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  • 1
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An A-to-G transition in the second intron was the sole mutation detected in four Yupik Eskimo patients with salt-wasting congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. Allele-specific hybridization should be an efficient means of performing prenatal diagnosis of the disease in this highly inbred population.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A new mouse monoclonal antibody (MoAb) 4E, which detects an epitope shared by HLA-B locus antigens, together with the MoAb W6/32, detecting a common HLA, B, C, determinant, and the MoAb 4B, detecting HLA-A2 and A28, were used to isolate HLA-A and -B antigens in sequential immunoprecipitation. The HLA antigens obtained from metabolically labeled cell extracts of B-lymphoblastoid cell lines or from phytohemagglutinin (PHA) activated peripheral blood lymphocytes were compared by one-dimensional isoelectric focusing (1D-IEF). The IEF banding patterns obtained with native HLA antigens segregated in a family with HLA. Neuraminidase treatment of isolated antigens reduced the number of bands to one or two, simplifying the analysis of characteristic patterns. Thus, we have cataloged IEF banding patterns for the majority of the serologically recognized HLA-A and -B allotypes obtained from 57 unrelated American Caucasians. While no HLA-A locus or HLA-B locus specific banding patterns were observed, the HLA-A antigens had, in general, slightly higher pl values than the HLA-B antigens. HLA-C antigens could not be detected in this assay system. The polymorphism detected by IEF banding patterns was as extensive as the serologically detected polymorphism identified by classical HLA serology. Moreover, variants for some HLA allotypes could be detected by this method. In addition to previously recognized A2 variants, new variants were identified for HLA-A1, A26, and Bw44. Each A1 and Bw44 variant was associated with particular haplotypes. The HLA-A2 antigens occurred on 43 HLA haplotypes in the unrelated Caucasian population. Only one of each A2 variants was identified in this population.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 29 (1989), S. 117-120 
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The HLA-C encoded gene products display several characteristics which distinguish them from HLA-A and -B. The HLA-C antigens are poorly expressed on the cell surface, they display multiple proteins with different isoelectric points, and alloimmunization to HLA-C antigens is less common. To investigate whether the multiple products result from differential splicing of HLA-C gene transcripts, we have isolated a full-length cDNA clone encoding the Cw6 antigen. Class I antigens produced by the cDNA clone in transfected cells were of the same relative mass as those observed in the parental cells when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Isoelectric focusing (IEF) gel analysis of the cDNA translated products in transfectants revealed multiple IEF bands. All IEF bands detected in the transfectants were also found in the parental cells, indicating that the multiplicity of the C-locus products was not due to differential splicing of HLA-C gene transcripts, but was probably due to post-translational modification. Comparison of the sequences of C-locus alleles with those of A and B alleles did not show any apparent sequences which would generate multiple IEF bands. Comparison of the coding regions for seven HLA-C alleles and one HLA-C-related class I gene with available data for 15 HLA-A and 20 HLA-B alleles demonstrated several unique features for the HLA-C locus. Six sites in the extra cellular domains, three in al and three in a3, were unique. While the cytoplasmic (CP) domain of HLA-A and -B are almost identical, the CP of HLA-C alleles is unique. Similar unique features of HLA-C are also observed in the transmembrane domain, resulting in locus-specific residues between positions 295 and 300. The present study has ruled out differential mRNA splicing as a mechanism for the multiplicity of Cw6 antigens and demonstrated unique HLA-C locus sequences.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract HLA-B 13 antigens were isolated from metabolically labeled cell extracts from Caucasian and Oriental donors by means of an HLA-B13-specific monoclonal antibody, SY1. Ethnic differences in B13 molecules were identified by one-dimensional isoelectric focusing in which the pI of desialated Oriental B13 molecules was found to be higher than that of Caucasians. An additional Caucasian variant pattern was detected by peptide mapping using limited proteolysis in sodium dodecyl sulfate analyzed by polyacrylamide gel electrophoresis. Dual allotypic determinants for B13 molecules were recognized by two HLA-B13-specific monoclonal antibodies, SY1 and TU110, as determined by their sensitivity to complement-dependent cell lysis. Whereas the SY1 target epitope was shared by both ethnic B13 molecules, the two ethnic B13 molecules carried different Tu110 target structures. The Caucasian variant molecules appear to carry altered allotypic determinants which are recognized by both SY1 and Tu110 antibodies. This study suggests that the HLA-1313 private structure may comprise two epitopes recognized by SY1 and Tü 110 antibodies, respectively, whose binding sites overlap. Present data also suggest that the private determinant was already present when the two racial groups diverged, and thus the mutations which gave rise to the variants may be of relatively recent origin.