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1.
J Tissue Viability ; 28(4): 167-172, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31288977

RESUMO

OBJECTIVES: There is currently a low level of evidence for the impact of patient education on the management of patients with chronic neurological disease at risk of developing pressure ulcers. The objective of this study was to assess the impact of a patient education programme on pressure ulcer prevention in patients with chronic spinal cord injuries. MATERIALS AND METHODS: This study included adult patients with any spinal cord injury, regardless of the cause. Participants attended 2 group workshops focusing on pressure ulcer prevention. Various clinical data were gathered during an initial individual interview and at 3, 6 and 12 months, along with rating scale values from the Hospital Anxiety and Depression Scale, Rosenberg self-esteem scale, Schwarzer self-efficacy scale, a quality of life scale (SF-36) and the revised Skin Management Needs Assessment Checklist (Revised SMnac), which was used as the primary endpoint. RESULTS: Twenty patients were included in the study. The mean patient age was 52 years (SD: 9,8). Sixteen patients had traumatic spinal cord injuries, with a median injury duration of 234 months (IQR: 123-407). Seventy-five percent had had a pressure ulcer in the twelve months prior to the study. Patient education was shown to have a significant impact on skin management ability, with a highly significant increase in the overall revised SMnac score at 3 months. These results were stable over time, from 6 to 12 months. Six patients developed a pressure ulcer during the study (30%). CONCLUSION: This study supports the hypothesis that a therapeutic educational program conducted at the chronic phase in spinal cord injured individuals has an impact.


Assuntos
Educação de Pacientes como Assunto/normas , Úlcera por Pressão/prevenção & controle , Traumatismos da Medula Espinal/complicações , Adulto , Idoso , Educação/métodos , Educação/normas , Educação/estatística & dados numéricos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Educação de Pacientes como Assunto/estatística & dados numéricos , Úlcera por Pressão/psicologia , Estudos Prospectivos , Psicometria/instrumentação , Psicometria/métodos , Qualidade de Vida/psicologia , Higiene da Pele/métodos , Higiene da Pele/normas , Traumatismos da Medula Espinal/psicologia
2.
Ann Readapt Med Phys ; 50(6): 373-6, 369-72, 2007 Jul.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-17482708

RESUMO

For many years, patients with multiple sclerosis (MS) were advised to avoid exercise because of the risk of increased neurological impairment. This article reviews the literature related to MS and physical exercise. Physical exercise depends on patients' physiological tolerance and response to exercise. MS patients can exhibit dysfunction of cardiovascular adjustment accompanied by respiratory involvement, which can alter aerobic capacity. These abnormalities tend to increase with the neurological impairment. Muscle weakness is the consequence of not only altered central motor drive but also disuse. Several studies have shown the benefits of physical training, with improvements in aerobic capacity, gait parameters and fatigue, and an influence on quality of life. Regular aerobic physical activity is necessary to maintain the benefit of physical training.


Assuntos
Terapia por Exercício , Esclerose Múltipla/terapia , Humanos
3.
Clin Exp Obstet Gynecol ; 33(4): 215-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17211968

RESUMO

OBJECTIVE: Women with multiple sclerosis frequently pose questions to physicians regarding the potential negative impact of pregnancy, especially on urinary disorders. About 50 to 80% of patients suffer from urinary disorders during the course of the disease. Trauma to the pelvic floor and the urethral sphincter during vaginal delivery may lead to the development of stress urinary incontinence. The purpose of this work was to study the consequences of pregnancy and childbirth on urinary problems. STUDY DESIGN: An inception cohort of 368 consecutive women suffering from multiple sclerosis (MS), according to the Poser criteria, were included in the study between June 1999 and June 2000. For each patient a full urological and obstetrical record was obtained. RESULTS: Two hundred and seventy-three women (74%) had had at least one pregnancy. The parous women were older at the time of the study (mean age: 45.5 years vs 35.5 years), and were older at MS onset (mean age: 32.8 years vs 25.7 years). The nulliparous women were more rapidly disabled, with a shorter time to reach an EDSS score of 3 from MS onset (mean time of 5.9 years versus 8.2 years in parous women). In parous women, 259 (95%) had had at least one vaginal delivery and 14 (5%) had had a caesarean only. Delivery modalities had no influence on urinary disorder frequency or the type of problems. CONCLUSION: On the basis of these data, there is actually no clear argument for systematically performing caesarean section in MS women. Urinary disorders in these women were mostly linked to the duration and the severity of the disease but not to pregnancy or delivery modalities. From our point of view, caesarean section must be decided only on classic obstetrical criteria as for healthy women independently of multiple sclerosis. However our data were open and retrospective.


