bluuebunny/crossref_metadata_2025 huggingface dataset:
SEROLOGICAL AND MOLECULAR ANALYSIS OF HLA IN ISRAELI PRIMARY SCLEROSING CHOLANGITIS PATIENTS
Authors: Amar A. , Brautbar C. , Goldin E. , Sherman L. , Barmeir S. , Shouval D. , Hansen J. A. , Smith A. G.
Published: April 2007

HLA class I and class II were investigated in 15 Israeli primary sclerosing cholangitis patients and compared to healthy controls. None of the well established serological specificities were found to be associated with the disease. HLA‐DR52 is serologically defined, but its subtypes DR52a, DR52b, and DR52c cannot be precisely defined by serological means. Therefore, we have used HLA‐DNA typing in order to assign the DR52 splits in PSC patients. Genomic DNA was amplified by PCR, dot‐blotted and hybridized with sequence specific oligonucleotide probes defining the known HLA‐DR52 associated alleles. Only 4 out of the 15 PSC patients tested were found to express DRB3*0101 the allele that encodes DR52a. Of the remaining 11 patients, 9 expressed DRB3*0202 haplotypes, with 2 patients expressing both DRB3*0101 and DRB3*0202, and the remaining 2 patients expressed no DRB3 allele. Our data indicate that there is no apparent association between PSC and the HLA antigens and alleles studied including the alleles of the DRB3 locus in the Israeli population. Thus HLA pheno/genotyping of PSC patients in the Israelis will not be useful for early and/or differential diagnosis of this disease.
MONOMORPHIC ORGANIZATION OF HUMAN DIVERSITY (DH) HEAVY CHAIN VARIABLE GENES
Authors: Chastagner P. , Theze J. , Zouali M.
Published: April 2007

While recent evidence indicates that human immunoglobulin heavy chain variable (VH) genes exhibit a high degree of heterogeneity, little is known concerning the polymorphism of the diversity (DH) gene complex. This locus comprises two clusters, major and minor, which are physically linked with the VH locus. In assessing the variability of the human major and minor DH clusters, we found no evidence for a substantial restriction site polymorphism. We also noted that, in contrast to what was found in the Japanese population, the DH1 gene is not deleted in an appreciable proportion of the European population. We propose that, because DH genes impart the critical functions associated with the third complementarity‐determining region, the genomic organization of the human DH locus has been evolutionarily conserved through selection pressure mechanisms.
FREQUENCY OF HLA‐DPB1 ALLELES IN MULTIPLE SCLEROSIS PATIENTS FROM NORTHERN IRELAND
Authors: Middleton D. , Savage D. A. , Cullen C. , Trainor F. , Mallon E. , Hawkins S.
Published: April 2007

Using sequence‐specific oligonucleotide probes, no altered distribution in the frequency of HLA‐DPB1 alleles was found in multiple sclerosis patients from Northern Ireland. Although present in the controls, linkage disequilibrium between HLA‐DPB1*0101 and HLA‐DR17 was not found in multiple sclerosis patients.
THE HLA‐DRB1*0405 HAPLOTYPE IS MOST STRONGLY ASSOCIATED WITH IDDM IN ALGERIANS
Authors: Djoulah S. , Khalil I. , Beressi J. P. , Benhamamouch S. , Bessaoud K. , Deschamps I. , Degos L. , Hors J.
Published: April 2007

Insulin‐dependent diabetes mellitus (IDDM) in Caucasians is strongly associated with HLA‐DR3‐DQ2 and DR4‐DQ8. In order to investigate the HLA class II associations with IDDM in Algerians, we have used polymerase chain reaction (PCR) and sequence specific oligonucleotide analysis (SSO) to identify DQA1, DQB1, and DRB1 alleles, haplotypes and genotypes in 50 unrelated IDDM patients and 46 controls from a homogeneous population in Western Algeria. Both DRB1*0301‐DQA1*0501‐DQB1*0201 (DR3‐DQ2) and DRB1*04‐DQA1*0301‐DQB1*0302 (DR4‐DQ8) haplotypes were found at increased frequencies among the patients compared to controls (45% vs. 13%, RR = 5.5, Pc < 10‐5 and 37% vs. 4%, RR = 12.9, Pc < 10‐4, respectively). Among the latter, in contrast to other Caucasian populations, only DRB1*0405‐DQA1*0301‐DQB1*0302 was significantly increased in the Algerian patients (25% vs. 1% in controls, RR = 30.3, Pc < 10‐3). Accordingly, the highest risk of disease was observed in DRB1*0301‐DQA1*0501‐DQB1*0201/DRB1*0405‐DQA1*0301‐DQB1*0302 heterozygotes (34% in patients vs. 0% in controls; RR = 49; Pc < 10‐3). This observation and its comparison with DR‐DQ haplotypes in other ethnic groups suggest that the DRB1*0405 allele which encodes an Asp57‐negative β chain may contribute to IDDM susceptibility in a similar way as Asp57‐negative DQβ chains.
FOETO‐MATERNAL COMPATIBILITY IN HLA‐DR, ‐DQ, AND ‐DP LOCI IN FINNISH COUPLES SUFFERING FROM RECURRENT SPONTANEOUS ABORTIONS
Authors: Laitinen T. , Koskimies S. , Westman P.
Published: April 2007

