bluuebunny/crossref_metadata_2025 huggingface dataset:
The HLA‐DQ7 and ‐DQ8 associations in DR4‐positive rheumatoid arthritis patients A combined analysis of data available in the literature
Authors: Fugger L. , Svejgaard A.
Published: December 2008

Several different lines of evidence have demonstrated that inherited susceptibility to rheumatoid arthritis (RA) is associated with the DRB1 genes encoding the HLA‐DR4 and HLA‐DR1 molecules. A contrasting hypothesis has recently been proposed, suggesting that, in general, the DRB1 locus is associated with protection to RA and that the RA‐associated DRB1 alleles are not responsible for the primary disease association but merely permissive for the susceptibility conferred by the HLA‐DQ alleles with which they are in linkage disequilibrium. We have performed a critical review of the literature on the HLA association in RA with special emphasis on studies in which both an HLA‐DR and ‐DQ association has been investigated. Our analyses provide strong evidence against the hypothesis that HLA‐DQ molecules play a major role in the general susceptibility to RA. Thus, the strongest association in rheumatoid arthritis is with DRB1 genes rather than DQB1 genes.
High‐resolution DNA typing in immunoglobulin A deficiency confirms a positive association with DRB 1*0301, DQBl*02 haplotypes
Authors: Reil A. , Bein G. , Machulla H.K.G. , Sternberg B. , Seyfarth M.
Published: December 2008

Selective immunoglobulin A (IgA) deficiency, the most common form of primary immunodeficiency, is related to the HLA genes. Previous studies demonstrated associations with particular HLA‐DR‐DQ haplotypes and a neutral amino acid at position 57 of the DQß chain was implicated in the susceptibility to selective IgA deficiency. In this study we reanalyzed the reported findings by high‐resolution DNA typing of the loci DRB1, DQB1 and DQA1. We compared the typing results of 74 IgA‐deficient individuals, detected by screening of blood donors, with those taken from 111 healthy controls. Results confirmed a strong positive association with DRB 1*0301, DQB1*02 and a negative association with DRB1*1501, DQB 1*0602. Considering the molecular interactions between HLA class II alleles and the peptides bound we conclude that the amino acid at position 57 of the DQß chain may contribute to the susceptibility to selective IgA deficiency, but not determine it. An extended statistical analysis strengthened the hypothesis that selective IgA deficiency might be communicated by the distinct haplotype DRB1*0301, DQB1*02.
HLA polymorphism and probability of finding HLA‐matched unrelated marrow donors for Chinese in Taiwan
Authors: Shaw C.‐K. , Chang T.‐K. , Chen S. N. , Wu S.
Published: December 2008

Tzu Chi Taiwan Marrow Donor Registry (TCTMDR) was established in 1993 to recruit and HLA‐type volunteers who would be willing to donate bone marrow. TCTMDR is currently the largest marrow registry for Chinese in the world, with over 150,000 prospective donors registered as of July 1997. We present here the gene and haplotype frequencies based on 80,353 HLA class I‐typed and 18,217 HLA class II‐typed healthy Chinese in Taiwan. The resulting frequencies are used for estimating the probability of finding an HLA‐matched donor for a patient. The common HLA class I antigens include Al (gene frequency: 32.9%), A2 (29.7%), A24 (17.5%) and A33 (11.0%); B60 (18.1%), B46 (12.8%), B58 (9.8%) and B13 (7.8%); Cw3 (51.4%), Cwl (11.6%) and Cw7 (8.6%). The common HLA class II antigens are DR4 (16.6%), DR9 (15.6%), and DR12 (14.0%); DQ7 (20.7%), DQ9 (12.7%), and DQ5 (12.1%). The common two‐locus haplotypes observed with a P‐value less than 0.001 are A2‐B46 (haplotype frequency: 8.5%), A33‐B58 (7.5%), A11‐B60 (6.6%); B58‐DR17 (7.0%), B46‐DR9 (6.4%) and B60‐DR4 (4.9%). The common three‐locus haplotypes are A33‐B58‐DR17 (5.3%), A2‐B46‐DR9 (3.9%) and A11‐B60‐DR4 (2.0%). As expected, the gene frequency pattern of Taiwanese is more closely related to that of southern Hans than to the pattern of northern Hans, Japanese, Caucasians and African‐Americans. Using our registry, 323 of 571 domestic patients (57%) successfully identified one or more matched donors. The empirical result correlated well with a mathematical simulation having an estimated 59% match when donor pool reaches 150,000.
A high‐resolution genotyping method for HLA‐C alleles and possible shared HLA‐C‐B haplotypes between Japanese and Caucasians
Authors: Wang H. , Tokunaga K. , Ishlkawa Y. , Tanaka H. , Kashlwasa K. , Shibata Y. , Juji T.
Published: December 2008

A genotyping system for HLA‐Cw alleles using methods of PCR‐single‐strand conformation polymorphism (SSCP) and PCR‐sequence‐specific primers (SSP) was developed. Genomic DNA from 167 random healthy Japanese individuals were investigated to determine HLA‐C allele frequencies and their associations with HLA‐A and ‐B loci. Nine alleles were frequently detected: Cw*0102 (18.3%), Cw*0304 (12.0%), Cw*1202 (11.4%), CW*0303 (10.5%), Cw*1403 (10.5%), Cw*0801 (10.2%), Cw*0702 (9.0%), Cw*1402 (6.0%) and Cw*0401 (5.1%). Several HLA‐C‐B haplotypes such as Cw*0303‐B62, Cw*0304‐B60, Cw*0501‐B44, Cw*0602‐B13, Cw*0602‐B37, Cw*0702‐B7, CW*1202‐B52, Cw*1402‐B51 and Cw*1502‐B51 were found to be shared by Japanese and Caucasians. With the PCR‐SSCP method we could detect differences in each exon of HLA‐C alleles, at a low cost and simply. This method is suitable for sequence‐level matching with a relatively small number of samples.
Characterization of an HLA‐B62 variant (B*1538) exhibiting an additional B52 serologic reactivity
Authors: Lee K.W. , Steiner N. , Hurley C.K.
Published: December 2008

