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Biomedical subjects

N Steiner

Publications and source records attributed to N Steiner.

At least 37 records · Page 2Linked to original sources

Novel HLA-B alleles, B*8201, B*3515 and B*5106, add to the complexity of serologic identification of HLA types.

Three class I alleles, B*8201, B*3515 and B*5106, have been described using DNA and cDNA sequencing. The B*8201 allele is most structurally related to B*5602, differing from it by 14 nucleotide substitutions resulting in 5 amino acid differences. The other two alleles, B*3515 and B*5106, differ from their most closely related HLA-B alleles by 2-3 nucleotide substitutions resulting in 1-2 amino acid substitutions, respectively. The majority of nucleotide substitutions marking these new alleles are observed in other HLA-B alleles suggesting that gene conversion and/or reciprocal recombination have created this diversity. All of the amino acid substitutions are predicted to alter the antigen binding site of the HLA-B molecule. The newly defined HLA-B allelic products were originally defined by their unusual serologic reactivity patterns. The B*8201 allelic product is serologically typed as a B "blank" or as a variant of B22 or B45. These patterns and the serologic reactivity of the other newly described allelic products are consistent with the protein sequence homology among specific HLA-B molecules. While serology remains a powerful tool for detecting HLA diversity, alleles generated by events resulting in the sharing of HLA sequence polymorphisms among alleles at a locus will continue to create complexity in the interpretation of typing results.

Alleles↗

Differences in peptide binding of DR11 and DR13 microvariants demonstrate the power of minor variation in generating DR functional diversity.

The influence of subtle HLA diversification on antigen binding was explored using murine L-cell transfectants expressing alleles in the DR11/DR13 family and a panel of peptides. The levels of binding among this family of DR microvariants were as diverse as the levels of binding among distantly related DR molecules. Even a single amino acid difference between allelic products had a profound effect on peptide binding. Specific amino acid substitutions, generated using site-directed mutagenesis to alter polymorphic residues at DR beta 32, 37, 57, 58, 67, 71, 86, demonstrated that a specific change within the context of a single DR molecule differed in its effect on the binding of specific peptides. In addition, a specific amino acid substitution had a differential effect on the binding level of a peptide to different DR molecules. Each polymorphic amino acid appeared to play a role in the binding of some peptide. Studies using the amino-terminal portion of the invariant chain CLIP peptide suggested that this peptide may offer varying degrees of competition in the binding of the cellular peptide pool in cells expressing different DR molecules. Finally, the results obtained with two strain-specific peptides from an immunodominant region of a malarial parasite show differential binding to two DR13 molecules, suggesting that immune pressure may promote parasite diversity. A dynamic interaction may exist between pathogens and the immune system shaping the HLA profile in a population. Thus even subtle diversification of the HLA molecules, possibly pathogen driven, can have a substantial effect on peptide binding and immune recognition.

Alleles↗

A description of a new DR allele, DRB1*1113.

We have discovered a previously unpublished HLA-DRB1 allele, observed in a patient (SB), his mother, and one sibling. The undefined allele gave sporadic positive reactions with sera in the DR52-associated group. SSOPH analysis utilizing both generic and group specific primers and probes also gave ambiguous results. SB typed clearly as a DRB1*0301 (paternal allele) but the DNA from SB also bound probes specific for DRB1*14 and DRB1*11. Sequencing revealed that the undefined allele was similar to a DRB1*14 allele with a segment of sequence found in DRB1*11 alleles. The patient was MLC reactive with donors who express DRB1*0301, *1401 and *0301, *11 and was nonreactive solely to DRB1*0301 (Dw3) homozygous typing cells.

Alleles↗

[Predictive factors of resistance to treatment of neuropathic pain].

The aim of this retrospective study was to examine factors related to symptomatic pain treatment in 992 hospitalized patients referred to the pain clinic. These patients accounted for 1440 different pains (1.5 pains/patient), of nociceptive (59%), or neuropathic (24%) origin, a combination of both (16%) and of unidentified (1%) origin. Patients resistant to therapy did not differ from nonresistant patients (62%) in terms of age, sex, or number of pains. Although recommended pharmacological treatments were pursued, the neuropathic origin of pain was a factor in resistance to treatment. Among the neuropathic pains resistant to treatment (42%) a central nervous origin is more frequently found. Resistance to pain was more frequently encountered after strokes, primitive tumor of the central nervous system or traumatic plexopathy, whereas peripheral lesions of the nervous system were more easily controlled by symptomatic treatment. This study shows that central neuropathic pain is more frequently associated with resistance to recommended pharmacological symptomatic treatments. This observation underlines the limits of conventional medical therapy.

