatives when using a predictive algorithm compared to simple scanning for the presence of primary anchor residues. We conclude that the peptide binding assay remains an important step in the identification of cytotoxic T lymphocyte (CTL) epitopes which can not be substituted by predictive algorithms.
Identification of a novel single‐nucleotide polymorphism (Val554Ile) and definition of eight common alleles for human IL4RA exon 11
Authors: Lozano F. , Places L. , Vilà J.‐M. , Padilla O. , Arman M. , Gimferrer I. , Suárez B. , López de la Iglesia A. , Miserachs N. , Vives J.
Published: March 2003

Abstract: The interleukin (IL)‐4 receptor α chain gene (IL4RA) is a polymorphic gene which is reportedly involved in the development of atopy. Of the 14 single‐nucleotide polymorphisms (SNP) reported to date in the coding region of IL4RA, 11 are positioned to exon 11. This big exon encodes more than two thirds of the mature protein, including most of the cytoplasmic region. Here we report the identification of a new IL4RA SNP at the first nucleotide of codon 554 (GTA→ATA) in exon 11, leading to an amino acid substitution from Val to Ile (V554I). Furthermore, we present complete nucleotide sequence data for eight common alleles resulting from combinations of 9 out of the 12 SNP at IL4RA exon 11. Homo‐ or heterozygous combinations of these eight alleles accounted for all the IL4RA exon 11 genotypes found in Caucasian individuals from our geographical area (Note).
Tissue distribution of the human CD97 EGF‐TM7 receptor
Authors: Jaspars L.H. , Vos W. , Aust G. , Van Lier R.A.W. , Hamann J.
Published: March 2003

Abstract: CD97 is a founding member of the EGF‐TM7 family of class II seven‐span transmembrane (7‐TM) receptors. CD97 has an extended extracellular region with several N‐terminal epidermal growth factor (EGF)‐like domains, which mediate binding to CD55. Previous studies demonstrated the expression of CD97 on activated lymphocytes, monocytes, macrophages, granulocytes, and numerous haematopoietic and nonhaematopoietic cell lines. Here, we determined the cellular distribution of human CD97 in situ by immunohistochemistry (IH) and immunofluorescence (IF). Abundant expression of CD97 was detected on all types of macrophages and dendritic cells, except for microglia. Within the lymphoid lineage, most T cells but only a few B cells express CD97. Germinal centre B cells do not express the molecule. Except for smooth muscle cells, no staining was found on other cells outside the immune system. However, analysis of a restricted set of epithelial tumors revealed CD97 expression on the malignant cells in thyroid and gastrointestinal tract cancer.
HLA‐DPA1 and DPB1 polymorphism in four Pacific Islands populations determined by sequencing based typing
Authors: Velickovic Z.M. , Carter J.M.
Published: March 2003

Abstract: Class II HLA‐DP antigens are heterodimers comprised of α and β chains coded by HLA‐DPA1 and HLA‐DPB1 genes. Both genes are polymorphic with substantial variation between different populations world wide. This work describes DPA1 and DPB1 polymorphism in four Pacific Island populations of Cook Islands, Samoa, Tokelau and Tonga, living in New Zealand. Using sequencing based typing four DPA1 alleles and twelve DPB1 alleles were observed in total among the four populations. There are two predominant DPA1 alleles DPA1*01031 and DPA1*02022 and three predominant DPB1 alleles DPB1*02012, DPB1*0401 and DPB1*0501. Fourteen DPA1‐DPB1 haplotypes in total are present in these four populations with three predominant haplotypes: DPA1*02022‐DPB1*0501, DPA1*01031‐DPB1*02012, and DPA1*01031‐DPB1*0401. Strong positive and negative disequilibrium was observed for individual DPA1‐DPB1 haplotypes. Significant differences in DPA1 and DPB1 allele and haplotype frequencies were observed between Tokelauan and other three populations. Phylogenetic analysis of genetic distances between the four Pacific Island populations and other Asian Oceanian populations have shown that Cook Islanders, Samoans and Tongans are more closely related to Asian populations whereas Tokelauans cluster towards non‐Austronesian populations of Papua New Guinea Highlanders and Australian Aborigines.
Identification of a new HLA‐DRB1*04 allele, DRB1*0437
Authors: Palou E. , Campos E. , Gil J. , Santos M. , Nogués N. , Ribera A.
Published: March 2003

