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1.
Anaesthesia ; 78(6): 747-757, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37096456

RESUMO

Vagus nerve stimulation is a well-established treatment option for patients with drug-resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri-operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services.


Assuntos
Epilepsia , Estimulação do Nervo Vago , Humanos , Estimulação do Nervo Vago/efeitos adversos , Epilepsia/etiologia , Estado Terminal , Arritmias Cardíacas , Anestesistas , Resultado do Tratamento
2.
Tissue Antigens ; 41(2): 72-80, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8475492

RESUMO

The HLA-A10 crossreacting group consists of the A25, A26, A34, A43 and A66 antigens. Here, we report allelic sequences for A43 and for 2 subtypes of both A26 and A34. Combining these results with previously determined sequences for A25, A26 and A66 enables molecular comparison of all the serologically defined A10 antigens. They form a closely related and well-defined group of alleles which may have originated with A*2601. Patterns of serological crossreactivity are correlated with sequence and a public epitope shared by A33 and members of the A10 family is localized to residues R62 and N63. The A*2501, A*4301 and A*6601 alleles appear to have derived from A*2601 by single gene conversion events with other HLA-A alleles. In the case of A*4301, the donor allele was probably an A29 allele as A*4301 has a small element of sequence in the alpha 1 helix (residues L62 and Q63) uniquely shared with A29. The chimaeric structure of A43 explains the reactivity of A43 molecules with both A10 and A29 alloantisera. The rare Oriental variant of A26 (A26v*) is encoded by an allele (A*2602) that differs from A*2601 by a unique nucleotide substitution which changes aspartate to asparagine at position 116 in the floor of the peptide binding groove. Thus A*2602 is a functionally distinct allele that originated by a point mutation. Alleles encoding A34 and A66 antigens are found to have very similar structures, explaining the difficulty in their serological definition.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Genes MHC Classe I , Antígenos HLA-A/genética , Isoanticorpos/imunologia , Alelos , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular Transformada , Sequência Consenso , Reações Cruzadas , Variação Genética , Antígenos HLA-A/imunologia , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico
3.
J Immunol ; 149(10): 3411-5, 1992 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-1431115

RESUMO

Alleles encoding five HLA-A and B Ag characteristic of black populations have been isolated and their nucleotide sequences determined. In each case, the "black" allele is similar to a "related" allele found in caucasoid populations. The primary differences between these pairs of alleles are localized clusters of nucleotide substitutions that change two to five residues of the Ag recognition site. The pattern of differences indicates that the pairs of black and caucasoid alleles diverged primarily as a result of interallelic conversion events.


Assuntos
Alelos , População Negra/genética , Conversão Gênica , Antígenos HLA-A/genética , Antígenos HLA-B/genética , África , Sequência de Aminoácidos , Humanos , Dados de Sequência Molecular , Estados Unidos , População Branca/genética
4.
Tissue Antigens ; 38(4): 152-64, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1801305

RESUMO

Sixty-five DNA sequences from human and chimpanzee major histocompatibility complex class I loci were searched for statistical evidence of past gene conversion. Twenty-four potential conversions were detected; they were distributed across both variable and conserved portions of the gene, and involved both classical and non-classical loci. The majority spanned less than 100 bp, comparable in length to the conversions observed in spontaneous mutations in mice. Both within-locus and between-locus conversions were observed. Certain areas of the antigen recognition site appear to have been the target for multiple conversion events. The implications of these findings for the evolution of the class I multigene family are discussed.


Assuntos
Conversão Gênica , Genes MHC Classe I , Complexo Principal de Histocompatibilidade , Pan troglodytes/genética , Alelos , Animais , Sequência de Bases , Sequência Consenso , Troca Genética , DNA/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos de Histocompatibilidade/genética , Humanos , Dados de Sequência Molecular , Família Multigênica , Pan troglodytes/imunologia , Filogenia , Alinhamento de Sequência
5.
Am J Clin Pathol ; 93(6): 754-9, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2189291