Analgesia↗

Nonrandom T cell receptor usage in the allorecognition of HLA-DR1 microvariation.

Microvariation within the DR1 Ag family has created two DR molecules which differ only at beta-chain residues 85 (Val/Ala) and 86 (Gly/Val). TCR utilized by human alloproliferative T lymphocyte clones which can distinguish between these microvariants have been characterized by cDNA sequencing. The alpha- and beta-chain cDNA utilize a diverse set of variable (V) gene segments although the same V segment may be used by different individuals suggesting that V segment usage by the alloreactive T lymphocyte clones is nonrandom. There appears to be no difference in the repertoire of V segments utilized by T lymphocytes that preferentially recognize specific DR1 allelic products (DR(alpha,beta 1*0101) or DR(alpha,beta 1*0102)) and T lymphocytes that recognize both DR1 molecules. In contrast, the junctional regions of both alpha- and beta-chains are diverse in length and sequence although some common elements can be observed among TCR which share V gene segments. Two TCR which share V alpha and V beta gene segments differ in fine specificity for specific DR1 allelic products implicating the junctional regions of alpha- and beta-chains in the recognition of differentially bound peptides and/or in recognition of DR beta-chain residues 85 and 86. The stimulation of many diverse TCR by the limited allelic variation between DR(alpha,beta 1*0101) and DR(alpha,beta 1*0102) molecules suggests that the effect of DR microvariation on human immune responsiveness may be substantial.

Amino Acid Sequence↗

[Reproduction data in breeding mares, diseases and losses among suckling foals and preventive husbandry in German stud farms].

By means of a survey, the reproductive rate of mares and the foal losses in ten Thoroughbred, Saddlebred and Pony studs in Germany, mainly from North-Rhine-Westfalia, were collected and evaluated. Data for the survey were recorded for 1985-1990. The study also examined the hygienic management in the surveyed studs, and the morbidity rate of suckling foals was obtained for 1990. In addition to the survey questionnaire each stud was visited once. Two studs of each horse group were visited several times every week from March to August in order to evaluate as exactly as possible the husbandry and morbidity of the suckling foals. The main results were: The abortion rate in Thoroughbred and Saddlebred horses was about 4.5%, of the Ponies 1%. After the 299th day of gestation, fetal mortality ranged from 3.2 to 3.5%. In the more intensively observed studs 33% of Thoroughbred foals, 42% of Saddlebred foals and 11% of Pony foals became ill. Saddlebred foals were more frequently affected by respiratory disease while Thoroughbred and Pony foals were mainly afflicted by diarrhea. The scope of husbandry measures was broader and more intensive in the Thoroughbred and Pony studs compared to the Saddlebred studs.

Abortion, Veterinary↗

DQ polymorphism: an analysis of DQw4 alpha and beta membrane proximal regions.

The complete coding sequences of cDNA clones encoding the DQw4 alpha and beta polypeptides have been determined from two individuals expressing the DRw18(3), DQw4 haplotype. Although the first domain nucleotide sequence of the DQ alpha cDNA is very similar to the DQw2 alpha sequence, the sequence of the membrane proximal region (encoding second domain, transmembrane, and cytoplasmic segments) is more similar to DQw3-like alpha-gene sequences. The nucleotide sequence of the membrane proximal region of the DQw4 beta gene is identical to the DQw8 sequence in contrast to the extensive differences in the region encoding the first domains of these polypeptides. These sequences have been used to determine the evolutionary relationships among DQ alpha and beta genes.

Alleles↗

The DR3(w18),DQw4 haplotype differs from DR3(w17),DQw2 haplotypes at multiple class II loci.

The polymorphism of HLA class II molecules in man is particularly evident when comparisons between population groups are made. This study describes a DR3 haplotype commonly present in the American black population. Unlike the Northern European population, in which almost all DR3 individuals are DQw2, approximately 50% of DR3-positive American blacks express a DQw4 allelic product. This study characterizes the DR subregion of that haplotype. cDNA sequence analysis has revealed a DR beta gene which differs at several positions from previously described DR3 beta 1 genes. It is postulated that a gene-conversion-like event with a DRw52 beta gene as donor has generated some of these differences. The haplotype carries a DRw52a allele as defined by oligonucleotide hybridization studies. DNA restriction fragment analysis using a family and several unrelated individuals has allowed us to identify DR alpha and beta fragments associated with the DR3(w18),DQw4 haplotype. The most striking observation is that the DR3(w18),DQw4 haplotype differs from DR3(w17),DQw2 haplotypes at multiple class II loci. Several genetic mechanisms including reciprocal recombination, gene conversion, and point mutation were involved in generating the differences between these haplotypes. Once established, the DR3(w18),DQw4 haplotype appears to be relatively stable in the population.

