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1.
Artigo em Inglês | MEDLINE | ID: mdl-38529209

RESUMO

Background: Hip resurfacing arthroplasty (HRA) provides an attractive alternative to total hip arthroplasty (THA) for the management of osteoarthritis in younger, more active patients; however, concerns persist over complications specific to HRA. The aims of this systematic review were to assess the documented long-term survival rates of the metal-on-metal BIRMINGHAM HIP Resurfacing System at a follow-up of at least 10 years and to analyze the functional outcomes and cause of failures. Methods: A systematic review was undertaken of all published cohort studies available in the MEDLINE, Cochrane, Embase, and PubMed research databases up to December 2021, as recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction was focused on survival rates, causes of failure, and functional outcomes. Survival estimates at 10 years were pooled in a meta-analysis, with each series weighted by its variance. Causes of failure were presented as a percentage of the pooled revisions. Results: A total of 11 studies were identified, encompassing 3,129 cases. Across the 9 studies that had reported a mean follow-up, the mean follow-up was 11.7 years (range, 9.55 to 13.7 years). We found a pooled 10-year survival rate of 95.5% (95% confidence interval, 93.4% to 97.1%). There were 149 revisions among the studies (range, 4 to 38 revisions per study), a rate of 4.8% of the total procedures performed. The 2 main causes of revision were aseptic loosening (20.1% of revisions) and adverse reactions to metal debris (20.1%). There were no revisions for dislocation. Of the studies that reported preoperative functional scores, all reported significant improvement in mean scores postoperatively except for 1 study in which the mean Tegner activity score did not significantly improve. Conclusions: When performed for appropriate indications, patients undergoing an HRA with use of the BIRMINGHAM HIP Resurfacing System can expect good implant survivorship at 10 years with acceptable functional results and low rates of dislocation and infection. This systematic review, however, confirms concerns regarding adverse reactions to metal debris as a leading cause of revision. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

2.
BMJ Mil Health ; 169(6): 493-498, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34848491

RESUMO

BACKGROUND: 'Non-compressible' haemorrhage is the leading cause of preventable battlefield death, often requiring surgical or radiological intervention, which is precluded in the pre-hospital environment. One-fifth of such bleeds are junctional and therefore potentially survivable. We examine the use of the Abdominal Aortic Junctional Tourniquet - Stabilized (AAJTS) among UK Combat Medical Technicians (CMTs) as a device to control junctional haemorrhage with external compression of the abdominal aorta-compression of junctional haemorrhage previously considered 'non-compressible.' This follows animal studies showing that the AAJTS achieves control of haemorrhage and improves physiological parameters. METHODS: CMTs were selected and applied the AAJTS to each other following a 1-hour training package. A consultant radiologist-operated hand-held ultrasound monitored flow changes in the subjects' common femoral artery. CMTs were then surveyed for their opinions as to utility and function. RESULTS: 21 CMTs were screened and 17 CMTs participated with 34 total applications (16 day and 18 low-light). 27/34 (79%) achieved a successful application. The median application time was 75 s in daylight and 57 s in low-light conditions. There was no significant difference in Body Mass Index (p=0.23), median systolic blood pressure (p=0.19), nor class of CMT (p=0.10) between successful and unsuccessful applications. Higher systolic blood pressure was associated with longer application times (p=0.03). Users deemed the device easy to use (median score 4.4 on a 5-point Likert scale). CONCLUSION: CMTs can use AAJTS successfully after a 1-hour training session in the majority of applications. Application was successful in both daylight and low-light conditions. Self-reported usability ratings were high.