RESUMO

To determine the utility of Southern blot analysis for fine-needle aspiration samples, the authors prospectively analyzed immunoglobulin, T-cell receptor, c-myc, and bcl-2 gene rearrangements in 27 cases of known or suspected lymphoma. Adequate DNA for analysis was obtained from 20 of 27 cases (74%), including 18 of 22 (82%) with non-Hodgkin's lymphoma (NHL). Patients whose tumors showed sclerosis, cellular degeneration, or necrosis yielded inadequate DNA. Of the 18 NHLs with successful Southern blot studies, 17 tumors had a B-cell lineage and one was an adult T-cell leukemia/lymphoma; clonal integration of the human T-cell leukemia virus I (HTLV-I) genome was present in the latter case. Four cases had bcl-2 rearrangements and two had c-myc rearrangements. One patient with follicular small cleaved cell NHL that evolved to a small noncleaved cell NHL had coexisting bcl-2 and c-myc rearrangement in the aspiration specimen of the high-grade NHL, suggesting sequential bcl-2 and c-myc activation during the tumor's progression. Southern blot analysis is a useful technique for establishing tumor cell lineage, clonality, and the presence of oncogene rearrangements in fine-needle aspiration specimens of NHL.


Assuntos
Linfoma não Hodgkin/patologia , Adulto , Biópsia , Biópsia por Agulha , Southern Blotting , DNA de Neoplasias/análise , Diagnóstico Diferencial , Feminino , Rearranjo Gênico do Linfócito B , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Linfonodos/patologia , Linfoma não Hodgkin/genética , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Prospectivos , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-myc , Receptores de Antígenos/análise
6.
J Immunol ; 144(9): 3619-29, 1990 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-2329283

RESUMO

The MHC contains many class I genes other than those known to present peptides to T lymphocytes. These additional class I genes vary between species and their functions are unknown. Genes involved in Ag presentation, HLA-A,B,C in humans, are highly diverse whereas other class I genes are of much more limited diversity. We have studied alleles of a gene, HLA-AR, that is closely linked and structurally related to HLA-A; properties consistent with these two loci having been formed by a gene duplication. Compared to HLA-A the diversity in HLA-AR is much less, and does not focus on residues of a putative Ag recognition site. However, the structure of HLA-AR alleles closely resembles those encoding Ag-presenting molecules, although the presence of one or two deleterious mutations prevents these alleles being active in Ag presentation. These results suggest HLA-AR derives from an Ag-presenting locus that became inactivated, possibly as a result of positive natural selection due to changing demands on T cell immunity. Thus absence of diversity may sometimes correlate with loss rather than preservation of function in class I MHC genes.


Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Complexo Principal de Histocompatibilidade , Alelos , Sequência de Aminoácidos , Células Apresentadoras de Antígenos/imunologia , Sequência de Bases , Evolução Biológica , Clonagem Molecular , Humanos , Íntrons , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Família Multigênica , Sinais Direcionadores de Proteínas/imunologia
7.
Proc Natl Acad Sci U S A ; 87(7): 2833-7, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2320591

RESUMO

A method for cloning full-length HLA-A,B cDNA (1.1 kilobases) by using the polymerase chain reaction (PCR) is described. Six HLA-A,B alleles (HLA-A2, -A25, -B7, -B37, -B51, and -B57) were cloned, and their structures were determined. Multiple PCR clones for each allele were sequenced to obtain both an accurate consensus sequence and an "authentic" clone having that sequence. Sequences from 50 clones encoding five different alleles permit assessment of the frequency and nature of PCR-produced errors. These include recombinations, deletions, and insertions in addition to point substitutions. Authentic clones were obtained at a frequency of between 30% and 70%, and analysis of three or four clones generally should be sufficient for characterization of an allele.


Assuntos
Clonagem Molecular/métodos , Genes MHC Classe I , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Alelos , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Transformação Celular Viral , Éxons , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Homologia de Sequência do Ácido Nucleico
9.
J Immunol ; 142(11): 3937-50, 1989 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-2715640

