bluuebunny/crossref_metadata_2025 huggingface dataset:
GENE FREQUENCY AND LINKAGE DISEQUILIBRIUM ANALYSIS OF HLA‐DRB1*04 HAPLOTYPES IN A SOUTH WALES POPULATION
Authors: Young N. T. , Darke C.
Published: April 2007

HLA‐DRB1*04 allele frequencies have been determined in 184 HLA‐DR4‐positive unrelated blood donors from the South Wales area, using group‐specific polymerase chain reaction (PCR) amplification and hybridization with sequence‐specific oligonucleotide probes, PCR amplification with sequence‐specific primers, and PCR single‐strand conformation polymorphism analysis.

Eight of the fifteen known HLA‐DR4 sequences were detected in this study. Linkage disequilibrium analysis of HLA‐DRB1 *04 and HLA‐B, ‐DR and ‐DQ alleles revealed distinct haplotypic associations for all the major alleles detected in this population, including the novel linkage of HLA‐B55 with DRB1*0407.

These results are relevant to the role of HLA‐DRB 1*04 haplotypes in determining allogeneic histocompatibility and disease susceptibility.
SEROLOGICAL IDENTIFICATION OF A NEW HLA‐B7 VARIANT ANTIGEN –HLA‐B7QUI
Authors: Fussell H. , Thomas M. , Street J. , Darke C.
Published: April 2007

A new HLA‐B antigen, HLA‐B7Qui that appears to be a variant of HLA‐B7 has been identified. This antigen, which is HLA‐Bw6 associated, reacts with approximately two‐thirds of cytotoxic antisera stimulated by HLA‐B7 or B27 that lack a B27 or B7 component, respectively. All anti‐B7+27 antisera (stimulated by either B7 or B27) react with B7Qui as do most B22‐stimulated sera possessing a B7 component. However, sera stimulated by B60, with or without a B7 component, fail to react with B7Qui.

Family studies show the B7Qui allele to be unique to the haplotype –HLA‐A32 CW6 B7Qui Bf*S C4A*6 C4B*1 DR11 DQ7 (GL02). Six Caucasoid subjects on the panel of 6861 HLA‐typed potential bone marrow donors have this antigen (phenotype frequency, 0.08745%; gene frequency, 0.04473%). Work undertaken during the 11th International Histocompatibility Workshop (Reekers et al., 1992) showed that B7Qui has the same isoelectric point as HLA‐B702 and HLA‐B703 (Bpot) and that B7Qui is distinct from the HLA‐B7 variants B703, B7SL, BDT, B7x40, BRI, and B41v.
A CLASS I cDNA FROM SPAFAS LINE‐11 CHICKENS
Authors: Pharr G. T. , Bacon L. D. , Dodgson J. B.
Published: April 2007

A chicken MHC class I (B‐F) cDNA from SPAFAS line 11 embryonic liver tissue was isolated and characterized by nucleotide sequencing. Comparing this sequence with previously described B‐FcDNAs highlights clustered nucleotide substitutions in exon 3, encoding amino acids located on the a‐helical region of the α2 domain.
A NEW PCR‐BASED TYPING OF THE RODGERS AND CHIDO ANTIGENIC DETERMINANTS OF THE FOURTH COMPONENT OF HUMAN COMPLEMEMT
Authors: Barba G.M.R. , Braun‐Heimer L. , Rittner C. , Schneider P.M.
Published: April 2007

The Rodgers (Rg) and Chido (Ch) blood groups are antigenic determinants of the fourth component of human complement C4. They are associated with the two isotypes of C4, C4A and C4B, respectively. They serve as markers to distinguish C4A from C4B as well as for the definition of subtypes of common and rare allotypes. As an alternative to the serological typing method using human alloantisera, a PCR typing procedure with sequence‐specific primers (PCR‐SSP) was designed. The method was tested on selected DNA samples from individuals with well‐defined C4 allotypes. No false‐positive or false‐negative typing results were obtained and all the determinant combinations could be distinguished. The PCR genotyping allowed the detection of all Rg/Ch sequence determinants of each isotype. Thus, reverse antigenicity could also be established in the presence of other C4 allotypes without a segregation study. To exclude the possibility that PCR‐typed determinants originate from a non‐expressed C4 null gene, a sequence‐specific PCR was established detecting a 2‐bp insertion in exon 29 described previously as a cause for C4A non‐expression. PCR Rg/Ch genotyping provides a fast and efficient method for routine typing in HLA haplotype and disease association studies.
POLYMORPHISM OF THE TUMOUR NECROSIS FACTOR BETA GENE IN MULTIPLE SCLEROSIS AND RHEUMATOID ARTHRITIS
Authors: Vandeyver C. , Raus P. , Stinissen P. , Philippaerts L. , Cassiman J.‐J. , Raus J.
Published: April 2007

We evaluated the TNF‐ß gene polymorphism in two HLA‐associated autoimmune diseases, multiple sclerosis (MS) and rheumatoid arthritis (RA). The TNF‐β allele and genotype frequencies were not significantly different in the patient populations, compared to controls. An increased frequency of the TNF‐β* 2 allele was observed in HLA‐DR2+ vs. HLA‐DR2‐ MS patients. No such association was seen in HLA‐DR4+ RA patients.
THE ASSOCIATION BETWEEN COELIAC DISEASE, DERMATITIS HERPETIFORMIS AND CERTAIN HLA‐ANTIGENS IN ICELANDERS
Authors: ÁRnason A. , Skaftadóttir I. , Sigmundsson J. , MOONEY E. , Björnsson J. , Cariglia N. , Pálsson G. , Gudjónsson H.
Published: April 2007

Twenty‐eight cases of coeliac disease (CD) and seven of dermatitis herpetiformis (DH) have been verified in Iceland. Standard serological techniques were used for HLA typing. Twenty‐five individuals with CD were typed, 21 (84%) of whom carried DR3, DQ2. Twelve of these 25 (48%) had DR3, DR7, DQ2, which makes them possibly homozygous for DQ2, and suggests that homozygosity of DQ2 increases the risk for CD. The four DH patients that were typed all had HLA‐B8, DR3, DQ2. It is concluded that CD and DH are associated with DR3, DQZ in Icelanders.
ANALYSIS OF HLA‐CLASS II DQA1, DQB1, DRB1 and DPB1 IN ITALIAN MULTIPLE SCLEROSIS PATIENTS
Authors: Ciusani E. , Allen M. , Sandberg‐Wollheim M. , Eoli M. , Salmaggi A. , Milanese C. , Nespolo A. , Gyllensten U.
Published: April 2007