Assuntos
Aorta Abdominal , Torniquetes , Animais , Humanos , Médicos de Combate , Hemorragia/terapia , Hemorragia/etiologia
3.
Injury ; 53(12): 4114-4122, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36333155

RESUMO

AIM: Some amputees are unable to adequately ambulate using conventional socket prosthetics, osseointegrated prosthetics have been described as an alternative strategy in this patient group. This paper aims to assess the effect of osseointegrated prosthetics, commonly simply referred to as osseointegration, in transfemoral amputees on health-related quality of life and cost analysis. METHODS: Two centre analysis of patients receiving transcutaneous femoral osseointegration using The Osseointegration Group of Australia Osseointegration Prosthetic Limb (OGAP-OPL) implant. Retrospective health utility and cost analysis of prospectively collected patient reported health outcome data. Osseointegration cost was compared with the yearly cost of a poorly fitting conventional prosthetic determining cost/Quality Adjusted Life Year. RESULTS: Eighty amputees received osseointegration. Mean age was 39 years (range 20-57) and 66% were male (n = 53). The majority of subjects underwent unilateral (n = 62, 77.5%) rather than bilateral surgery (n = 18, 22.5%). Trauma was the most common indication (n = 59, 74%). Maximum follow up was 10.5-years. Mean preoperative EQ5D HUV in pooled data was 0.64 (SEM 0.025) increasing to 0.73 (0.036) at 5-years and 0.78 (0.051) at 6 years with continued improvement up to 10.5-years. In subgroup analysis those with a starting EQ5D HUV <0.60 reached a cost/QALY of <£30,000 at 5-years postoperatively and show statistically significant improvement in EQ5D HUV. The UK military experience was wholly positive with a mean starting EQ5D HUV of 0.48 (0.017) with significant (p < 0.05) improvement in EQ5D HUV at each time point and a resultant reducing cost/QALY at each time point being £28,616.89 at 5 years. CONCLUSION: There is both a quality of life and financial argument in favour of osseointegration in select patients with above transfemoral amputations. In those unable to mobilise satisfactorily with traditional prostheses and a pre-intervention score of <0.60, a consistent cost effectiveness and quality of life benefit can be seen. Such patients should be considered for osseointegration as these patients reap the maximum benefit and cost effectiveness of the device. This evidence lends strongly to the debate advocating the use of osseointegration through centrally funded resources, including the NHS.


Assuntos
Amputados , Membros Artificiais , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , Osseointegração , Qualidade de Vida , Análise Custo-Benefício , Estudos Retrospectivos , Desenho de Prótese , Resultado do Tratamento , Amputação Cirúrgica
4.
BMJ Mil Health ; 167(4): 275-279, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33472811

RESUMO

INTRODUCTION: The positive impact of advances in military medicine and the influence these have had on civilian medical practice have been well documented throughout history: this review will be looking specifically between 2009 and 2020. AIMS: Review of innovations that have been implemented or have influenced civilian practice within the areas of trauma, disease outbreak management and civilian systems between 2009 and 2020. This review will also aim to explore the impact that working with or within the military can have on individuals within civilian healthcare systems and the future challenges we face to maintain skills. RESULTS: Using a narrative approach to this review, we found that there have been numerous changes to trauma management within the UK, based on military practice and research during conflict, which have improved survival outcomes. In addition, the use of niche military skills as part of a coordinated response, during both internal and international disease outbreaks, are thought to have supported civilian systems enabling an efficient and prolonged response. Furthermore, adaptation of military concepts and their application to the NHS through consultant-led prehospital teams, centralisation of specialties in the form of major trauma centres and the introduction of guidelines to manage 'major incidents and mass casualty events' in 2018 have improved patient outcomes. CONCLUSION: From 2009 to 2020, lessons learnt from the British and other nations' militaries have been integrated into UK practice and have likely contributed to improved outcomes in the management of major incidents both nationally and internationally.


Assuntos
Incidentes com Feridos em Massa , Medicina Militar , Militares , Humanos , Centros de Traumatologia , Reino Unido/epidemiologia
5.
Injury ; 52(5): 1221-1226, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33454061