Antigens bearing the B62 serologic specificity are a heterogeneous group being encoded by at least 10 alleles and are widespread in most populations including the Korean population (10.5%). This study characterized a new allele encoding a B62 molecule with extra B52 serologic reactivity from a Korean family and unrelated individuals. Based on the DNA sequence, it appears that the single nucleotide substitution at codon 171 (TACCAC), resulting in an amino acid change from tyrosine to histidine, is responsible for creating the extra reactivity. B*1538 was confirmed by PCR‐SSP using a primer annealing to codon 171 in two additional unrelated individuals also exhibiting the same serologic reaction pattern. The haplotype associated with the novel allele, A31‐B*1538‐Bw6‐Cw3‐DRB1*1101‐DRB3*02‐DQB1*0301, was identified in the family members and two unrelated individuals. The novel B*1538 allele and its associated haplotype adds to the HLA diversity in this population.
HLA‐B14 subtyping by semi‐nested PCR‐SSP and haplotype distribution in a Spanish population
Authors: Santos S. , Balas A. , Lillo R. , Garcia‐Sanchez F. , Merino J.L. , Vicario J.L.
Published: December 2008

HLA‐B14 serological subtyping is very limited probably due to the internal position of the unique amino acid residue that differentiates B64 and B65 molecules. In order to carry out an accurate B14 subtyping we have designed a semi‐nested PCR‐SSP procedure that can differentiate B*1401 and B*1402 in any HLA‐A, ‐B or ‐C antigen combination. A panel of 133 B14‐positive and 31 B14‐negative healthy and unrelated Spanish individuals were studied. Additionally, 45 B14‐bearing haplotypes (‐A,‐B,‐C,‐DRB1,‐DRB3/DRB4/DRB5,‐DQA1,‐DQB1) were available through family studies. The relative frequencies of HLA‐B14 subtypes were 74% for B*1402 and 26% for B*1401, in agreement with those found in other Central European populations, but differing from those in Wales, where the relative presence of B64 goes to 41%. A total of 11/17 and 18/28 different haplotypes for B*1401 and B*1402, respectively, were identified. Both alleles showed the strongest association to Cw8 (43/45), indicating a primary ancestral B14‐Cw8 association. However, B14 subtypes evidenced very distinguishable haplotype distributions. B*1401 is strongly associated with the common HLA class II haplotype DRB1*0701‐DQA1*0201‐DQB1*02 (13/17), while B*1402 is mainly associated to DRB1*0102 (16/28). Three major haplotypes were identified: A32‐Cw8‐B*1401‐DR7‐DQ2 (5/17), A33‐Cw8‐B*1402‐DRB1*0102‐DQ5 (5/28) and A2‐Cw8‐B*1402‐DRB1*0102‐DQ5 (5/28).
HLA‐DRB and ‐DQB1 alleles in Polish patients with hepatitis B associated membranous nephropathy
Authors: Vaughan R.W. , Zurowska A. , Moszkowska G. , Kondeatis E. , Clark A.G.B.
Published: December 2008

Abstract: We have studied the HLA‐DRB and ‐DQB1 alleles of 42 paediatric patients who have suffered from membranous nephropathy associated with a hepatitis B infection (HBVMN). These patients were all from the Gdansk area of Northern Poland and the disease was diagnosed by light and electron microscopy. The control population consisted of 55 healthy children, approximately age matched, from schools in Gdansk. In addition we have also analysed 40 patients chronically infected with hepatitis B, without any renal involvement, as hepatitis B disease controls. The HLA alleles were defined using PCR/SSP. As idiopathic membranous nephropathy and low responsiveness to hepatitis B vaccine have been found to be associated with DR3 in Caucasoids, our hypothesis was that the HBVMN patients would show an increase in DR3. Our results indicate that, although there is a small increase in the frequency of DRBl*0301 in the HBVMN patients (16/42 38%) when compared to the healthy controls (15/55 31%), this does not approach significance. There is a significant increase in the frequency of DQBl*0303 in the HBVMN patients vs the healthy controls, after correction for the number of antigens detected (P) (13/42 vs 2/55, RR=11.6, P=0.0007, Pc=0.02). A similar increase in DQBl*0303 is seen in the HBVMN patients when compared to the hepatitis controls (13/42 vs 4/40) but this is only significant before correction (RR=4.3, P=0.04).
HLA polymorphisms in Italian bone marrow donors: a regional analysis
Authors: Rendine S. , Borelli I. , Barbanti M. , Sacchi N. , Roggero S. , Curtoni E.S.
Published: December 2008

Abstract: The aim of this study was to analyse the genetic structure of the Italian bone marrow donor population on the basis of HLA polymorphisms. Maximum likelihood estimates of gene and haplotype frequencies, goodness of fit to Hardy‐Weinberg predictions and heterozygosity were calculated for 18 Italian administrative regions. Moreover, the phenotypic peculiarity of the regional populations was assessed by analysing the number of “typical phenotypes” found in each region. Multivariate analyses carried out on HLA‐A and HLA‐B gene frequencies gave a genetic pattern of the donor pools that reflects the structure of the Italian population determined in previous population genetic studies. Sardinia shows a very large genetic difference with respect to the other regions; of these, the central‐southern regions are well‐differentiated from the central‐northern. Southern regions present higher genetic heterogeneity and a higher probability of providing donors with phenotypes not already present in the Italian bone marrow registry. The large sample size of the bone marrow donor registry allowed us to estimate gene and haplotype frequencies with greater accuracy than in previous studies. Our results may be of use in determining strategies for donor recruitment and selecting unrelated donors for patients requiring bone marrow grafting, as well as for anthropological, epidemiological and population genetics studies.
Diversity of HLA‐DR2 in North Indians: the changed scenario after the discovery of DRB1*1506
Authors: Rani R. , Mukherjee R. , Stastny P.
Published: December 2008