Abstract: In this report we describe the identification of a novel DRB1*04 allele, DRB1*0437, found in a Spanish individual. The routine HLA typing, in the context of bone marrow transplantation, by polymerase chain reaction‐sequence‐based typing (PCR‐SBT) made possible the identification of this new allele. This allele is identical to DRB1*0402 except for a single nucleotide substitution at position 286 (A→C), changing the encoded Isoleucine to a Leucine. The DRB1*0437 allele conserves the same two acidic residues at codons 70 and 71 that confer to DRB1*0402 its association to some autoimmune diseases.
Linkage disequilibrium of HLA‐A11 and A1 with one of the polymorphisms of the gamma‐aminobutyric acid receptor type B
Authors: Anaya M. , Romero T. , Sofia R.D. , Yunis E.J.
Published: March 2003

Abstract: The gamma‐aminobutyric acid receptor type B 1 (GABAB R1) is located approximately at 200 kb telomeric to HLA‐A on chromosome 6. It has 11 single‐nucleotide polymorphisms (SNPs). We studied the most common of its SNPs (T1974C) in a panel of 118 normal Caucasians from New England and 161 epileptic patients of Caucasian ancestry residing in USA. The frequency of the polymorphism did not differ between patients and controls. Here, we report that the allele C of this SNP in the GABAB R1 gene is in linkage disequilibrium with HLA‐A11 (P<0.00001) and to a lesser extent with HLA‐A1 (P<0.01).
MCP‐1 promoter polymorphism in Spanish patients with systemic lupus erythematosus
Authors: Aguilar F. , González‐Escribano M.F. , Sánchez‐Román J. , Núñez‐Roldán A.
Published: March 2003

Abstract: The possible role of the functional polymorphism located in the regulatory region of the monocyte chemoattractant protein‐1 (MCP‐1) gene in the susceptibility to systemic lupus erythematosus (SLE) was investigated. Two hundred and seventy‐six SLE patients (among them, 99 with lupus nephritis and 55 with cutaneous vasculitis) and 194 ethnically matched healthy controls were included in the study. Genotyping for −2518 (A/G) MCP‐1 gene polymorphism was performed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) analysis. No association between −2518 (A/G) MCP‐1 polymorphism and susceptibility to SLE nor to lupus nephritis was found. However, a significant increase in the frequency of genotype AG and a decrease in the frequency of genotype AA were found among patients with cutaneous vasculitis (51% of AG vs. 32% in individuals without cutaneous vasculitis; P=0.008, OR=2.2, 95% CI: 1.18–4.25; and 47% of AA vs. 64%; P=0.03, OR=0.5, 95% CI: 0.27–0.96, respectively). These results indicate an association between the presence of G at position −2518 in the MCP‐1 promoter region and the presence of cutaneous vasculitis among patients with SLE. This polymorphism does not seem to influence the susceptibility to SLE nor the appearance of lupus nephritis. Further studies are necessary in order to elucidate the role of this polymorphism in the pathogenesis of other inflammatory autoimmune diseases.
NONCOMPLIANCE WITH IMMUNOSUPPRESSIVE MEDICATIONS AFTER RENAL TRANSPLANTATION
Authors: Ghods AJ , Nasrollahzadeh D
Published: March 2003