RESUMO

Terrorist attacks have become more acute, less predictable and frequently involve use of explosives and gunfire to inflict mass casualty to civilians. Resource demand has been reported in Role 3 Medical Facilities but the continued resource required to manage blast and ballistic injuries has not been quantified. This study aimed to assess the resource required for blast and ballistic injuries at the United Kingdom's Role 4 Medical Facility. Military patients admitted to the Queen Elizabeth Hospital (Role 4 Medical Facility) from Afghanistan with blast or ballistic injuries during the 2012 calendar year were retrospectively reviewed. Injury pattern, theatre resource, length of stay and cost analysis were performed. This study included 99 blast and 53 gunshot wound (GSW) patients. Blast patients were more likely to suffer polytrauma than GSW (53% vs 23%), underwent more surgical procedures and utilized double the theatre time. Blast injury patients had a longer length of stay in hospital. The average cost per patient for blast patients was double that of the GSW injury cohort. The Queen Elizabeth experience represents a continuous flow of severely injured military casualties whilst managing concurrent civilian trauma over a long period. This workload has encouraged systematic advancements in managing high numbers of injured patients from point of wounding to rehabilitation. Distribution of resource, theatre planning and multi-disciplinary team working are critical in effectively managing Major Incidents such as terror attacks. Drawing on previous Role 4 Medical Facility experience can aid UK hospitals in terms of strategy and resource distribution.


Assuntos
Traumatismos por Explosões , Militares , Ferimentos por Arma de Fogo , Afeganistão , Traumatismos por Explosões/epidemiologia , Traumatismos por Explosões/cirurgia , Explosões , Humanos , Estudos Retrospectivos , Reino Unido/epidemiologia , Ferimentos por Arma de Fogo/epidemiologia , Ferimentos por Arma de Fogo/cirurgia
6.
J R Nav Med Serv ; 101(2): 129-33, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26867412

RESUMO

Expedition medical planning is integral in ensuring participant safety and maximising the likelihood of achieving the expedition aims. The task of producing a medical plan will often fall to a medical officer of limited experience. The aim of this article is to provide a concise, practical guide to aid junior medical officers (MOs) in forming a robust and pragmatic medical plan.


Assuntos
Expedições , Medicina Selvagem , Humanos
7.
Cochrane Database Syst Rev ; (3): CD004348, 2006 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-16856042

RESUMO

BACKGROUND: Treating the world's 40.3 million persons currently infected with HIV/AIDS is an international responsibility that involves unprecedented organizational challenges. Key issues include whether care should be concentrated or decentralized, what type and mix of health workers are needed, and which interventions and mix of programs are best. High volume centres, case management and multi-disciplinary care have been shown to be effective for some chronic illnesses. Application of these findings to HIV/AIDS is less well understood. OBJECTIVES: Our objective was to evaluate the association between the setting and organization of care and outcomes for people living with HIV/AIDS. SEARCH STRATEGY: Computerized searches from January 1, 1980 to December 31, 2002 of MEDLINE, EMBASE, Dissertation Abstracts International (DAI), CINAHL, HealthStar, PsychInfo, PsychLit, Social Sciences Abstracts, and Sociological Abstracts as well as searches of meeting abstracts and relevant journals and bibliographies in articles that met inclusion criteria. Searches included articles published in English and other languages. SELECTION CRITERIA: Articles were considered for inclusion if they were observational or experimental studies with contemporaneous comparison groups of adults and/or children currently infected with HIV/AIDS that examined the impact of the setting and/or organization of care on outcomes of mortality, opportunistic infections, use of HAART and prophylaxis, quality of life, health care utilization, and costs for patient with HIV/AIDS. DATA COLLECTION AND ANALYSIS: Two authors independently screened abstracts to determine relevance. Full paper copies were reviewed against the inclusion criteria. The findings were extracted by both authors and compared. The 28 studies that met inclusion criteria were too disparate with respect to populations, interventions and outcomes to warrant meta-analysis. MAIN RESULTS: Twenty-eight studies were included involving 39,776 study subjects. The studies indicated that case management strategies and higher hospital and ward volume of HIV-positive patients were associated with decreased mortality. Case management was also associated with increased receipt of ARVs. The results for multidisciplinary teams or multi-faceted treatment varied. None of the studies examined quality of life or immunological or virological outcomes. Healthcare utilization outcomes were mixed. AUTHORS' CONCLUSIONS: Certain settings of care (i.e. high volume of HIV positive patients) and models of care (i.e. case management) may improve patient mortality and other outcomes. More detailed descriptions of care models, consistent definition of terms, and studies on innovative models suitable for developing countries are needed. There is not yet enough evidence to guide policy and clinical care in this area.