Abstract: DRB1*1506, a new allele of DR2, differs from DRB1*1501 only at codon 50 in the second exon, where the nucleotide sequence has changed from GTG to GCG resulting in an amino acid substitution from valine to alanine in DRB1*1506. Since codon 50 was considered non‐polymorphic until the discovery of this new allele by sequence‐based typing, it became necessary to study what fraction of subjects thought to have DRB1*1501 actually had DRB1*1506. For this purpose, 116 DNA samples with DR2 coming from normal healthy individuals, leprosy patients and childhood tuberculosis patients were amplified using PCR and hybridized with 32P‐labeled probes specific for DRB1*1501, DRB1*1502, DRB1*1503, DRB1*1506, DRB1*1601 and DRB1*1602. The oligonucleotide probe for DRB1*1506 was designed to span codons 47–52 based on the published nucleotide sequence. DRB5, DQA1 and DQBl‐specific amplifications and hybridizations were also carried out to study the diversity of DR2 haplotypes. It was found that 21 % of the samples identified previously as DRB1*1501 were actually DRB1*1506. DRB1*1506 was found to be associated with DQBl*0502 and DQB1*0601. Haplotypes of DRB1*1501, DRB1*1502, DRB1*1506 and DRB1*1602 showed a marked heterogeneity. Besides the rare haplotypes which have not yet been reported in any other populations, haplotypes characteristic of different ethnic groups, such as Croatians, South Chinese and Gypsies, were also found in the North Indians, suggesting the extent of racial admixture and migrations to and from India.
Polymorphism and distribution of HLA‐DR2 alleles and haplotypes in a Greek population
Authors: Constantinidou N. , Chaidaroglou A. , Van den Berg‐Loonen E.M. , Koniavitou K.
Published: December 2008

Abstract: HLA‐DR2 serological subtyping has indicated that the DR16 serotype appears at a higher frequency relative to the DR15 serotype in the Greek population, differing from the distribution observed in most other Caucasian groups. In this study, we have analyzed by the PCR‐SSP technique a DR2‐positive group of unrelated Greek individuals selected from our normal control panel for the different DRB1, DRB5, DQB1 and DQA1 DR2‐associated alleles present. Six of the 50 individuals analyzed were homo‐zygous for DR2, contributing a total of 56 haplotypes for DR2. The observed frequencies of the DR2‐related DRB1 alleles were as follows: 58.9% for the DRB1*1601, 7.1% for the DRB1*1602, 25.0% for the DRBl*1501 and 7.1% for the DRB1*1502 allele. The rare allele DRB1*1605 was detected in one heterozygous sample and its presence was definitively established by DNA sequencing. The alleles *1503, *1504, *1505, *1603 and *1604 were not detected. Three DRB5 alleles were identified: DRB5*0202 (67.8%), DRB5*0101 (25.0%) and DRB5*0102 (7.1%). Ten different DRB1/DQB1/ DQA1 DR2‐associated haplotypes were denned. The most frequently observed haplotype was DRBl*1601‐DQBl*0502‐DQAl*0102 (relative frequency =57%) followed by DRB1*1501‐DQB1*0602‐DQA1*0102 (relative fre‐quency=14.3%). In conclusion, the refined analysis of the DR2‐associated DRB1 alleles in the Greek population revealed the prevalence of the DRB1*1601 allele. The rare allele DRB1*1605 was demonstrated once. A considerable variety of different DR2‐related DR/DQ haplotypes was detected and the overall haplotypic frequencies in the Greek population are distributed differently compared to those reported for most other Caucasian populations.
Three new DP alleles identified in sub‐Saharan Africa: DPB1*74O1, DPAl*02013, and DPAl*0302
Authors: Steiner L.L. , Cavalli A. , Zimmerman P.A. , Boatin B.A. , Titanji V.P.K. , Bradley J.E. , Lucius R. , Nutman I.B. , Begovich A.B.
Published: December 2008

Abstract: HLA‐DP genotyping of over 400 individuals from sub‐Saharan Africa identified three new DP alleles: DPB1*7401, DPAl*02013, and DPAl*0302. DNA sequencing confirmed that DPB1*7401, found in one individual, is a novel combination of previously described sequence motifs in the six variable regions of DPB1. DPA1*02013, found in one individual, is identical to DPAl*02012 except for two silent substitutions, a T to C transition in codon 37, and an A to G transition in codon 38. DPAl*0302, identified in seven individuals, is identical to DPAl*0301 except for a C to T transition at the second position of codon 66. The identification of these novel alleles brings the total number of reported DPB1 alleles to 77 and DPA1 alleles to 11.
The nature of polymorphism of the HLA‐DRB intron sequences is lineage specific
Authors: Blasczyk R. , Kotsch K. , Wehling J.
Published: December 2008

Abstract: The sequence database of HLA‐DRB genes is mainly derived from mRNA analysis or has focused exclusively on the polymorphism of the 2nd exon. Little is known about the non‐coding sequences of the different DRB alleles which represent about 94% of the genes. In this study we have determined the sequence of the 3′ 500 bp intron 1 fragment adjacent to exon 2 in all serologically defined HLA‐DRB genes and their most frequent allelic subtypes. The intron sequences turned out to be highly polymorphic. Similar to the class I introns, this variability was not characterized by random point mutations but by a highly systematic diversity reflecting the lineage‐specific relationship of the HLA‐DR alleles. With a few exceptions in DRB1*15, 13 and 08 as well as DRB4 and 5, the variability mirrors the serological diversity. As well as delivering insight into the genetic relationship between the different DRB alleles, these sequences will provide an extremely valuable basis for developing advanced DRB sequencing strategies for clinical purposes.
Polymorphisms at tumor necrosis factor (TNF) loci are not associated with Chagas' disease
Authors: Beraún Y. , Nieto A. , Collado M.D. , González A. , Martín J.
Published: December 2008