We studied the allelic constitution at the HLA class II DQA1, DQB1, DRB1 and DPB1 in 94 Italian multiple sclerosis (MS) patients and 98 controls. No significant increase in the frequency of DR2 alleles was detected among MS patients, as previously observed both in European and some Italian studies. A slight increase was found for the DQA 1*0301 and DQB 1*0602 alleles in the MS patients. No significant association was found with the glutamine residue at position 34 of the DQ α chain, which was noted previously in MS patients from northern Europe.
AN ANALYSIS OF HLA CLASS II GENE POLYMORPHISM IN BRITISH AND GREEK IDIOPATHIC MEMBRANOUS NEPHROPATHY PATIENTS
Authors: Vaughan R. W. , Tighe M. R. , Boki K. , Alexoupolos S. , Papadakis J. , Lanchbury J. S. S. , Welsh K. I. , Williams D. G.
Published: April 2007

Fifty‐two British and 29 Greek idiopathic membranous nephropathy (IMN) patients were analysed for DRB, DQA1, DQB1 and DPB1 gene polymorphism using second exon amplification and sequence‐specific oligonucleotides (SSO). In addition 100 British and 92 Greek controls were analysed.

A highly significant increased frequency of the DRB 1*0301 allele was found in IMN patients from Britain (80%), when compared to controls (27%, OR 10.6, P= 0.000004). A lower frequency of DRB 1 *0301 was observed in Greek IMN patients (33%), but this was just significant before correction, when compared to Greek controls (15%, OR 3, P= 0.02). The DRB3 allele most often associated with DRB 1 *0301 was DRB3*0101 (OR 4.2, P= 0.00025) in British patients and DRB3*0201/2 (OR 11, P=0.006) in Greek patients. In Greek IMN patients a decrease in DR16 was found (OR 0.08, P=0.004), and the overall incidence of DR2 was significantly lowered when both sets of IMN patients were combined (OR 0.21, χ2 17.6, P= 0.00013).

The incidence of DQA1 *0501 was raised in both Greek (96%vs. 66%, OR 9.7, χ2 6.9, P= 0.009) and British IMN (85%vs. 45%, OR 7.4, χ2 20, P= 0.00007) patients. This gives some support to a proposal for a major role for this allele in IMN. However, DQB1 *0201 was also raised in both Greek (50%vs. 21%, OR 3.6, χ2 8.1, P= 0.005) and British (90%vs. 44%, OR 10, χ2 21.7, P=0.00004) IMN patients. The DQA1*0102 allele was significantly lowered in Greek IMN patients (15%vs. 32%, OR 0.05, 12.2, P=0.0008), probably reflecting a lowering in the DR16 haplotype. No significant difference was observed in the frequencies of DPB alleles in patients and controls.

It is concluded that DRB 1*0301 has the strongest association with British Caucasoid IMN. The Greek Caucasoid IMN association with DRB 1*0301 is weaker, and a role for other alleles has not been eliminated.
BIOCHEMICAL DEFINITION OF DLA‐A AND DLA‐B GENE PRODUCTS BY ONE‐DIMENSIONAL ISOELECTRIC FOCUSING AND IMMUNOBLOTTING
Authors: Kubens B.S. , Krumbacher K. , Grosse‐Wilde H.
Published: April 2007

The serologically defined canine MHC gene products (DLA‐A and DLA‐B) were investigated by one‐dimensional isoelectric focusing after detergent phase separation, and immunoblotting (1D‐IEF). The animals studied (n= 36) represented three different breeds. Since DLA‐A and DLA‐B antigens are MHC class I and class II molecules, respectively, cross‐reactive polyclonal antibodies specific for human class I or class II molecules were utilized to visualize the protein pattern. The relative positions of the bands were correlated with the DLA‐A and DLA‐B antigens. In most cases DLA antigens of identical serological type did not differ in their 1D‐IEF pattern except for DLA‐A9 and the serologically undefined DLA‐B gene product DLA‐B ‘blank’. For DLA‐A9, two subtypes (A9.1 and A9.2) were identified in Beagle and associations of A9.1 with the haplotype A9.B4 and of A9.2 with A9, B6 were seen. In contrast, the haplotype A9, B6 in Labradors was associated with A9.1. Whereas all six serologically defined DLA‐A antigens possessed distinct isoelectric points (IEP), not all DLA‐B antigens could be differentiated by 1D‐IEF: B5 as well as B13 coband with one B ‘blank’ specificity (BE1).

Furthermore, a second B ‘blank’(BE2) could be identified by 1D‐IEF, underlining the advantage of this technique in the immunogenetic analysis of DLA gene products in dogs.
MOLECULAR TYPING AND HAPLOTYPIC ASSOCIATIONS OF HLA‐B*44 SUBTYPES
Authors: Varney M.D. , Boyle A.J. , Tait B.D.
Published: April 2007

The heterogeneity of HLA‐B44 is confirmed and the sequence difference between the two major subtypes, B*4402,*4403, is attributed to one polymorphic site in the third exon. A method is described to discriminate B*4402 and B*4403, and the occurrence and linkage disequilibrium of B*44 subtypes is discussed. No example of B*4401 polymorphism in exon 2 was observed.
METHYLATION PATTERNS OF I ε REGION IN B CELLS STIMULATED WITH INTERLEUKIN 4 AND EPSTEIN‐BARR VIRUS IN PATIENTS WITH A HIGH LEVEL OF SERUM IgE
Authors: Kuwabara N. , Kondo N. , Fukutomi O. , Fujii H. , Orii T.
Published: April 2007