Noncompliance with immunosuppressive medications in renal transplant recipients results in a higher rate of acute‐rejection episodes, allograft dysfunction, graft loss and patient death. We studied the incidence and risk factors of medications noncompliance in 286 renal transplant recipients who were consecutively seen at our renal transplant clinic between February and April 2002. One hundred and seventy were male, 116 female. Their age ranged from 12 to 70 years (mean 39.1±11.6). The length of time since the date of transplantation ranged from 5 to 231 months (mean 76.7±53.5). The results of the study showed 70 patients (24.5%) to be noncompliant (7.7% noncompliant minor and 16.8% noncompliant major). The time since the date of transplantation was a significant risk factor in both the noncompliant minor and major groups (P<0.001 and P<0.001, respectively). The other risk factors associated with major noncompliance was young age (P<0.001), lower level of education (P<0.01), lower socioeconomic class (P<0.05), and addiction and psychiatric disorders (P<0.05). Transplant recipients with major noncompliance also had more acute‐rejection episodes (P < 0.001) and allograft dysfunction (P <0.01). We conclude that noncompliance with immunosuppressive medications is very common in renal transplant recipients, resulting in significant acute‐rejection episodes and allograft failure.
RELATIONSHIP BETWEEN PARKINSON'S DISEASE AND HLA‐ANTIGENS IN TURKISH PATIENTS
Authors: Yilmaz E , Apaydin H , Özekmekçi S , Ertan S , Erkol G
Published: March 2003

This study focused on the immunogenetic aspect of Parkinson's disease (PD). The frequencies of HLA‐A, ‐B, ‐C, ‐DR and ‐DQ antigens were determined in 40 patients with idiopathic PD, and were compared with those in a representative sample of the Turkish population (n=160). Compared with values for the Turkish population, the frequencies of HLA‐B22 and HLA‐DR14 (6) antigens were higher in the PD group, with relative risks (RR) of 9.55 and 15.48, respectively. These frequency differences were statistically significant. The frequency of HLA‐A24 (9) was also higher in the PD patients, but to a lesser extent than the antigens noted earlier (RR=2.38). The frequencies of HLA‐DQ7 (3), HLA‐DQ4, HLA‐DR11 (5), HLA‐DR1 and HLA‐DR7 were lower in the PD group, with RR values of 0.177, 0.187, 0.69, 0.85 and 0.93, respectively. None of these frequency differences were statistically significant. The frequency of the HLA‐DQ4 antigen in the PD group was significantly lower than that in the Turkish population, and this difference was significant when the corrected P‐value was used.
RELATIONSHIP OF HLA‐DR EXPRESSION WITH REJECTION AND MONONUCLEAR CELL INFILTRATION IN RENAL ALLOGRAFT BIOPSIES
Authors: Handan Özdemir B , Kaynak Aksoy P , Nihan Haberal A , Demirhan B , Haberal M
Published: March 2003

Research on renal biopsies has shown that HLA class I antigens are distributed throughout the renal parenchyma, but that the distribution of HLA‐DR varies greatly. We investigated HLA‐DR expression in the biopsies of 90 renal transplants, and also semiquantitatively assessed the proportions of CD68‐, CD3‐, and HLA‐DR‐positive infiltrating cells by immunohistochemistry. The relationships between tubular DR expression and interstitial lymphocyte and macrophage infiltration were examined.

Forty of the biopsies showed acute rejection (AR), 33 showed chronic rejection (CR), 10 showed suspected rejection (SR), and seven showed no evidence of rejection (NR). HLA‐DR expression was noted in 35/40 (87.5%) of the AR cases, 22/33 (66.6%) of the CR cases, and 6/10 (60%) of the SR cases. Only one (14.3%) of the NR cases exhibited HLA‐DR antigen expression in the renal tubules. The proportions of lymphocyte and macrophage infiltration observed in the interstitium were significantly correlated with the tubular DR expression in all cases (P<0.01). Six months after the biopsies were carried out, 24/35 (68.6%) of the AR patients with tubular DR expression showed second‐episode rejection or deteriorated renal function. The remaining 11 AR cases with tubular DR expression had stable renal function at this stage. The cases that had no significant tubular DR expression had no problems with rejection or functional deterioration.