Abstract: The aim of this study was to investigate whether the polymorphisms at the TNF loci are associated with Chagas' disease. We determined the TNFA (positions ‐308, ‐244 and ‐238) and TNFB genotypes in a sample of 85 serologically positive chagasic individuals and in 87 healthy controls from a Peruvian population where Trypanosoma cruzi infection is endemic. Patients were subdivided according to the presence (n=33) or absence (n=52) of chagasic chronic cardiomyopathy, in order to search for genetic differences associated with this pathological condition. No significant differences either between patients and controls or between asymptomatic and cardiomyopath‐ic individuals were observed with respect to TNFA or TNFB polymorphisms when these were considered individually or as extended haplotypes.
Novel HLA‐A and HLA‐B alleles
Authors: Hurley C.K. , Steiner N. , Kosman C. , Mitton W. , Koester R. , Bei M. , Bush J. , McCormack J. , Hahn A. , Henson V. , Hoyer R. , Wade J.A. , Hartzman R.J. , Ng J.
Published: December 2008

Abstract: Nine novel HLA‐A and HLA‐B alleles are described: A*2609, A*6803, A*6806, B*1539, B*1540, B*2712, B*4103, B*5109, and B*5603. Most appear to have arisen by gene conversion events. B*5603 appears to have arisen by a reciprocal recombination event joining exon 2 of a B*55/*56 allele with exon 3 of a B*15 allele. Serologically, the antigen encoded by this allele types with broad B22‐ and Bw6‐specific alloantisera. Also unique, the antigen encoded by B*2712 does not react with B27‐spedfic alloantisera but does react with Bw6‐specifk alloantisera.
Determination of gene frequencies for two common haemochromatosis mutations in the Danish population by a novel polymerase chain reaction with sequence‐specific primers
Authors: Steffensen R. , Varming K. , Jersild C.
Published: December 2008

Abstract: Hereditary haemochromatosis (HH), a condition of abnormal iron metabolism which leads to iron overload and organ damage, previously known as bronze diabetes or idiopathic haemochromatosis, is the most common disease‐producing genetic disorder among Europeans. Two mutations, C282Y and H63D, are described for the candidate gene, HFE, reported as being responsible for the disease. Since molecular testing of these mutations will be of value in early diagnosis of haemochromatosis, the aim of this study was to develop a simple, fast and inexpensive technique for the determination of the polymorphism in the HFE gene on a large scale. We designed sequence‐specific primers for polymerase chain reaction (PCR‐SSP) and tested 200 randomly selected healthy Danes and found the result completely comparable to results obtained by a previously described method, PCR‐RFLP. The gene frequencies in the Danish population are similar to reported results for the White population, with a frequency of 0.068 for the C282Y mutation and a frequency of 0.128 for the H63D mutation.
Molecular analysis and polymorphism of the DLA‐DQB genes
Authors: Wagner J.L. , Hayes‐Lattin B. , Works J.D. , Storb R.
Published: December 2008

Abstract: Partial‐length cDNA clones and full‐length genomic clones corresponding to a complete canine DQB class It gene were isolated. Southern analyses suggested the presence of two DQB genes ‐ one of which appeared to be a pseudogene lacking exon 2 called DQB2. The other DQB gene, called DQB1, was isolated from a genomic phage clone and contained six exons. The DQB1 clone was restriction mapped, and exon 2 was sequenced from 70 dogs. Twenty alleles were found. Most of the amino acid substitutions occurred at putative positions in the peptide binding site. Inheritance of these sequences showed Mendelian segregation with one or two alleles per dog. Cluster analysis of the nucleotide and predicted amino acid sequences subdivided the canine DQB1 alleles into four major allelic groups. The number of nonsynonymous changes was higher than the number of synonymous changes in the putative antigen recognition sites suggestive of positive selection.
Polymorphism of TAPASIN and its linkage disequilibria with HLA class II genes in the Japanese population
Authors: Furukawa H. , Kashiwase K. , Yabe T. , Ishikawa Y. , Akaza T. , Tadokoro K. , Tohma S. , Inoue T. , Tokunaga K. , Yamamoto K. , Juji T.
Published: December 2008

Abstract: Tapasin plays an important role in HLA class I assembly. The gene has been mapped on the human MHC region. We identified two alleles of TAPASIN in the Japanese population and analyzed the association of the alleles with HLA‐DPB1, ‐DQB1 and ‐DRB1 alleles. The allele frequencies of TAPASIN*01 and *02 were estimated to be 0.37 and 0.63, respectively, in the Japanese population. TAPASIN showed strong linkage disequilibrium with the HLA‐DPB1 locus. Several frequent four‐locus haplotypes were identified, including DRB1*0901‐DQB1*0303‐DPB1*0501‐TAPASIN*02, DRB1*0901‐DQB1*0303‐DPB1*0201‐TAPASIN*02 and DRB1*1302‐DQB1*0604‐DPB1*0401‐TAPASIN*02.
Microsatellites in the HLA region: 1998 update
Authors: Foissac A. , Cambon‐Thomsen A.
Published: December 2008

Abstract: In order to update the review published in Tissue Antigens in 1997, we present here a new overview on microsatellites in the HLA region, including additional information, with focus on the following points:

• Description of 103 microsatellite characteristics in the HLA region, 50 markers having been newly described since 1996.

• An integrated map of the HLA region, including microsatellites and some HLA genes, revealing an important microsatellite density in the MHC (Class I, Class II and Class HI regions).

• A synthesis of microsatellite analysis in disease studies, summarizing results of microsatellite approaches in 24 pathologies, including autoimmune diseases, HLA‐associated or HLA‐linked diseases and cancers.

• Other applications of HLA region microsatellites in population or transplantation studies.
HLA restriction patterns of gliadin‐ and astrovirus‐specific CD4+ T cells isolated in parallel from the small intestine of celiac disease patients
Authors: Molberg Ø. , Lundin K.E.A. , Nilsen E.M. , Scon H. , Kett K. , Brandtzaeg P. , Thorsby E. , Sollid L.M.
Published: December 2008