The polymorphism of Major Histocompatibility Complex (MHC) class II genes DRB, DQA, DQB, and DPA was studied by Taq I Restriction Fragment Length Polymorphism (RFLP) in recurrent spontaneous abortions (RSA). The study group consisted of 35 primary abortion (PA) couples (no children) and 15 secondary abortion (SA) couples (1‐2 children before abortions). We found no increase in DR‐DQ compatibility between the mother and the foetus in the Finnish RSA group. In contrast to findings in some other populations, foeto‐maternal incompatibility was increased in the PA group. Thus, our results do not support the theory that increased MHC class II compatibility is a cause of abortions as such. The Finns are a small and relatively isolated population with a unique gene inheritance. Thus, one can speculate that, if the human MHC class II is in the linkage with disadvantageous ‘fertility genes’, and these genes might nonetheless still be clustered in only a few MHC haplotypes among the Finns. This would be the reason, that DR‐DQ sharing is not seen. The presence of rare HLA alleles, such as DR2 and DR6, among the aborters also supports this. In addition, this study extends our previous findings on MHC class III in regards to PA and SA couples differing immunogenetically from each other. In MHC class II, this was most obvious in the DPA1 locus. The vast majority of SA women were heterozygous for the two most common DPA1 alleles (14.0kb and 13.5kb), resulting in significantly smaller chances for a DPA1 mismatched foetus to occur in the SA group than in the controls or in the PA women.
DNA TYPING FOR HLA‐DPB1‐ALLELES IN GERMAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS USING THE POLYMERASE CHAIN REACTION AND DIG‐ddUTP‐LABELLED OLIGONUCLEOTIDE PROBES
Authors: Yao Z. , Hartung K. , Deicher H.G. , Brunnler G. , Bettinotti M.P. , Keller E. , Paul C. , Gawron C. , Mikschl S. , Albert E. ,   The Members of The SLE Study Group
Published: April 2007

Genomic DNA of 178 German Caucasian patients with systemic lupus erythematosus are studied for HLA‐DP locus by using PCR and DIG‐ddUTP‐labelled oligonucleotide probes. A significant increase of DPB1*0101 is observed in SLE patients compared with healthy controls (χ < 2 < = 15.27, p.c. <0.004). DPB1*0501 and *0901 are also slightly increased (χ2= 5.85, P < 0.05, p.c. = NS; χ2= 5.64, P < 0.05, p.c. = NS). There is no significant difference in frequency of DP alleles between male and female patients. Since a linkage disequilibrium between HLA‐B, DR and DP loci is found in our SLE patients, an analysis is performed assessing the relative importance of these HLA‐markers to SLE. The results show that the increase of DPB1*0101 in SLE patients is associated with the HLA‐B8, DR3 haplotype and it suggests a more important role for HLA‐B8, DR3 or genes within this haplotype than for DPB1*0101 in the genetic predisposition for SLE.
GENETIC CONTROL OF LEISHMANIA MAJOR INFECTION IN CONGENIC, RECOMBINANT INBRED AND F2 POPULATIONS OF MICE
Authors: Mock B. , Blackwell J. , Hilgers J. , Potter M. , Nacy C.
Published: April 2007

The outcome of subcutaneous infection with L. major NIH 173 was evaluated in a series of recombinant inbred and congenic strains, as well as F2 progeny generated from a genetic linkage testing stock carrying the visible markers Ra, Os, and Pt. The disease parameters monitored were the incidence of open or necrotic lesions and footpad depths of infected feet, and the incidence and number of amastigotes in livers following infection. Regions of mouse chromosomes 2, 4, 7, 8, 12 and 15 were excluded from linkage to a gene (Scl‐1)involved in the susceptibility of inbred strains of mice to cutaneous infection with L. major NIH 173 by F2 and congenic strain analyses. Strain distribution patterns generated for Scl‐1 in the CXB and CXS recombinant inbred strains suggested linkage to the distal end of mouse Chromosome 11.
MAPPING OF GENES CONTROLLING LEISHMANIA MAJOR INFECTION IN CXS RECOMBINANT INBRED MICE
Authors: Roberts M. , Mock B.A. , Blackwell J.M.
Published: April 2007

Previous studies demonstrated that growth of the primary lesion following Leishmania major infection in inbred mice comes under the control of a single major gene designated Scl‐1. Preliminary mapping studies had suggested a chromosome 8 location for the gene. In this paper a more detailed study of different disease phenotypes (lesion growth, splenomegaly, liver parasite load) in 14 CXS recombinant inbred (RI) mouse strains was undertaken in order to obtain a more definitive map location for the gene. Using the Kruskal‐Wallis generalization of the Wilcoxon Rank‐Sum Test to assign RI strains to parental phenotypes, high concordances with genes at the mid (11‐3) to distal end (Dlb‐1, Hox‐2, Sigje, Mtv‐3 and Es‐3) of chromosome 11 were demonstrated with two strains (LV39 and NIH173) of L. major given as promastigotes subcutaneously into the shaven rump. The results suggest that the most likely location for the previously described single major gene (Scl‐1) regulating early lesion expansion is at the distal end of mouse chromosome 11, with the possibility that a gene located more proximally influences later phases of the infection.
GENETIC BASIS FOR DIABETES RESISTANCE IN NOD/WEHI MICE
Authors: Baxter A. G. , Hamilton F. , Mandel T. E. , Augustine C. , Cooke A. , Morahan G.
Published: April 2007

The basis for diabetes resistance in low diabetes incidence NOD/Wehi mice was examined in a breeding study. NOD/Wehi mice were crossed with high diabetes incidence NOD/Lt mice producing F1 hybrid mice which expressed a low incidence of diabetes. To distinguish between genetic and environmental causes for diabetes resistance, these F1 mice were backcrossed to NOD/Lt mice resulting in BC1 hybrid mice which expressed an intermediate incidence of diabetes. Similar results were obtained by examining the severity of insulitis in the hybrid mice. As both the incidence of diabetes and severity of insulitis in the hybrid mice were consistent with a single dominant gene mediating diabetes resistance, an attempt to localize this gene was made. Although over 140 loci which display polymorphism amongst inbred strains were typed in both parental lines, only a single locus, D8Mit9, was found to differ. As heterozygotes at D8Mit9 were not over represented amongst 45 diabetic BC1 hybrid mice examined, it was concluded that a resistance gene was not linked to this locus.
MHC IN SYSTEMIC LUPUS ERYTHEMATOSUS: A STUDY ON A KUWAITI POPULATION
Authors: Fouad F. , Johny. K. , Kaaba S. , Alkarmi T. O. , SHARMA P. , Al‐Harbi S.
Published: April 2007