RESUMO

The nucleotide sequences encoding 14 HLA-A,B,C and 5 ChLA-A,B,C molecules have been determined. Combining these sequences with published data has enabled the polymorphism in 40 HLA-A,B,C and 9 ChLA-A,B,C alleles to be analyzed. Diversity is generated through assortment of point mutations by recombinational mechanisms including gene and allelic conversions. The distribution and frequency of silent and replacement substitutions indicate that there has been positive selection for allelic diversity in the 5' part of the gene (exons 1 to 3) and for allelic homogenization and locus specificity in the 3' part of the gene (exons 4 to 8). These differences may correlate with the lengths of converted sequences in the two parts of the gene and frequency of the CpG dinucleotide. Locus-specific divergence of HLA-A,B, and C demonstrates that recombinational events involving alleles of a locus have been more important than conversion between loci. This contrasts with the predominance of gene conversion events in the evolution of mutants of the H-2Kb gene. However, a striking example of gene conversion involving HLA-B and C alleles of an oriental haplotype has been found. Comparison of human and chimpanzee alleles reveals extensive sharing of polymorphisms, confirming that diversification is a slow process, and that much of contemporary polymorphism originated in ancestral primate species before the emergence of Homo sapiens. There is less polymorphism at the HLA-A locus compared to HLA-B, with greater similarity also being seen between HLA-A and ChLA-A alleles than between HLA-B and ChLA-B alleles. Although greater diversity is seen in the 5' "variable" exons of HLA-B compared to HLA-A, there is increased heterogeneity in the 3' "conserved" exons of HLA-A compared to HLA-B.


Assuntos
Alelos , Genes MHC Classe I , Antígenos HLA/genética , Polimorfismo Genético , Animais , Sequência de Bases , Conversão Gênica , Ligação Genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Humanos , Dados de Sequência Molecular , Pan troglodytes/genética , Recombinação Genética , Homologia de Sequência do Ácido Nucleico
10.
J Immunol ; 142(1): 306-11, 1989 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-2909619

RESUMO

Genes encoding the serologically cross-reactive HLA-B51 and HLA-Bw52 molecules were isolated and the exons sequenced. HLA-B51 genes obtained from Caucasian and Oriental individuals were identical. HLA-Bw52 differs from HLA-B51 by four nucleotide substitutions in exon 2 encoding the alpha 1 domain. These comprise one isolated silent substitution in codon 23 and a cluster of three coding substitutions in codons 63 and 67. Amino acid substitutions of N----E at position 63 and F----S at position 67 are the only differences between HLA-B51 and HLA-Bw52 and these residues are postulated to form HLA-B51 specific epitopes. HLA-B51 could have been formed from HLA-Bw52 by the combination of a genetic exchange with HLA-B8 and a point mutation. Similarity of HLA-B51 and HLA-Bw52 with HLA-Bw58 suggest they also share a common ancestor.


Assuntos
Genes MHC Classe I , Antígenos HLA-B/genética , Sequência de Aminoácidos , Animais , Composição de Bases , Sequência de Bases , Clonagem Molecular , Reações Cruzadas , Antígenos HLA-B/imunologia , Antígenos HLA-B/isolamento & purificação , Antígeno HLA-B51 , Antígeno HLA-B52 , Humanos , Camundongos , Dados de Sequência Molecular , Conformação Proteica , Homologia de Sequência do Ácido Nucleico
12.
Nature ; 335(6187): 268-71, 1988 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-3412487

RESUMO

Major histocompatibility complex (MHC) glycoproteins bind processed fragments of proteins and present them to the receptors of T lymphocytes. The extraordinary polymorphism of class I MHC molecules in man (HLA-A, B and C) and mouse (H-2 K, D and L) poses many questions concerning their diversification and evolution. Comparison of allelic sequences within a species suggests diversity is generated by the assortment of point mutations into varied combinations by mechanisms of recombination and gene conversion. We have now compared class I MHC alleles in two closely related species: humans (Homo sapiens) and chimpanzees (Pan troglodytes). Chimpanzee homologues of HLA-A, HLA-B and a non-classical gene have been identified. No features distinguishing human and chimpanzee alleles could be found. Individual HLA-A or B alleles are more closely related to individual chimpanzee alleles than to other HLA-A or B alleles. These results show that a considerable proportion of contemporary HLA-A and B polymorphism existed before divergence of the chimpanzee and human lines. The stability of the polymorphism indicates that hyper-mutational mechanisms are not necessary to account for HLA-A, B and C diversity.