Assuntos
Esclerose Múltipla/complicações , Parto , Complicações na Gravidez , Transtornos Urinários/etiologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez
4.
Ann Readapt Med Phys ; 49(1): 32-6, 2006 Feb.
Artigo em Francês | MEDLINE | ID: mdl-16236378

RESUMO

INTRODUCTION: Multiple sclerosis (MS) is a neurological disease of the central nervous system that most often affects young people. It is characterized by various debilitating symptoms. The aim of this study was to assess physical activities in patients with MS and how these affect their quality of life. METHODS: Forty-five patients were questioned about their physical activities. The following were taken into account: the characteristics of MS within each patient, the level of disease severity (EDSS score) and the quality of life (on the SEP-59 questionnaire). RESULTS: Fifteen patients had to give up a physical activity because of their illness but more so due to ataxia, fatigue and muscular weakness. Fifteen patients take part in a physical activity, the principal motivation being for their personal well-being. The mean EDSS was 4.2. Answers on the SEP-59 revealed found that patients with MS who took part in a physical activity had significantly better well-being in general. DISCUSSION AND CONCLUSION: Physical activities seem to improve the quality of life of patients with MS who, in general, already have a poor quality of life in relation to the general population. Knowing that muscular function is improved through exercise in patients with an EDSS less than 6, it would seem advantageous for them to take part in a regular physical activity.


Assuntos
Exercício Físico/psicologia , Esclerose Múltipla/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença
5.
J Mol Biol ; 267(3): 537-47, 1997 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-9126836

RESUMO

Many of the cis-dominant mutations that lead to respiratory deficiency by preventing maturation of specific yeast mitochondrial transcripts are found to affect the ribozyme core of group I and group II introns. We have searched for suppressors of mutations in the ribozyme-encoding sections of a group II intron, the first intron in the COX1 gene of Saccharomyces cerevisiae, which was independently subjected to in vitro site-directed mutagenesis. Three of the original mutants bore multiple mutations, which act synergistically, since for most individual mutations, suppressors could be obtained that ensured at least partial recovery of respiratory competence and splicing. Out of a total of ten suppressor mutations that were identified, three were second-site substitutions that restored postulated base-pairings in the ribozyme core. Remarkably, and as is observed for group I introns, at least half of the cis-dominant mutations in the first two group II introns of the COX1 gene affect sites that have been shown to participate in RNA tertiary interactions. We propose that this bias reflects cooperativity in the formation of ribozyme tertiary but not secondary structure, on the one hand, and the need for synergistic effects in order to generate a respiratory-deficient phenotype in the laboratory on the other. Finally, a novel in vivo splicing product of mutant cells is attributed to bimolecular splicing at high concentrations of defective transcripts.


Assuntos
Íntrons/genética , Splicing de RNA/genética , RNA Mensageiro/genética , Supressão Genética , Sequência de Bases , Complexo IV da Cadeia de Transporte de Elétrons/genética , Modelos Genéticos , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA Fúngico/química , RNA Fúngico/genética , RNA Mensageiro/química , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Análise de Sequência de DNA
6.
Ann N Y Acad Sci ; 1063: 79-82, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16481494

RESUMO

Rickettsiae survival implicates adaptation to different environmental conditions. We hypothesized that multiple copies of genes in bacteria with reduced genomes might account for such a process. Transcription of spoT and sca paralogs was thus analyzed in R. conorii and R. felis.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Genes Bacterianos , Família Multigênica , Rickettsia conorii/genética , Rickettsia felis/genética , Animais , Proteínas da Membrana Bacteriana Externa/biossíntese , Regulação Bacteriana da Expressão Gênica , RNA Bacteriano/biossíntese , RNA Bacteriano/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica
7.
Ann N Y Acad Sci ; 1063: 26-34, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16481487

RESUMO

Rickettsia felis has been recently cultured in XTC2 cells. This allows production of enough bacteria to create a genomic bank and to sequence it. The chromosome of R. felis is longer than that of previously sequenced rickettsiae and it possess 2 plasmids. Microscopically, this bacterium exhibits two forms of pili: one resembles a conjugative pilus and another forms hair-like projections that may play a role in pathogenicity. R. felis also exhibits several copies of ankyrin-repeat genes and tetratricopeptide encoding gene that are specifically linked to pathogenic host-associated bacteria. It also contains toxin-antitoxin system encoding genes that are extremely rare in intracellular bacteria and may be linked to plasmid maintenance.