HLA alleles were studied in Kuwaiti patients with Systemic lupus erythematosus (SLE). Although significant association of B5, B8, and DR3 has been reported in the literature, the most common phenotype for our patients is A3, DR2 as susceptible alleles and DQ1 as a protective gene.
HSP70‐Hom NcoI POLYMORPHISM AND HLA‐ASSOCIATIONS IN THE FINNISH POPULATION AND IN PATIENTS WITH ANKYLOSING SPONDYLITIS OR REACTIVE ARTHRITIS
Authors: Westman P. , Partanen J. , Leirisalo‐Repo M. , Koskimies S.
Published: April 2007

The NcoI polymorphism of the HSP70‐Hom gene was investigated in the Finnish population and in two HLA‐B27‐associated autoimmune diseases. The two HSP70‐Hom alleles were shown to be strongly associated to some specific HLA‐B/DR haplotypes in random Finnish population and the segregation of the alleles as a part of these haplotypes was confirmed in 18 families. In addition, the HSP70‐Hom alleles of 31 patients with ankylosing spondylitis (AS) and 38 with reactive arthritis (ReA) were compared with each other and with 56 unrelated healthy HLA‐B27 positive individuals. The results indicated that the HSP70‐Hom polymorphic variation is not connected independently to the different pathogenesis of AS and ReA, as no statistically significant differences between the patient groups and/or controls could be found. The HSP70‐Hom status was investigated also in 28 homozygous HLA typing cells and when compared with previously published results of HSP70‐1 and HSP0‐2 polymorphisms, it appeared that these three MHC Class‐III linked HSP70 genes segregated in fixed allelic combinations.
DUAL ROLE OF MANNAN‐BINDING PROTEIN IN INFECTIONS: ANOTHER CASE OF HETEROSIS?
Authors: Garred P. , Harboe M. , Oettinger. T. , Koch C. , Svejgaard A.
Published: April 2007

Human mannan‐binding protein (MBP) is a serum lectin that participates in the immune defence by mediating phagocytosis and activation of complement. Variant MBP alleles causing dominant low‐serum concentrations have high frequencies in all populations studied, and therefore, low MBP concentrations may confer selective advantages to those individuals carrying the variant alleles. Mycobacterium leprae, the causative agent of leprosy, is an obligate intracellular parasite dependent on phagocytosis to invade host cells. The serum concentrations of MBP in 36 Ethiopian patients (median: 1688μgl‐1) with lepromatous or borderline lepromatous leprosy were significantly (P<0.001) higher than in 26 healthy Ethiopian blood donors (median: 368μgl‐1) Only 17% of the patients vs. 58% of the donors (P = 0.0019) had the relatively low MBP concentrations usually associated with variant alleles. Functional studies revealed that M. leprae and M. tuberculosis sonicates bind MBP as strongly as pure mannan. These observations suggest a role for mycobacteria as a selective force in the positive selection of alleles causing low levels of MBP and warrant genetic studies of patients infected with these bacteria.
HLA‐A LOCUS DNA TYPING OF THE 4AOH CELL PANEL BY ARMS PCR
Authors: Krausa P. , Browning M. J. , Moses J. H. , Bodmer J. G.
Published: April 2007

As part of the Fourth Asia‐Oceania Histocompatibility (4AOH) Workshop, the authors have demonstrated a method of DNA‐based tissue typing of the HLA‐A locus using ARMS‐designed primers in a panel of specific PCR reactions. The study was carried out blind under Workshop conditions and the results confirm the method as an accurate means of determining HLA‐A locus tissue types.
HLA‐DQA1 AND DQB 1 ALLELE AND GENOTYPE CONTRIBUTION TO IDDM SUSCEPTIBILITY IN AN ETHNICALLY MIXED POPULATION
Authors: Balducci‐Silano P. L. , Layrisse Z. , Dominguez E. , Amaro R. , Gunczler P. , Lanes R. , Zaro R.
Published: April 2007

HLA‐DRB1, DQA1 and DQB1 alleles have been determined in 42 families with one IDDM proband and 64 healthy controls, by oligotyping (PCR‐SSO) using primers and probes from the XI International Histocompatibility Workshop. A positive DRB1 *03 and DRB1 *04 association with the disease was observed, whereas DRB 1*11 and DRB 1 *07 showed negative association but 19% of patients carried DRB1 alleles different to DRB 1 *03 or *04. When single alleles were considered, DQA1 *03 showed the strongest association with susceptibility to the disease (RR = 8.2, Pc = 0.00001) but this association was outgrown by 2 and 3 allele combinations, with genotype DRB 1 *04‐DQA 1 *03‐DQB1*0302/DRB1*03‐ DQA 1*0501‐ DQB 1*0201 showing the strongest association (RR = 28, Pc = 0.002). Application of the relative predispositional effect (RPE) method to our data, revealed a further susceptibility risk provided by the DRB1*13‐DQA1*0102‐DQB 1*0604 haplotype once DR3 and DR4 haplotypes were removed. When DQA1‐DQB1 genotypes were analysed for presence of Arg 52 (DQ α) and absence of Asp 57 (DQ β), genotypes SS/SS were found significantly increased in diabetics. Interestingly, one of the strongest associations with the disease was observed with the DQA 1*03‐DQB 1*0201 combination encoded mainly by genes in trans (RR = 11.7 Pc = 0.00004). These observations and their comparison with DR‐DQ haplotypes in more homogeneous ethnic groups support the stronger influence of the DQ molecule rather than the individual DR or DQ alleles in the susceptibility to IDDM. They also emphasize the need for detailed HLA haplotype studies in non‐Caucasian and ethnically mixed populations to gain further insight into the nature of genetic and environmental factors contribution to autoimmunity.
THE HLA‐DRB1*0101 ALLELE IS RESPONSIBLE FOR HLA SUSCEPTIBILITY TO LICHEN RUBER PLANUS
Authors: Carcassi C. , Cottoni F. , Floris L. , Nasa G. La , Mulargia M. , Baldini G. , Senes G. , Orru S. , Montesu M. A. , Cerimele D. , Contu L.
Published: April 2007

