bluuebunny/crossref_metadata_2025 huggingface dataset:
The Incidence of Intraoperative Hypotension and the Importance of Timely Detection
Authors: Sirait Robert H
Published: January 2024

Aims: Intraoperative hypotension (IOH) is a common condition faced by anesthesiologists intraoperatively which poignanting patients undergoing surgery under general and neuraxial anesthesia. Its occurrence is associated with dangerous morbid situations found perioperatively that can lead into fatal complications, such as acute kidney failure, direct myocardial injury, and even can end in mortality. Despite advanced closed hemodynamic monitoring and protocols utilizing goal directed therapy, recent trend of management is remaining reactive. Anesthesiologists tend to intervene when the episode of hypotension has already occurred. This literature review aimed to discuss the incidence of intraoperative hypotension and its urgency to overcome intraoperatively.

Conclusion: The incidence of IOH varies based on the type of surgery, type of anesthesia and fragility of the patient, for example having comorbidities. Due to the rapid development of IOH which is unwanted, the effort reducing the hypotensive burden intraoperatively, as soon as possible is mandatory. By carefully predicting and preventing IOH through closed monitoring of patient’s blood pressure will surely improve patient outcome and prevent adverse unwanted post-operative event.
Identification of a Novel Streptomyces Species for Management of Plant Disease
Authors: Yamunarani K. , Sangeetha S. , Chitra K. , Dhanalakshmi K. , Dhanushkodi V.
Published: January 2024

Native isolates of groundnut stem rot casual organism, Sclerotium rolfsii Sacc. Were collected from major groundnut growing areas of Tamil Nadu. Selected isolates were screened, characterized and indentified the virulent isolate (GNSR1). Several native bacterial and fungal antagonists were isolated against GNSR1. Two antagonistic isolates, viz., GNRAJK1 and GNRAVR14, were found to have antagonistic effects on GNSR1. Morphology and spore structure of isolated antagonists, GNRAJK1 and GNRAVR14, were studied under Light microscopy, Biochemical test, Thin layer chromatography and Biolog analysis. It confirmed the group of micro organisms as Streptomyces based on gram staining, medium specific growth, visual morphological characters, cell wall amino acid studies and spore forming chraracters.  The genus and species level of the antagonists were identified by Fatty Acids Methyl Esters (FAME) Analysis. The isolate GNRAJK1 had a SIM index of 0.007 and was identified as Streptomyces violaceusniger, and GNRAVR14 had a SIM index of 0.013 and was identified as Streptomyces exfoliatus.
Role of Biostimulants in Inducing Resistance for Phytosanitary Management
Authors: Oliveira Vinicius de Souza , Marchiori Johnatan Jair de Paula , Ferreira Lusiane de Sousa , Holtz Anderson Mathias , Ferreira Tatiane Cristovam , Vargens Fernanda Nery , Magnani Bruna de Oliveira , Scárdua Marcos Delboni , Bruni Bruno Silva , Milbratz Camila Groner
Published: January 2024

Biostimulants perform functions that improve plant metabolism and can positively interfere with processes such as respiration, photosynthesis, synthesis of nucleic acids and absorption of ions. Furthermore, they improve the roots’ ability to absorb nutrients. Thus, bistimulants can help to induce plant resistance by improving the nutritional capacity of plants, making them more tolerant to pathogen attack. Therefore, the use of biostimulants can have beneficial effects, providing an increase in plant productivity, whether through stimulating their physiology or controlling diseases.
Conversion of Low-Density Polyethylene (LDPE) and Mixed Low-Density Polyethylene with Polyethylene Terepthalate (LDPE and PET) into Hybrid Fuel
Authors: Dauda Aminu , Aminu Zainab Bilyaminu , Olaleye Abdul Ademola , Adamu Nurudeen , Musa Yau
Published: January 2024

This research aims to provide the recycling techniques of low-density polyethylene (LDPE) and mixture of polyethylene terephthalate (PET) with low-density polyethylene (LDPE) waste. As a means of converting abundant waste to wealth, pyrolysis of LDPE and mixed LDPE - PET was carried out in a batch reactor made of stainless steel at temperatures between 450 – 460OC. The vapor produced from melting the waste was condensed to form the liquid hydrocarbon (fuel oil) product. The effect of reaction time and product yield were investigated. The physicochemical properties of the pyrolysis oil measured include density, specific gravity, flash point, color, fire point, flammability and viscosity. For the LDPE the flash point, fire point, density, specific gravity, and viscosity was found to be 39.5 oC, 48 oC, 8.1872, 0.793g/cm, 0.775g/cm3, and 1.566 cSt respectively while for the Mixture of LDPE with PET the flash point, fire point, density, specific gravity, viscosity and Sulphur content was found to be 44 oC, 48 oC, 8.1872, 0.7837g/cm, 0.7916 g/cm3, 1.1660 cSt and 8.1872 respectively. These values were found to be within the range of kerosene values. The fuel was tested in both kerosene lamp and petrol generator.
Development of a computed tomography algorithm for ion temperature measurement
Authors: Murata Yukihiro , Takeuchi Shinya , Tawara Takeshi , Ono Yasushi
Published: March 2003

A new algorithm for 2D ion temperature measurement was developed by including Gaussian fitting of Doppler broadened spectral lines in tomography reconstruction. A modified Bessel function model and squared cosine function model were used to satisfy both the annular boundary conditions in space and the Gaussian profile of spectral lines in wavelength. This method was found much more robust against projection signal errors than the conventional Gaussian‐fitting method at each wavelength. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 142(4): 1–8, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10114
Evolutionary relationships between HLA‐B alleles as indicated by an analysis of intron sequences
Authors: Gomez‐Casado E. , Vargas‐Alarcón G. , Martinez‐Laso J. , Granados J. , Varela P. , Alegre R. , Longás J. , González‐Hevilla M. , Martín‐Villa J.M. , Arnaiz‐Villena A.
Published: March 2003

