bluuebunny/crossref_metadata_2025 huggingface dataset:
Forecasting Housing Markets: Lessons Learned
Authors: Hendershott Patric H. , Weicher John C.
Published: March 2003

Forecasting changes in housing finance (instruments and institutions), housing demand (tenure, quantity, and real price), and housing production requires forecasting numerous exogenous factors—inflation, government policy, and demographic forces being the most obvious—and interpreting their impacts on the housing market. We use forecasts made over the last two decades to illustrate the importance of these variables and of interpreting their impacts appropriately.
Are Immigrants a Drain on the Public Fisc? State and Local Impacts in New Jersey
Authors: Garvey Deborah L. , Espenshade Thomas J. , Scully James M.
Published: March 2003

Objectives. To explore differences in the appointment and election method of selecting state high court justices in promoting gender diversity, and to explore the effect of existing gender diversity within the political institutions on the selection of women to office. Methods. Our data include all justices who have been selected to state courts of last resort from 1980 through 1997. We use logistic regression analysis to test the effect of existing gender diversity on a high court on the likelihood that a woman will be selected to fill a vacancy. Results. Women are significantly more likely to be selected to a state high court when initially appointed, and this effect is particularly pronounced when the governor is Democratic. When an appointment system is used, women are much more likely to be appointed to an all‐male court than to a gender‐diverse court. Conclusions. Appointment systems are more likely to create gender diversity on state courts; however, this effect operates primarily to diversify all‐male courts. This difference between appointment and election systems may reflect differences in knowledge between elite actors and the mass public about the composition of the institution.
Household Members and Employment Outcomes of Recent Immigrants: A Network Approach
Authors: Enchautegui Maria E.
Published: March 2003

Objective. The objective of this article is to investigate the effect of household members on the employment outcomes of recent immigrants conceptualizing the household as an employment network unit. Methods. I use data from the 1994 and 1996 March Current Population Surveys and make a taxonomy of the household composition based on the network’s employment capability. Logit and regression models of employment and earnings are estimated. Results. Results show that co‐residence with long‐term immigrants is detrimental, while co‐residence with fellow recent immigrants is beneficial for the employment outcomes of recent immigrants. Conclusions. I conclude that some types of job networks may have a negative impact on the economic incorporation of recent immigrants, that household network effects on employment outcomes are gendered, and that their effectiveness is conditioned by labor market segmentation according to recency of arrival.
Dynamic Asset Allocation under Inflation
Authors: Brennan Michael J. , Xia Yihong
Published: March 2003

We develop a simple framework for analyzing a finite‐horizon investor's asset allocation problem under inflation when only nominal assets are available. The investor's optimal investment strategy and indirect utility are given in simple closed form. Hedge demands depend on the investor's horizon and risk aversion and on the maturities of the bonds included in the portfolio. When short positions are precluded, the optimal strategy consists of investments in cash, equity, and a single nominal bond with optimally chosen maturity. Both the optimal stock‐bond mix and the optimal bond maturity depend on the investor's horizon and risk aversion.
A Monte Carlo Method for Optimal Portfolios
Authors: Detemple Jérôme B. , Garcia Ren , Rindisbacher Marcel
Published: March 2003

This paper proposes a new simulation‐based approach for optimal portfolio allocation in realistic environments with complex dynamics for the state variables and large numbers of factors and assets. A first illustration involves a choice between equity and cash with nonlinear interest rate and market price of risk dynamics. Intertemporal hedging demands significantly increase the demand for stocks and exhibit low volatility. We then analyze settings where stock returns are also predicted by dividend yields and where investors have wealth‐dependent relative risk aversion. Large‐scale problems with many assets, including the Nasdaq, SP500, bonds, and cash, are also examined.
The Leader of Human Immunodeficiency Virus Type 1 Genomic RNA Harbors an Internal Ribosome Entry Segment That Is Active during the G
2
/M Phase of the Cell Cycle
Authors: Brasey Ann , Lopez-Lastra Marcelo , Ohlmann Theophile , Beerens Nancy , Berkhout Ben , Darlix Jean-Luc , Sonenberg Nahum
Published: March 2003

The 5′ leader of the human immunodeficiency virus type 1 (HIV-1) genomic RNA contains highly structured domains involved in key steps of the viral life cycle. These RNA domains inhibit cap-dependent protein synthesis. Here we report that the HIV-1 5′ leader harbors an internal ribosome entry site (IRES) capable of driving protein synthesis during the G
2
/M cell cycle phase in which cap-dependent initiation is inhibited. The HIV-1 IRES was delineated with bicistronic mRNAs in in vitro and ex vivo assays. The HIV-1 leader IRES spans nucleotides 104 to 336 and partially overlaps the major determinants of genomic RNA packaging. These data strongly suggest that, as for HIV-1 transcription, IRES-mediated translation initiation could play an important role in virus replication during virus-induced G
2
/M cell cycle arrest.
The ORF45 Protein of Kaposi's Sarcoma-Associated Herpesvirus Is Associated with Purified Virions
Authors: Zhu Fan Xiu , Yuan Yan
Published: March 2003