Serological studies have demonstrated that lichen ruber planus is associated with the HLA‐DR1 antigen. This association was also confirmed by us in the Sardinian population. To establish which DRB1 molecular alleles are involved, we studied a selected group of 14 DR1 positive patients affected by cutaneous idiopathic lichen planus and a group of DR1 positive healthy controls using PCR with sequence‐specific primers (PCR‐SSP).

Comparisons between the allele frequencies in patients and controls showed a positive association with cutaneous idiopathic lichen planus for the DRB 1*0101 allele (RR = 5.8, P= 0.0097). DRB1*0101 and DRB1*0102 are associated with the same DQA1 and DQB1 alleles and are different only for two amino acids in positions 85 and 86 of the DRB 1 gene. In our case report predisposition to cutaneous idiopathic lichen planus is correlated with a valine in position 85 and a glycine in position 86 at the second exon of the DRB 1 gene.
T CELL RECEPTOR DELTA LOCUS POLYMORPHISM IN RHEUMATOID ARTHRITIS
Authors: Vandevyver C. , Geusens P. , Cassiman J.‐J. , Raus J.
Published: April 2007

In order to identify new susceptibility markers for Rheumatoid Arthritis (RA), we analysed the dinucleotide repeat polymorphism at the T cell receptor delta locus (TCRD) in 65 RA patients and 99 healthy Belgian controls. A significant under‐representation of the A4‐A5 TCRD genotype was observed in the RA population.
‘BIO‐ID’: RESTRICTED USE OF HLA MARKERS TO DETECT DOUBLE REGISTRATION ON COMPUTER FILES
Authors: Hors J. , Busson M. , Raffoux C. , Baouz A. , Weser A.
Published: April 2007

We propose to use the extreme diversity of HLA in order to detect, by anonymous check, double registration on computer files, of patients waiting for organ transplantation. A simulation on a panel of 69461 unrelated individuals, caucasoid, confirms the relevance of the method.
HLA‐DRB1*0401 IS ASSOCIATED WITH SUSCEPTIBILITY TO INSULIN‐DEPENDENT DIABETES MELLITUS INDEPENDENTLY OF THE DQB1 LOCUS
Authors: Tait B. D. , Drummond B. P. , Varney M. D. , Harrison L. C.
Published: April 2007

The distribution of DRB1*04 alleles and DRB1/DQB1 haplotypes was analysed in 57 DR4+ caucasoid subjects with insulin‐dependent diabetes mellitus (IDDM) and 96 DR4+ healthy controls selected on the basis of DR serology, and the findings were analysed in relation to age at diagnosis of IDDM. DNA samples were amplified using specific DR and DQ primers and hybridized with sequence‐specific oligonucleotide probes.

A significantly increased combined frequency of DRB 1*0401 and 0402 was observed in IDDM subjects aged ≤12 years at diagnosis (allele frequency 88.4% compared with 62.0% in controls, P < 0.025). There was a non‐significant increase in DRB 1*0401 and 0402 in IDDM subjects ≤12 years when compared with IDDM subjects >12 years (P < 0.1). DRB 1 *0404 was decreased in the total IDDM subject group compared with controls (4.8% vs. 19.0%, P < 0.025) but did not reach statistical significance in the individual age at diagnosis groups. In contrast, the frequency of DQB1 *0302 was increased uniformly across both ages at diagnosis groups.

In controls DRB 1*0401 occurred in haplotype association with DQB 1*0301 in a significantly greater frequency than with DQB 1*0302. However, 95.0% of DRB 1*0401 IDDM subjects were DQB 1*0302. DRB 1*0404, which was decreased in frequency in IDDM subjects, occurred in association significantly more frequently with DQB 1 *0302 in controls. These results imply that DRB 1 and DQB 1 have independent roles as HLA susceptibility genes in IDDM. DQB1 may have a permissive role whereas DRB1 could influence the rate at which underlying disease progresses to clinical IDDM.
DIFFERENT PATTERNS OF HLA‐DR ANTIGEN EXPRESSION IN NORMAL EPITHELIUM, HYPERPLASTIC AND NEOPLASTIC MALIGNANT LESIONS OF THE BREAST
Authors: Concha A. , Ruiz‐Cabello F. , Cabrera T. , Nogales F. , Collado A. , Garrido F.
Published: April 2007

Fifteen samples of non‐tumoural breast tissue, 24 cases of benign lesions, four biopsies of inflammatory carcinomas and 94 tumour samples of primitive mammary carcinomas were analysed for HLA class II expression. We found, first, that HLA class II antigens were detectable in all cases of non‐neoplastic breast tissue. Secondly, HLA class II antigen expression was notably increased in benign neoplasms and hyperplastic lesions. In contrast, only 32 out of 94 carcinomas showed expression of HLA‐DR antigens, 17 tumours had HLA‐DP antigens and 11 carcinomas were positive for the presence of DQ molecules. The expression of class II antigen was associated with the degree of histological differentiation (P < 0.05) but was independent of stromal leucocytic infiltration. Thirdly, HLA‐DR was very strongly expressed in intravascular tumoural thrombi, especially in the ‘inflammatory carcinomas’. The immunephenotype of inflammatory infiltrate was analysed in benign and malignant lesions. In malignant lesions the mean number of inflammatory cells was significantly higher than in benign lesions. Interestingly, we found no differences in the amount and composition of inflammatory infiltrate between HLA‐DR positive and negative tumours.
MATERNAL HLA CLASS II ALLOGENOTYPES ARE MARKERS FOR THE PREDISPOSITION TO FETAL LOSSES IN FAMILIES OF WOMEN WITH UNEXPLAINED RECURRENT FETAL LOSS
Authors: Christiansen O. B. , Andersen H. H. , Hosjbjerre M. , Kruse T. A. , Lauritzen S. L. , Grunnet N.
Published: April 2007