The HLA‐B locus is the most polymorphic of the class I genes encoded within the human major histocompatibility complex. This polymorphism is mainly located in exons 2 and 3, which code for the molecule’s α1 and α2 domains and includes the antigenic peptide binding site. However, information about adjacent non‐coding regions (introns 1 and 2) has not been extensively reported but could be very important in establishing an understanding of the evolutionary mechanisms involved in the polymorphism generation of HLA‐B and the Mhc loci. In the present work, introns 1 and 2 of 14 HLA‐B alleles are studied and their significance is discussed; 10 have been sequenced in our own laboratory and the other 4 have been previously reported by others. Different serological families share the complete intron 1 sequence; at this region, 12 out of 14 HLA‐B alleles could be included in four groups with the same intron 1 sequence: a) B*0702, B*4201, B*4801; b) B*27052, B*4002, B*4011; c) B*40012, B*4101, including B*4501, B*5001 (these latter two alleles have specific characteristics in both introns 1 and 2, which may reflect a common evolutionary pathway); and d) B*44031, B*44032
Note. The other alleles, B*1402, and B*1801, do not have identical intron 1 sequences compared to any of the described groups, but share many similarities with them. The B*1801 evolutionary pathway seems to be very specific since it branches separately from other alleles both in intron 1 and intron 2 dendrograms. On the other hand, HLA‐B allelic group distribution and similarities according to intron 1 sequences were not confirmed when using intron 2, especially in the cases of B*4002, B*4101 and B*4801. This would suggest that both point mutations fixed by genetic drift and gene conversion events are involved in HLA‐B diversification. The latter events could be supported by the strong homology between intron 1 and, to a lesser extent, intron 2, and also the CG content within them. Finally, the precise knowledge of these non‐coding regions could be important for developing DNA base typing strategies for the HLA‐B alleles.
HLA‐A*9, a probable secondary susceptibility marker to ankylosing spondylitis in Basque patients
Authors: De Juan M.D. , Reta A. , Cancio J. , Belzunegui J. , Cuadrado E.
Published: March 2003

HLA‐B27 is strongly associated to ankylosing spondylitis (AS). The objective of our study was to analyze HLA‐B27 association, B27 subtype distribution and frequency of other HLA class I and DR antigens in a group of Basque AS patients. HLA class I antigens were typed serologically and HLA‐B27 and A9 subtypes were determined by DNA typing in samples from 46 patients with AS, 54 B27‐positive spondyloarthropathies, 82 healthy subjects and 20 B27‐positive controls. A class I HLA 9.2 kb PvuII restriction fragment length polymorphism (RFLP), previously associated with AS, was analyzed in a representative group of patients and controls. We found that HLA‐B*2705 conferred a relative risk of 126 for AS in this group. HLA‐A9 (A*2402) allele was significantly increased in AS patients compared with healthy controls and B27‐positive control group (Pcorr<0.0001) and also increased in patients affected with peripheral arthritis. No association between class I HLA 9.2 Kb RFLP and AS was found. These results suggest that HLA‐A*9 allele itself or another linked gene could act as a secondary and independent susceptibility allele to AS.
A novel HLA allele, HLA‐B*5113, identified in the Kolla Amerindians of North‐West Argentina
Authors: Scott I. , Dunn P.P.J. , Day S. , Pesoa S. , Little A‐M. , Madrigal J.A. , Vullo C.
Published: March 2003

A novel HLA‐B51 allele, B*5113 Note, was identified in a Kolla Amerindian individual from North‐West Argentina. HLA‐B*5113 1 differs from B*51011 by two nucleotide substitutions, one synonymous, the other non‐synonymous. The resulting amino acid difference at residue 116 in the HLA‐B molecule’s peptide binding site is likely to affect the nature of the peptides which bind to this molecule. The finding of this novel allele supports previous findings of increased diversity at HLA‐B in Amerindian groups.
The South Amerindian allotype HLA‐B*3909 has the largest known similarity in peptide specificity and common natural ligands with HLA‐B27
Authors: Yagüe J. , Ramos M. , Vázquez J. , Marina A. , Albar J.P. , López de Castro J.A.
Published: March 2003

HLA‐B*3909 has only been found among South Amerindians, and presumably arose locally in these populations. It differs from B*3901 by a single Tyr to Ser change at position 99. To analyze the influence of this polymorphism on peptide specificity, pool sequence analysis and sequencing of multiple individual ligands from B*3901 and B*3909 were carried out. Both allotypes bind peptides with Arg2 or His2 and nonpolar C‐terminal residues. However, whereas His2 is the predominant B*3901 motif, a majority of the B*3909‐bound peptides have Arg2. In addition, B*3909 binds peptides with Pro2, and also shows an increased preference for Pro3. In spite of their differences, both subtypes bind overlapping peptide repertoires, as indicated by the identification of several identical ligands from their respective peptide pools. B*3909 is significantly more similar in its peptide specificity to HLA‐B27 than B*3901. This is due to the increased preference of B*3909 for Arg2 and to low suitability of HLA‐B27 for His2. The similarity between HLA‐B27 and B*3909 was confirmed by identification of a natural ligand common to both allotypes. In addition, multiple HLA‐B27 ligands bound efficiently B*3909 in vitro. The results indicate that, among the HLA class I allotypes of known peptide specificity, B*3909 is the most similar in its peptide binding properties to HLA‐B27, which is absent in South Amerindians. This may have implications for the susceptibility of individuals in these populations to spondyloarthropathies.
HLA‐DR‐DQ alleles and HLA‐DP alleles are independently associated with susceptibility to different stages of post‐schistosomal hepatic fibrosis in the Chinese population
Authors: Hirayama K. , Chen H. , Kikuchi M. , Yin T. , Gu X. , Liu J. , Zhang S. , Yuan H.
Published: March 2003