Assuntos
DNA Bacteriano/análise , Genoma Bacteriano , Rickettsia felis/crescimento & desenvolvimento , Rickettsia felis/genética , Análise de Sequência de DNA , Animais , Técnicas Bacteriológicas , Humanos , Rickettsia felis/patogenicidade , Rickettsia felis/ultraestrutura
8.
Ann Readapt Med Phys ; 48(1): 29-33, 2005 Feb.
Artigo em Francês | MEDLINE | ID: mdl-15664681

RESUMO

OBJECTIVE: To assess the benefit of a program of rehabilitation involving eccentric isokinetic muscle strengthening for hamstrings of patient with multiple sclerosis. PATIENTS AND METHODS: A total of 28 patients with multiple sclerosis and abnormalities when walking who underwent a program of rehabilitation involving eccentric isokinetic muscle strengthening associated with classical neurological rehabilitation. Assessment was by use of an isokinetic test, clinical examination and score on a visual analog scale (VAS) about quality of walking at the beginning and end of the rehabilitation program and three months later. The rehabilitation program involved eccentric isokinetic exercises during 12 sessions. RESULTS: Patients with multiple sclerosis and difficulty walking showed weak hamstrings on manual muscular testing. After 12 sessions of isokinetic eccentric rehabilitation, hamstring and quadriceps strength increased, VAS score increased, and recurvatum of the knee improved in 26 cases. Three months later, the score for quality of walking remained the same, but that for strength returned to a previous level. CONCLUSION: Hamstring strength in patients with multiple sclerosis can be improved without complication with use of eccentric isokinetic rehabilitation. This is an interesting way to improve the quality of walking in these patients.


Assuntos
Terapia por Exercício , Esclerose Múltipla/reabilitação , Músculo Esquelético/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Contração Muscular/fisiologia , Medição da Dor
9.
Ann Readapt Med Phys ; 48(5): 225-30, 2005 Jun.
Artigo em Francês | MEDLINE | ID: mdl-15914257

RESUMO

INTRODUCTION: Stroke is the most disabling chronic disease among adults. The assessment of quality of life is of great importance to improve the management of patients with stroke sequelae returning to the community. METHOD: A total of 93 patients and their referring clinicians were contacted. Quality of life of patients three years after stroke was assessed by use of the Short-Form Health Survey (SF-36). RESULTS: Thirteen patients died during this period. Fifty participated in the study. The average age was 66.8 years. The patients who died were older and had an initial greater impairment after stroke than survivors. In most of the cases, a life plan, built during the inpatient rehabilitation period, could be achieved. Just six patients had to change their way of life during the three years after stroke. A total of 44% of the patients needed human assistance for basic daily living activities. Patients with stroke had lower scores on the SF-36 than their healthy peers. All subscale scores differed for patients with stroke, as compared with health peers. Initial disability, the occurrence of falls, age and urinary incontinence at the time of the study indicated poor prognosis. DISCUSSION: Our results are close to those previously published: a great number of people who survive stroke live with sequelae that requires assistance in the home and have decreased quality of life. These results stress the importance of follow-up by a rehabilitation team to prevent altered quality of life, with a special care to urinary incontinence and falls, especially in old people with abundant sequelae of stroke.


Assuntos
Serviços de Assistência Domiciliar , Qualidade de Vida , Acidente Vascular Cerebral/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
10.
Gene ; 83(1): 25-38, 1989 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-2556330

RESUMO

It is well known that the yeast Saccharomyces cerevisiae can be affected by mutations, called 'petite colonie', which correspond to the loss of the major part of the mitochondrial DNA and the concomitant amplification of the remaining sequence, the basic repeat unit (BRU). We describe here a new phenomenon, the internal overamplification (IOA), due to the differential amplification (up to 20-fold) of short sequences within the BRU. These IOAs are very stable and stimulate the recombination. We discuss here the possible mechanisms giving rise to the appearance and maintenance of the IOAs within the BRU and their effect on the recombination process.