Human IgE synthesis requires the presence of both interleukin 4 (IL‐4) and T‐cells. However, it is not clear what role IL‐4 and T‐cells play in the induction of IgE synthesis at the level of gene regulation. B cells that were obtained from patients with a high level of serum IgE and from healthy donors were immortalized by Epstein‐Barr virus. We examined IgE production of these B cells stimulated with IL‐4. Supernatant IgE levels of patient's B cells cultured with or without IL‐4 were higher than those of healthy donor's B cells. Our results indicated that B cells stimulated with IL‐4 from patients produced IgE, germline C ε transcript, and S μ S ε recombination. The germline C e transcript was dose‐dependently induced in the presence of IL‐4 and related to the supernatant IgE level. In B cells stimulated with IL‐4 that were obtained from patients, (some of the) DNA near or within the I e region was (already partly) unmethylated, unlike those from healthy donors, and there was a loss of methyl groups of the DNA upon the addition of IL‐4 in B cells from both patients and normal donors. IgE synthesis of B cells stimulated with IL‐4 in patients with a high level of serum IgE is due to an accessibility in the immunoglobulin heavy‐chain isotype switch, and this may reflect the accessibility in synthesis of germline C ε transcript, which may be caused by the increase of opening chromatin structures because of their unmethylation in the I ε region.
HLA‐DQB1 AND DQA1 MATCHING BY AMBIENT TEMPERATURE PCR‐SSCP
Authors: Clay T.M. , Culpan D. , Pursall M.C. , Bradley B.A. , Bidwell J.L.
Published: April 2007

We have developed a polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) protocol for rapid matching of DQA1 and DQB1 alleles. Electrophoresis can be performed at ambient temperature within the range 18‐28°C without continuous gel cooling. The method has been tested on 27 patient‐potential bone marrow donor pairs for DQB1 and 31 pairs for DQA1. Bone marrow pairs were chosen to represent a broad range of common alleles based upon previous restriction fragment length polymorphism (RFLP) analysis type assignments. Samples were re‐typed by PCR with sequence‐specific primers (PCR‐SSP) and the results compared to matching by PCR‐SSCP analysis. There was a 100% correlation between PCR‐SSP and PCR‐SSCP analysis for DQB1, and a 97% correlation for DQAl matching.
THE CAYAPA INDIANS OF ECUADOR: A GENETICALLY ISOLATED GROUP WITH UNEXPECTED COMPLEMENT C7 M/N ALLELE FREQUENCIES
Authors: Sölder B. M. , Stefano G. F. De , Dierich M. P. , Würzner R.
Published: April 2007

The Cayapa Indians live in north‐western Ecuador in close proximity to a Black population of African ancestry. C7 M/N allotyping has proved to be a good technique for plasma genetic analysis in several populations. Investigation of 124 Cayapa plasma samples revealed the highest allele frequency of C7*N observed in any population examined so far (0.36 versus 0.225 or lower). The marked difference in frequency compared with several Oriental populations, which are believed to have been derived from the same Asian population as native Amerindians, may reflect the effect of a small founder population followed by a high degree of genetic isolation. The allele frequency of 0.12 for C7*N determined for the neighbouring Black population supports the conclusion that there has been a lack of genetic admixture of Cayapas with other populations, confirming the results of ethnohistorical investigations and other protein polymorphism studies.
FREQUENCIES OF HLA‐A24 AND HLA‐DR4‐DQ8 ARE INCREASED AND THAT OF HLA‐B BLANK IS DECREASED IN CHRONIC TOXIC OIL SYNDROME
Authors: Arnaiz‐Villena A. , Martinez‐Laso J. , Corell A. , Allende L. , Rosal M. , Gomez‐Reino J.J. , Vicario J.L.
Published: April 2007

The cause of toxic oil syndrome (TOS) has not yet been definitively determined, but some genetic susceptibility factors (certain HLA antigens and female sex) have been identified in 236 patients. Similarities with genetic factors for scleroderma and hydralazine‐induced lupus (i.e. in TOS female sex and HLA‐A24, Pcorrected= 0.00001 and DR4, Pcorrected= 0.04, respectively) may provide a clue to the responsible xenobiotic and its pathogenesis, and may also help in understanding the basis of the related eosinophilia‐myalgia syndrome associated with tryptophan ingestion. In this paper it is also established that a human class I antigen (HLA‐A24) and, independently, an HLA class II haplotype (DR4‐DQ8, Pcorrected= 0.04) and arginine 52 in the α‐DQ chains (Pcorrected= 0.03) are associated with TOS susceptibility, similarly to insulin‐dependent diabetes. This further supports the classification of TOS as an autoimmune disease. Also, the increased frequency of a particular set of low‐frequency HLA class I antigens in chronic TOS patients (i.e. B27, B37, B38 and B49) and the probable decrease in the frequency of HLA‐B homozygotes in surviving patients (Pcorrected= 0.008) may provide an objective model to explain the maintenance of the HLA polymorphism: less frequent HLA alleles may be more advantageous in the event of unexpected human contact with unusual xenobiotics (not only microbes); however, other mechanisms working together to preserve and generate HLA polymorphism may coexist.
IMMUNOGENETIC FACTORS IN HPV‐ASSOCIATED CERVICAL CANCER: INFLUENCE ON DISEASE PROGRESSION
Authors: Duggan‐Keen M. F. , Keating P. J. , Stevens F. R. A. , Sinnott P. , Snijders P. J. F. , Walboomers J. M. M. , Davidson S. , Hunter R. D. , Dyer P. A. , Stern P. L.
Published: April 2007

No HLA allele or specificity was significantly different in frequency between a group of 150 cervical cancer patients from north‐west England and controls (correctedPvalues). HLA‐DRB 1*1501/DQB 1*0602 was non‐significantly increased, particularly among patients with HPV16‐positive tumours. HLA‐B7‐positive patients had a significantly poorer clinical outcome than HLA‐B7‐negative patients. A significant component of the genotypic effect is down‐regulation of HLA‐B7 expression by the tumour cells.
DISTRIBUTION OF HLA‐G ALTERNATIVE mRNAs INCLUDING SOLUBLE FORMS IN NORMAL LYMPHOCYTES AND IN LYMPHOID CELL‐DERIVED LEUKEMIA
Authors: Amiot L. , Onno M. , Drénou B. , Marchand B. le , Lamy T. , Semana G. , Fauchet R.
Published: April 2007