Evaluation of human leukocyte antigen (HLA) class I and class II genes was performed on patients from China with Schistosomiasis japonica. Patients were categorized as grade 0 (n=44), grade I (n=81), grade II (n=99), or grade III (n=6) based on increasing severity of hepatic fibrosis due to repeated Schistosoma japonicum infections. These results show that the HLA‐DRB1*1101‐DQA1*0501‐DQB1*0301 (Pc<0.02) and HLA‐DRB1*1501‐DRB5*0101 (Pc<0.02) haplotypes are associated with protection and susceptibility to grade I fibrosis, respectively, and that the HLA‐DPA1*0103 ‐DPB1*0201 haplotype (Pc<0.02) is associated with protection from both grade II and III severe fibrosis. There was no association between HLA‐B DNA haplotypes and the disease. These findings indicate that the HLA‐class II molecules play a role in preventing or promoting fibrotic liver change after deposition with Schistosome eggs. Moreover, a tendency was observed within the HLA class II genes for the HLA‐DR‐DQ alleles to be associated with protection against early changes in liver fibrosis, whereas HLA‐DP alleles were associated with protection from the late phase of fibrosis or severe hepatosplenic schistosomiasis.
Identification of a novel DRB1‐allele (DRB1*0106) by sequence‐based typing
Authors: Palou E. , Mongay L. , Arias M.T. , Isart F. , Suárez B. , Massó M. , Fabregat V. , Martorell J. , Gayá A.
Published: March 2003

We report herein the identification of a new DRB1 allele using sequence‐based typing. The new allele, DRB1*0106, was detected during routine HLA typing of a patient undergoing bone marrow transplantation. DRB1*0106 is identical to DRB1*0101 except for two codons, 71 (AGG→GCG) and 86 (GGT→GTG), changing the encoded arginine to alanine and glycine to valine. Both sequences were confirmed by polymerase chain reaction with sequence‐specific primers (PCR‐SSP). The polymorphism at codon 71 has not been, until now, identified in DRB1*01 alleles, although it is present in all the DRB1*15 alleles as well as DRB1*1309 and DRB1*1424.
HLA‐DM can partially replace the invariant chain for HLA‐DR transport and surface expression in transfected endocrine epithelial cells
Authors: Serradell L. , Muntasell A. , Catálfamo M. , Martí M. , Costa M. , De Préval C. , Jaraquemada D.
Published: March 2003

The function of HLA class II molecules as peptide presenters to CD4+ T cells depends on the expression of associated molecules such as the invariant chain (Ii) and DM responsible for the correct transport of and high‐stability peptide binding to the class II dimers. In organs affected by autoimmune diseases, endocrine epithelial cells express class II molecules, which presumably are involved in the presentation of self‐peptides to autoreactive T cells. We have transfected the rat insulinoma cell line RINm5F with different combinations of HLA‐DR, Ii and HLA‐DM cDNAs and have studied how Ii and DM affect the transport and stability of class II molecules expressed by the different transfectants. Immunofluorescence and biochemical analysis showed that cells transfected with DR and DM in the absence of Ii expressed mostly stable molecules in their surface, and showed a lower accumulation of DR molecules in the endoplasmic reticulum (ER) than cells expressing only DR. This suggests that, in the absence of invariant chain, DM molecules can not only exchange peptides other than class II‐associated invariant chain peptide (CLIP) but may also be involved in the transport of class II molecules out of the ER towards the endosomal route. In addition, these data confirm that expression of DR alone or DR+Ii do not allow the formation of sodium dodecyl sulphate (SDS)‐stable complexes, that cells expressing DR+Ii have most DR molecules occupied by CLIP and that Ii and DM molecules allow regular routing and peptide loading of class II molecules.
A DNA‐based detection and screening system for identifying HLA class I expression variants by sequence‐specific primers
Authors: Bunce M. , Procter J. , Welsh K.I.
Published: March 2003

Molecular methods are now commonplace for HLA typing and they have replaced traditional serological methods in many histocompatibility laboratories. A consequence of reliance on molecular methods using primers or probes based on existing sequence information is that unsequenced or partially‐sequenced null, or low expressed variants are not discriminated from expressed alleles. Failure to identify null alleles might have deleterious implications for allogeneic transplants. Expression variants may be classified into two categories: unique mutations and repeat mutations. For example, the alleles A*0303N, A*2409N, and B*1526N have apparently unique mutations. In contrast, repeat mutations may occur frequently at points where unusual nucleotide sequences make accurate DNA replication by DNA polymerases difficult. One example is between nucleotide positions 621–627, where HLA class I alleles may exhibit between three and seven consecutive cytosine residues. Incorrect insertion of an extra cytosine in this region is the cause of expression failure in A*2411N and A*0104N alleles. We hypothesise that insertion of an extra cytosine into the cytosine island between nucleotide positions 621–627 is likely to recur not only in other HLA‐A alleles but also in HLA‐B and even HLA‐C alleles. We describe here a polymerase chain reaction using sequence‐specific primers (PCR‐SSP) system that can not only detect all previously‐sequenced HLA class I expression variants but can also screen for mutations between positions 621–627 in HLA‐A, B or C alleles which may give rise to potentially null alleles. Overall, in this study HLA class I expression variants were identified in 5 of 931 tested samples (0.53%).
Molecular characterization of HLA class I in Colombians carrying HLA‐A2: high allelic diversity and frequency of heterozygotes at the HLA‐B locus
Authors: Fleischhauer K. , Agostino A. , Zino E. , Mazzi B. , Benazzi E. , Arevalo‐Herrera M. , Herrera S. , Bordignon C. , Romero P.
Published: March 2003