Abstract: Celiac disease is a common HLA‐DQ2‐associated enteropathy caused by an abnormal T‐cell‐mediated immune response to ingested wheat gliadin proteins. We have previously isolated in situ activated mucosal T cells from celiac disease patients and demonstrated that these T cells were gliadin specific and predominantly DQ2 restricted. In contrast to this, glia‐din‐specific T cells isolated from peripheral blood display a variable HLA restriction pattern, thereby indicating that the skewed DQ restriction of T cells resident in the celiac lesions could be dictated by a preference for DQ‐mediated antigen presentation in the mucosa of CD patients. To address this, we analyzed the HLA restriction of T cells recognizing astrovirus, a common gastroentetitis virus, isolated from intestinal mucosa of six celiac disease patients. As an internal control, gliadin‐specific T cells were isolated and analyzed in parallel. The gliadin‐specific mucosal T cells were marked in their DQ2 restriction, whereas the parallel astrovirus‐specific T cells were predominantly restricted by DR molecules. Our data indicate that the repertoire of T cells present in celiac lesions is determined by the priming anti‐gen(s) and not by a skewing in the expression of functional HLA class II isotypes in the disease affected small intestinal mucosa.
TAP polymorphism is not associated with ankylosing spondylitis and complications with acute anterior uveitis in HLA‐B27‐positive Japanese
Authors: Konno Y. , Numaga J. , Mochizuki M. , Mitsui H. , Hirata R. , Maeda H.
Published: December 2008

Abstract: HLA‐B27 is associated with the etiology of ankylosing spondylitis (AS) and acute anterior uveitis (AAU). Transporter associated with antigen processing (TAP) 1 and TAP2 polymorphism influences the range of peptide presented by HLA class I molecules. In this report, contribution of TAP polymorphism to the susceptibility to AS and AAU was studied in HLA‐B27‐positive Japanese individuals. Patients were classified into three groups: 16 AS patients, 14 AAU patients and 22 patients with both AS and AAU. Twelve HLA‐B27‐positive healthy individuals were included as a control. TAP polymorphism was detected by PCR‐RFLP methods. Significant differences in frequencies of TAP1 alleles were not found between patient groups. None of the TAP2 frequencies showed increased or decreased frequencies compared with HLA‐B27‐positive healthy controls. In comparison with a random Japanese control, TAP2D allele frequency was significantly increased in the AAU group, but failed to reach a significant level in a group consisting of the AAU‐only patients and the patients with both AS and AAU. All of the patient groups were noted to have a significantly increased prevalence of the TAP2H allele as compared to random controls; however, the higher frequency of this allele was detected in HLA‐B27 healthy controls as well. These observations suggest a linkage disequilibrium between TAP2D, TAP2H and HLA‐B27 in Japanese.
HLA‐B*27 subtyping by PCR‐RFLP in Spanish patients with ankylosing spondyiitis
Authors: Fraile A. , Martin J. , Löpez‐Nevot M.A. , Mataran L. , Nieto A.
Published: December 2008

Abstract: We describe the use of restriction analysis on PCR‐amplified DNA for detecting all B*27 subtypes except B*2710 and B*2711 (i.e. from B*2701 to B*2709). After detecting B*27 by Sty I, double digestions consisting of Sty I plus another informative enzyme led to subtype assignment. We used mismatched primers to create restriction sites when necessary. The method avoids group‐specific amplifications and other laborious optimization procedures. It was successfully tested on a panel of well characterized cell lines covering different B*27 subtypes. Then, we studied a group of 57 ankylosing spondyiitis patients and 746 controls from the south of Spain. B*27 showed a very strong association with the disease (OR=211.27, P=\0˜7). B*2702 and B*2705 distribution in controls (20% and 77.1%, respectively) differed from previously reported data in the Spanish population. We unexpectedly found the B*2707 allele in our population (one control).
Multiple transcripts of the killer cell immunoglobulin‐like receptor family, KIR3DLL (NKB1), are expressed by natural killer cells of a single individual
Authors: Vyas Y. , Selvakumar A. , Steffens U. , Dupont B.
Published: December 2008

Abstract: Natural killer (NK) cells express receptors that are ligands for HLA class I molecules. One family of such NK receptors are called killer cell immunoglobulin‐like receptors (KIR). The KIR2DL (inhibiting) and KIR2DS (activating) molecules recognize HLA‐Cw antigens, while the KIR3DL (inhibiting) and KIR3DS (activating) molecules interact with HLA‐B antigens with the Bw4 epitope. No NK receptors have yet been identified for HLA‐B antigens with the Bw6 epitope. We here report four novel full length cDNA transcripts encoding KIR3DLl‐like proteins isolated from mRNA obtained from interleukin‐2‐activated peripheral blood mononuclear cells of a donor with two HLA‐B antigens expressing the Bw6 epitope. These four transcripts belong to a group of closely related KIR3DLl‐like molecules initially defined by the cDNA clone NKB1. They differ from NKB1 by only 2 to 7 nucleotides and have 2 to 4 codon changes within the 423 residues of the mature protein. All transcripts were detected by RT‐PCR, together with the previously reported KIR3DL1 transcripts, NKB1 and KIR3DLlv, in mRNA from NK cells of 10 of 10 donors tested, and in seven of eight NK clones derived from one donor. Functionally, the KIR3DL1 receptors expressed by five DX9‐positive NK clones were not inhibiting NK‐mediated cytotoxicity when tested against the 721.221 B‐lymphoblastoid cell line expressing a HLA‐B antigen with Bw4 epitope. All NK clones were, however, inhibited by 721.221 cells transfected with a HLA‐B antigen carrying the Bw6 epitope1.
Molecular analysis of HLA class I (HLA‐A and ‐B) and HLA class II (HLA‐DRB1) genes in Japanese patients with multiple sclerosis (Western type and Asian type)
Authors: Ono T. , Zambenedetti M.R. , Yamasaki K. , Kawano Y. , Kamikawaji N. , Ito H. , Sakurai M. , Nishimura Y. , Kira J. , Kanazawa I. , Sasazuki T.
Published: December 2008