The non‐classical HLA‐G gene is the only class I antigen expressed in trophoblasts at the maternofetal interface. In placenta, the HLA‐G gene produces several alternatively spliced isoforms encoding bound‐membrane proteins (G1, G2, G3 and G4) lacking, respectively, exon 7; exons 7 and 3; exons 7, 3 and 4, and exons 7 and 4. In addition, two isoforms (G1s and G2s) containing an intron 4 sequence are able to encode soluble antigens. We have recently reported that the HLA‐G gene is transcriptionally active in lymphocytes and is not transcribed in CD34+ cells, polynuclear cells or monocytes. To investigate the functional significance of the different isoforms in lymphocytes, we studied their distribution in normal T and B lymphocytes and in malignant lymphoid cells by using the RT‐PCR technique followed by hybridization with exon‐specific probes and sequencing assays. In transcriptionally active lymphocytes, the HLA‐G primary transcript is the major form and is differentially spliced in B and T lymphocytes: (i) G1s is found in several samples of T and B cells whereas G2s is only transcribed in T lymphocytes, (ii) the G4 isoform is never detected in B lymphocytes. In addition, we have shown that HLA‐G is inactive in some samples of lymphocytes. Our data suggest that HLA‐G transcription is regulated at the initiation level and at the subsequent splicing. These two levels of regulation may be dysregulated in some cases of T‐ALL and CLL. The potential functions of the HLA‐G alternative forms in lymphocytes, such as peptide binding and modulation of the immune response, are discussed.
HLA FIVE‐LOCUS HAPLOTYPES IN FINNS
Authors: Ikäheimo I. , Silvennoinen‐Kassinen S. , Tiilikainen A.
Published: April 2007

The extreme polymorphism of HLA genes makes them a powerful tool for distinguishing between different genetic populations. Five‐locus HLA haplotypes of Finns (from Oulu, Northern Finland) are described here in order to characterize further the migration pathways of the population to Finland after the Ice Age.

From random families, 364 haplotypes were obtained. The most frequent Finnish haplotype A3,Cw4,B35,DR1,DQ1 (7.7%) is a Caucasoid ancestral haplotype and is shared with Italians of Celtic and non‐Celtic origin. The haplotype A1,Cw7,B8,DR3,DQ2, which occurs in 4.7% of Finns, is the most frequent haplotype in Caucasoids. The haplotypes A3,Cw7,B7,DR2,DQ1 (3.6%) and A2,Cw7,B7,DR2,DQ1 (2.5%) are shared with several Caucasoid populations and the latter also with Jamaican blacks. A2,Cw5,B44,DR5,DQ3 (0.8%) is shared with Italians of Celtic and non‐Celtic origin, A2,Cw6,B13,DR7,DQ2 (1.1%) with Caucasoids in the USA and A9,Cw4,B35,DR1,DQ1 (0.8%) with Mongoloids. The haplotypes A2,CW3,B62,DR4,DQ3 (3.0%), A2,Cw2,B27,DR8,DQ4 (1.7%), A2,Cw3,B62,DR6,DQ1 (1.4%) and A2,Cw1,B27,DR4,DQ3 (1.4%) were also found to be among the most frequent in the Finnish population.

The most frequent HLA haplotypes are consistent with the postulated ancient migration of populations from southern Scandinavia and Germany to Finland, the most frequent haplotype suggesting a common Celtic origin and one less frequent haplotype suggesting an influence from the east.
CORRELATION BETWEEN TUMOUR AND SERUM β2m EXPRESSION IN PATIENTS WITH BREAST CANCER
Authors: Klein T. , Levin I. , Niska A. , Koren R. , Gal R. , Schachter J. , Kfir B. , Narinski R. , Warchaizer† S. , Klein B.
Published: April 2007

HLA class I antigens are composed of a major histocompatibility complex (MHC) encoded heavy chain that is associated non‐covalently with a light chain β‐2 microglobulin (β‐2m). When the HLA complex is metabolized, β‐2m is shed into the serum. A large variety of human and experimental tumours have altered MHC class I expression. In a previous study we observed elevated mean β‐2m serum levels in breast cancer patients, as compared to controls. To study the relationship between tumour expression and serum levels, we examined 54 patients with breast cancer. Tumour β‐2m was determined by immunohistochemistry and serum levels by the ELISA technique. Of the 54 patients, 38 had low and 16 had high β‐2m expression on the tumour. There was a significant correlation between tumour β‐2m and serum β‐2m levels (P= 0.02), with patients whose tumours expressed high β‐2m having high serum β‐2m levels. There was an inverse correlation between tumour grade and tumour β‐2m expression which approached statistical significance (P= 0.06). These findings suggest that in a substantial number of patients the high serum levels derive from shedding of β‐2m from tumour cells. These levels may have implications for tumour growth and metastases due to influences on immunological responses.
HLA‐DR2 HAPLOTYPIC DIVERSITY IN POPULATIONS OF SOUTH‐EAST ASIA, NORTHERN CHINA, MELANESIA AND AUSTRALIAN ABORIGINES USING PCR‐RFLP FOR DRB1, DRB5, DQA1 AND DQB1. A NOVEL DRB1 ALLELE: DRB1 * 16022
Authors: Trejaut J. , Bhatia K. , Greville W.D. , Hu K. R. , Duraisamy G. , Nuchprayoon C. , Donald J. , Aziz† A. , Dunckley H.
Published: April 2007