Kaposi's sarcoma-associated herpesvirus (KSHV) ORF45 is encoded by an immediate-early gene in the KSHV genome. This protein was recently shown to interact with interferon regulatory factor 7 and inhibit virus-mediated alpha/beta interferon induction (Zhu et al., Proc. Natl. Acad. Sci. USA 99:5573-5578, 2002). ORF45 was characterized as a phosphorylated protein, and it is localized in the cytoplasm of infected cells. In this report, we provide evidence that ORF45 is associated with KSHV virions. (i) ORF45 was detected in gradient-purified virions by Western blotting along with known structural proteins of KSHV including gB, K8.1, and major capsid protein. In contrast, ORF50/Rta, K8α, and ORF59/PF8 were not detected in the same virion preparation. (ii) ORF45 comigrates with KSHV virions in sucrose gradient ultracentrifugation. (iii) Virion-associated ORF45 was resistant to trypsin digestion but became sensitive after the virions were treated with detergent which destroys the viral envelope. (iv) ORF45 remained associated with tegument-nucleocapsid complex when virion-specific glycoproteins were removed after detergent treatment. (v) An ORF45 protein band was visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of extensively purified KSHV virions and identified by mass spectrometry. (vi) By immunoelectron microscopy, virus-like structures were specifically stained by anti-ORF45 antibody. Based on the evidence, we conclude that ORF45 is associated with purified KSHV virions and appears to be a tegument protein. The presence of ORF45 in KSHV virions raised the possibility that this protein may be delivered to host cells at the start of infection and therefore have the opportunity to act at the very early stage of the infection, suggesting an important role of ORF45 in KSHV primary infection.
Recruitment of Polymerase to Herpes Simplex Virus Type 1 Replication Foci in Cells Expressing Mutant Primase (UL52) Proteins
Authors: Carrington-Lawrence Stacy D. , Weller Sandra K.
Published: March 2003

The ordered assembly of the herpes simplex virus (HSV) type 1 replication apparatus leading to replication compartments likely involves the initial assembly of five viral replication proteins, ICP8, UL9, and the heterotrimeric helicase-primase complex (UL5-UL8-UL52), into replication foci. The polymerase and polymerase accessory protein are subsequently recruited to these foci. Four stages of viral infection (stages I to IV) have been described previously (J. Burkham, D. M. Coen, and S. K. Weller, J. Virol.
72:
10100-10107, 1998). Of these, stage III foci are equivalent to the previously described promyelocytic leukemia protein (PML)-associated prereplicative sites and contain all seven replication proteins. We constructed a series of mutations in the putative primase subunit, UL52, of the helicase-primase and have analyzed the mutant proteins for their abilities to form intermediates leading to the formation of replication compartments. The results shown in this paper are consistent with the model that the five proteins, ICP8, UL5, UL8, UL9, and UL52, form a scaffold and that formation of this scaffold does not rely on enzymatic functions of the helicase and primase. Furthermore, we demonstrate that recruitment of polymerase to this scaffold requires the presence of an active primase subunit. These results suggest that polymerase recruitment to replication foci requires primer synthesis. Furthermore, they support the existence of two types of stage III intermediates in the formation of replication compartments: stage IIIa foci, which form the scaffold, and stage IIIb foci, which contain, in addition, HSV polymerase, the polymerase accessory subunit, and cellular factors such as PML.
PWA AND THE LATTICE
Authors: Morningstar Colin
Published: March 2003

The valuable role which lattice simulations of quarks and gluons can play in providing insights from QCD relevant for partial wave analyses of hadronic scattering processes is discussed.
COMPUTING FLOQUET MULTIPLIERS FOR FUNCTIONAL DIFFERENTIAL EQUATIONS
Authors: LUZYANINA TATYANA , ENGELBORGHS KOEN
Published: March 2003

Floquet multipliers determine the local asymptotic stability of a periodic solution and, in the context of parameter dependence, determine also its bifurcations. This paper deals with numerical aspects of the computation of the Floquet multipliers for three classes of functional differential equations: ordinary differential equations (ODEs), differential equations with constant delay (DDEs) and differential equations with state-dependent delay (sd-DDEs). Using a collocation approach for computing periodic solutions, we obtain an approximation of the (corresponding) monodromy operator, a monodromy matrix. The eigenvalues of this matrix form an approximation to the Floquet multipliers. The accuracy of the computed multipliers is an important issue in bifurcation analysis of a dynamical system. As far as we know, no prior work on the study of the convergence and accuracy of computed Floquet multipliers for DDEs and sd-DDEs exists. We analyze the dependency of the accuracy of the computed multipliers on the parameters and on the type of collocation approximation. In particular, we show that the accuracy of the computed trivial multiplier is not always comparable to the accuracy of the computed periodic solution and the accuracy of the other computed multipliers.
An efficient method for network topology identification based on an SOM algorithm
Authors: Hosaka Koji , Goya Takeshi , Umehara Daisuke , Kawai Makoto
Published: March 2003

In this paper we consider a large number of wireless terminals that are interconnected by a multihop wireless network called an ad hoc network. Design of routing protocols is a crucial problem in ad hoc networks. Location information of wireless terminals is an effective measure for ad hoc network routing. This paper presents a method to identify network topology implying terminal location and connections among terminals. A modified Self‐Organizing Map (SOM) algorithm is proposed to apply to the network topology identification. This method exploits information of the received power levels of the signals that are transmitted by other terminals. This paper has evaluated how network topology is identified by means of an example graph made by random numbers. The results show that only one bit information about the received power level in each terminal can identify network topology accurately with a mean error of about 10% for more terminals than a certain value. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 142(4): 34–44, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10100
Evidence for novel fate of Flk1+ progenitor: Contribution to muscle lineage
Authors: Motoike Toshiyuki , Markham David W. , Rossant Janet , Sato Thomas N.
Published: March 2003