Assuntos
Genes MHC Classe I , Pan troglodytes/genética , Polimorfismo Genético , Alelos , Animais , Sequência de Bases , Bovinos , Humanos , Camundongos , Coelhos , Homologia de Sequência do Ácido Nucleico , Suínos
13.
J Immunol ; 141(2): 642-51, 1988 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-3133413

RESUMO

Two cDNA cloned from a Hereford cow B cell line (BL-3) have allowed the determination of the complete coding region for two class I molecules encoded by the bovine MHC (BoLA). The predicted protein sequences have all the features expected of expressed class I molecules that present peptide Ag to cytotoxic T cells. Comparison with class I molecules from other species strongly suggests these cDNA are derived from different genes and provides evidence for the existence of a second expressed class I BoLA locus. The BoLA proteins show greater similarity to HLA than to H-2 molecules, correlating with the cross-reactions of W6/32 and other murine anti-HLA-A,B,C mAb with BoLA molecules. The basis for the W6/32 epitope and the preferential association of H-2 class I H chains with bovine beta 2-m is examined.


Assuntos
Clonagem Molecular , DNA/isolamento & purificação , Genes MHC Classe I , Antígenos de Histocompatibilidade/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Membrana Celular/metabolismo , Reações Cruzadas , Feminino , Antígenos HLA/imunologia , Antígenos de Histocompatibilidade/imunologia , Antígenos de Histocompatibilidade/isolamento & purificação , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Camundongos , Dados de Sequência Molecular , Sinais Direcionadores de Proteínas/genética , Sinais Direcionadores de Proteínas/isolamento & purificação , Homologia de Sequência do Ácido Nucleico , Microglobulina beta-2/genética
14.
Proc Natl Acad Sci U S A ; 85(11): 4005-9, 1988 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3375250

RESUMO

Diversity in 39 HLA-A, -B, and -C molecules is derived from 20 amino acid positions of high variability and 71 positions of low variability. Variation in the structurally homologous alpha 1 and alpha 2 domains is distinct and may correlate with partial segregation of peptide and T-cell receptor binding functions. Comparison of 15 HLA-A with 20 HLA-B molecules reveals considerable locus-specific character, due primarily to differences at polymorphic residues. The results indicate that genetic exchange between alleles of the same locus has been a more important mechanism in the generation of HLA-A, -B, and -C diversity than genetic exchange events between alleles of different loci.


Assuntos
Antígenos HLA/genética , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Evolução Biológica , Genes , Humanos , Dados de Sequência Molecular , Polimorfismo Genético , Conformação Proteica , Recombinação Genética
15.
Immunogenetics ; 27(4): 281-7, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3257938

RESUMO

Adrenal 21-hydroxylase deficiency is strongly associated with HLA-Bw47. This rare HLA allele and the HLA-B13 allele are both found in positive genetic linkage disequilibrium with HLA-A3, -Cw6, -DR7 and also display serological cross-reactivity. To investigate the relationship between these two alleles at the structural level, the nucleotide sequences of the HLA-B13 and HLA-Bw47 genes have been determined. They differ by 28 nucleotides, resulting in 14 amino acid substitutions: 5 in the alpha 1 domain, 8 in the alpha 2 domain, and 1 in the transmembrane region. Comparison of HLA-Bw47 nucleotide sequence with other HLA-B sequences shows a segment of 228 bp identical with B44 in the alpha 1 domain and a segment of 218 bp identical with B27 in the alpha 2 domain, but only a 91 bp segment of identity with B13 in the alpha 1 domain. The complex pattern of substitutions and their degree of divergence indicate that HLA-B13 and HLA-Bw47 alleles are not related by a simple mutational event.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Antígenos HLA/genética , Antígenos HLA-B , Esteroide Hidroxilases/deficiência , Alelos , Sequência de Aminoácidos , Sequência de Bases , Reações Cruzadas , Antígenos HLA/imunologia , Antígeno HLA-B13 , Humanos , Ponto Isoelétrico , Dados de Sequência Molecular , Homologia de Sequência do Ácido Nucleico
16.
J Immunol ; 139(3): 936-41, 1987 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-3496393

RESUMO

The genetic events that produce diversity in class I MHC genes and proteins has been investigated by using a family of closely related HLA-A alleles. Five genes coding for HLA-A2.2Y, HLA-A2.3, and HLA-Aw68.2 have been isolated. Exon sequences are compared with the known sequences for HLA-A2.1, HLA-A2.2F, HLA-A2.4, HLA-Aw68.1, and HLA-Aw69. Pairwise comparison of the eight unique sequences shows that point mutation, reciprocal recombination, and gene conversion have all contributed significantly to the diversification of this family of alleles. These results are compared with those of other studies that have emphasized the role of gene conversion. A predominance of coding substitutions in the alpha 1 and alpha 2 domains is found, consistent with positive selection for polymorphism being a major factor in the fixation of these alleles. In the three cases examined, genes for phenotypically identical proteins gave identical nucleotide sequences, indicating that most, if not all, of the class I polymorphism is detectable by immunological methods. The apparent stability of the sequences suggests that the events generating some of the alleles occurred before the origin of modern Homo sapiens.