The polymorphism of the human leucocyte antigen HLA‐DR2 and the heterogeneity of HLA‐DR2 class II‐related haplotypes (HLA‐DRB1‐DRB5‐DQA1‐DQB1) were investigated in four populations of east and south‐east Asia (SEA) and five Melanesian populations using TaqI restriction fragment length polymorphism (RFLP) analysis, and the polymerase chain reaction (PCR) amplification‐based techniques PCR‐RFLP and sequence‐specific oligonucleotide (SSO) typing. The haplotype DRB1*1502‐DRB5*0101‐DQA1*0102‐DQB1*0601 was common in Malaysians, Javanese, Thursday Islanders, Madang, Goroka and the Australian Aborigines, while DRB1*16021‐DRB5*0101‐DQA1*0102‐DQB1*0502 was common in the Thai and Thursday Islanders. DRB1*1501‐DRB5*0101‐DQA1*0102‐DQB1*0602 was present at a high frequency in Northern Chinese, Goroka, Watut and Australian Aborigines. The study describes four rare or unusual haplotypes: HLA‐DRB1*1501‐DRB5*0101‐DQA1*0101‐DQB1*0601, DRB1*1502‐DRB5*0101‐DQA1*0101‐DQB1*0502, DRB1*1502‐DRB5*0102‐DQA1*0102‐DQB1*0502 and DRB1*1501‐DRB5*0101‐DQA1*0101/2‐DQB1*0503; the latter two were confirmed by segregation in two Javanese families. A new DR2 allele, initially detected by PCR‐RFLP and confirmed by DNA sequencing as DRB1 * 16022 (previously designated DRB1 * 16Madang), was seen in a Madang individual. A new HLA‐DR2 TaqI RFLP subtype, locally designated as DR15U, is also described. This RFLP subtype segregated in a Javanese family and correlated with a typically SEA haplotype, DRB1*1502‐DRB5*0102‐DQA1*0101‐DQB1*0501. The allele HLA‐DR16Thai, determined by TaqI DRB RFLP, was found by PCR‐RFLP and SSO typing to correlate with a unique SEA haplotype, HLA‐DRB1*16021‐DRB5*0101‐DQA1*0102‐DQB1*0502, and was observed in the Thai, Malaysian, Thursday Islander, Javanese and Northern Chinese populations.
DIFFERENTIAL EXPRESSION OF THE DOWN‐REGULATORY FUNCTION OF CD8 CELLS IN TRICHOSANTHIN‐INDUCED IMMUNOSUPPRESSION AND ITS GENETIC CONTROL IN HUMANS
Authors: Chou K.‐Y. , Chan M. , Bias W. B.
Published: April 2007

Trichosanthin (Tk), a plant protein isolated from a Chinese medicinal herb, was shown in our previous experiments to suppress mitogenic, antigenic and allogeneic responses of human lymphocytes. Two non‐toxic pathways, the CD8‐dependent and the CD8‐independent, were identified as being involved in inducing the suppression. In this communication, we report that, in a subgroup of healthy subjects, only the CD8‐dependent pathway was found to operate. In cell cultures from the other subjects, removal of CD8 cells from the culture did not diminish the suppression, implying that the down‐regulatory function of the CD8 cells was not expressed in the presence of Tk. Two types of subject, CD8 mediators (M+) (CD8‐dependent pathway operating) and non‐mediators (M−) (CD8‐independent pathway operating), were thus distinguishable. A ‘mediation index’(MI) was calculated as MI (%) = RR of CD8‐depleted cell culture ‐ RR of non‐CD8‐depleted cell culture. Of 68 unrelated subjects tested, 21 (30.9%) could be classified as M+, with a mean ‘mediation index’ of 13.4±4.0, while 47 (69.1%) were M−, with a mean MI of −5.6±4.3 (t= 17.2, P < 0.001). The M+ and M− groups exhibited an essentially non‐overlapping bimodal distribution of MI. Among the 40 Caucasoids in the panel, nine of 14 M+ subjects were HLA‐DR7, DQ2 (χ2= 14.652, Pc= 0.00084). The two DR7‐DQ3 panel members, however, were M−, suggesting that DQ2 might be associated with M+. Segregation patterns in two families revealed that the M+ phenotype is a Mendelian dominant trait.
FINGERPRINTING OF HLA CLASS I GENES FOR IMPROVED SELECTION OF UNRELATED BONE MARROW DONORS
Authors: Martinelli G. , Farabegoli P. , Buzzi M. , Panzica G. , Zaccaria A. , Bandini G. , Calori E. , Testoni N. , Rosti G. , Conte R. , Remiddi C. , Salvucci M. , De Vivo A. , Tura S.
Published: April 2007

The degree of matching of HLA genes between the selected donor and recipient is an important aspect of the selection of unrelated donors for allogeneic bone marrow transplantation (UBMT). The most sensitive methods currently used are serological typing of HLA class I genes, mixed lymphocyte culture (MLC), IEF and molecular genotyping of HLA class II genes by direct sequencing of PCR products. Serological typing of class I antigenes (A, B and C) fails to detect minor differences demonstrated by direct sequencing of DNA polymorphic regions. Molecular genotyping of HLA class I genes by DNA analysis is costly and work‐intensive. To improve compatibility between donor and recipient, we have set up a new rapid and non‐radioisotopic application of the ‘fingerprinting PCR’ technique for the analysis of the polymorphic second exon of the HLA class I A, B and C genes. This technique is based on the formation of specific patterns (PCR fingerprints) of homoduplexes and heterodu‐plexes between heterologous amplified DNA sequences. After an electrophoretic run on non‐denaturing polyacrylamide gel, different HLA class I types give allele‐specific banding patterns. HLA class I matching is performed, after the gel has been soaked in ethidium bromide or silver‐stained, by visual comparison of patients’ fingerprints with those of donors. Identity can be confirmed by mixing donor and recipient DNAs in an amplification cross‐match. To assess the technique, 10 normal samples, 22 related allogeneic bone marrow transplanted pairs and 10 unrelated HLA‐A and HLA‐B serologically matched patient‐donor pairs were analysed for HLA class I polymorphic regions. In all the related pairs and in 1/10 unrelated pairs, matched donor‐recipient patterns were identified. This new application of PCR fingerprinting may confirm the HLA class I serological selection of unrelated marrow donors.
HLA‐DQA1 AND ‐DQB1 GENOTYPING BY PCR‐RFLP, HETERODUPLEX AND HOMODUPLEX ANALYSIS
Authors: Teutsch S. M. , Bennetts B. H. , Castle M. , Hibbins M. , Heard R. N. S. , Stewart G. J.
Published: April 2007