Polymerase chain reaction using sequence‐specific oligonucleotide probes (PCR‐SSOP) typing was used to analyze HLA class I A, B and C alleles in three different Colombian populations. Fifty‐nine samples were from Hispano‐American Mestizos living in the urban areas of Cali (referred to here as Aso population). Forty‐four and thirty samples were from the African Black populations of Zacarias (Zac) and Punta Soldado (PS), respectively. Samples were selected for expression of HLA‐A2 by monoclonal antibody staining and allele‐specific hybridization, and their HLA‐A2 subtype distribution has been reported previously. Although only a limited number of samples was analyzed, the data suggest the existence of a remarkable degree of HLA class I polymorphism in the populations studied, with representatives of most serological classes. Despite their common African origin, the populations Zac and PS, both resident in malaria endemic regions, showed some striking differences in allelic distribution for all three class I loci. Furthermore, the samples from Aso and PS, but not Zac, showed a low percentage of blank alleles at the HLA‐B locus (0 and 0.4%, respectively), suggesting the possibility of a heterozygote advantage for HLA‐B alleles in Colombian populations.
HLA genotyping of 5,000‐ and 6,000‐year‐old ancient bones in Japan
Authors: Anzai T. , Naruse T.k. , Tokunaga K. , Honma T. , Baba H. , Akazawa T. , Inoko H.
Published: March 2003

We used polymerase chain reaction (PCR)‐based DNA typing to identify HLA class II alleles of two individuals from ancient human remains. Genomic DNAs were isolated from two ancient human skeletons excavated from the Sanganji and Kitakogane sites in the main and northern islands of Japan, respectively. They were archaeologically estimated to be approximately 5,000 and 6,000 years old respectively, representing the remnants from the Jomon era. High molecular weight DNA was extracted by the standard proteinase K‐phenol extraction method followed by purification with a Centricon‐30 micro concentrator. Several rounds of PCR successfully gave rise to amplification of the HLA‐DRB1 and ‐DQA1 genes. The PCR‐restriction fragment length polymorphism (PCR‐RFLP) and sequencing based typing (PCR‐SBT) methods revealed that those ancient individuals possessed the DRB1 and DQA1 alleles which are highly prevalent among the modern north Asian as well as Japanese populations.
HLA‐A*30 alleles and associated haplotypes in the Korean population
Authors: Lee K.W. , Tang T.F. , Yang S.Y.
Published: March 2003

HLA‐A30 is one of the serologically characterized specificities and has been known to exhibit different haplotypic associations in different ethnic groups. This study reveals the presence of two HLA‐A*30 alleles, A*3001 (31/48; 64.6%) and A*3004 (17/48; 35.4%), with each allele existing as a distinct haplotype in the Korean population. One haplotype, A*3001‐Cw*0602‐B*1302‐DRB1*0701‐DQA1*02‐DQB1*02, found in 77.4% of A*3001‐positive individuals is likely identical to the haplotype previously identified by serology in Asians and European Caucasians. A second haplotype, A*3004‐Cw*0802‐B*1401‐DRB1*0404‐DQA1*03‐DQB1*0402, found in 64.7% of A*3004‐positive individuals has not previously been described. Conserved and distinct haplotypic associations of the two A*30 alleles imply that the two haplotypes may have evolved separately and are relatively new in this population.
Polymorphism in the tumor necrosis factor B gene is associated with Palmoplantar pustulosis
Authors: Hashigucci K. , Yokoyama M. , Niizeki H. , Yamasaki Y. , Akiya K. , Tojo T. , Urushibara T. , Yamazaki Y. , Shimizu H. , Nishikawa T.
Published: March 2003

We investigated the allele and genotype distribution of a polymorphism of the tumor necrosis factor (TNF) B gene and the frequency of HLA‐DR9 in 49 patients with Palmoplantar pustulosis (PPP) and 51 healthy controls. We found that the frequency of TNFB2 in the PPP patients was significantly higher than that in the controls. Furthermore, the DR9‐TNFB2 haplotype was significantly more frequent in the PPP patients (P=0.0045). These results suggest that TNFB2 may confer susceptibility to PPP.
HLA‐Cw*1701 is associated with two sub‐Saharan African‐derived HLA haplotypes: HLA‐B*4201, DRB1*03 and HLA‐B*4202 without DRB1*03
Authors: Clavijo O.P. , Delgado J.C. , Yu N. , Fraser P.A. , Yunis E.J.
Published: March 2003

Different extended haplotypes have been described for many ethnic groups, such as African‐Americans. The complotype FC(1,90)0 is in linkage disequilibrium with HLA‐B42, DRB1*0302 in African‐Americans and Southern African Xhosa individuals, suggesting a common ancestry. In order to analyze the distribution of Cw*17 alleles (Cw*1701, 1702) in relation to this African‐derived extended haplotype, we studied a large panel of samples from African‐American individuals and additionally a group of selected samples carrying HLA‐B42, DR3 and HLA‐B42, non‐DR3 antigens. HLA alleles were assigned using sequence‐specific amplification (SSP) and sequence‐specific oligonucleotide probe hybridization (SSOP). We have found that all haplotypes (10 in total) carrying the extended haplotypes [HLA‐B42, FC(1,90)0, DRB1*0302] were positive for HLA‐Cw*1701. Interestingly, HLA B*4201 was found in all samples (17 in total) carrying HLA‐B42, DR3, Cw*1701, whereas HLA‐B*4202 was found in 10 out of 13 samples from individuals carrying HLA B42, Cw*1701 non‐DR3. These findings suggest that HLA‐Cw*17 polymorphism is conserved in different ethnic populations and that HLA‐B42 alleles seem to separate at least different African‐derived haplotypes. The historical context of these findings are important for the study of human evolution and they may be useful for the development of strategies in the search for possible donors in organ transplantation for African‐derived populations.
Unusual association of the DRB4 null allele, DRB4*0103102N, with HLA DRB1*0402 in a sample of Austrian patients
Authors: Gassner C. , Ellemunter H. , Zahn R. , Albert E.D. , Blasczyk R. , Schönitzer D.
Published: March 2003