The HLA allogenotypes DRl/Br, DR3 and DR10 (entitled risk HLA markers) have been reported as being genetic markers for the predisposition to experience unexplained recurrent fetal losses. The aim of the study was to determine whether the putative risk HLA markers might also be markers for the risk of pregnancy loss in sisters and wives of brothers of women with unexplained recurrent fetal losses. Information concerning pregnancy outcomes among the relatives of 146 consecutive women with unexplained recurrent fetal losses was collected. Ninety‐five of the full sisters, 69 of the full brothers and 50 of the wives of the brothers were HLA typed. Sisters who had experienced at least one previous pregnancy loss (affected women) shared more HLA haplotypes with the proband than unaffected sisters, when the proband was positive for the risk markers (P= 0.02). More affected than unaffected sisters and brothers’ wives were positive for the risk markers (P< 0.005 andP< 0.03; respectively). The lowest estimate of the odds ratio for experiencing pregnancy loss among sisters and brothers’ wives who were positive compared with those negative for the risk markers was 3.5 (95% credible interval = 1.9‐5.8). It is concluded that maternal DRl/Br, DR3 and DR10 allogenotypes seem to be genetic markers for the risk of pregnancy loss among relatives of women with unexplained recurrent fetal losses. The pattern of inheritance suggests a polygenic mode of inheritance with alleles linked to the risk HLA markers interacting with non‐HLA linked genes expressed on the fetus or the trophoblast.
POPULATION ANALYSIS OF PROTECTION BY HLA‐DR AND DQ GENES FROM INSULIN‐DEPENDENT DIABETES MELLITUS IN SWEDISH CHILDREN WITH INSULIN‐DEPENDENT DIABETES AND CONTROLS
Authors: Kockum I. , Sanjeevi C.B. , Eastman S. , Landin‐Olsson M. , Dahlouist G. , Lernmark Å. ,   Co‐Authors
Published: April 2007

A negative association between insulin‐dependent diabetes mellitus (IDDM) and HLA‐DR, DQA1 or DQB1 was found in a large population‐based investigation of childhood‐onset patients (more than 420 patients) and controls (more than 340 controls) from Sweden. The relative risk was decreased for several haplotypes that were negatively associated with IDDM: DR15‐DQA1*0102‐DQB1*0602, DR7‐DQA1*0201‐DQB1*0303, DR14‐DQA1*0101‐DQB1*0503, DRI1‐DQAI*0501‐DQB1*0301, DR13‐DQA1*0103‐DQB1*0603 and DR4‐DQA1*0301‐DQB1*0301. In a relative predispositional effect (RPE) analysis, however, only the DR15‐DQA1*0102‐DQB1*0602 haplotype was significantly decreased, which suggests that the major protective effect for IDDM is carried by this haplotype. This was supported by the observation that all genotypes which were negatively associated with IDDM, except DR7/13, included at least one allele from the DR15‐DQA1*0102‐DQB1*0602 haplotype. Relative predispositional effect (RPE) analysis of genotypes showed further that the DR15‐DQA1*0102‐DQB1*0602 haplotype was also negatively associated with IDDM when combined with any other haplotype, whether negatively or positively associated with IDDM. This supports previous suggestions that DR15‐DQA1*0102‐DQB1*0602 acts dominantly. However, both the stratification and the predispositional allele test failed to distinguish the negative association between IDDM and DR15 from that of DQBT0602. On the other hand, these tests indicated that DQA1*0102 was not likely to explain the negative association between IDDM and the DR15‐DQA1*0102‐DQB1*0602 haplotype. We conclude that the
HLA CLASS II REGION GENES AND SUSCEPTIBILITY TO DERMATITIS HERPETIFORMIS: DPB1 AND TAP2 ASSOCIATIONS ARE SECONDARY TO THOSE OF THE DQ SUBREGION
Authors: Hall M. A. , Lanchbury J. S. , Ciclitira P. J.
Published: April 2007

Classical dermatitis herpetiformis (DH) is associated with similar HLA class I, II and III polymorphisms to coeliac disease (CD). The two diseases share distinctive pathological changes to the small intestinal mucosa which reverse on withdrawal of dietary gluten. In order to determine the locus primarily associated with DH, and to examine whether there is a common genetic link predisposing to the enteropathy seen in both DH and coeliac disease, HLA‐DR, DQ and DP subregion associations were investigated by HLA genotyping in 23 DH patients and 64 healthy controls. We also studied polymorphisms of the TAP2 locus, which is located between the DP and DQ subregions. Genotyping was carried out by PCR of genomic DNA with allelic assignment by sequence‐specific oligonucleotide (SSO) hybridization or amplification refractory mutation system (ARMS). The strongest associations in the patient group were with HLA DRB1*0301 (91% vs 22% of controls), HLA DQB1*02 (100% vs 32% of controls) and DPB1*0101 (39% and 14%). These associations are similar to those described for CD. 100% of DH patients were positive for the DQA1*0501/DQB1*02 dimer in cis or trans and, by analogy with CD, this is probably responsible for presenting gliadin peptide implicated in the disease process. Homozygosity for DQ2 was significantly increased in the CD patient group compared to the DH patient group (65% versus 39%), and so differences in dosage of HLA class II genotypes between DH and CD may be responsible for the milder gastrointestinal symptoms characteristic of DH.
LONG‐RANGE PCR AMPLIFICATION AS AN ALTERNATIVE STRATEGY FOR CHARACTERIZING NOVEL HLA‐B ALLELES
Authors: Curran M. D. , Williams F. , Earle J. A. P. , Rima B. K. , van Dam M. G. , Bunce M. , Middleton D.
Published: April 2007