Assuntos
Administração de Caso/organização & administração , Infecções por HIV/terapia , Equipe de Assistência ao Paciente/organização & administração , Terapia Assistida por Computador/organização & administração , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/terapia , Infecções por HIV/mortalidade , Humanos
8.
J Sports Sci ; 19(2): 117-27, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11217010

RESUMO

Information--movement coupling is a fundamental concept, integral to theorizing on the coordination of goal-directed activity in ecological psychology. In this paper, we examine the implications of this concept for the design of experimental research and the organization of practice during the acquisition of movement coordination in sport tasks. The task vehicle for our analysis is interceptive actions, in particular self-paced extrinsic timing tasks exemplified by serving in sports such as volleyball. Recent research highlighting the relevance of information--movement coupling for the process of practice in sport is discussed. We conclude that information--movement coupling represents an important principle for the structural organization of research and practice in self-paced extrinsic timing tasks and that further work is required to verify its significance across a range of sport movements.


Assuntos
Percepção/fisiologia , Esportes/fisiologia , Análise e Desempenho de Tarefas , Feminino , Humanos , Masculino , Projetos de Pesquisa , Sensibilidade e Especificidade , Fatores de Tempo , Reino Unido
9.
Mol Cell Neurosci ; 17(2): 354-63, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11178872

RESUMO

Inherited congenital myoclonus of Poll Hereford calves is an autosomal recessive disease characterized by hyperesthesia and myoclonic jerks of the skeletal musculature that occur both spontaneously and in response to sensory stimuli. Binding studies have previously shown that myoclonus is associated with specific loss of [(3)H]strychnine-binding sites from spinal cord and brain stem in affected calves. In order to identify the mutation responsible for myoclonus, we examined the candidate genes, glycine receptor alpha1 (Glra1) and beta (Glrb) subunits, in affected and normal cattle. A nonsense mutation was found at amino acid 24, located in exon 2 of the Glra1 gene in both cDNA and genomic sequences from affected but not control animals. Immunohistochemistry, with a monoclonal antibody to alpha and beta subunits of the glycine receptor, revealed a loss of cell surface immunoreactivity in myoclonic animals, suggesting a failure in the assembly of the receptor that could explain the characteristic phenotype of the disease.


Assuntos
Códon sem Sentido , Mioclonia/genética , Receptores de Glicina/genética , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação/genética , Química Encefálica , Bovinos , Clonagem Molecular , DNA Complementar , Testes Genéticos , Glicinérgicos/metabolismo , Glicinérgicos/farmacologia , Imuno-Histoquímica , Dados de Sequência Molecular , Fenótipo , Polimorfismo Genético , Receptores de Glicina/análise , Receptores de Glicina/metabolismo , Estricnina/metabolismo , Estricnina/farmacologia
10.
EMBO J ; 16(1): 110-20, 1997 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-9009272

RESUMO

Fast synaptic neurotransmission is mediated by transmitter-activated conformational changes in ligand-gated ion channel receptors, culminating in opening of the integral ion channel pore. Human hereditary hyperekplexia, or startle disease, is caused by mutations in both the intracellular or extracellular loops flanking the pore-lining M2 domain of the glycine receptor alpha1 subunit. These flanking domains are designated the M1-M2 loop and the M2-M3 loop respectively. We show that four startle disease mutations and six additional alanine substitution mutations distributed throughout both loops result in uncoupling of the ligand binding sites from the channel activation gate. We therefore conclude that the M1-M2 and M2-M3 loops act in parallel to activate the channel. Their locations strongly suggest that they act as hinges governing allosteric control of the M2 domain. As the members of the ligand-gated ion channel superfamily share a common structure, this signal transduction model may apply to all members of this superfamily.