Summary: Flk1 is one of the specific cell surface receptors for vascular endothelial growth factor and one of the most specific markers highlighting the earliest stage of hematopoietic and vascular lineages. However, recent new evidence suggests that these Flk1+ mesodermal progenitor cells also contribute to muscle lineages. All evidence is based on the experiments using in vitro differentiation and in vivo transplantation systems. Although this approach revealed a differentiation potential range of Flk1+ cells that is wider than previously expected, it fails to determine whether Flk1+ cells contribute to muscle lineage as part of the normal developmental process. To obtain direct evidence for the fate of Flk1+ cells in development, we used a knock‐in mouse line where Cre is expressed in Flk1+ cells. Studies with these Cre lines provide direct evidence that Flk1+ cells are progenitors for muscles, in addition to hematopoietic and vascular endothelial cells. genesis 35:153–159, 2003. © 2003 Wiley‐Liss, Inc.
Tissue‐specific developmental requirements of Drosophila tyrosine hydroxylase isoforms
Authors: Friggi‐Grelin Florence , Iché Magali , Birman Serge
Published: March 2003

Summary: Drosophila tyrosine hydroxylase (DTH) is a key enzyme in dopamine (DA) biosynthesis, which is expressed in neural and hypodermal DA‐synthesizing cells. We previously reported that two DTH isoforms are produced in flies through tissue‐specific alternative splicing that show distinct regulatory properties. We have now selectively expressed each DTH isoform in vivo in a pale (ple, i.e., DTH‐deficient) mutant background. We show that the embryonic lethality of ple can be rescued by expression of the hypodermal, but not the neural, DTH isoform in all DA cells, indicating that the hypoderm‐ isoform is absolutely required for cuticle biosynthesis and survival in Drosophila. In addition, we report new observations on the consequences of DTH overexpression in the CNS and hypoderm. Our results provide evidence that tissue‐specific alternative splicing of the DTH gene is a vital process in Drosophila development. genesis 35:175–184, 2003. © 2003 Wiley‐Liss, Inc.
Profile of gene expression induced by the tumour promotor TPA in murine epithelial cells
Authors: Schlingemann Joerg , Hess Jochen , Wrobel Gunnar , Breitenbach Ute , Gebhardt Christoffer , Steinlein Peter , Kramer Heidi , Fürstenberger Gerhard , Hahn Meinhard , Angel Peter , Lichter Peter
Published: March 2003

Malignant transformation of mouse skin by chemical carcinogens and tumour promoters, such as the phorbol ester 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), is a multistage process that leads to squamous cell carcinoma (SCC) formation. In an effort to identify tumour‐associated genes, we studied the influence of short‐term TPA‐treatment on the gene expression profile of murine skin. A comprehensive microarray with some 5,000 murine gene specific cDNA fragments was established and hybridised with pooled RNA derived from control and TPA‐treated dorsal skin samples. Of these genes, 54 were up‐ and 35 were down‐regulated upon TPA application. Additionally, we performed suppression subtractive hybridisation (SSH) with respective RNA pools to generate and analyse a cDNA library enriched for TPA‐inducible genes. Expression data of selected genes were confirmed by quantitative real‐time PCR and Northern blot analysis. Comparison of microarray and SSH data revealed that 26% of up‐regulated genes identified by expression profiling matched with those present in the SSH library. Besides numerous known genes, we identified a large set of unknown cDNAs that represent previously unrecognised TPA‐regulated genes in murine skin with potential function in tumour promotion. Additionally, some TPA‐induced genes, such as Sprr1A, Saa3, JunB, Il4rα, Gp38, RalGDS and Slpi exhibit high basal level in advanced stages of skin carcinogenesis, suggesting that at least a subgroup of the identified TPA‐regulated genes may contribute to tumour progression and metastasis. © 2003 Wiley‐Liss, Inc.
CTLA4 promoter and exon 1 dimorphisms in multiple sclerosiso
Authors: Flinstad Harbo H. , Gulowsen Celius E. , Vartdal F. , Spurkland A.
Published: March 2003

The human cytotoxic T‐lymphocyte‐associated protein 4 (CTLA4) gene may be a candidate susceptibility gene in multiple sclerosis (MS). In this study the distribution of the dimorphisms of exon 1 (+49 A/G) and promoter (−318 C/T) regions of the CTLA4 gene was analysed in 296 unrelated Norwegian MS patients and 271 matched controls by polymerase chain reaction and restriction fragment length polymorphism. The frequency of the exon 1 (+49) A‐G genotype was increased in patients (57%) compared with controls (44%) (Pcorrected=0.01), and even more increased in patients with relapsing remitting MS (59%) (Pcorrected=0.006). No other significant differences were found between clinical subgroups of patients or between HLA‐DRB1*1501, DQB1*0602‐positive and negative patients and controls.
Significant association of HLA‐B and HLA‐DRB1 alleles with cleft lip with or without cleft palate
Authors: Sakata Y. , Tokunaga K. , Yonehara Y. , Bannai M. , Tsuchiya N. , Susami T. , Takato T.
Published: March 2003

Nucleotide sequence level typing of HLA‐B, ‐DRB1, and ‐DPB1 alleles was performed on Japanese patients with cleft lip with or without cleft palate (CL/P). Two HLA‐B alleles, B*1501 and B*5101, showed a significant positive association with CL/P. The increase of B*1501 was evident in female patients (OR=3.6, Pc=0.003), whereas the increase of B*5101 was evident in male patients (OR=3.7, Pc< 0.001). One HLA‐DRB1 allele, HLA‐DRB1*0802 also showed an increase in CL/P patients. Conversely, HLA‐B*4403 and DRB1*1302 were not observed in the patient group (Pc=0.01 and Pc=0.02, respectively). No HLA‐DPB1 alleles showed significant association with CL/P. Thus, the present study indicates that HLA alleles, or closely linked loci, may be involved in the pathogenesis of CL/P.
Correction of HLA‐Cw*0501 and identification of HLA‐Cw*0711
Authors: Baurain J.‐F. , Coulie P.G.
Published: March 2003