Amino Acid Sequence↗

Polymorphism of the HLA-D region in American blacks. A DR3 haplotype generated by recombination.

The polymorphism of HLA class II molecules in man is particularly evident when comparisons between population groups are made. This study describes a DR3 haplotype commonly present in the American black population. Unlike the Northern European population in which almost all DR3 individuals are DQw2, approximately 50% of DR3-positive American blacks express a serologically undefined DQ allelic product. DNA restriction fragment analysis with the use of several unrelated individuals and an informative family has allowed us to identify unique DQ alpha- and beta-fragments associated with the DR3, DQw- haplotype. Based on fragment size, the DQ alpha genes of the DR3, DQw- and DRw8, DQw- haplotypes are similar as are the DQ beta genes of DR3, DQw-; DRw8, DQw-; and DR4, DQw- haplotypes. In addition, a DX beta gene polymorphism has been identified which is associated with some DR3 haplotypes including the American black DR3, DQw- haplotype. cDNA sequence analysis has revealed a DQw2-like alpha gene and a DQ beta gene which is similar to that previously described for a DR4, DQw- haplotype. It is postulated that recombination between DQ alpha and DQ beta genes and between the DQ and DX subregions has generated the various DR3 haplotypes and has played an important role in creating diversity in the HLA-D region.

Amino Acid Sequence↗

DR and DQ beta cDNA sequences associated with a DR2 haplotype.

Three cDNA clones encoding a DQ beta and two DR beta polypeptides have been isolated and sequenced from an American black individual expressing a DR2,DQw1 haplotype. The sequences of the cDNA clones are identical to previously described DR and DQ sequences from a DR2,Dw2 cell. The differences between DQw1-associated beta chains from DR2 and DR1 haplotypes is substantial, although a DQw1-specific sequence can be identified. The identical DQ and DR beta sequences found in unrelated individuals from different racial backgrounds suggests that class II structural polymorphism within the human population will be limited.

Amino Acid Sequence↗

Physiological assessment of severe chronic asthma in children.

Measurements of maximum expiratory flows and lung volumes were made on 6 occasions at weekly intervals in 14 children who were known over several years to have severe chronic asthma. 11 of the 14 had persistent lung hyperinflation and marked reduction in maximum expiratory flow rates although there was considerable variability in individual measurements. The other 3 usually had hyperinflation and reduced expiratory flow rates. 3 times daily measurements at home of peak expiratory flow rate did not contribute further to assessment. The results of the study indicated that one or two measurements of maximum expiratory flow calculated from a maximum expiratory flow volume curve and of lung volumes recorded in a body plethysmograph are of value in identifying the child with severe chronic asthma.

Adolescent↗

ABO blood groups and HBs AG subtypes and titers in healthy carriers.

The investigation covered 457 'healthy' HBsAg carriers detected following a screening by CEP. HBsAg in the sera of these subjects were subtyped by ID and titrated by CEP. The results obtained were analyzed according to the cases investigated. Differences were found between the distribution of blood groups among the normal unselected population and among 'healthy' carriers, where the incidence of AB subjects was much higher. The difference was more marked for the carriers of HBsAg/ad.

ABO Blood-Group System↗

Beclomethasone dipropionate aerosol for asthmatic children requiring maintenance oral steroid therapy.

A single-blind crossover trial comparing beclomethasone dipropionate by inhalation with prednisolone by mouth in the treatment of asthmatic children over a period of 10 months is reported. Fourteen children aged between nine and 16 years entered the trial. All had severe chronic asthma requiring maintenance oral prednisolone therapy in doses ranging from 2 to 7-5 mg/day. Beclomethasone dipropionate given by inhalation in a dose of 400 mug/day was found to be a satisfactory alternative to prednisolone by mouth for controlling the symptoms of asthma. During the course of this trial, three of the children died suddenly during acute exacerbations of asthma. All three had evidence of extensive inflammation of the tracheobronchial tree.

Adolescent↗