Assuntos
Canais de Cloreto/metabolismo , Receptores de Glicina/metabolismo , Reflexo de Sobressalto , Transdução de Sinais , Regulação Alostérica , Sequência de Aminoácidos , Sítios de Ligação , Linhagem Celular , Agonistas dos Canais de Cloreto , Canais de Cloreto/genética , Eletrofisiologia , Humanos , Ativação do Canal Iônico , Dados de Sequência Molecular , Mutagênese , Receptores de Glicina/agonistas , Receptores de Glicina/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Taurina/metabolismo , beta-Alanina/metabolismo
11.
J Sports Sci ; 15(6): 621-40, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9486439

RESUMO

This paper builds on recent theoretical concerns regarding traditional conceptualizations of the skill acquisition process. The implications for the process of practice in sport contexts are explored with reference to the information-processing approach to motor behaviour and the newer ecological paradigm. Issues are raised with current principles of practice based on traditional theoretical ideas. A practice strategy that gives greater weight to the guided exploration of the practice workspace jointly defined by the properties of the individual's subsystems, the specific task and the environment is advocated. Such a constraints-led perspective supersedes previous distinctions between rudimentary and voluntary skills. Sports scientists, coaches, teachers and movement rehabilitation therapists are invited to review current practices in the light of recent theoretical advances from the ecological perspective.


Assuntos
Destreza Motora/fisiologia , Prática Psicológica , Esportes/fisiologia , Adaptação Fisiológica , Comportamento/fisiologia , Cognição/fisiologia , Meio Ambiente , Humanos , Processos Mentais/fisiologia , Modelos Biológicos , Modelos Psicológicos , Percepção/fisiologia , Modalidades de Fisioterapia , Desempenho Psicomotor/fisiologia , Esportes/educação , Análise e Desempenho de Tarefas
13.
Brain Res Mol Brain Res ; 35(1-2): 211-9, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8717357

RESUMO

The inhibitory glycine receptor (GlyR) is a pentameric receptor comprised of alpha and beta subunits, of which the beta subunit has not been characterised in humans. A 2106 bp cDNA, isolated from a human hippocampal cDNA library, contained an open reading frame of 497 amino acids which encodes the beta subunit of the human GlyR. The mature human GlyR beta polypeptide displays 99% amino acid identity with the rat GlyR beta subunit and 48% identity with the human GlyR alpha 1 subunit. Neither [3H]strychnine binding nor glycine-gated currents were detected when the human GlyR beta subunit cDNA was expressed in the human embryonic kidney 293 cell line. However, co-expression of the beta subunit cDNA with the alpha 1 subunit cDNA resulted in expression of functional GlyRs which showed a 4-fold reduction in the EC50 values when compared to alpha 1 homomeric GlyRs. Glycine-gated currents of alpha 1/beta GlyRs were 17-fold less sensitive than homomeric alpha 1 GlyRs to the antagonists picrotoxin, picrotoxinin and picrotin, providing clear evidence that heteromeric alpha 1/beta GlyRs were expressed. The beta subunit appears to play a structural rather than ligand binding role in GlyR function. Fluorescence in situ hybridisation was used to localise the gene encoding the human GlyR beta subunit (GLRB) to chromosome 4q32, a position syntenic with mouse chromosome 3. In situ hybridisation using the human GlyR beta subunit cDNA showed that the murine GlyR beta subunit gene (Glrb) maps to the spastic (spa) locus on mouse chromosome 3 at bands E3-F1. This is consistent with the recent finding that a mutation in the murine GlyR beta subunit causes the spa phenotype. It also raises the possibility that mutations in the human beta subunit gene may cause inherited disorders of the startle response.


Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 4 , Receptores de Glicina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Clonagem Molecular , DNA Complementar , Biblioteca Gênica , Glicina/metabolismo , Hipocampo/metabolismo , Humanos , Rim , Cinética , Substâncias Macromoleculares , Camundongos , Dados de Sequência Molecular , Mutação , Fases de Leitura Aberta , Ratos , Receptores de Glicina/biossíntese , Receptores de Glicina/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Estricnina/metabolismo
14.
J Sports Sci ; 12(6): 495-528, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7853448

RESUMO

This review examines the viability of the natural physical alternative to traditional cognitive modelling of the sport performer. It is concluded that the natural physical perspective offers an attractive framework for the study of movement control and co-ordination in sport, but, at present, does not seem capable of superseding cognitive explanations. As a consequence of the nature of the questions they are asking, natural physical theorists offer a significant avenue for interdisciplinary research in sports science. Significant differences in the philosophy underpinning both theoretical views are acknowledged, but growing support for an integrated approach to motor control is highlighted. A major task for sports scientists may be to verify empirically the nature of an integrated model of the sport performer.