We describe a new HLA‐C allele, Cw*0711, that differs from Cw*0704 by one residue in the intracytoplasmic region, and correct two errors in the published sequence of Cw*0501 Note.
Allele resolution of HLA‐A using oligonucleotide probes in a two‐stage typing strategy
Authors: Williams F. , Meenagh A. , Maxwell A.p. , Middleton D.
Published: March 2003

High‐resolution polymerase chain reaction using sequence‐specific oligonucleotide probes (PCR‐SSOP) typing methods for HLA‐A identification have been established. The four systems, which operate independently of each other, are intended for use as secondary typing systems following HLA‐A identification with a medium‐resolution PCR‐SSOP technique. The systems, all using digoxigenin‐labelled probes, are based on group specific amplifications for resolution of: i) HLA‐A*29 & ‐A*33; ii) HLA‐A*24 & ‐A*30; and iii) HLA‐A*26, ‐A*25, ‐A*11, ‐A*34, ‐A*66 and ‐A*68 alleles, respectively. The fourth system, for the detection of HLA‐A*02 alleles, is a modification of a previously reported PCR‐SSOP subtyping system. The methods have been applied to individuals from the local bone marrow registry and HLA‐A allele frequencies for the Northern Ireland population have been established.
Significant association of a single nucleotide polymorphism in the tumor necrosis factor‐alpha (TNF‐α) gene promoter with human narcolepsy
Authors: Hohjoh H. , Nakayama T. , Ohashi J. , Miyagawa T. , Tanaka H. , Akaza T. , Honda Y. , Juji T. , Tokunaga K.
Published: March 2003

Narcolepsy is a sleep disorder in which multiple factors, including environmental and genetic factors, are involved. A genetic factor strongly associated with the disorder has been found in the human leukocyte antigen (HLA) class II region: the haplotype, DRB1*1501–DQB1*0602, predisposes to narcolepsy. No susceptibility genes other than the HLA‐haplotype have been found. In this paper, we performed an association study of the tumor necrosis factor‐alpha (TNF‐α) gene located in the HLA class III region with human narcolepsy, in which we examined the known single‐nucleotide polymorphisms (SNPs) in the promoter region in 49 narcoleptic patients, who were all positive for DRB1*1501, and 111 healthy control individuals. The results indicated that the frequency of the genotype at position −857 (−857SNP) was significantly different between the patients and controls, and the allele frequencies of –857SNP revealed that the frequency of –857T was significantly increased in the patients as compared with that in the controls (P=0.0068). In addition, haplotypes presumed from HLA‐DRB1, –857SNP and HLA‐B loci suggested that –857T was mainly associated with DRB1 alleles other than DRB1*1501: the significant increase in frequency of –857T in the patients was not caused by allelic association with DRB1*1501. Therefore, it is conceivable that the TNF‐α with –857T was associated with narcolepsy independently of the strong association of DRB1*1501 with the disorder. Altogether, the data presented here lead us to propose that TNF‐α could be a new susceptibility gene in human narcolepsy.
Expression of the membrane protein tyrosine phosphatase CD148 in human tissues
Authors: Autschbach F. , Palou E. , Mechtersheimer G. , Rohr C. , Pirotto F. , Gassler N. , Otto H.F. , Schraven B. , Gaya A.
Published: March 2003

CD148, a receptor‐like protein tyrosine phosphatase also known as HPTP‐η/DEP‐1, is involved in signal transduction in leucocytes and is thought to contribute to mechanisms of cellular differentiation. We have investigated the in situ expression of CD148 in various fresh‐frozen tissues by immunohistology and analyzed its expression on subpopulations of activated peripheral blood leucocytes by flow cytometry. In lymphoid organs, CD148 was found to be widely expressed on B and T cells, granulocytes, macrophages, certain dendritic cells as well as mature thymocytes. The cellular level of CD148 was increased after in vitro activation of peripheral blood leucocytes. Comparative analysis of tissue samples from normal gut and from patients with active Crohn′s disease showed that leucocytes expressing CD148 are significantly upregulated in inflamed tissues and that a subset of these cells co‐express the activation marker CD25. In non‐lymphoid tissues, CD148 was found to be present on many epithelial cell types with glandular and/or endocrine differentiation as well as on fibrocytes, melanocytes and Schwann cells. CD148 expression was maintained also in malignant counterparts of such tissues. However, a marked loss of CD148 immunoreactivity was apparent in some of the investigated high‐grade carcinomas. In summary, our results confirm a role of CD148 as a leucocyte activation marker. Among non‐hematopoietic cells, CD148 is expressed by characteristic types of epithelial and non‐epithelial cells. Downregulation of CD148 might promote dedifferentiation and autonomous growth of such cells in malignant tumors.
In vitro exposure of acute promyelocytic leukemia cells to arsenic trioxide (As2O3) induces the solitary expression of CD66c (NCA‐50/90), a member of the CEA family
Authors: Di Noto R. , Boccuni P. , Costantini S. , Dello Russo A. , Lo Pardo C. , Copia C. , Annunziata M. , Cimino R. , Ferrara F. , Del Vecchio L.
Published: March 2003