PCR‐RFLP typing methods for DQA1 and DQB1 in conjunction with the analysis of heteroduplex and homoduplex patterns have allowed a simple method for typing all of the major DQA1 and DQB1 alleles. This method has advantages over PCR amplification with sequence‐specific primers (PCR‐SSP), PCR hybridization with sequence‐specific oligonucleotide probes (PCR‐SSO) and other PCR‐RFLP strategies for typing DQ alleles. The analysis of heteroduplex and homoduplex patterns can be used in conjunction with other PCR typing systems such as PCR‐SSP as a confirmatory step with little additional work. In addition, a PCR‐RFLP strategy was designed for resolving the DQB 1*0602 and DQB 1 *0603 alleles, which involved the use of a primer containing a base mutation, creating a new restriction site which distinguished the two alleles. These techniques have enabled resolution of the major homozygous and heterozygous combinations of these DQA1 and DQB I alleles. The PCR‐RFLP technique does not require the large number of oligonucleotides that are necessary for both the PCR‐SSP and PCR‐SSO techniques and is thus both time and cost effective for infrequent or small numbers of samples.
HLA‐G POLYMORPHISM AND ALLELIC ASSOCIATION WITH HLA‐A IN A FINNISH POPULATION
Authors: Karhukorpi J. , Ikaheimo I. , Silvennoinen‐Kassinen S. , Tiilikainen A.
Published: April 2007

The polymorphism of the HLA‐G gene can be identified by PCR‐RFLP analysis. This short communication describes the PCR‐RFLP analysis of HLA‐G polymorphisms in exons 2 and 3 and the association of different HLA‐G and HLA‐A alleles in 26 healthy Finnish families.
Information criteria for astrophysical model selection
Authors: Liddle Andrew R.
Published: April 2007

Model selection is the problem of distinguishing competing models, perhaps featuring different numbers of parameters. The statistics literature contains two distinct sets of tools, those based on information theory such as the Akaike Information Criterion (AIC), and those on Bayesian inference such as the Bayesian evidence and Bayesian Information Criterion (BIC). The Deviance Information Criterion combines ideas from both heritages; it is readily computed from Monte Carlo posterior samples and, unlike the AIC and BIC, allows for parameter degeneracy. I describe the properties of the information criteria, and as an example compute them from Wilkinson Microwave Anisotropy Probe 3-yr data for several cosmological models. I find that at present the information theory and Bayesian approaches give significantly different conclusions from that data.
Plasmodium and Host Lactate Dehydrogenase Molecular Function and Biological Pathways: Implication for Antimalarial Drug Discovery
Authors: Wiwanitkit Viroj
Published: April 2007

Lactate dehydrogenase is an enzyme that catalyses the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+. Lactate dehydrogenase is present at high levels in humans and Plasmodium spp. However, the function of lactate dehydrogenase in malarial infection is not well characterized. In this investigation, a new gene ontology technology is used to predict molecular function and biological pathways of lactate dehydrogenase. In comparison with human lactate dehydrogenase, the P. falciparum lactate dehydrogenase has similar molecular functions such as l‐lactate dehydrogenase activity. Furthermore, P. falciparum lactate dehydrogenase has l‐malate dehydrogenase activity. Although the amino acid sequences for human and P. falciparum lactate dehydrogenase are very different, the molecular functions are similar. This suggests that any non‐selective therapeutic treatment aimed at blocking P. falciparum lactate dehydrogenase function may affect human lactate dehydrogenase. In contrast, a selective lactate dehydrogenase inhibitor targeting the l‐malate dehydrogenase function of P. falciparum and its corresponding tricarboxylic acid cycle provides an attractive therapeutic opportunity.
K+ as a vasodilator in resting human muscle: implications for exercise hyperaemia
Authors: Juel C. , Olsen S. , Rentsch R. L. , González‐Alonso J. , Rosenmeier J. B.
Published: March 2007

Aim:  Potassium (K+) released from contracting skeletal muscle is considered a vasodilatory agent. This concept is mainly based on experiments infusing non‐physiological doses of K+. The aim of the present study was to investigate the role of K+ in blood flow regulation.

Methods:  We measured leg blood flow (LBF) and arterio‐venous (A‐V) O2 difference in 13 subjects while infusing K+ into the femoral artery at a rate of 0.2, 0.4, 0.6 and 0.8 mmol min−1.

Results:  The lowest dose increased the calculated femoral artery plasma K+ concentration by approx.1 mmol L−1. Graded K+ infusions increased LBF from 0.39 ± 0.06 to 0.56 ± 0.13, 0.58 ± 0.17, 0.61 ± 0.11 and 0.71 ± 0.17 L min−1, respectively, whereas the leg A‐V O2 difference decreased from 74 ± 9 to 60 ± 12, 52 ± 11, 53 ± 9 and 45 ± 7 mL L−1, respectively (P < 0.05). Mean arterial pressure was unchanged, indicating that the increase in LBF was associated with vasodilatation. The effect of K+ was totally inhibited by infusion (27 μmol min−1) of Ba2+, an inhibitor of Kir2.1 channels. Simultaneous infusion of ATP and K+ evoked an increase in LBF equalled to the sum of their effects.

Conclusions:  Physiological infusions of K+ induce significant increases in resting LBF, which are completely blunted by inhibition of the Kir2.1 channels. The present findings in resting skeletal muscle suggest that K+ released from contracting muscle might be involved in exercise hyperaemia. However, the magnitude of increase in LBF observed with K+ infusion suggests that K+ only accounts for a limited fraction of the hyperaemic response to exercise.
Vascular adaptations to 8‐week cycling training in older men
Authors: Thijssen D. H. J. , De Groot P. C. E. , Smits P. , Hopman M. T. E.
Published: March 2007

Aim:  Because age‐related changes in the large conduit arteries (increased wall thickness, and attenuated arterial compliance and endothelial function) are associated with cardiovascular pathology, prevention is of paramount importance. The effects of endurance training (i.e. walking or cycling) in older humans are assessed in cross‐sectional studies, examining the brachial and carotid arteries (supplying non‐trained areas). The purpose of this study was to assess the effects of 8‐week endurance training in older men on conduit artery characteristics in the trained and non‐trained vascular beds.