Abstract: The types of HLA‐A, ‐B and ‐DRB1 genes were studied in 146 Japanese patients with multiple sclerosis (MS) using polymerase chain reaction‐sequence‐specific oligonucleotide probe analysis. Fifty‐seven patients who displayed selective clinical involvement of the optic nerve and spinal cord were classified as having Asian type MS. The other 89 patients had disseminated central nervous system involvement and were classified as having Western type MS. The frequency of HLA‐B*5101 was increased in both types of MS patients compared with controls. The frequency of HLA‐DRB1*1501 was increased in Western type MS and the frequency of HLA‐DRBl*0802 was increased in Asian type MS compared to controls. After correction of P values, the association of Western type MS patients with HLA‐DRB1*1501 was statistically significant (Pc=0.0003) whereas other HLA alleles showed no significant association. These results suggest that HLA class I (HLA‐A and ‐B) alleles may not contribute to a strong susceptibility to MS in Japanese compared to HLA class II (HLA‐DRB1) alleles.
Genetic susceptibility to gluten sensitive enteropathy in Irish setter dogs is not linked to the major histocompatibility complex
Authors: Polvi A. , Garden O.A. , Houlston R.S. , Maki M. , Batt R.M. , Partanen J.
Published: December 2008

Abstract:Gluten sensitive enteropathy (GSE) in Irish setter dogs has been proposed as an animal model for human celiac disease (CD), in which the major histocompatibility complex (MHC) class II alleles HLA DQAl*0501 and DQBl*0201 play an important role. To investigate whether an orthologous MHC class II region is involved in canine GSE, we undertook a linkage study in two large families of gluten sensitive Irish setter dogs. A total of 44 dogs in these pedigrees were genotyped for DQA1, DQB1 and C.2202 alleles, along with 30 unrelated healthy Irish setters. No genetic linkage between the DQ or C.2002 loci and GSE was detected. In contrast to CD, susceptibility to canine GSE does not appear to be determined by variation within the MHC class II gene cluster. Therefore, canine GSE may not be an appropriate model for CD, but nevertheless remains an important disease for advancing knowledge of pathological processes in the intestine.
DQ‐haplotype analysis in rhesus macaques: implications for the evolution of these genes
Authors: Sauermann U.
Published: December 2008

Abstract: The DQA1 and DQB1 alleles of 258 rhesus monkeys (Macaca mulatto) of different origin were typed by PCR‐RFLP. Five novel Mamu‐DQA1 and five novel ‐DQB1 alleles were detected and 15 Mamu‐DQAl‐DQB1 haplotypes were identified. Haplotype analysis confirmed the conservation of the DQA1*O1‐DQB1*O6 haplotypes in evolution. The most conspicuous finding was the tight linkage between the Mamu‐DQAl and DQB1 alleles. Almost in every case the Mamu‐DQA1 allele was linked to only one particular Mamu‐DQB1 allele. Although there also are constraints in the formation of DQ haplotypes in humans, such tight linkages are not observed. These findings support the hypothesis of some kind of co‐evolution between DQA1 and DQB1 alleles and may reflect a stronger force of natural selection in macaques than in humans.
HALOPERIDOL (SERENASE®) IN THE PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING
Authors: Dyrberg V.
Published: December 2008

The prophylactic use of haloperidol reduced postoperative nausea from 28.6% to 7.6% in males and from 49.5% to 20.3% in females during the first six postoperative hours. Vomiting was reduced from 14.3% to 2.4% in males and from 32.3% to 10.8% in females. Similar results were obtained for the next 18 hours.

The findings in the control groups suggest that the incidence of postoperative nausea and vomiting is independent of the age of the patient and the duration of the anaesthesia. A higher over‐all incidence of postoperative nausea and vomiting was found in women than in men. Analysis of the operations performed suggested that a difference exists between the two sexes in the reaction to intraperitoneal manipulation, and that this is the factor which causes a higher incidence of postoperative vomiting in women than in men.

Haloperidol 5 mg was found to be more active as an antiemetic than 50 mg of chlorpromazine. It reduced the incidence of reflex movements during light anaesthesia and produced complete amnesia for the anaesthetic period, while some of the controls afterwards gave evidence of some degree of awareness during the anaesthesia.

Haloperidol is recommended for the treatment of established postoperative vomiting and for prophylaxis on special indications.

Die prophylaktische Anwendung von Haloperidol verminderte die postoperative Nausea bei Mannern von 28,6% auf 7,6%, bei Frauen von 49,5% auf 20,3 % wahrend der ersten sechs postoperativen Stunden. Erbrechen wurde bei Männern von 14,3% auf 2,4% und bei Frauen von 32,3% auf 10,8% vermindert. Ähnliche Ergebnisse wurden für die nächsten 18 Stunden erreicht.

Die Befunde in den Kontrollgruppen machen es wahrscheinlich, dass der Prozentsatz der postoperativen Nausea und des Erbrechens vom Alter des Patienten und der Dauer der Narkose unabhängig ist. Der Gesamtbefall von postoperativer Nausea und Erbrechen war bei Frauen höher als bei Männern. Eine Aufschlüsselung der durchgeführten Operationen lässt darauf schliessen, dass ein Unterschied zwischen den beiden Geschlechtern bezüglich ihrer Reaktionen auf intraperitoneale Manipulationen besteht, und dass es wohl dieser Faktor ist, der für den höheren Anteil von postoperativem Erbrechen bei Frauen verantwortlich ist.

5 mg Haloperidol erwies sich als wirksameres Antiemetikum als 50 mg Chlorpromazin. Es verminderte Reflexbewegungen in oberflächlicher Anaesthesie und erzeugte komplette Amnesie für die Zeit der Anaesthesie, während manche Kontroll‐Patienten angaben, gewisse Wahrnehmungen während der Narkose gemacht zu haben.

Haloperidol wird für die Behandlung des bereits bestehenden postoperativen Erbrechens und zur Prophylaxe bei besonderen Indikationen empfohlen.
TRIS(HYDROXYM ETHYL) AMINO‐M ETHANE (THAM) USED AS A BUFFER IN BRONCHOSCOPY AND “APNOEIC OXYGENATION”
Authors: Andersen Nikaan
Published: December 2008

In order to facilitate transbronchial pressure measurement in the left auricle, four patients with moderately severe cardiac disease were anaesthetised with a combination of “apnoeic oxygenation” and intravenous infusion of a buffer, tris(hydroxymethyl)amino‐methane (THAM). During 15 to 25 minutes of “apnoeic oxygenation” the patients were fully oxygenated, and the extreme fall in pH induced by accumulation of carbon dioxide was prevented. Blood pressure and pulse rate remained within normal limits; the cardiac rhythm was steady; there was ample urinary output just after anaesthesia, probably with a small loss of electrolytes, and the patients recovered soon after anaesthesia without any adverse effects.