Tissue typing for HLA class II antigens is routinely performed by serological, and/or DNA‐based methods. Accuracy, absence of cross‐reactivity and controllable level of resolution are striking advantages of molecular methods. However, a disadvantage of molecular typing, compared to serological methods, is the identification of unexpressed alleles. Whereas serology allows a more or less direct insight into antigen presence, molecular biology is an indirect method and results must also be interpreted by considering the biological pathways of protein expression. We believe that identification of nonexpressed MHC alleles is of importance for transplantation, since nonexpressed MHC allele positive individuals could give rise to antibody formation against the respective expressed MHC product in donor tissue. Usually, the nonexpressed DRB4*0103102N is encountered in association with DRB1*0701‐DQB1*03032, which facilitates correct DNA typing. Here we describe the unusual association of this unexpressed DRB4*0103102N, with DRB1*0402‐DQB1*0302 in a sample of Austrian patients.
Trans‐speciation maintenance in the MHC region of a polymorphism which includes a polymorphic dinucleotide locus, and the de novo arisal of a polymorphic tetranucleotide microsatellite
Authors: Crouau‐Roy B.
Published: March 2003

Alleles and the surrounding regions of DQCAR, a dinucleotide repeat tightly linked to HLA‐DQB1, were sequenced in a range of primate species including man. Three polymorphic regions can usefully be defined in the description of these sequences: the dinucleotide GT repeat itself, the anonymous region 5′ of this repeat, and a variable CTGT repeat in the 3′ region. The 5′ sequence displayed six alleles in the individuals studied. One of these alleles was invariably associated with substitutions in the GT repeat and absence of the CTGT repeat, the others with pure, polymorphic GT repeats and variation in the numbers of CTGT repeats. Haplotypes can be classified by the allele in the 5′ region. Those carrying allele 1 were only found in man, those with allele 2 in man, chimpanzee and gorilla. The third haplotype (indicated by the presence of allele 3) was found in chimpanzee, gorilla and orang‐utan, the fourth in chimpanzee and gibbon, the fifth in baboon, guenon and mangabey and the sixth in guenon and macaque. The alleles in the 5′ region, but from different species, are thus often more similar than alleles from the same species, a phenomenon already shown for some HLA genes. This suggests that major histocompatibility sequences and surrounding sequences shared a correlated evolutionary history. The new polymorphic tetranucleotide microsatellite (CTGT, 3rd region) has possibly arisen de novo from the pre‐existing dinucleotide GT. This study provides information not only on the molecular evolution of this particular microsatellite but also of the trans‐speciation maintenance of polymorphism of its surrounding sequences.
HLA‐B*4021: hybrid linking the B15 and B40 families
Authors: Lee K.W.
Published: March 2003

Twenty alleles encoding molecules with the B60 or B61 serologic specificity have been reported thus far. This study characterized a new allele encoding a molecule exhibiting partial serologic reactivity with B15‐ and B40‐related alloantisera from unrelated Korean individuals. Based on the DNA sequence, it appears that the novel allele has a sequence identical to some of alleles in B*15 family including B*1501 in exon 2. The sequence in exon 3, however, is identical to alleles in the B*40 family (B*4001/07/10/12) and B*4803. This implies that the novel allele, B*4021, has evolved by a reciprocal gene recombination involving members of these two families. The haplotype associated with B*4021 is likely to be A11‐Cw4‐B*4021‐DRB1*04‐DRB4*01‐DQA1*03‐DQB1*0301.
Association of DRB1*1501 with disseminated Mycobacterium avium complex infection in North American AIDS patients
Authors: LeBlanc S.B. , Naik E.G. , Jacobson L. , Kaslow R.A.
Published: March 2003

The HLA class II allele, DR2 (DRB1*1501), has been repeatedly found to be associated with development of tuberculosis and leprosy. We searched for associations of these and other class II alleles with disseminated Mycobacterium avium complex infection (DMAC) in North American Caucasian homosexual AIDS patients. Molecular typing for HLA‐DRB1 and ‐DQB1 alleles in 176 cases of DMAC and 176 matched controls showed an association of accelerated onset of disease with DRB1*1501 (and the closely linked DQB1*0602) that was stronger upon adjustment for the degree and duration of CD4+ cell deficiency (P=0.04) and in multivariate analysis (P=0.02) than in unadjusted analysis. A similar trend was seen with DRB1*0701, and no other allele showed a relationship of similar magnitude. M. avium complex organisms may more effectively evade host defenses in individuals carrying an HLA polymorphism identical to that associated with M. tuberculosis and M. leprae.
A novel HLA‐A24 (A*2420) allele identified in the Atayal tribe of Taiwan
Authors: Scheltinga S.A. , Lai S.‐M. , Van Der Zwan A.‐W. , Tilanus M.G.J. , Wu S.
Published: March 2003

The Taiwan indigenous population groups are classified into different tribes according their linguistic classification and cultural anthropology. One of the tribes, the Atayal, showed a high frequency of A24 alleles by SSOP analysis. High‐resolution sequencing based typing identified a A*2402 variant “A*2420” which was found in 6 unrelated individuals. High‐resolution typing is required to identify HLA polymorphism in the Taiwanese minority groups ( Note).
Identification of the novel allele HLA‐B*1546 which belongs to the serological B72 type: implications for bone marrow transplantation
Authors: Elsner H.‐A. , Wölpl A. , Goldmann S.F. , Blasczyk R.
Published: March 2003

The identification of the novel allele HLA‐B*1546, which has serological B50 and B72 reactivity, was found in two members of a family of Turkish origin. In the sequence analysis the new allele differs from B*1501 by four nucleotides in exon 2. Its structure suggests that it may have originated by gene conversion with B*40, B*41, B*44, B*4501, B*47, B*4901 or B*50. At the protein level, the new allele has three amino acid differences compared to B*1501. Sequence alignment demonstrates that amino acid residue 46 is crucial for serological B72 reactivity. Due to substantial differences with other B*15 variants a possible mismatch may impair clinical outcome of bone marrow transplantation( Note).
Molecular analysis of HLA‐DRB1, ‐DQA1 and ‐DQB1 polymorphism in Turkey
Authors: Saruhan‐Direskeneli G. , Uyar F.A. , Bakar Ş. , Eraksoy M.
Published: March 2003

Acknowledgments:

This study is supported by a grant (SBAG1529) from TÜBITAK (Turkish Research Council) and the Research Fund of the University of Istanbul.