Methods:  In eight healthy sedentary older men (70 ± 3 years), characteristics of the large conduit arteries [common femoral (CFA), superficial femoral (SFA), carotid (CA), and brachial artery (BA)] were measured before and after 8‐week cycling training. Functional [arterial compliance and flow‐mediated dilation (FMD)] and structural (diameter and intima‐media thickness) conduit artery properties were measured using echo‐Doppler. Peak blood flow, representing structural peripheral adaptations, was measured using venous occlusion plethysmography.

Results:  After training, peak leg blood flow was increased (P < 0.01) and baseline diameter and flow were increased in the CFA (P < 0.05). Cycling training enhanced arterial compliance of the SFA (P = 0.03), but did not affect the FMD (P = 0.32) or the intima‐media thickness of the SFA. Exercise training did not alter characteristics of the BA or CA.

Conclusion:  Eight weeks of endurance training in older men altered functional and structural characteristics of the lower extremity vasculature, whereas no changes are reported for the conduit arteries in the non‐trained areas (BA or in the CA).
Protection of estrogens against the progression of chronic liver disease
Authors: Shimizu Ichiro , Ito Susumu
Published: March 2007

Hepatitis C virus infections are recognized as a major causative factor of chronic liver disease. A characteristic feature of chronic hepatitis C, alcoholic liver disease and non‐alcoholic fatty liver disease is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory and oxidative stimuli, and to produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. Estradiol is a potent endogenous antioxidant. Hepatic steatosis was reported to become evident in an aromatase‐deficient mouse and was diminished in animals after treatment with estradiol. Our previous studies showed that estradiol suppressed hepatic fibrosis in animal models, and attenuated HSC activation by suppressing the generation of reactive oxygen species in primary cultures. Variant estrogen receptors were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. A better understanding of the basic mechanisms underlying the gender‐associated differences observed in the progression of chronic liver disease would provide valuable information relative to the search for effective antifibrogenic therapies.
Acute inflammation alters bicarbonate transport in mouse ileum
Authors: Zhang Hui , Ameen Nadia , Melvin James E. , Vidyasagar Sadasivan
Published: March 2007

T‐cell mediated acute inflammation of the ileum may occur during Crohn's disease exacerbations. During ileal inflammation, absorption of nutrients and electrolytes by villus cells is decreased with a concomitant increase in crypt and/or villus fluid secretion. These alterations lead to fluid accumulation and the subsequent diarrhoea. Net intestinal fluid secretion consists of HCO3−‐rich plasma‐like fluid. However, the regulation and mechanisms of HCO3− secretion in normal and acutely inflamed ileum are not clearly understood. To study this phenomenon, anti‐CD3 monoclonal antibody (mAb)‐ induced in vivo ileal inflammatory mouse models was used for in vitro functional studies with Ussing chamber and pH stat techniques. Three hours after anti‐CD3 mAb injection, ileal mucosa stripped of muscular and serosal layers showed a significant increase in short circuit current (Isc) (0.58 ± 0.07 μEq h−1 cm2versus 1.63 ± 0.14 μEq h−1 cm2). The cAMP‐stimulated Isc component was sensitive to glibenclamide but not to DIDS, suggesting that a cystic fibrosis transmembrane conductance regulator (Cftr)‐mediated anion conductance was responsible. Basal Cl−‐dependent HCO3− secretion, measured using a pH stat technique, was decreased significantly in anti‐CD3‐injected mice, with a simultaneous increase in Cl−‐independent HCO3− secretion that was also inhibited by glibenclamide. Experiments using Cftr−/− mice showed neither an increase in Isc nor an increase in HCO3− secretion, confirming the role for Cftr protein in stimulating anion secretion following anti‐CD3 treatment. Western blot analysis indicated that Cftr protein levels were unaltered by anti‐CD3 treatment, at least acutely. Finally, an immunoassay for cAMP showed significant increases in intracellular cAMP in villus cells, but not in crypt cells. These studies therefore suggest a shift from a predominantly electroneutral Cl−HCO3− exchange in normal mice, to a predominantly electrogenic anion secretion including HCO3− that occurs via functional Cftr during anti‐CD3‐mediated acute inflammation.
Transcriptional up‐regulation of nitric oxide synthase II by nuclear factor‐κB at rostral ventrolateral medulla in a rat mevinphos intoxication model of brain stem death
Authors: Chan Julie Y. H. , Wu Carol H. Y. , Tsai Ching‐Yi , Cheng Hsiao‐Lei , Dai Kuang‐Yu , Chan Samuel H. H. , Chang Alice Y. W.
Published: March 2007

As the origin of a ‘life‐and‐death’ signal that reflects central cardiovascular regulatory failure during brain stem death, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this vital phenomenon. Using a clinically relevant animal model that employed the organophosphate pesticide mevinphos (Mev) as the experimental insult, we evaluated the hypothesis that transcriptional up‐regulation of nitric oxide synthase I or II (NOS I or II) gene expression by nuclear factor‐κB (NF‐κB) on activation of muscarinic receptors in the RVLM underlies brain stem death. In Sprague‐Dawley rats maintained under propofol anaesthesia, co‐microinjection of muscarinic M2R (methoctramine) or M4R (tropicamide), but not M1R (pirenzepine) or M3R (4‐diphenylacetoxy‐N‐dimethylpiperidinium) antagonist significantly reduced the enhanced NOS I–protein kinase G signalling (‘pro‐life’ phase) or augmented NOS II–peroxynitrite cascade (‘pro‐death’ phase) in ventrolateral medulla, blunted the biphasic increase and decrease in baroreceptor reflex‐mediated sympathetic vasomotor tone that reflect the transition from life to death, and diminished the elevated DNA binding activity or nucleus‐bound translocation of NF‐κB in RVLM neurons induced by microinjection of Mev into the bilateral RVLM. However, NF‐κB inhibitors (diethyldithiocarbamate or pyrrolidine dithiocarbamate) or double‐stranded κB decoy DNA preferentially antagonized the augmented NOS II–peroxynitrite cascade and the associated cardiovascular depression exhibited during the ‘pro‐death’ phase. We conclude that transcriptional up‐regulation of NOS II gene expression by activation of NF‐κB on selective stimulation of muscarinic M2 or M4 subtype receptors in the RVLM underlies the elicited cardiovascular depression during the ‘pro‐death’ phase in our Mev intoxication model of brain stem death.
Development of the Cantonese speech intelligibility index
Authors: Wong Lena L. N. , Ho Amy H. S. , Chua Elizabeth W. W. , Soli Sigfrid D.
Published: April 2007