Arsenic trioxide (As2O3) is a useful drug for the treatment of acute promyelocytic leukemia (APL), acting through a complex mechanism involving the induction of apoptosis. We investigated by flow cytometry whether in vitro treatment of APL leukemic cells with As2O3 determined specific surface membrane changes. Twelve APL bone marrow aspirates were analyzed following 7 days of in vitro treatment with As2O3 (0.25, 0.5 and 2.5 μM) with regard to the expression of a series of differentiation antigens. Twelve acute myeloid leukemia (AML) samples of non‐APL morphotype were analyzed as controls. Exposure of APL as well as non‐APL samples to any concentration of As2O3 did not affect the expression of β2 integrins (CD11a and CD11b), CD45 isoforms (RA, RB and R0), CD44/H‐CAM, CD33 and the CEA‐related antigen family members CD66ade and CD66b, thus failing to disclose any maturating effect. Of interest, in all APL samples (but not in AML) every tested dose of As2O3 determined a dramatic upregulation of CD66c display: intermediate concentration (0.5 μM) of As2O3 increased the median percentage of CD66c+ cells from 5% in control cultures (25th–75th percentile 2–12%) to 80% in drug‐exposed cultures (25th–75th percentile 58–90%) (P<0.001). The induction of solitary expression of CD66c is a new finding which demonstrates As2O3 capability of generating phenotypic changes absolutely restricted to APL cells. Moreover, these results provide experimental basis for considering the involvement of the newly described CD66 signalling pathway in As2O3‐driven programmed cell death.
Heterogeneity of Taiwan’s indigenous population: possible relation to prehistoric Mongoloid dispersals
Authors: Lin M. , Chu C.C. , Lee H.L. , Chang S.L. , Ohashi J. , Tokunaga K. , Akaza T. , Juji T.
Published: March 2003

Taiwan’s 9 indigenous tribes (Tsou, Bunun, Paiwan, Rukai, Atayal, Saisiat, Ami, Puyuma, Yami) are highly homogeneous within each tribe, but diversified among the different tribes due to long‐term isolation, most probably since Taiwan became an island about 12,000 years ago. Homogeneity of each tribe is evidenced by many HLA‐A,B,C alleles having the world’s highest ever reported frequencies, e.g. A24 (86.3%), A26 (18.8%), Cw10 (36.8%), Cw7 (66%), Cw8 (32.1%), B13 (27.9%), B62 (37.4%), B75 (18%), B39 (53.5%), B60 (33.3%), and B48 (24%). Also, all of these tribes have HLA class I haplotype frequencies greater than 10%, with A24‐Cw7‐B39 in Saisiat (44.5%) being the highest, suggesting Taiwan’s indigenous tribes are probably the most homogeneous ( the “purest”) population in the world. A24‐Cw8‐B48, A24‐Cw10‐B60 and A24‐Cw9‐B61 found common to many Taiwan indigenous tribes, have also been observed in Maori, Papua New Guinea Highlanders, Orochons, Mongolians, Inuit, Japanese, Man, Buryat, Yakut, Tlingit, Tibetans and Thais. These findings suggest Taiwan’s indigenous groups are more or less genetically related to both northern and southern Asians. Principal component analysis and the phylogenetic tree (using the neighbor‐joining method) showed close relationship between the indigenous groups and Oceanians. This relationship supports the hypothesis that Taiwan was probably on the route of prehistoric Mongoloid dispersals that most likely took place along the coastal lowland of the Asian continent (which is under the sea today). Cultural anthropology also suggests a relationship between Taiwan’s indigenous tribes and southern Asians and to a lesser extent, northern Asians. However, the indigenous groups show little genetic relationship to current southern and northern Han Chinese.
Study of host‐ and virus‐related factors associated with spontaneous hepatitis C virus clearance
Authors: Alric L. , Fort M. , Izopet J. , Vinel J.‐P. , Bureau C. , Sandre K. , Charlet J.‐P. , Beraud M. , Abbal M. , Duffaut M.
Published: March 2003

Epidemiologic parameters, virologic characteristics and frequency of HLA class II DR and DQ antigens were compared between 63 subjects with spontaneous hepatitis C virus clearance (group 1) and 282 patients with chronic active hepatitis C virus infection (group 2). DRB1*1101 and moreover DQB1*0301 alleles were more frequent in group 1 than in group 2 (33.8% vs. 14.7% and 64.4% vs. 28.6%; P=0.012 and P=0.003, respectively). The frequency of DQB1*02 was lower in group 1 than in group 2 (25.4% vs. 49%; P=0.04). No difference was observed in viral genotype distribution between group 1 and group 2. Univariate analysis showed that female sex and contamination by intravenous drug use were associated with self limited infection. However, by multivariate analysis, the only independent factor associated with hepatitis C virus RNA clearance was female sex (P=0.004). In conclusion, spontaneous hepatitis C virus RNA clearance is determined by class II antigens (mainly DQB1*0301) and female sex, while viral genotype plays no role.
Prospective analysis suggests susceptibility genes for deficiencies of IgA and several other immunoglobulins on the [HLA‐B8, SC01, DR3] conserved extended haplotype
Authors: Alper C.A. , Marcus‐Bagley D. , Awdeh Z. , Kruskall M.S. , Eisenbarth G.S. , Brink S.J. , Katz A.J. , Stein R. , Bing D.H. , Yunis E.J. , Schur P.H.
Published: March 2003

The extended major histocompatibility complex (MHC) haplotype [HLA‐B8, SC01, DR3] is increased in frequency among patients with immunoglobulin (Ig)A deficiency and common variable immunodeficiency. Because the genomic region from HLA‐B to HLA‐DR/DQ is virtually the same on all instances of the haplotype in the general population, we reasoned that all independent instances of [HLA‐B8, SC01, DR3] carry MHC susceptibility genes for these disorders. To define immunoglobulin deficiencies determined by genes on this haplotype and their mode of expression and penetrance, serum immunoglobulin class and IgG subclass concentrations were determined prospectively in homozygotes and heterozygotes of this haplotype and in Caucasian controls. Prevalence of individual immunoglobulin deficiencies in persons with [HLA‐B8, SC01, DR3] ranged from 13% to 37%, significantly higher than rates in non‐carriers or general controls. We found significantly increased frequencies of IgA and IgG4 deficiency only in homozygotes (13.3% and 30%, respectively) compared with heterozygotes (1.7% and 3.4%) or non‐carriers (1.6% each), suggesting recessive expression. In contrast, IgD and IgG3 deficiencies were significantly more common in both homozygotes (36.7% and 30%) and heterozygotes (20.3% and 17.5%) compared with controls (4.9% and 3.4%), suggesting dominant inheritance. These results indicate multiple distinct susceptibility genes, some recessive and others dominant, for deficiency of IgA, IgD, IgG3 or IgG4 (but not for IgE, IgG1, IgG2 or IgM) on [HLA‐B8, SC01, DR3]. These observations may also help to explain the observed associations of [HLA‐B8, SC01, DR3] with both IgA deficiency and common variable immunodeficiency and the common occurrence of IgG subclass deficiencies in some patients with IgA deficiency.
DLA‐DQB1 alleles and bone marrow transplantation experiments in narcoleptic dogs
Authors: Wagner J.L. , Storb R. , Storer B. , Mignot E.
Published: March 2003