We report the evaluation of MHC class II polymorphism in the population of Turkey. HLA‐DRB1, ‐DQA1 and ‐DQB1 have been investigated by polymerase chain reaction and sequence‐specific oligonucleotide probe hybridisations (PCR/SSO) and sequence‐specific priming (SSP) in 250 randomly selected healthy individuals. We also report the allelic distribution of these genes. The most frequent alleles detected were DRB1*1101 (0.104), *0301 (0.092), *0701 (0.090), DQA1*0501 (0.334), *0102 (0.164) and *03 (0.148) and DQB1*0301 (0.256), *02 (0.164), *0302 (0.128). The frequent ‘putative’ three‐locus haplotypes carry the most frequent alleles at these loci. The most frequently detected class II “haplotypes” are DRB1*1101 DQA1*0501 DQB1*0301 (0.100), DRB1*0301 DQA1*0501 DQB1*02 (0.092) and DRB1*0701 DQA1*0201 DQB1*02 (0.072). The distribution of alleles and ‘putative’ haplotypes has shown common features with other Mediterranean populations. The results extend the HLA map to another Mediterranean country and provide a database for further HLA‐disease association studies and transplantation applications.
A new HLA‐A*02 allele, A*0234, detected by polymerase chain reaction using sequence‐specific primers (PCR‐SSP)
Authors: Moses J.H. , Greville W.D. , Downes J. , McClenahan W. , Kennedy A. , Dunckley H.
Published: March 2003

A novel HLA‐A*02 allele, A*0234, was identified in a potential unrelated bone marrow donor typed by polymerase chain reaction using sequence‐specific primers (PCR‐SSP). Positive reactions obtained upon testing with PCR‐SSP did not fit any known combination of alleles indicating the possible presence of a novel allele. Sequencing of clones from this individual revealed the presence of a novel allele, HLA‐A*0234. The sequence of exons 2, 3 and part of exon 4 showed that A*0234 differed from A*02011 by a single nucleotide in exon 2 at position 282 (C to G). The nucleotide substitution results in an amino acid change at residue 70 (Histidine to Glutamine) in the α1 domain ( Note).
HLA class I antigen downregulation by interleukin (IL)‐10 is predominantly governed by NF‐κB in the short term and by TAP1+2 in the long term
Authors: Terrazzano G. , Romano M.F. , Turco M.C. , Salzano S. , Ottaiano A. , Venuta S. , Fontana S. , Manzo C. , Zappacosta S. , Carbone E.
Published: March 2003

The present study was designed to determine the molecular mechanisms by which interleukin (IL)‐10 prevents the HLA class I antigen expression at the cell surface. In this context, the potential role of transporter associated with antigen presentation 1+2 (TAP1+2) molecules and NF‐κB transcription factors was addressed. The IL‐10 effect was investigated in a human lymphoblastoid cell system defective for TAP1+2 genes (T2 cell line) and in the related TAP1+2 transfectants (T3 cell line). In this experimental system, after 48 h of incubation in the presence of IL‐10, the HLA class I antigen downmodulation was observed in the T3 but not in the T2 cell line, suggesting a potential role of TAP1+2 molecules. In the same experimental conditions, the NF‐κB activity was unaffected. Instead, after 3 h of exposure to IL‐10, the HLA downmodulation was observed in both cell lines, the NF‐κB factors activity being strongly reduced. In addition, the transfection of the inhibitor of NF‐κB, IκBα, prevented the IL‐10 effect on HLA class I antigen expression in the T3 cell line. This phenomenon was observed after 3 h but not 48 h of IL‐10 incubation. These evidences indicate a time dependent involvement of TAP1+2 antigens and of NF‐κB activity in the IL‐10‐induced major histocompatibility complex (MHC) class I downmodulation.
Increased β2‐microglobulin‐free HLA class I heavy chain serum levels in the course of immune responses to viral antigens and to mismatched HLA antigens
Authors: Puppo F. , Brenci S. , Contini P. , Bignardi D. , Hamby C.V. , Filaci G. , Ghio M. , Scudeletti M. , Picciotto A. , Indiveri F. , Ferrone S.
Published: March 2003

Besides being present in serum in association with β2‐μ, HLA class I heavy chains are also present in serum as β2‐μ‐free moieties. The increase in serum levels of β2‐μ‐associated HLA class I heavy chains in conditions associated with an activation of the immune system have prompted us to measure the serum levels of β2‐μ‐free HLA class I heavy chains in the course of immune responses to viral antigens and to mismatched histocompatibility antigens. The serum level of β2‐μ‐free HLA class I heavy chains, like that of β2‐μ‐associated HLA class I heavy chains was significantly increased in patients affected by advanced HIV‐1 infection or by chronic hepatitis C (CHC). In the latter group of patients an association was found between a reduction in the β2‐μ‐free HLA class I heavy chain serum level and response to therapy with interferon α and ribavirin. Moreover, the β2‐μ‐free HLA class I heavy chain serum level was increased more than that of β2‐μ‐associated HLA class I heavy chains during episodes of liver ischemia following liver transplantation and in the course of acute graft rejection and of acute graft‐versus‐host‐disease (GVHD) after allogeneic bone marrow transplantation (BMT). These results suggest that the serum levels of β2‐μ‐free and β2‐μ‐associated HLA class I heavy chains are independently regulated. Furthermore, β2‐μ‐free HLA class I heavy chain serum level may be a useful marker to monitor response to therapy in CHC patients and the clinical course of liver and bone marrow grafts.
Criteria to define HLA haplotype loss in human solid tumors
Authors: Ramal L.M. , Feenstra M. , Van Der Zwan A.‐W. , Collado A. , Lopez‐Nevot M.A. , Tilanus M. , Garrido F.
Published: March 2003