These findings are consistent with the theory that expression of HLA‐DR antigens on renal tubular cells may be a marker of rejection and poor graft outcome.
Complementary DNA sequence of the novel HLA‐B*3704 allele
Authors: Estefanía E. , Gómez‐Lozano N. , De Pablo R. , Moreno M.E. , Vilches C.
Published: March 2003

Abstract: The novel HLA‐B*3704 allele was identified by polymerase chain reaction with sequence specific oligoneucletides (PCR‐SSO) in a Spanish Caucasoid individual whose T‐lymphocytes showed an ambiguous HLA‐B phenotype. The nucleotide sequence of B*3704 was determined after reverse transcription‐polymerase chain reaction (RT‐PCR) amplification and molecular cloning of its complete coding region. B*3704 differs from B*3701 by a single nucleotide replacement that induces the substitution of histidine for tyrosine 171. Residue 171 is located in the alpha‐helix of the alpha‐2 domain, lining the A pocket of the peptide‐binding site. Therefore, the His171 substitution seen in HLA‐B*3704 is likely to affect its antigen‐presenting properties and is probably responsible for the differentiated serological phenotype of this allele in comparison with B*3701.
Cloning and complete sequence of a novel HLA‐A null allele, A*0253 N, with a termination codon generated by a C to G mutation in exon 2
Authors: Wu G.‐G. , Cheng L.‐H. , Deng Z.‐H. , Wang L.‐X. , Wei T.‐L. , Yang C.‐S. , Zhao T.‐M.
Published: March 2003

Abstract: A novel HLA‐A null allele, A*0253 N, has been identified in two generations of a Chinese family using combined serological and molecular cloning approaches. Full‐length genomic DNA sequencing indicated that this new allele differs from HLA‐A*02011 by a single C to G substitution at nucleotide position 324 in exon 2. This mutation results in an amino acid change from a tyrosine codon to a stop codon at position 108. A PCR‐SSP based method was developed to distinguish A*0253 N from A*02 alleles. No further individuals of A*0253 N were found in 718 Chinese blood donors who carry the HLA‐A*02 allele1.
Identification of the novel allele B*4427 and a confirmatory sequence (B*44022)
Authors: Canossi A. , Papola F. , Liberatore G. , Del Beato T. , Piancatelli D. , Tessitore A. , Vicentini M.T. , Maccarone D. , Aureli A. , Cervelli C. , Di Rocco M. , Casciani C.U. , Adorno D.
Published: March 2003

Abstract: This report presents a novel allele, HLA‐B*4427, which was identified in a bone marrow donor of Caucasian origin, and a confirmatory sequence (B*44022). Sequence analysis revealed the new allele differs from B*44021 by a single nucleotide exchange at position 668 (C→T), which is located in exon 4. At the protein level, it is the only B*44 variant to produce an Ala in place of a Val at codon 199. Its structure suggests that it may have originated from a point mutation in B*44021 or by gene conversion with a variety of HLA‐B alleles. Cloning and sequencing of the allele B*44022 revealed a sequence identical to B*44021 and B*44 exon 4, with the codon GTC (Val) in position 199.
Identification of a new HLA‐DPB1 allele,HLA‐DPB1*9001
Authors: Bengtsson M. , Danielsson F. , Jansson I.E. , Johansson U.
Published: March 2003

Abstract: During routine typing of a potential bone marrow donor, a new HLA DPB1 allele was identified. The new allele, officially named HLA DPB1*9001, differs from HLA DPB1*01011 in the second hypervariable region, where a single nucleotide substitution in position 191 changes the codon 35 from TAC to TTC with a predicted amino acid change from Tyr to Phe.
Novel HLA‐DRB1 alleles revealed by sequencing based typing, DRB1*04053 and DRB1*1143
Authors: Greville W.D. , Chapman G. , Hogbin J‐P. , Dunckley H.
Published: March 2003