We have developed a simple, rapid and reliable method for specifically amplifying and cloning full‐length HLA‐B genes from genomic DNA. Using this methodology we characterized three alleles of interest at the molecular level. Two of the alleles appeared in our routine class I PCR‐SSOP typing system, a variant of B*5801 found in the Daudi cell line and RCE 56 and a variant of B*4101 found in a number of volunteer donors on our Bone Marrow Donor Registry. The third, a variant B35 allele found in RCE 80, was first identified as unusual by serology. Our sequencing analysis of exon 2 and exon 3 identified two of these alleles as the recently reported novel HLA‐B*5802 and HLA‐B*4102 alleles, while the third represents a new B35 allele officially designated B*3513.
Escaping from modified Newtonian dynamics
Authors: Famaey Benoit , Bruneton Jean-Philippe , Zhao HongSheng
Published: April 2007

We present a new test of modified Newtonian dynamics (MOND) on galactic scales, based on the escape speed in the solar neighbourhood. This test is independent from other empirical successes of MOND at reproducing the phenomenology of galactic rotation curves. The galactic escape speed in MOND is entirely determined by the baryonic content of the Galaxy and the external field in which it is embedded. We estimate that the external field in which the Milky Way must be embedded to produce the observed local escape speed of ∼550 km s−1 is of the order of a0/100, where a0 is the dividing acceleration scale below which gravity is boosted in MOND. This is compatible with the external gravitational field actually acting on the Milky Way.
Promoting Health Literacy Through the Health Education Assessment Project
Authors: Marx Eva , Hudson Nancy , Deal Tami B. , Pateman Beth , Middleton Kathleen
Published: April 2007

Background:  The Council of Chief State School Officers’ State Collaborative on Assessment and Student Standards Health Education Assessment Project (SCASS‐HEAP) allows states to pool financial and human resources to develop effective ready‐to‐use health education assessment resources through a collaborative process. The purpose of this article is to describe the extensive ongoing development of the SCASS‐HEAP and its benefits for important stakeholders in health and education.

Methods:  A review of the products from the first decade of the SCASS‐HEAP was undertaken.

Results:  The SCASS‐HEAP supports a comprehensive systems approach to helping educators focus effectively on the most important skills and issues in child and adolescent health and gives health education a place at the school reform table, providing visibility and credibility and promoting the essential links between health and learning.

Conclusion:  State education agencies and school districts can use SCASS‐HEAP materials for assessment and, perhaps more importantly, to help teachers modify and improve instruction at the classroom level for increased student learning.
Use of Brief Interventions for Drug Abusing Teenagers Within a Middle and High School Setting
Authors: Winters Ken C. , Leitten Willa , Wagner Eric , O’Leary Tevyaw Tracy
Published: April 2007

Background:  Promising and encouraging results have been recently reported on the use of briefer interventions for adolescent drug abusers. Because middle‐ and high‐school‐based drug abuse intervention programs have grown in popularity over the past several decades, the use of brief interventions (BIs) in school settings merits consideration.

Methods:  We review several clinical and school contextual issues pertaining to the scientific efficacy, feasibility, and application of BIs for students who are abusing drugs.

Results:  Several advantages for employing BIs in a school setting are identified, including the relatively high base rate of students with mild‐to‐moderate drug involvement and the likelihood that school counselors can readily learn BI techniques. Caveats of implementing BIs include practical, systemic, and clinical barriers.

Conclusions:  Despite concerns, schools are a viable setting in which to screen youth for drug abuse problems and to conduct a BI.
Association of the Presence of State and District Health Education Policies With School Tobacco Prevention Program Practices*
Authors: Boerm Melynda , Gingiss Phyllis , Roberts‐Gray Cynthia
Published: April 2007

Background:  Texas does not require health education or tobacco use prevention education (TUPE) in its middle schools. During planning for the Texas Tobacco Prevention Initiative, this baseline research was conducted to (1) describe tobacco prevention and control practices in middle schools prior to the pilot, (2) analyze implementation of a state law prohibiting tobacco use on campuses and at school events, and (3) identify how schools are influenced by district policies requiring health education.

Methods:  Written surveys derived from the 2000 School Health Education Profile Tobacco Module developed by the Centers for Disease Control and Prevention were completed by principals and health coordinators at schools in districts requiring health education (n = 31) and schools without district requirements (n = 32).

Results:  School tobacco policy familiarity and enforcement were consistently reported in response to a state law with rigorous recommendations prohibiting tobacco use. Significantly more activity in numerous components of TUPE was reported in schools in districts with a health education requirement.