Human narcolepsy is a neurological disorder known to be tightly associated with HLA‐DQB1*0602. A clinically similar disorder has been described in various dog breeds. The canine form of the disease is inherited as an autosomal recessive disorder in Labrador retrievers and Doberman pinschers (canarc‐1) but occurs sporadically in other breeds, most typically dachshunds and poodles. In this study, we have examined if there is a relationship between the development of narcolepsy and specific dog leukocyte antigen (DLA)‐DQB1 alleles. Ninety‐nine dogs were typed for DLA‐DQB1–31 with narcolepsy and 68 control animals. Recent studies have linked the development of autosomal recessive canine narcolepsy to a disruption of the hypocretin receptor 2 (Hcrtr2) gene on the same chromosome as the canine MHC region (CFA12), but not close to the DLA. Four Hcrtr2‐positive families (two Doberman pinscher families, one Labrador retriever family, one dachshund family) were analyzed at the DLA‐DQ level. No relationship was found between narcolepsy and DLA in Hcrtr2‐mediated narcolepsy but loose genetic linkage was observed (Zmax=2.3 at θ=25%, m=40). Bone marrow transplantation between two DLA identical affected (Hcrtr2−/−) and unaffected (Hcrtr2+/−) siblings was also performed and found not to be successful neither in transmitting narcolepsy nor in relieving the symptoms in Doberman pinschers. DLA‐DQB1 was next studied in 11 dogs with sporadic (non‐familial) narcolepsy and in unrelated control animals of the same and different breeds. The allelic and carrier frequencies of various DLA‐DQB1 alleles were analyzed. There was no strong positive or negative correlation between the development of narcolepsy and specific DLA‐DQB1 alleles. These results do not support the involvement of DLA‐DQ in canine narcolepsy, whether of sporadic or familial origin.
HLA class II typing of whole genome amplified mouth swab DNA
Authors: Gillespie K.M. , Valovin S.J. , Saunby J. , Hunter K.M. , Savage D.A. , Middleton D. , Todd J.A. , Bingley P.J. , Gale E.A.M.
Published: March 2003

Postal collection of mouth swabs provides a cheap and convenient means of DNA sampling but hitherto has not provided sufficient genetic material for HLA typing by polymerase chain reaction using sequence‐specific primers (PCR‐SSP). This study examined the feasibility of collecting mouth swabs from a test population by post, amplifying the DNA by whole genome amplification and genotyping for selected HLA class II alleles. We optimised a strategy for whole genome amplification or primer extension preamplification using a random 15 base pair primer which resulted in a 1,000‐fold increase in DNA template. The amplified DNA was of sufficient quality for analysis of selected HLA Class II alleles by PCR‐SSP and PCR using sequence‐specific oligonucleotide probes. To test the reliability of our data, blood DNA from 30 individuals in 10 families, previously tested for all DRB1 alleles in a routine diagnostic laboratory, was then tested in our laboratory for DRB1 *03 and *04 following whole genome amplification. Further whole genome amplified product from another 10 families was tested for DRB1 *03, *04 in our laboratory and then tested for all DRB1 alleles in a routine diagnostic laboratory. One repeat typing was required to achieve 100% concordance between laboratories. Amplification of whole genome amplified DNA by PCR‐SSP was then extended successfully to low‐resolution HLA DRB1, DQA1, DQB1 and DPB1 typing. Mouth swab collection by post, followed by whole genome amplification of DNA provides an effective strategy for genetic analysis of large cohorts. We have optimised conditions for HLA class II typing on whole genome amplified DNA collected by mouth swab, but this method could potentially be applied to low concentrations of DNA from other sources.
Identification of seventeen novel KIR variants: fourteen of them from two non‐Caucasian donors
Authors: Rajalingam R. , Gardiner C.M. , Canavez F. , Vilches C. , Parham P.
Published: March 2003

The killer‐cell immunoglobulin‐like receptors (KIR) expressed by human natural killer (NK) cells are encoded by a family of genes on chromosome 19. The number of KIR genes varies with haplotype and the individual genes exhibit polymorphism. To investigate KIR diversity we studied KIR cDNA and genes of four human donors: two Caucasians, one Black American and one Asian Indian. From analysis of these donors seventeen novel KIR variants were identified and characterized. Fifteen of the new variants appear to have a simple allelic relationship with a known KIR, whereas two of them combine the sequences of two different KIR genes. Fourteen of the seventeen KIR variants were isolated from the two non‐Caucasoid blood donors. These data show that much human KIR diversity remains to be characterized, particularly in non‐Caucasoid populations.
A MAGE‐3 peptide recognized on HLA‐B35 and HLA‐A1 by cytolytic T lymphocytes
Authors: Schultz E.S. , Zhang Y. , Knowles R. , Tine J. , Traversari C. , Boon T. , Van Der Bruggen P.
Published: March 2003