Abstract: We report the discovery of two HLA‐DRB1 alleles by sequencing based typing (SBT). DRB1*04053 differs from previously reported DRB1 alleles by a single synonymous nucleotide substitution, resulting in a unique polymorphism at codon 93. DRB1*1143 differs from previously identified DRB1 alleles by a single non‐synonymous nucleotide substitution, resulting in a polymorphism observed in other DRB1 and DRB3 alleles1.
Identification of a novel HLA‐DRB1 allele, DRB1*0108, by sequence‐based DRB typing in two siblings
Authors: Martinez‐Gallo M. , Martinez‐Lostao L. , Martinez‐Carretero M.A. , Gago I. , Maroto P. , Rodriguez‐Sanchez J L. , De La Calle‐Martin O.
Published: March 2003

Abstract: We report here a novel DRB1 allele identified during sequence‐based HLA‐DRB typing. This allele was detected during routine HLA typing of a patient and his family prior to bone marrow transplantation. The new allele, DRB1*0108, was found in the patient and in a brother. Molecular cloning and sequencing confirmed that the new DRB1 allele is identical to DRB1*0101 at exon 2 except for a single nucleotide substitution at codon 37 (ΤCC→ΤΑC), changing the encoded serine to tyrosine. This position of the β1 domain lies in the floor of the antigen‐binding groove and shows the highest polymorphism among DRB1 alleles.
Predicting time on the waiting list for HLA matched corneal grafts
Authors: Böhringer D. , Reinhard T. , Böhringer S. , Enczmann J. , Godehard E. , Sundmacher R.
Published: March 2003

Abstract: Recent studies report the beneficial effect of HLA matching for the long‐term prognosis of penetrating keratoplasty (KP). This improvement in prognosis, however, has to be weighed against the additional waiting time while a HLA compatible graft is found. Precise estimation of this additional waiting period is a prerequisite for informed consent on the waiting policy. A mathematical model based on survival analysis and HLA haplotype frequencies was used to estimate time on the waiting list for each of 1400 HLA typed patients registered at the Lions Cornea Bank North Rhine Westfalia (NRW). Additionally, the waiting period for each patient was retrospectively determined. Both values were tested for correlation. This analysis was performed for acceptance of up to two mismatches on HLA‐A, ‐B and ‐DR. The median predicted waiting period was compatible with the median waiting period in retrospective simulation. Correlation of both entities was statistically significant also. Predicted time on the waiting list as derived from the patient's HLA genotype and a comprehensive database of HLA haplotype frequencies is thus a valuable tool for management of HLA‐matching in KP.
Point mutation in the α helix of the HLA‐C α2 domain generates a novel HLA‐C allele,HLA‐Cw*0106, in a Han Chinese individual in Taiwan
Authors: Wu S. , Lai C.‐Y. , Lai S.‐M. , Chen S.‐P. , Chou F.‐C. , Shiao Y.‐M. , Huang C.‐S.
Published: March 2003

Abstract: We report herein the identification of a new HLA‐C allele using sequence‐based typing (SBT). This novel allele, HLA‐Cw*0106, was found in a Han Chinese individual from Taiwan. This individual was typed using SBT as having a class I HLA genotype of HLA‐A*0206/0207, HLA‐B*4601/5601, and HLA‐Cw*0102/0106. This new allele differs from HLA‐Cw*0102 in one of the nucleotides of the polymorphic exon 3 at codon 152 (GAG→GTG; E152V). This residue is located in the α helix of the HLA‐C α2 domain and may have the potential to affect the binding of HLA‐C molecules with antigenic peptides and/or the interactions with the T cell receptor. This new allele was detected in a few individuals of Han Chinese in Taiwan, but has not yet been observed in the aboriginal populations in Taiwan.
PCR‐SSOP molecular typing of HLA‐C alleles in an Iranian population
Authors: Buhler S. , Sanchez‐Mazas A. , Zanone R. , Djavad N. , Tiercy J.‐M.
Published: March 2003