The side effects of THAM were minimal, probably because the dose was kept well below 500 mg per kg. It is concluded that this method of anaesthesia might be of value in rare cases in bronchoscopic procedures.

Zur Durchführung von transbronchialen Druckmessungen im linken Vorhof wurden 4 Patienten mit mittelschweren Herzerkrankungen mittels einer Kombination von ←apnoischer Oxygenation→ und i.v. Infusion einer Pufferlösung (THAM) narkotisiert. Während einer 15–25 Minuten dauernden ←apnoischen Oxygenation→ zeigten die Patienten voile Sauerstoffsättigung und ein extremer Abfall des pH als Folge der CO2‐Anreicherung konnte verhindert werden. Blutdruck und Pulsfrequenz bewegten sich innerhalb der normalen Grenzen; der Herzrhythmus war gleichbleibend; die Harnausscheidung unmittelbar nach der Narkose war ausreichend, wahrscheinlich mit geringem Verlust von Elektrolyten, und die Patienten erholten sich bald nach der Narkose ohne irgendwelche Störungen.

Die Nebenwirkungen von THAM waren gering, wahrscheinlich weil die Dosis unter 500 mg/kg gehalten wurde. Abschliessend wurde festgestellt, dass diese Art der Anaesthesie in seltenen Fällen auch bei bronchoskopischen Eingriffen wertvoll sein könnte.
EFFECT OF SUCCINYLCHOLINE ON UTERINE MOTILITY
Authors: Wiqvist N. , Wahlin A.
Published: December 2008

The effect of succinylcholine on the uterus was studied in animal experiments and in pregnant women. No noticeable change of the motility could be demonstrated.

Die Wirkung von Succinylcholin auf den Uterus wurde in Tierversuchen und an schwangeren Frauen studiert. Dabei konnten keine merklichen Änderungen der Motilität festgestellt werden.
PROPHYLAXIS WITH CORTIGOSTEROIDS IN SURGICAL PATIENTS RECEIVING CORTISONE OR OTHER STEROID THERAPY
Authors: Solem Jan H. , Lund Ivar
Published: December 2008

The keystone to a favourable outcome of a surgical operation in steroid‐treated patients is to make sure that such patients without exception are registered as “a steroid case” before operation. It was found adventageous to let the responsibility of obtaining information about previous medication and of prophylactic corticosteroid treatment rest with the anaesthetist in charge of the case.

During the last 4 years the following scheme was adopted in Ullevål Hospital. Patients who had received corticoids within the last four weeks before operation were given additional hormones according to a standard schedule. In the other “steroid cases” no coverage was given, but these patients were carefully observed for signs of impending circulatory insufficiency. In the 78 patients treated with cortisone or cortisone‐like steroids, this system worked out satisfactorily. There were no fatal cases, and no serious complications occurred, either in the 48 cases receiving prophylactic cortisone, or in the 30 “steroid cases” in which such treatment was omitted. The prophylactic steroid treatment followed the same standard scheme in all cases, consisting of heavy doses of cortisone. None of these patients showed any signs of delayed wound healing or wound infection.

Der Schlüssel zum günstigen Ausgang einer Operation an steroidbehandelten Patienten ist, sich zur Regel zu machen, diese Patienten ausnahmslos vor der Operation als ←Steroid Fälle→ zu registrieren. Es erwies sich als günstig die Verantwortung für die Einholung von Erkundigungen über die stattgehabte Medikation und die prophylaktische Corticosteroidbehandlung dem für diesen Fall beigezogenen Anaesthesisten zu übertragen.

Während der letzten 4 Jahre wurde am Ullevål Spital nach folgendem Schema vorgegangen: Patienten, die innerhalb der letzten 4 Wochen vor der Operation Corticoide eingenommen hatten, wurden zusatzliche Hormone nach einem bestimmten Standardschema gegeben. Den anderen ←Steroid‐Fallen→ wurde keine Schutztherapie gegeben, dafür wurde bei diesen Patienten genauestens beobachtet, ob Zeichen einer drohenden Kreislaufinsuffizienz auftraten. Das Ergebnis dieses Systems war bei den 78 Patienten, die mit Cortison oder Cortison‐ähnlichen Steroiden behandelt wurden, zufriedenstellend. Weder unter den 48 Fällen, die prophylaktisch Cortison erhielten, noch bei den 30 Steroid Fällen, die unbehandelt blieben, wurden Todesfälle oder ernstliche Komplikationen beobachtet. Die prophylaktische Steroid‐Behandlung, bestehend in hohen Dosen von Cortison, erfolgte bei alien Fällen nach dem gleichen Schema. Keiner der Patienten wies Zeichen einer verzögerten Wundheilung oder einer Wundinfektion auf.
ESTIMATION OF FLUOTHANE BY GAS CHROMATOGRAPHY
Authors: Dyfverman A. , Sjövall J.
Published: December 2008

A method for the determination of fluothane in organs and body fluids was worked out. It is in part based on suggestions of Butler and Hill (1961)1. The fluothane was distilled into n‐heptane and the heptane solution analysed by gas chromatography. The method was used for the estimation of the fluothane content of blood, brain and liver from a patient who died after anaesthesia with fluothane.

Eine Methode für die Bestimmung von Fluothan in Organen und Körperflüssigkeiten wird beschrieben. Sie lehnt sich teilweise an ein von Butler und Hill (1961)1 veröffentliches Verfahren an. Das Fluothan wird in eine mit n‐Heptan beschickte Vorlage destilliert, worauf die Heptanlösung gaschromato‐graphisch untersucht wird. Die Methode wurde zur Bestimmung von Fluothan in Blut, Gehirn und Leber eines während einer Fluothananaesthesie verstorbenen Patienten verwendet.
A METHOD FOR COMPARING THE EFFECTIVENESS OF LOCAL ANAESTHETICS
Authors: von Dardel Otto , Lindahl Olov
Published: December 2008

A method has been evolved by which different anaesthetics can be compared. The anaesthetic mixed with a pain‐eliciting substance was administered by jet injection. By repeated injection in a group of 20 volunteer subjects numerical values were obtained for the pain‐inhibiting effect of different concentrations of a particular agent. A comparison was made of procaine, Xylocaine, Carbocaine, L 67 and tetracaine in concentrations from 0.0001 to 1.0 per cent.