Conclusions:  Results have implications for intervention programs planned in schools located in states seeking to develop or strengthen state laws, or in states without health education or specific health content requirements.
Similar patterns of learning and performance variability for human discrimination of interaural time differences at high and low frequencies
Authors: Zhang Yuxuan , Wright Beverly A.
Published: April 2007

Sound source localization on the horizontal plane is primarily determined by interaural time differences (ITDs) for low-frequency stimuli and by interaural level differences (ILDs) for high-frequency stimuli, but ITDs in high-frequency complex stimuli can also be used for localization. Of interest here is the relationship between the processing of high-frequency ITDs and that of low-frequency ITDs and high-frequency ILDs. A few similarities in human performance with high- and low-frequency ITDs have been taken as evidence for similar ITD processing across frequency regions. However, such similarities, unless accompanied by differences between ITD and ILD performance on the same measure, could potentially reflect processing attributes common to both ITDs and ILDs rather than to ITDs only. In the present experiment, both learning and variability patterns in human discrimination of ITDs in high-frequency amplitude-modulated tones were examined and compared to previously obtained data with low-frequency ITDs and high-frequency ILDs. Both patterns for high-frequency ITDs were more similar to those for low-frequency ITDs than for high-frequency ILDs. These results thus add to the evidence supporting similar ITD processing across frequency regions, and further suggest that both high- and low-frequency ITD processing is less modifiable and more noisy than ILD processing.
Determination of a response function of a thermocouple using a short acoustic pulse
Authors: Tashiro Yusuke , Biwa Tetsushi , Yazaki Taichi
Published: April 2007

This paper reports on an experimental technique to determine a response function of a thermocouple using a short acoustic pulse wave. A pulse of 10ms is generated in a tube filled with 1bar helium gas. The temperature is measured using the thermocouple. The reference temperature is deduced from the measured pressure on the basis of a laminar oscillating flow theory. The response function of the thermocouple is obtained as a function of frequency below 50Hz through a comparison between the measured and reference temperatures.
Reconstruction of source distributions from sound pressures measured over discontinuous regions: Multipatch holography and interpolation
Authors: Lee Moohyung , Bolton J. Stuart
Published: April 2007

In the present work, a method of alternating orthogonal projections is described in the context of near-field acoustical holography; it allows missing (or “not measured”) data to be recovered, thus relieving the strictness of measurement requirements related to the use of the discrete Fourier transform. The method described here provides the detailed foundation for the patch holography procedure that has previously been introduced to mitigate finite measurement aperture effects by allowing the sound field to be iteratively extended beyond the measurement aperture. It is also shown that the latter iterative algorithm can be used regardless of the spatial distribution of measured data: i.e., patches can be discontinuous. Numerical simulations performed by using a synthetic sound field created by a point-driven, simply supported plate were used to demonstrate the latter point. In particular, a multipatch holography procedure is described that allows a source distribution to be reconstructed from the hologram pressure measured over multiple, unconnected patches. It is finally shown that a related approach allows spatial resolution enhancement by interpolation between measured points.
Ultrasonic transient bounded-beam propagation in a solid cylinder waveguide embedded in a solid medium
Authors: Laguerre Laurent , Grimault Anne , Deschamps Marc
Published: April 2007

A semianalytical solution alternative and complementary to modal technique is presented to predict and interpret the ultrasonic pulsed-bounded-beam propagation in a solid cylinder embedded in a solid matrix. The spectral response to an inside axisymmetric velocity source of longitudinal and transversal cylindrical waves is derived from Debye series expansion of the embedded cylinder generalized cylindrical reflection/transmission coefficients. So, the transient guided wave response, synthesized by inverse double Fourier-Bessel transform, is expressed as a combination of the infinite medium contribution, longitudinal, transversal, and coupled longitudinal and transversal waveguide sidewall interactions. Simulated (f,1∕λz) diagrams show the influence of the number of waveguide sidewall interactions to progressively recover dispersion curves. Besides, they show the embedding material filters specific signal portions by concentrating the propagating signal in regions where phase velocity is closer to phase velocity in steel. Then, simulated time waveforms using broadband high-frequency excitation show that signal leading portions exhibit a similar periodical pattern, for both free and embedded waveguides. Debye series-based interpretation shows that double longitudinal/transversal and transversal/longitudinal conversions govern the time waveform leading portion as well as the radiation attenuation in the surrounding cement grout. Finally, a methodology is deduced to minimize the radiation attenuation for the long-range inspection of embedded cylinders.
Morphological predictability and acoustic duration of interfixes in Dutch compounds
Authors: Kuperman Victor , Pluymaekers Mark , Ernestus Mirjam , Baayen Harald
Published: April 2007

This study explores the effects of informational redundancy, as carried by a word’s morphological paradigmatic structure, on acoustic duration in read aloud speech. The hypothesis that the more predictable a linguistic unit is, the less salient its realization, was tested on the basis of the acoustic duration of interfixes in Dutch compounds in two datasets: One for the interfix -s- (1155 tokens) and one for the interfix -e(n)- (742 tokens). Both datasets show that the more probable the interfix is, given the compound and its constituents, the longer it is realized. These findings run counter to the predictions of information-theoretical approaches and can be resolved by the Paradigmatic Signal Enhancement Hypothesis. This hypothesis argues that whenever selection of an element from alternatives is probabilistic, the element’s duration is predicted by the amount of paradigmatic support for the element: The most likely alternative in the paradigm of selection is realized longer.
Effects of carrier pulse rate and stimulation site on modulation detection by subjects with cochlear implants
Authors: Pfingst Bryan E. , Xu Li , Thompson Catherine S.
Published: April 2007

Most modern cochlear-implant speech processors convey speech-envelope information using amplitude-modulated pulse trains. The use of higher-rate carrier pulse trains allows more envelope detail in the signal. However, neural response properties could limit the efficacy of high-rate carriers. This study examined effects of carrier rate and stimulation site, on psychophysical modulation detection thresholds (MDTs). Both of these variables could affect the neural representation of the carrier and thus affect perception of the modulation. Twelve human subjects with cochlear implants were tested. Phase duration of symmetric biphasic pulses was modulated sinusoidally at 40Hz. MDTs were determined for monopolar stimulation at two carrier rates [250 and 4000pulses∕s (pps)], three stimulation sites (basal, middle, and apical), and five stimulus levels (10%, 30%, 50%, 70%, and 90% of the dynamic range). MDTs were lower for 250pps carriers than for 4000pps carriers in 71% of the 180 cases studied. Effects of carrier rate were greatest at the apical stimulation site and effects of stimulation site on MDTs depended on carrier rate. The data suggest a distinct disadvantage to using carrier pulse rates as high as 4000pps. Stimulation site should be considered in evaluating modulation detection ability.
On the existence of localized shear horizontal acoustic waves in a piezoelectric plate with two semi-infinite same/different coatings
Authors: Chen Shi , Tang Tiantong , Wang Zhaohong
Published: April 2007