Abstract: Antigens encoded by MAGE genes are of particular interest for cancer immunotherapy because of their strict tumoral specificity and because they are shared by many tumors. Antigenic peptide EVDPIGHLY encoded by MAGE‐3 and known to be presented by HLA‐A*0101 is currently being used in therapeutic vaccination trials. We report here that a cytolytic T‐lymphocyte (CTL) clone, which is restricted by HLA‐B*3501, recognizes the same peptide and, importantly, lyses HLA‐B*3501 tumor cells expressing MAGE‐3. These results infer that the current clinical use of peptide EVDPIGHLY can now be extended to HLA‐B*3501 patients.
HLA‐DPB1 typing by polymerase chain reaction amplification with sequence‐specific primers
Authors: Aldener‐Cannavá A. , Olerup O.
Published: March 2003

Abstract: DPB1 is the second most polymorphic class II locus with currently 84 recognized alleles, i.e. DPB1*0101 to DPB1*8101. Most of the alleles have been described during the last few years using oligonucleotide and sequencing techniques and relatively little is known about the role and importance of the polymorphic residues as regards to the function of DP molecules. In the present study, polymerase chain reaction (PCR) primers were designed for identification of all the phenotypically different DPB1 alleles by PCR amplification with sequence‐specific primers. Forty‐eight standard genomic PCR reactions per sample were performed in order to achieve this resolution. Unique amplification patterns were obtained in 2983 of 3160 (94.4%) possible genotypes. The primers were combined so that only very rare genotypes gave rise to ambiguous patterns. Sixty‐four Histocompatibility Workshop cell lines and 150 DNAs provided by the UCLA DNA exchange were investigated by the DPB1 primer set. All typing results were conclusive. Analysis of the distribution of DPB1 alleles was performed in 200 Caucasian samples, 100 African samples and 40 Oriental samples. The population study by the DPB1 PCR‐SSP method showed a characteristic distribution of HLA‐DPB1 alleles. Each ethnic group had one, or two, frequent DPB1 allele(s) and the frequency of homozygotes was high, suggesting that balancing selection does not appear to be affecting the evolution of the DPB1 locus (Note).
Identification and nucleotide sequence of HLA‐A*02015
Authors: Guttridge M.G. , Darke C.
Published: March 2003

Abstract: A novel HLA‐A*02 allele, A*02015, is described that possess a unique non‐coding substitution of G to A at position 113 in exon 3 (Note).
Diversity of HLA among Taiwan’s indigenous tribes and the Ivatans in the Philippines
Authors: Chu C.‐C. , Lin M. , Nakajima F. , Lee H.‐L. , Chang S.‐L. , Juji T. , Tokunaga K.
Published: March 2003

Abstract:Taiwan’s indigenous tribes, especially the east coast tribes are not only closely related to Oceania but also with the Australian aborigines. The Ivatans of the Batan Islands in the Philippines are closely related to the Yami tribe of Taiwan as cultural and anthropological studies have shown. Many DRB1 alleles (*15021, *16021, *0404, *04051, *11011, *12021, *1401, *08032) have high allele frequencies (>20%) in certain tribes, suggesting Taiwan’s indigenous tribes are homogeneous populations. These high frequency DRB1 alleles and also some HLA‐A‐B‐DR haplotypes found in Taiwan’s indigenous tribes are also found in Oceania, Australian aborigines, south and north east Asians and American Indians, lending further support to our previous findings that Taiwan’s indigenous tribes are more or less genetically related to both northern and southern Asians, possibly as well as Amerindians. HLA‐A*2402 with a remarkably high frequency among Taiwan’s indigenous tribes (52.1%∼86.3%), especially the central mountain tribes, possibly represents not only founder effects and population bottlenecks, but also positive selection of the allele. Although the Ami tribe has the highest ever reported frequencies of the DRB1*0404 and DRB1*0405, these alleles have not been found to be associated with rheumatoid arthritis as previously described for Caucasians. In addition, DRB1*1401 has a high frequency in most tribes but is not associated with psoriasis as previously indicated in some studies, suggesting the involvement of some additional genetic and/or environmental factors mechanism in the development of these diseases.
Gene frequencies of human neutrophil antigens in the Tunisian blood donors and Berbers
Authors: Abid S. , Zili M. , Bouzid L. , Kibech R. , Foudhaili N. , Joudi K. , Regaya Z. Ren , Abdennaji B. , Mrad R. , Boukef K.
Published: March 2003

Abstract:Human neutrophil antigens play an important role in provoking immune neutropenia and transfusion‐reactions. The aim of this study was to determine granulocyte‐specific antigens on the neutrophil Fcγ receptor IIIb (FcγRIIIb, CD16b), namely, the HNA‐1a(NA1) and HNA‐1b(NA2) antigens and their gene frequencies in Tunisian blood donors and Berbers. One hundred and ninety‐nine unrelated healthy Tunisian blood donors and Berbers were typed for HNA‐1a and HNA‐1b(NA1 and NA2), using polymerase chain reaction with sequence‐specific primers (PCR‐SSP). In 24 granulocyte samples, the HNA‐1a and HNA‐1b phenotypes was additionally determined by the granulocyte immunofluorescence test (GIFT) and correlated with the genotyping results. A subsequent analysis of the genotyping study showed that, the HNA‐1a and HNA‐1b gene frequencies observed, were 0.342 and 0.658 for Berbers, and 0.311 and 0.668 for blood donors, respectively. In the genotyping study conducted, it was determined that the HNA‐1a and HNA‐1b gene frequencies observed in Tunisian blood donors and Berbers are similar to those previously reported in other white populations.
Chemokine receptor CCR5 polymorphisms and Chagas’ disease cardiomyopathy
Authors: Calzada J.E. , Nieto A. , Beraún Y. , Martín J.
Published: March 2003