Assuntos
Antígenos HLA/genética , Complexo Principal de Histocompatibilidade , Alelos , Sequência de Aminoácidos , Sequência de Bases , DNA Recombinante , Éxons , Genes , Antígenos HLA/classificação , Antígeno HLA-A2 , Humanos , Modelos Genéticos , Polimorfismo Genético , Homologia de Sequência do Ácido Nucleico
17.
J Immunol ; 137(11): 3671-4, 1986 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-2431040

RESUMO

All HLA-B locus molecules have either the Bw4 or Bw6 epitopes. In addition, the Bw4 epitope is found on HLA-Aw23, Aw24, and A32, and Bw6 is also found on HLA-Cw3. The structural basis for these determinants and the evolution of their distribution among products of the HLA-B locus has been a long standing puzzle. To identify residues that may be involved in these determinants, we have cloned a gene for A32 and sequenced the protein encoding exons. Comparison of the predicted protein sequence with other HLA-A,B,C sequences identified residues 79 through 83 of the alpha 1 domain as having a pattern of polymorphic substitution that correlates with the presence and absence of the Bw4 and Bw6 epitopes.


Assuntos
Antígenos HLA/imunologia , Antígenos HLA-A/imunologia , Sequência de Aminoácidos , Clonagem Molecular , Epitopos , Genes , Antígenos HLA/genética , Antígenos HLA-A/genética , Antígenos HLA-B , Humanos , Polimorfismo Genético
19.
Nature ; 307(5952): 609-13, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6320017

RESUMO

The protein oligomer forming the gap junction channel has been analysed in two Ca2+-sensitive states by electron microscopy of membranes in frozen aqueous solutions. Switching between states occurs by a small cooperative rearrangement involving tilting of the subunits, which may be responsible for the effect of Ca2+ on channel permeability in vivo.


Assuntos
Junções Intercelulares/ultraestrutura , Proteínas de Membrana , Animais , Cálcio/fisiologia , Conexinas , Junções Intercelulares/fisiologia , Fígado/ultraestrutura , Ratos , Difração de Raios X
20.
J Cell Biol ; 97(5 Pt 1): 1459-66, 1983 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-6630291

RESUMO

Rat liver gap junctions were isolated in Ca2+-free media and analyzed in controlled environments by x-ray diffraction of partially oriented pellets. Different treatments of the same preparations were compared. The ordered hexagonal lattices gave rise to detail that was sensitive to low Ca2+ concentrations (0.05 mM), but not to Mg2+ (up to 0.16 mM) or pH (between 6.0 and 8.0). The major Ca2+-mediated responses were reductions in the intensity of the (1, 0) peak and in the off-equatorial contributions to the (2, 1) peak, and changes of scale equivalent to a decrease (approximately 2%) in lattice dimension, but an increase (approximately 4%) in the dimension perpendicular to the lattice. A simple structural interpretation of these findings is that Ca2+ induces the subunits of the channel-forming assembly, the connexon, to align more nearly parallel to the channel, thereby causing the connexon to become slightly longer and more radially compact. The rearrangement is of the same nature as one found under less physiological circumstances by electron microscopy (Unwin, P. N. T., and G. Zampighi, 1980, Nature (Lond.)., 283:545-549), and may be part of a coordinated mechanism by which the channel closes.


Assuntos
Cálcio/farmacologia , Junções Intercelulares/ultraestrutura , Animais , Concentração de Íons de Hidrogênio , Junções Intercelulares/efeitos dos fármacos , Fígado/ultraestrutura , Magnésio/farmacologia , Microscopia Eletrônica , Ratos , Ratos Endogâmicos , Difração de Raios X
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