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In a previous report we described how cross-immunizations of pairs of transgenic mice expressing different HLA class I antigens led to the production of antibodies directed exclusively at polymorphic epitopes. This was ascribed to self-tolerance of HLA that prevents immune responses to monomorphic epitopes and focuses responses on polymorphic ones. In the present report we extend our findings and demonstrate that immunizations of class I transgenic mice with HLA transfected mouse fibrosarcoma as well as with human lymphoblastoid cells also preferentially yield antibodies to polymorphic epitopes. This was the case whether or not immunizations were carried out across locus barriers [e.g., Tg (HLA-A *0201) or Tg (HLA-Cw*0301) transgenic mice immunized with HLA-B27 transfectants] or within the same locus [e.g., Tg (HLA-B*1302) transgenic mice immunized with HLA-B27 transfectants or B27-expressing lympho-blastoid cell]. Use of an extended immunization protocol with four or more booster injections favored antibodies of IgG isotype with affinities high enough to lyse normal peripheral blood lymphocytes (PBLs) in complement-dependent cytotoxicity assays and to immunoprecipitate HLA antigens. The specificities covered by the monoclonal antibodies (mAbs) could be either broad or narrow, depending on the genetic distance of the HLA antigens or alleles involved. For instance, a Tg(HLA-B*1302) transgenic mouse immunized with B27 produced both broad B7/B27-specific antibodies, Bw4-specific antibodies, and one antibody reacting with all B alleles except B13 and with some C alleles. On the other hand, a Tg(HLA-B*1302) transgenic mouse immunized with Bw47 transfectants responded narrowly with an antibody to Bw60 and Bw47. Thus it appears that by choosing appropriate recipient mice and closely related or more distant HLA antigens, antibodies of a programmed specificity can be generated.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It has previously been shown that a mouse monoclonal antibody, designated 4E, reacts with an epitope common to all HLA-B and -C antigens and those of the HLA-Aw19 cross-reactive group, namely, HLA-A29,-A30, -A31, -A32, -Aw33, and -Aw74. In order to pinpoint the amino acid residues which comprise the public specificity recognized by 4E, an HLA-A29 cDNA clone was isolated and its predicted amino acid sequence compared with those of other clonedHLA class I genes. The isolated HLA-A29 cDNA corresponded to the rarer of the twoA29 variant alleles,A29.1. Two amino acid residues of HLA-A29.1, gln-144 and arg-151, were found in all 24HLA-B andHLA-C alleles examined but were present in only one of 15HLA-A alleles for which sequence data are available. Importantly, this exceptional allele wasHLA-A32, another member of the HLA-Aw19 cross-reactive group. Gln-144 and arg-151 should be capable of jointly contributing to the binding site for 4E, as they are situated in successive alpha-helical subregions and are predicted to be juxtaposed in the three-dimensional HLA molecule. Four other residues in the first or second external domains of HLA-A29.1 (thr-9, leu-62, gln-63, and his-102) were unique among theHLA-A alleles, but none of these was found in corresponding positions ofHLA-B or-C alleles and thus failed to correlate with presence or absence of the 4E determinant. These observations are consistent with the notion that gln-144 and arg-151 define a determinant common to HLA-B, HLA-C, and the HLA-Awl9 cross-reactive group and the binding site of the monoclonal antibody 4E.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 47 (1997), S. 30-36 
    ISSN: 1432-1211
    Keywords: Key words Conservation ; HLA ; Introns ; Class I ; Locus-specific
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The protein-coding sequences of the major histocompatibility complex (MHC) genes are characterized by extraordinarily high polymorphism, apparently maintained by balancing selection, which favors diversity in the peptide-binding domains of the MHC glycoproteins. Here we report that the introns flanking the polymorphic exons of the human MHC class I loci HLA-A, -B, and -C genes have been relatively conserved and have become locus-specific apparently as a result of recombination and subsequent genetic drift, leading to homogenization within loci over evolutionary time. Thus, HLA class I genes have been shaped by contrasting evolutionary forces maintaining polymorphism in the exons and leading to conservation in the introns. This study provides the first extensive analysis of the introns of a highly polymorphic gene family.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A panel of blood donors and family members were studied for their electrophoretic patterns of C4, Cha and Rga antigens and HLA-A, B and C lymphocyte antigens. The electrophoretic variants of C4 were determined according to the method of O'Neill et a/.1 and Cha and Rga typing was carried out using ...
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Human genetics 〈Berlin〉 57 (1981), S. 307-311 
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The genetic polymorphism of the vitamin B12 transport protein transcobalamin II (TC II) was studied in a Caucasian population and in families. There are five codominent alleles of TC II which show a Mendelian mode of inheritance. No genetic linkage of TC II was found with gene loci for ADA, GLOI, Pi, HLA, AB0 and AK1. TC II like proteints could be detected on autoradiograph of PAGE in two patients with congenital homozygosity for functional TC II deficiency. These vitamin B12 binding proteins in the patients' serum were shown not to be normal R-proteins.
    Type of Medium: Electronic Resource
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