Short tandem repeat (STR) markers are currently used to define loss of heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and chromosome 15 STR markers are applied to define loss of HLA and related genes (e.g. TAP and β2m). The number of STR identified in the HLA region is still increasing. In this study, seven representative STR markers covering the 6p/6q arms of chromosome 6 including the HLA region and two for chromosome 15 flanking the β2m gene, were selected as minimally required for reliable LOH studies. A multiplex polymerase chain reaction (PCR) strategy is proposed when small number of cells are available in microdissected tumor samples.
Identification of a novel HLA‐B46 allele, B*4602, in Japanese
Authors: Akesaka T. , Kashiwase K. , Shimamura M. , Ishikawa Y. , Tanaka H. , Fujii M. , Akaza T. , Hando K. , Yuasa S. , Takahashi T. , Juji T.
Published: March 2003

The B*4602 was identified in a healthy Japanese donor. The B46 variant antigen differed serologically from B46. The nucleotide sequence of B*4602 differed from that of B*4601 by a single base (from A to G) at position 293 in exon 2. The substitution changed the amino acid Asp at position 74 to Gly. The gene frequency of B*4602 in the Japanese population is extremely low. The presumed haplotype of B*4602 was HLA‐A2‐Cw1‐B*4602‐DRB1*09. This is the first report of polymorphism of the B46 antigen ( Note).
A new allele, HLA‐B*1555, identified in an African patient awaiting bone marrow transplantation
Authors: Hoddinott M.A. , Cox S.T. , McWhinnie A.J. , Marsh S.G.E. , Ogilvie H. , Madrigal J.A. , Little A.‐M.
Published: March 2003

Human HLA genes exhibit extreme polymorphism, the extent of which is emphasised by the identification of an ever increasing number of new alleles by DNA‐based typing strategies. Here we describe a novel allele, belonging to the HLA‐B*15 group, which was identified in an African patient awaiting a bone marrow transplant. This individual was shown to exhibit two HLA‐B alleles, B*5301 and a new allele which has been named B*1555. B*1555 differs from B*1531 in exon 3 by a single nucleotide substitution. This substitution results in a change in the amino acid residue at position 97, which is located within the β‐pleated sheet region of the HLA molecule ( Note).
The nucleotide sequence of a new DMB allele, DMB*0106
Authors: McTernan C.L. , Mijovic C.H. , Cockram C.S. , Barnett A.H.
Published: March 2003

The HLA‐DM genes (DMA and DMB) are encoded in the major histocompatibility complex (MHC) on human chromosome 6. They are involved in the loading of antigenic peptide onto class II molecules as part of the class II antigen‐processing and ‐presentation pathway. During a study of Oriental subjects (11 Chinese and 26 Japanese subjects), one Chinese subject was identified as having a new DMB allele using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). This was confirmed with sequencing. The new allele was found to have Glu (GAG) and Thr (ACT) at positions 144 and 179 respectively. This was a previously unpublished combination of polymorphic sites, and was submitted to GenBank and assigned the accession number AF072680, and named HLA‐DMB*0106 ( Note).
A MAGE‐A1 peptide presented to cytolytic T lymphocytes by both HLA‐B35 and HLA‐A1 molecules
Authors: Luiten R.M. , Demotte N. , Tine J. , Van Der Bruggen P.
Published: March 2003

Antigens encoded by melanoma antigen (MAGE) genes are of particular interest for cancer immunotherapy because of their strict tumoral specificity and because they are shared by many tumors. Antigenic peptide EADPTGHSY encoded by MAGE‐A1 and known to be presented by HLA‐A1 is currently being used in therapeutic vaccination trials. We report here that a cytotoxic T‐lymphocyte (CTL) clone, which is restricted by HLA‐B35, recognizes the same peptide and, importantly, lyses HLA‐B35 tumor cells expressing MAGE‐A1. This peptide can be presented to CTL by both HLA‐B*3501 and HLA‐B*3503 molecules, which are expressed by approximately 19% of Caucasians. These results infer that the current clinical use of peptide EADPTGHSY can now be extended to HLA‐B35 patients.
The nucleotide sequence of two new DP alleles, DPA1*02015 and DPB1*8401, identified in a Chinese subject
Authors: McTernan C.L. , Mijovic C.H. , Cockram C.S. , Barnett A.H.
Published: March 2003

The HLA‐DP genes (HLA‐DPA1 and ‐DPB1) are encoded by the major histocompatibility complex (MHC) on human chromosome 6. They are involved in the presentation of antigen to CD4+ T cells as part of the class II antigen‐presentation pathway. During a small study of Oriental subjects (11 Chinese and 26 Japanese subjects), one Chinese subject was identified as having numerous heterozygous sites within the second exon of both DPA1 and DPB1. These were further analysed using novel codon‐specific primers. Sequencing analysis using these primers determined the subject to have DPA1*0103/*02015 and DPB1*0501/*8401; these new alleles have been submitted to GenBank and assigned the accession numbers AF098794 and
AF077015, respectively (
Note*).
HLA‐B*4012: a new allele with unique serological features
Authors: Elsner H.‐A. , O’Brien B.J. , Bryan C.F. , Meyer J.A. , Diederich D.A. , Pierce G.E. , Lau M. , Terasaki P.I. , Blasczyk R.
Published: March 2003