The pain‐inhibiting effect was found to diminish with dilution of the anaesthetic. For 1.0 per cent, solutions the effect of the various agents was from 7 to 19 times greater than for procaine. Tetracaine was the most effective, followed by Xylocaine.

The method is applicable principally in the evaluation of various local anaesthetics as additives to drugs that per se cause pain on injection. It is also applicable in comparisons of anaesthetics with respect to their effectiveness in infiltration anaesthesia; in this case the method does not permit the various parameters to be evaluated individually, but provides only a measure of the total anaesthetic effect.

Es wurde eine Methode zum Vergleich verschiedener Anaesthetika entwickelt. Das Anaesthetikum wird gemeinsam mit einer schmerzerzeugenden Substanz mittels einer Düsen‐Spritze gleichzeitig intra‐ und subcutan eingebracht. Durch wiederholte “Injektion” innerhalb einer Gruppe von 20 Freiwilligen konnten numerische Werte für den schmerzverhütenden Effekt verschiedener Konzentrationen eines bestimmten Mittels erhalten werden. Procain, Xylocain, Carbocain, L 67 und Tetracain wurden in Konzentrationen von 0,0001 bis 1,0% verglichen.

Die schmerzverhütende Wirkung nahm mit der Verdünnung des Anaesthetikums ab. Bei der 1%‐igen Lösung war die Wirkung der verschiedenen Agentien 7 bis 19 mal stärker als die des Procains. Tetracain war das wirksamste, gefolgt von Xylocain.

Die Methode ist prinzipiell geeignet zur Auswertung verschiedener Lokalanaesthetika unter Zusatz von Mitteln, deren Injektion an sich schmerzvoll wäre. Sie ist auch anwendbar für den Vergleich der Wirksamkeit verschiedener Infiltrationsanaesthetika; in diesem Fall erlaubt sie zwar nicht die individuelle Auswertung der verschiedenen Parameter, gibt jedoch ein gutes Mass für den Gesamt‐Anaesthesieeffekt.
THE ACTION OF SUCCINYLGHOLINE ON THE RENAL FUNCTION
Authors: Granberg P.‐O. , Wåhlin Å.
Published: December 2008

The renal haemodynamics under the effect of succinylcholine was studied in five volunteer subjects during superficial barbiturate anaesthesia. The glomerular filtration rate (Cin) and renal blood flow (Cpah) decreased under the action of standard apnoeic doses of succinylcholine. The kidneys seem to react to the agent in another way than do, for example, the skin, the striated muscles and the intestine, in which tissues an increase in the peripheral blood flow was recorded under similar conditions.

Die renale Hämodynamik unter der Wirkung von Succinylcholin wurde an 5 Freiwilligen während einer oberflächlichen Barbituratnarkose untersucht. Die Glomerulusfiltrationsrate (Inulin‐Clearance) und die Nierendurchblutung (PAH‐Clearance) waren während der Wirkung normaler apnoischer Dosen von Succinylcholin reduziert. Die Niere scheint auf dieses Agens anders zu reagieren als etwa der Darm, an denen unter gleichen Versuchsbedingungen eine Vermehrung der peripheren Durchblutung festgestellt worden war.
SERUM CHOLINESTERASE ANENZYMIA Report of a Case Confirmed by Enzyme‐histochemical Examination of Liver‐Biopsy Specimen
Authors: Doenicke A. , Gürtner Th. , Kreutzberg G. , Remes I. , Spiess W. , Steinbereithner K.
Published: December 2008

A report is given on a 76‐year‐old woman who suffered from apnoea for 9 hours after administration of 40 mg succinyldicholine chloride. Serological examinations showed normal protein fractions, normal acetylcholinesterase (specific ChE) activity and complete absence of SChE (non‐specific ChE) activity. Enzyme‐histochemical examinations of a liver‐biopsy specimen also failed to reveal any activity. ChE could not be detected with butyryl thiocholine or acetyl thiocholine as substrates, whereas non‐specific esterases reacted entirely normal. There was no correlation between liver function (especially albumin synthesis) and ChE activity in this case of anenzymia. The fatty infiltration of the liver is discussed as an effect of the ChE anenzymia. It became evident that even complete absence of SChE may occur without any symptoms of illness or any serious disturbances in the serum proteins. The use of depolarising relaxants and of certain other esters (as is known in the case of atypical ChE) may, however, lead to serious complications.

Es wird über eine 76‐jährige Patientin berichtet, bei der nach 40 mg Succinylbischolinchlorid eine 9‐stündige Apnoe auftrat.

Die serologischen Untersuchungen ergaben normale Eiweissfraktionen, eine normale Acetylcholinesterase‐ (spezifische ChE) und ein vollständiges Fehlen der Serumcholinesteraseaktivität (unspezifische ChE). Die enzymhistochemischen Untersuchungen nach Leberbiopsie liessen ebenfalls keinerlei Aktivität erkennen. Weder mit Butyryl‐ noch mit Acetylthiocholin als Substrat gelang ein Cholinesterasenachweis, wohingegen unspezifische Esterasen völlig normal reagierten. Das gleichsiimige Verhalten von Leberfunktion (besonders Albuminsynthese) und ChE‐Aktivität ist bei der Anenzymie nicht zu finden. Die festgestellte Leberverfettung wird als Folge der Anenzymie der ChE diskutiert.

Es zeigte sich, dass auch bei völligem Fehlen der Serumcholinesterase keine manifesten Krankheitssymptome auftreten, dass aber (wie von der atypischen ChE bekannt) nach Anwendung depolarisierender Relaxantien und bestimmter anderer Ester lebensgefährliche Komplikationen auftreten können.