Assuntos
Atividade Motora/fisiologia , Destreza Motora/fisiologia , Esportes/fisiologia , Esportes/psicologia , Humanos , Modelos Psicológicos , Pesquisa
15.
Nat Genet ; 7(2): 131-5, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7920629

RESUMO

Hereditary hyperekplexia, an autosomal dominant neurologic disorder characterized by an exaggerated startle reflex and neonatal hypertonia, can be caused by mutations in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor (GLRA1). Spasmodic (spd), a recessive neurologic mouse mutant, resembles hyperekplexia phenotypically, and the two disease loci map to homologous chromosomal regions. Here we describe a Glra1 missense mutation in spd that results in reduced agonist sensitivity in glycine receptors expressed in vitro. We conclude that spd is a murine homologue of hyperekplexia and that mutations in GLRA1/Glra1 can produce syndromes with different inheritance patterns.


Assuntos
Mutação , Mutação Puntual , Receptores de Glicina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , DNA Complementar/genética , Humanos , Camundongos , Camundongos Endogâmicos A , Camundongos Mutantes Neurológicos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Ratos , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico
16.
J Biol Chem ; 268(20): 14906-11, 1993 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-8392063

RESUMO

Developmental stage- and tissue-specific expression of the rat growth hormone (rGH) gene is conferred by DNA sequences within 237 base pairs of the transcription start site. Although binding of a number of transcription factors including Pit-1, Sp1, GHF3, and thyroid hormone receptor (T3R) stimulates rGH expression, several studies have suggested that interactions between these factors are important in determining cell specificity and responsiveness to extracellular signals. We have directly tested this hypothesis by creating a set of nested insertional mutations at two positions in the rGH promoter. Sequences were inserted at either position -148, separating GHF-3 and T3R binding sites from the downstream Pit-1 and Sp 1 binding sites, or at -51, separating the above elements from the TATA box. All insertions were made in the context of the rGH gene -237/+8 5'-flanking DNA, linked to a chloramphenicol acetyltransferase reporter gene and tested for activity by transient transfection in GC pituitary tumor cells. Insertions at both -148 and -51 caused sharp distance-dependent reductions in serum-stimulated expression such that insertions of 23 base pairs at -51 or 44 base pairs at -148 were sufficient to isolate the effects of sequences upstream of the insertion point. Insertions at -148 reduced T3 responsiveness severalfold but had little or no effect on stimulation by forskolin, whereas insertions at -51 reduced both T3 and forskolin responsiveness. Our results are consistent with the hypothesis that expression and regulation of the rGH gene is dependent on short-range protein-protein interactions, which are more critically dependent on spacing than the relative orientation of the transcription factor binding sites.


Assuntos
AMP Cíclico/metabolismo , Hormônio do Crescimento/genética , Regiões Promotoras Genéticas , Tri-Iodotironina/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Sangue , Células Cultivadas , Cloranfenicol O-Acetiltransferase/genética , Colforsina/farmacologia , DNA/metabolismo , Dados de Sequência Molecular , Mutagênese Insercional , Ratos
17.
Neuron ; 9(3): 491-6, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1326295

RESUMO

The distinction between receptor-binding sites for agonists and antagonists underpins the pharmacological differences between these two classes of ligands. In the glycine receptor, antagonist (strychnine) binding requires an interaction with residues Lys-200 and Tyr-202. We now demonstrate that the agonist-binding site of this receptor is located at the residue Thr-204. The agonist-binding site interaction is thus likely to be mediated by hydrogen bonding and not by ionic interactions. Our results demonstrate that, in contrast to other studies of ligand-gated ion channel receptors, agonist- and antagonist-binding sites are composed of distinct amino acid residues.


Assuntos
Alanina/metabolismo , Glicina/metabolismo , Receptores de Neurotransmissores/metabolismo , Estricnina/metabolismo , Taurina/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Ligação Competitiva , Glicina/antagonistas & inibidores , Humanos , Ligantes , Dados de Sequência Molecular , Mutação , Receptores de Glicina , Receptores de Neurotransmissores/química , Receptores de Neurotransmissores/genética
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