Abstract: HLA‐C alleles were characterized by a polymerase chain reaction‐sequence specific oligonucleotide probe (PCR‐SSOP) hybridization protocol in a sample of 120 Iranians from Tehran. A total of 23 alleles were identified with the four most predominant – Cw*0401, Cw*0602, Cw*1202, and Cw*0701/06 – accounting for almost 50% of HLA‐C alleles. A comparison of HLA‐C diversity among several populations indicates that Iranians stand at an intermediate genetic position between Europeans and Africans, an observation that may be related to their geographical location at a continental crossroads. The results also reveal a very high correlation between genetic and geographic distances on a global scale. A total of 30 HLA‐C‐DRB1 haplotypes were found in the Iranians, with the highest frequencies of 6.6% and 6.04 % being for Cw*0602‐DRB1*0701 and Cw*1202‐DRB1*1502, respectively.
HLA‐B*4431: A new HLA‐B variant with a complex ancestral history involving  HLA‐B*44, B*40 and B*07 alleles
Authors: Przemeck M. , Elsner H.‐A. , Sel S. , Pastucha L.T. , Blasczyk R.
Published: March 2003

Abstract: We here describe the identification of the new allele HLA‐B*4431, which was found in three members of a Turkish family. Sequencing of the new allele following haplotype‐specific PCR amplification revealed that exon 2 is identical to HLA‐B*4402, whereas exon 3 resembles a HLA‐B*40 variant with the exception of position 572, where a single nucleotide transversion (C > G) leads to an amino acid exchange (Trp162Ser). The generation of the 3′ part of B*4431 may be best explained by a separate recombination between B*40 and B*07. Although B*4431 consists of B44 in its α1 domain and of B60(40) in its α2 domain; the new allele only displayed B44 seroreactivity, which demonstrates that epitopes crucial for B60(40) specificity must be located in the α1 domain.
Characterization of the murine CD30 ligand (CD153) gene: Gene structure and expression
Authors: Goldie‐Cregan L.C. , Croager E.J. , Abraham L.J.
Published: March 2003

Abstract: CD153 (CD30 ligand) has been described as a 40‐kDa type II transmembrane glycoprotein belonging to the TNF superfamily and is expressed primarily by activated T cells, B cells and monocytes. In this study, we have determined that the murine CD153 gene consists of four exons, with three intervening introns, spaced over approximately 26 kb of genomic sequence. Sequence analysis of the murine CD153 promoter and 5′ flanking region revealed the presence of a TATA box element immediately upstream of two tsp sites, together with putative binding motifs for a variety of lymphoid‐specific transcription factors. 5′RACE analysis of LPS‐stimulated RAW264.7 macrophage cDNA identified at least four transcriptional start sites for murine CD153, with two sites occurring downstream of the previously predicted translation initiation codon. Additionally, 5′ RACE analysis identified multiple murine CD153 polyadenylation sites. Our results indicate that primary murine CD153 transcripts may vary from 26 kb to approximately 28 kb in length.
Molecular and serological identification of the HLA‐A*3404 allele
Authors: Voorter C.E.M. , Hepkema B.G. , Lems S.P.M. , Van Den Berg‐Loonen E.M.
Published: March 2003

Abstract: In this report we describe a novel HLA‐A*34 allele, A*3404, which was initially detected by an unusual serological pattern in two unrelated individuals. Sequencing revealed that the new allele was identical to A*3402 in exons 2 and 3, except for a single nucleotide difference at position 238, changing codon 56 from glycine to arginine. The codon change resulted in positive serological reactions with several sera recognizing A30 and/or A31, implicating an important role for this position in epitope recognition. The allele was identified twice on the haplotype A*3404, B*1402, Cw*0802, DRB1*14, DQB1*05.
Surface antigens of human mesangial cells: impact of growth surface or IL‐1α
Authors: Sengoelge G. , Perschl A. , Ferrara I. , Hörl W.H. , Sunder‐Plassmann G.
Published: March 2003