Assuntos
DNA Mitocondrial , Amplificação de Genes , Recombinação Genética/fisiologia , Saccharomyces cerevisiae/genética , Sequência de Bases , Enzimas de Restrição do DNA/análise , Densitometria , Dados de Sequência Molecular , Mutação , Mapeamento por Restrição
11.
Biomed Pharmacother ; 53(8): 380-5, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10554672

RESUMO

Multiple sclerosis is a chronic demyeliniting disease of the central nervous system which is characterized by an extreme multiplicity of clinical features. Multiple sclerosis can have a profound impact on the quality of life of patients. The induced handicap varies from one patient to an other, and depends on the location of the demyeliniting lesions. Among the symptoms, sensory-motor disorders and genito-sphincter dysfunctions are some of the more disabling. Thus, up to 70% of patients suffer from urinary troubles, and 15 years after the onset of the illness, 50% of patients have difficulties for deambulation. A good knowledge of these pathologies is necessary to improve the management of patients suffering from multiple sclerosis.


Assuntos
Doenças Urogenitais Femininas/etiologia , Gastroenteropatias/etiologia , Doenças Urogenitais Masculinas , Esclerose Múltipla/complicações , Transtornos de Sensação/etiologia , Doenças Urogenitais Femininas/fisiopatologia , Gastroenteropatias/fisiopatologia , Humanos , Esclerose Múltipla/fisiopatologia , Desempenho Psicomotor/fisiologia , Transtornos de Sensação/fisiopatologia , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/fisiopatologia
12.
Ann Biol Clin (Paris) ; 62(4): 479-86, 2004.
Artigo em Francês | MEDLINE | ID: mdl-15297246

RESUMO

In order to ensure the quality of analytical results, clinical laboratories shall have a perfect control of process and equipments of measurement. Therefore is recommended individualisation of metrological function, generally entrusted the quality manager. This quality manager will draw up a metrological traceability, verifications and confirmations, control of non conformities, follow-up and evaluation of metrological function.


Assuntos
Testes de Química Clínica/normas , Técnicas de Laboratório Clínico/normas , Documentação/normas , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Testes de Química Clínica/instrumentação , Técnicas de Laboratório Clínico/instrumentação , Falha de Equipamento , Humanos , Manutenção/normas , Padrões de Referência , Sistema de Registros/normas , Pesos e Medidas/normas
13.
Ann Biol Clin (Paris) ; 62(1): 121-5, 2004.
Artigo em Francês | MEDLINE | ID: mdl-15047503

RESUMO

Clinical laboratories shall have a perfect control of "in vitro diagnostic medical devices" to ensure the quality of their analytical results. This introductory presentation to a serie of documents of recommendations tackles the different standards of metrology concerning the requirements to reference materials, metrological traceability, metrological confirmation, management of measurement as well as uncertainty of measurement. The standards concerning clinical laboratories are then succinctly described.


Assuntos
Técnicas de Laboratório Clínico/normas , Padrões de Referência
14.
Ann Readapt Med Phys ; 44(2): 72-80, 2001 Mar.
Artigo em Francês | MEDLINE | ID: mdl-11587655

RESUMO

OBJECTIVES: To evaluate the frequency and types of musculoskeletal problems of French instrumental musicians. METHODS: Voluntary musicians answered an anonymous questionnaire about their musical practices, their medical history, and the evaluation of the troubles they feel during playing music. The musicians have been contacted in music schools, professional and not-professional orchestras. RESULTS: During this study 635 musicians received a questionnaire. 141 answered it (22.5%): 76.6% suffer from overuse syndrome, 17% from entrapment neuropathies, 5.7% from occupational hand cramp. The main topographies are spine (60.9%) and wrist and hand (52.5%). Instrumental characteristics are exposed. CONCLUSION: Instrumental musicians often present musculoskeletal problems. A specific management would be useful to limit eventual drammatical consequences.