A Speech Intelligibility Index (SII) for the sentences in the Cantonese version of the Hearing In Noise Test (CHINT) was derived using conventional procedures described previously in studies such as Studebaker and Sherbecoe [J. Speech Hear. Res. 34, 427–438 (1991)]. Two studies were conducted to determine the signal-to-noise ratios and high- and low-pass filtering conditions that should be used and to measure speech intelligibility in these conditions. Normal hearing subjects listened to the sentences presented in speech-spectrum shaped noise. Compared to other English speech assessment materials such as the English Hearing In Noise Test [Nilsson et al., J. Acoust. Soc. Am. 95, 1085–1099 (1994)], the frequency importance function of the CHINT suggests that low-frequency information is more important for Cantonese speech understanding. The difference in frequency importance weight in Chinese, compared to English, was attributed to the redundancy of test material, tonal nature of the Cantonese language, or a combination of these factors.
Resonance wood [Picea abies (L.) Karst.] – evaluation and prediction of violin makers’ quality-grading
Authors: Buksnowitz Christoph , Teischinger Alfred , Müller Ulrich , Pahler Andreas , Evans Robert
Published: April 2007

The definition of quality in the field of resonance wood for musical instrument making has attracted considerable interest over decades but has remained incomplete. The current work compares the traditional knowledge and practical experience of violin makers with a material-science approach to objectively characterize the properties of resonance wood. Norway spruce [Picea abies (L.) Karst.] has earned a very high reputation for the construction of resonance tops of stringed instruments and resonance boards of keyboard instruments, and was therefore chosen as the focus of the investigation. The samples were obtained from numerous renowned resonance wood regions in the European Alps and cover the whole range of available qualities. A set of acoustical, anatomical, mechanical and optical material properties was measured on each sample. These measurements were compared with subjective quality grading by violin makers, who estimated the acoustical, optical and overall suitability for violin making. Multiple linear regression models were applied to evaluate the predictability of the subjective grading using the measured material characteristics as predictors. The results show that luthiers are able to estimate wood quality related to visible features, but predictions of mechanical and acoustical properties proved to be very poor.
The role of the external ear in vertical sound localization in the free flying bat, Eptesicus fuscus
Authors: Chiu Chen , Moss Cynthia F.
Published: April 2007

The role of the external ear in sonar target localization for prey capture was studied by deflecting the tragus of six big brown bats, Eptesicus fuscus. The prey capture performance of the bat dropped significantly in the tragus-deflection condition, compared with baseline, control, and recovery conditions. Target localization error occurred in the tragus-deflected bat, and mainly in elevation. The deflection of the tragus did not abolish the prey capture ability of the bat, which suggests that other cues are available used for prey localization. Adaptive vocal and motor behaviors were also investigated in this study. The bat did not show significant changes in vocal behaviors but modified its flight trajectories in response to the tragus manipulation. The tragus-deflected bat tended to attack the prey item from above and had lower tangential velocity and larger bearing from the side, compared with baseline and recovery conditions. These findings highlight the contribution of the tragus to vertical sound localization in the free-flying big brown bat and demonstrate flight adaptations the bat makes to compensate altered acoustic cues.
Near equivalence of human click-evoked and stimulus-frequency otoacoustic emissions
Authors: Kalluri Radha , Shera Christopher A.
Published: April 2007

Otoacoustic emissions (OAEs) evoked by broadband clicks and by single tones are widely regarded as originating via different mechanisms within the cochlea. Whereas the properties of stimulus-frequency OAEs (SFOAEs) evoked by tones are consistent with an origin via linear mechanisms involving coherent wave scattering by preexisting perturbations in the mechanics, OAEs evoked by broadband clicks (CEOAEs) have been suggested to originate via nonlinear interactions among the different frequency components of the stimulus (e.g., intermodulation distortion). The experiments reported here test for bandwidth-dependent differences in mechanisms of OAE generation. Click-evoked and stimulus-frequency OAE input/output transfer functions were obtained and compared as a function of stimulus frequency and intensity. At low and moderate intensities human CEOAE and SFOAE transfer functions are nearly identical. When stimulus intensity is measured in “bandwidth-compensated” sound-pressure level (cSPL), CEOAE and SFOAE transfer functions have equivalent growth functions at fixed frequency and equivalent spectral characteristics at fixed intensity. This equivalence suggests that CEOAEs and SFOAEs are generated by the same mechanism. Although CEOAEs and SFOAEs are known by different names because of the different stimuli used to evoke them, the two OAE “types” are evidently best understood as members of the same emission family.
Effects of ocean thermocline variability on noncoherent underwater acoustic communications
Authors: Siderius Martin , Porter Michael B. , Hursky Paul , McDonald Vincent ,   the KauaiEx Group
Published: April 2007

The performance of acoustic modems in the ocean is strongly affected by the ocean environment. A storm can drive up the ambient noise levels, eliminate a thermocline by wind mixing, and whip up violent waves and thereby break up the acoustic mirror formed by the ocean surface. The combined effects of these and other processes on modem performance are not well understood. The authors have been conducting experiments to study these environmental effects on various modulation schemes. Here the focus is on the role of the thermocline on a widely used modulation scheme (frequency-shift keying). Using data from a recent experiment conducted in 100-m-deep water off the coast of Kauai, HI, frequency-shift-key modulation performance is shown to be strongly affected by diurnal cycles in the thermocline. There is dramatic variation in performance (measured by bit error rates) between receivers in the surface duct and receivers in the thermocline. To interpret the performance variations in a quantitative way, a precise metric is introduced based on a signal-to-interference-noise ratio that encompasses both the ambient noise and intersymbol interference. Further, it will be shown that differences in the fading statistics for receivers in and out of the thermocline explain the differences in modem performance.