In this paper, the existence theorem of localized shear horizontal acoustic waves in a piezoelectric plate with two semi-infinite same/different coatings is established. Some properties of the waves in the waveguide structures are also discussed. The results show that the waveguides have some advantages and provide more choice for the designs of acoustic devices.
Auditory and nonauditory factors affecting speech reception in noise by older listeners
Authors: George Erwin L. J. , Zekveld Adriana A. , Kramer Sophia E. , Goverts S. Theo , Festen Joost M. , Houtgast Tammo
Published: April 2007

Speech reception thresholds (SRTs) for sentences were determined in stationary and modulated background noise for two age-matched groups of normal-hearing (N=13) and hearing-impaired listeners (N=21). Correlations were studied between the SRT in noise and measures of auditory and nonauditory performance, after which stepwise regression analyses were performed within both groups separately. Auditory measures included the pure-tone audiogram and tests of spectral and temporal acuity. Nonauditory factors were assessed by measuring the text reception threshold (TRT), a visual analogue of the SRT, in which partially masked sentences were adaptively presented. Results indicate that, for the normal-hearing group, the variance in speech reception is mainly associated with nonauditory factors, both in stationary and in modulated noise. For the hearing-impaired group, speech reception in stationary noise is mainly related to the audiogram, even when audibility effects are accounted for. In modulated noise, both auditory (temporal acuity) and nonauditory factors (TRT) contribute to explaining interindividual differences in speech reception. Age was not a significant factor in the results. It is concluded that, under some conditions, nonauditory factors are relevant for the perception of speech in noise. Further evaluation of nonauditory factors might enable adapting the expectations from auditory rehabilitation in clinical settings.
Some roles of the vocal tract in clarinet breath attacks: Natural sounds analysis and model-based synthesis
Authors: Guillemain Philippe
Published: April 2007

A simplified physical model mainly devoted to the reproduction of some transients of clarinet-like instruments is presented. From time-frequency analyses of natural clarinet sounds, it is shown that the vocal tract can play a significant role in some attacks as well as in the permanent regime. The model proposed consists in supplying a pressure source at the entrance of a cylindrical bore attached to the mouthpiece, allowing one to reach various vocal tract configurations. For real-time synthesis purposes, a digital scheme solving the physical problem is proposed. It is shown that this synthesis model is able to reproduce some of the complex features observed during the attacks of the natural sounds analyzed, as well as known effects of the vocal tract in permanent regime.
Noise in the adult emergency department of Johns Hopkins Hospital
Authors: Orellana Douglas , Busch-Vishniac Ilene J. , West James E.
Published: April 2007

While hospitals are generally noisy environments, nowhere is the pandemonium greater than in an emergency department, where there is constant flow of patients, doctors, nurses, and moving equipment. In this noise study we collected 24h measurements throughout the adult emergency department of Johns Hopkins Hospital, the top ranked hospital in the U.S. for 16 years running. The equivalent sound pressure level (Leq) throughout the emergency department is about 5dB(A) higher than that measured previously at a variety of in-patient units of the same hospital. Within the emergency department the triage area at the entrance to the department has the highest Leq, ranging from 65 to 73dB(A). Sound levels in the emergency department are sufficiently high [on average between 61 and 69dB(A)] to raise concerns regarding the communication of speech without errors—an important issue everywhere in a hospital and a critical issue in emergency departments because doctors and nurses frequently need to work at an urgent pace and to rely on oral communication.
Discrimination of interval size in short tone sequences
Authors: Hill Toby J. W. , Summers Ian R.
Published: April 2007

This study investigates the discrimination of small changes of interval size in short sequences of musical tones. Major, minor and neutral thirds were varied in increments of 15cents. The nine subjects had varying degrees of amateur musical experience—their level of musical training was lower than that of professional musicians. In some experiments the stimuli were presented purely melodically and in others they were presented together with a sustained tone at a higher pitch. Some subjects were able to make use of the additional cues from beats in the latter case. Category widths for identification were measured at around 70cents and just-noticeable differences in frequency were measured at around 10cents. Little significant variation of inter-stimulus sensitivity index d′ was observed across the stimulus sets, i.e., there was little evidence for “anchors” or “landmarks” within the range of tunings employed. However, for major thirds, discrimination of the 15cent increment between 400 and 415cents was reduced compared to discrimination of other 15cent increments within the stimulus sets.
Sound quality assessment of wood for xylophone bars
Authors: Aramaki Mitsuko , Baillères Henri , Brancheriau Loïc , Kronland-Martinet Richard , Ystad Sølvi
Published: April 2007

Xylophone sounds produced by striking wooden bars with a mallet are strongly influenced by the mechanical properties of the wood species chosen by the xylophone maker. In this paper, we address the relationship between the sound quality based on the timbre attribute of impacted wooden bars and the physical parameters characterizing wood species. For this, a methodology is proposed that associates an analysis-synthesis process and a perceptual classification test. Sounds generated by impacting 59 wooden bars of different species but with the same geometry were recorded and classified by a renowned instrument maker. The sounds were further digitally processed and adjusted to the same pitch before being once again classified. The processing is based on a physical model ensuring the main characteristics of the wood are preserved during the sound transformation. Statistical analysis of both classifications showed the influence of the pitch in the xylophone maker judgement and pointed out the importance of two timbre descriptors: the frequency-dependent damping and the spectral bandwidth. These descriptors are linked with physical and anatomical characteristics of wood species, providing new clues in the choice of attractive wood species from a musical point of view.