Abstract: The interactions of mesangial cells (MC) with their environment are important events in glomerular physiology and pathology, yet a detailed characterization of the MC‐surface antigens mediating these interactions is still lacking. In this study, a comparative phenotype analysis of primary human MC in culture using 191 monoclonal antibodies directed against 108 antigens was performed by flow‐cytometry. The MC were grown on three different surfaces (human matrix, fibronectin, polystyrene) and cultured in the presence or absence of IL‐1α. Seventy‐one antibodies recognizing 35 different antigens (integrins: CD29, 49b, 49c, 49e, 51, 61; immunoglobulin gene family: CD54, 58, 90, 106, 146, 147, 166; growth factor receptors: CD105, 140b; apoptosis related: CD95; hemostatis related: CD141, 142; miscellaneous: CD44, 109, 138, 151, 157, 165, and 11 nonclustered antigens) reacted with mesangial cells. CD58, 109, 146, 147, 151, 157, 165, and 166 are reported for the first time to be present on human mesangial cells. In comparison to growth on polystyrene, CD44, 54, 95, 105, 109, 140b, 146, 147, 157, 165 and 166, were up‐regulated on fibronectin, and CD44, 54, 90, 95, 105, 106, 109, 138, 140b, 141, 142, 146, 147, 151, 157, 165 and 166 were up‐regulated on human matrix. The stimulation by IL‐1α up‐regulated CD44, 49e, 51, 54, 61, 106 on MC on polystyrene; CD49e, 51, 61, 106, 146, 165 on MC on fibronectin, and CD49e, 51, 54 on MC grown on human matrix. This analysis of surface antigen expression provides new information to enable a better understanding of the role of mesangial cells in glomerular pathophysiology.
New HLA–DRB1*07 allele identified from microlymphocytotoxicity/SSP discrepancies
Authors: Donvito B. , Perrier P. , Tonye Libyh M. , Tabary T. , Philbert F. , Reveil B. , Cohen J.H.M.
Published: March 2003

Abstract: A HLA–DRB1*07 variant allele has been identified in a cadaver kidney donor. Serological typing using monoclonal antibodies detected HLA–DR4 and HLA–DR7. HLA class II DNA typing using sequence‐specific primer (PCR‐SSP) polymerase chain reaction only detected DRB1*04, while sequence‐specific oligonucleotide (PCR‐SSO) polymerase chain reaction confirmed the presence of both DRB1*04 and DRB1*07 alleles, although two extra reactions were also found. Exon 2 of the HLA‐DRB1*07 was isolated using allele‐specific PCR, then cloned and sequenced. Four mutations, at positions 170 (T → C), 171 (C → T), 174 (C → G), and 179 (C → A), were observed. These mutations changed codons 57 and 60 (V → A; S → Y, respectively). This amino acid sequence at position 56–61 is only found in DRB1*0811.
Biological activities of retro and diastereo analogs of a 13‐residue peptide with antimicrobial and hemolytic activities
Authors: Subbalakshmi C. , Nagaraj R. , Sitaram N.
Published: March 2003

Abstract: The biological activities of synthetic retro and diastereo analogs of PKLLKTFLSKWIG (SPFK), a 13‐residue peptide with antimicrobial and hemolytic activities, have been investigated. Retro peptides with C‐terminal acid and amide exhibited antibacterial activities comparable with those of SPFK. Their hemolytic activities were, however, only marginally lower. The diastereo analog with C‐terminal acid was not antibacterial and was weakly hemolytic. Amidation of this analog could restore antibacterial activity. Both retro analogs were unordered in aqueous medium but had a propensity for a helical structure in trifluoroethanol. However, diastereo analogs were unordered in both aqueous medium and trifluoroethanol. Thus, reversing the sequence in a short amphiphilic peptide may not always result in the selective loss of biological activity such as hemolytic activity. Also, introduction of enantiomeric amino acids in a short peptide to generate a diastereomer may result in loss of structure as well as antimicrobial and hemolytic activities, unless compensated by an increase in positive charges.