Abstract: In this study we investigated the possible role of two CCR5 gene polymorphisms, CCR5Δ32 deletion and CCR5 59029 A→G promoter point mutation, in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease. These CCR5 polymorphisms were assessed in 85 seropositive (asymptomatic, n=53; cardiomyopathic, n=32) and 87 seronegative individuals. The extremely low frequency (0.009) of the CCR5Δ32 allele in our population did not allow us to analyse its possible influence on T. cruzi infection. We found no differences in the distribution of CCR5 59029 promoter genotype or phenotype frequencies between total chagasic patients and controls. However, we observed that the CCR5 59029‐A/G genotype was significantly increased in asymptomatic with respect to cardiomyopathic patients (P=0.02; OR=0.33, 95% CI 0.10–0.94). In addition, the presence of the CCR5 59029‐G allele was also increased in asymptomatics when compared with cardiomyopathics (P=0.02; OR=0.35, 95% CI 0.12–0.96). Our data suggest that the CCR5 59029 promoter polymorphism may be involved in a differential susceptibility to chagasic cardiomyopathy.
Calreticulin binds to the α1 domain of MHC class I independently of tapasin
Authors: Turnquist H.R. , Vargas S.E. , McIlhaney M.M. , Li S. , Wang P. , Solheim J.C.
Published: March 2003

Abstract: Prior to binding to antigenic peptide, the major histocompatibility complex (MHC) heavy chain associates with an assembly complex of proteins that includes calreticulin, tapasin, and the transporter associated with antigen processing (TAP). Our data show that calreticulin can bind weakly to Ld without tapasin's assistance, and that deglycosylation of the α1 domain results in a primary loss of binding to calreticulin rather than tapasin. We have also shown that high amounts of wild‐type tapasin are still unable to associate with MHC class I in the absence of the MHC class I/calreticulin interaction, confirming the central role of calreticulin in the formation of the MHC class I assembly complex.
Identification of a novel HLA DRB1 exon 2 sequence, DRB1*1345
Authors: Bengtsson M. , Jansson I.E. , Danielsson F. , Henrysson H. , Källsten K.
Published: March 2003

Abstract: Five different haplotypes in the human HLA D region are recognized based on their gene composition. The HLA DR52 associated DRB1 alleles include DRB1*03/08/11/12/13/14 and are characterized by the YST sequence motif in the codons 10–12 but vary in other polymorphic regions. The mechanisms generating the extensive variability are not entirely clear. Some alleles have probably arisen from point mutations, but most polymorphism has probably been caused by intralocus gene conversion, and the distinction between the ancient serologically defined groups is more and more difficult. This report describes the identification of a novel DRB1* allele – DRB1*1345 – found in a kidney transplant recipient from East Africa. The new allele shows the closest resemblance to DRB1*1114 and DRB1*1323. It differs from both those alleles at codons 57, 58 and 60, where the new allele carries the ‘A‐H’ sequence motif common to DRB1*14 alleles such as 1401/04/07/10/16/25. This motif is only found in one other DRB1*13 allele namely DRB1*1343.
Association of single nucleotide polymorphisms in the IL‐18 gene with sarcoidosis in a Japanese population
Authors: Takada T. , Suzuki E. , Morohashi K. , Gejyo F.
Published: March 2003

Abstract: Interleukin‐18 (IL‐18) and interleukin‐12 (IL‐12) synergistically stimulate interferon‐γ (IFN‐γ) production from Th1 cells. The levels of serum IL‐18 and IFN‐γ and bronchoalveolar lavage fluid IL‐18 were elevated in patients with sarcoidosis. The polymorphisms of the IL‐18 gene may play a possible role in expression regulation of the gene. We investigated the roles of the polymorphisms in the development of sarcoidosis. We examined two single nucleotide polymorphisms of the IL‐18 gene in 119 patients with sarcoidosis and 130 healthy control subjects. Our results showed that the frequency of sarcoidosis patients with the CA genotype at position ‐607 was significantly higher than that with the AA genotype (OR = 2.200) and a significantly higher proportion of patients had the C allele at ‐607 compared with that of the controls (OR = 2.123). No significant differences were seen in the distribution of the genotypes or phenotype frequencies at position ‐137. There was no specific organ involvement associated with a certain genotype or phenotype. In IL‐18 gene polymorphisms, the C allele at position ‐607 might be a genetic risk factor for sarcoidosis in this Japanese population.
Corneodesmosin DNA polymorphisms in MHC haplotypes and Japanese patients with psoriasis
Authors: Hui J. , Oka A. , Tamiya G. , Tomizawa M. , Kulski J. K. , Penhale W.J. , Tay G.K. , Iizuka M. , Ozawa A. , Inoko H.
Published: March 2003

Abstract: In order to examine the relationship between corneodesmosin (CDSN) and psoriasis we have determined the presence of CDSN polymorphisms by DNA sequencing in (a) nine B‐LCL cell lines of major histocompatibility complex ancestral haplotypes known to be associated with psoriasis vulgaris including 13.1AH, 46.1AH, 46.2 and 57.1AH, and in (b) a group of 267 unrelated individuals comprising Japanese psoriasis patients (n = 101) and Japanese subjects without the disease (n = 166). Three novel CDSN gene sequences were identified. In addition, we have classified the 18 alleles into seven main groups based on phylogeny of non‐synonymous substitutions. However, we have found no statistically significant differences between the patients and the unaffected individuals in any of these groups. These findings indicate that CDSN is not a major psoriasis susceptibility gene.