We have defined the new allele HLA‐B*4012, which had been isolated from a black individual. It was initially recognized as a serologically unique allele when typing her father for renal transplantation. The HLA class I phenotype was A*0201,*6602; B*4001,*4012; Bw6; Cw*0304,*1505. Sequencing from exon 1 through intron 3 of B*4012 was performed. B*4012 is identical to B*4001 and B*4010 in exon 3, and in the 3′ part of exon 2, but it is unique in that exon 1 and the 5′ part of exon 2 are identical to B*1503, B*1509, B*1510, B*1518, B*1523, and B*1529. The generation of this allele is best explained by a recombination event in exon 2 (break point between nucleotides 205 and 222 from the beginning of the coding region) of B*4001 or B*4010 with one of these B*15 variants as a donor allele. Its unique serological feature (B48, B60, B70, and B72 reactivity) is consistent with the sequence data of its donor alleles ( Note).
New HLA‐DRB1* nucleotide sequence of Italian origin: HLA‐DRB1*13022
Authors: Martinetti M. , Pizzochero C. , Asti M. , Salvaneschi L.
Published: March 2003

High‐resolution polymerase chain reaction using sequence‐specific primer typing of the HLA‐DRB1 gene of an Italian patient waiting for unrelated bone marrow transplantation revealed a new allelic variant of HLA‐DRB1*13. Sequencing the exon 2 of DRB1* gene demonstrated a G→C transition at the nucleotide 216 resulting in a silent mutation at codon 72: CGG→CGC. The closest sequence was the HLA‐DRB1*1302 and the new allele was named HLA‐DRB1*13022. This variant was carried by the haplotype HLA‐A*24; Cw*0702; B*39; DRB1*13022; DRB3*0301; DQA1*0102; DQB1*0604 as demonstrated by a family study (
Note).
Identification of a novel allele, DRB1*1340, in two Brazilian individuals
Authors: Maciag P.C. , Junes K.S. , Villa L.L. , Petzl‐Erler M.L.
Published: March 2003

We identified a novel HLA‐DRB1 allele, named DRB1*1340 by the WHO HLA Nomenclature Committee, in two Brazilian individuals. Typing by polymerase chain reaction using sequence‐specific oligonucleotide probes (PCR‐SSOP) showed a DRB1*13 allele with an unusual hybridization pattern. DNA sequencing of both strands and comparison of the sequence with previously described DRB1 alleles revealed that the most similar allele is DRB1*1301, from which DRB1*1340 differs by a single nucleotide (T→A) in exon 2, at position 127, codon 47 (Phe→Tyr). The sequence received accession number AJ237964 from the EMBL database ( Note).
A new HLA‐DPA1 allele, DPA1*02016, identified in African‐American population
Authors: McDaniel D.O. , Nguyen C. , McDaniel L.S.
Published: March 2003

A new HLA‐DPA1 allele has been found in the African‐American population. This newly discovered type is homologous with the DPA1*02011 allele, except in codon 38 of the DPA1 sequence. The variant of DPA1 was detected by sequence‐specific oligonucleotide (SSO) typing, and specified by cloning and sequencing methods. GenBank accession number is AF165160. The WHO Nomenclature Committee has officially assigned the name DPA1*02016 (
Note).
Homozygous HLA‐G*0105N healthy individuals indicate that membrane‐anchored HLA‐G1 molecule is not necessary for survival
Authors: Castro M.J. , Morales P. , Rojo‐Amigo R. , Martinez‐Laso J. , Allende L. , Varela P. , Garcia‐Berciano M. , Guillen‐Perales J. , Arnaiz‐Villena A.
Published: March 2003

HLA‐G is expected to play an important role during fetal development. Recently, a healthy individual homozygous for the HLA‐G*0105N allele has been described, suggesting that HLA‐G expression was not essential for fetal survival. We now report studies of one family with five healthy siblings homozygous for HLA‐G*0105N, who had been normally delivered; three of these siblings were females who also had normal deliveries. In addition, HLA‐G*0105N cDNA has been fully sequenced, and normal G1 membrane anchored protein cannot be translated since after the codon 130 cytosine deletion (exon 3) a reading frameshift is observed leading to the existence of premature stop codon at position 189 (beginning of exon 4). Other protein isoforms (G2, G3 and G6), all containing the leader peptide and the α1 domain, are possible and their messenger mRNAs were found; any of these may undertake the necessary HLA‐G functions. Our data show that the membrane anchored HLA‐G molecule is not necessary in either mother or fetus for a normal pregnancy and survival. Also, individuals homozygous for HLA‐G*0105N are healthy and with no indications of immunodeficiency or autoimmunity (
Note).
Sequence‐based typing of HLA‐B: the B7 cross‐reacting group
Authors: Voorter C.E.M. , Van Der Vlies S.A. , Van Den Berg‐Loonen E.M.
Published: March 2003

The large number of polymorphic sites in the HLA‐B locus makes sequencing an efficient way of detecting and analysing them. Most polymorphic sites are located in the α1 and α2 domains of the molecule, encoded by exons 2 and 3 of the gene. An HLA‐B‐specific sequence‐based typing (SBT) strategy was designed for routine application identifying the polymorphic sites in these domains. Exons 2 and 3 were amplified separately using amplification primers located in intron 1, intron 2 and intron 3. Separate amplification of exons 2 and 3 resulted in short polymerase chain reacting (PCR) products and enabled a solid‐phase sequencing approach, which made correct assignment of heterozygous positions possible due to low background. A one‐step sequencing reaction was performed using fluorescent dye‐labelled sequencing primers. One forward sequencing reaction was performed for exon 2, whereas for exon 3, two forward sequencing reactions were needed using two different sequencing primers located in intron 2 and exon 3. The combined sequences of exon 2 and 3 were used for automatic alignment to an HLA‐B sequence database and automatic allele assignment. A total of 355 individuals with at least one allele belonging to the B7 cross‐reacting group (B7, 13, 22, 27, 40, 41, 42, 47, 48, 81 and 82) were typed for HLA‐B by SBT. In the B7 group 48 different alleles were identified, in the non‐B7 group a further 59 alleles were sequenced, 9 new alleles were identified. The sequencing strategy described has proven to be reliable and efficient for high‐resolution HLA‐B typing.