Assuntos
Transtornos Traumáticos Cumulativos/etiologia , Cãibra Muscular/etiologia , Doenças Musculoesqueléticas/etiologia , Música , Saúde Ocupacional , Adolescente , Adulto , Idoso , Transtornos Traumáticos Cumulativos/epidemiologia , Feminino , Mãos , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/epidemiologia
15.
Ann Readapt Med Phys ; 47(4): 169-76; discussion 177-8, 2004 May.
Artigo em Francês | MEDLINE | ID: mdl-15130715

RESUMO

OBJECTIVE: The aim of this study was the assessment of visual biofeedback in the management of balance disorders after stroke. MATERIAL AND METHODS: This is a prospective randomised trial, which compares visual biofeedback training and traditional balance training. Twenty-seven patients took part in this study: 13 in the first group and 14 in the second group. The rehabilitation program in the first group consists in an association of visual biofeedback and traditional training during 3 weeks. For the second group traditional training was used alone. Clinical, functional and forceplate assessments were performed before and after the program of rehabilitation. RESULTS: All the patients had a clinical and functional improvement. However, patients who have benefited from biofeedback training had a significant improvement of the forceplate parameters with closed eyes. DISCUSSION AND CONCLUSION: Those results confirm the interest of rehabilitation in balance disorders after stroke. The use of biofeedback training incorporated into functional physiotherapy affords added benefits probably by a best integration of proprioceptive informations.


Assuntos
Biorretroalimentação Psicológica , Hemiplegia/reabilitação , Equilíbrio Postural , Reabilitação do Acidente Vascular Cerebral , Adulto , Idoso , Biorretroalimentação Psicológica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Visão Ocular
16.
Ann Readapt Med Phys ; 47(5): 204-8, 2004 Jun.
Artigo em Francês | MEDLINE | ID: mdl-15183257

RESUMO

UNLABELLED: The effects of the modifications of temperature are well known in patients affected by multiple sclerosis (MS). They are variable and can influence daily living. This sensibility can be used in the management of the disabilities. METHOD: An epidemiological study was realized on a cohort of 191 patients suffering from MS referred to the MS clinic of Rennes (France). All the patients were questioned about the influence of heat and cold on their clinical symptoms (fatigue spasticity, walking disorders, vision, em leader ). Correlations with the main clinical characteristics were studied. POPULATION: One hundred ninety-one patients, 129 women and 62 men with an average age of 47.6 +/- 10 years were interviewed. Average score EDSS was of 5.2 +/- 1.5. The mean duration of MS was 13.5 +/- 10 years. RESULTS: One hundred forty-seven patients (77%) reported a sensibility to the temperature. Heat deteriorated function in 104 cases and 82 patients improved with cold. Paradoxically 20 patients reported to be deteriorated with cold and 19 improved with heat. Fatigue and walking were the most sensitive to temperature fluctuations. No particular clinical profile could be established. Fifty percent of the patients used this sensibility with therapeutic aim in everyday life. DISCUSSION: The clear influence of temperature fluctuations on the clinical symptom was confirmed in this study. However, there is a great variability from one patient to another. Different hypotheses have been evoked to explain this phenomenon. The most likely is an influence on the nervous specific conductivity. In routine practice cold physiotherapy will be proposed on case by case basis and still has an interesting place in the rehabilitation management.


Assuntos
Esclerose Múltipla/fisiopatologia , Temperatura , Adulto , Idoso , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Rev Rhum Ed Fr ; 61(11): 823-8, 1994 Dec.
Artigo em Francês | MEDLINE | ID: mdl-7858577

RESUMO

Heterotopic ossification is common in patients with spinal cord or brain injury. Whereas the articular complications of heterotopic ossification have been well documented, the vascular complications are less well known. We report three cases with vascular compression and discuss the diagnosis and treatment in the light of a review of the literature.


Assuntos
Veia Femoral , Ossificação Heterotópica/complicações , Adulto , Traumatismos Craniocerebrais/complicações , Ácido Etidrônico/uso terapêutico , Humanos , Indometacina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/tratamento farmacológico , Traumatismos da Medula Espinal/complicações , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/etiologia
18.
Ann Phys Rehabil Med ; 53(2): 118-23, 2010 Mar.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-19962953

RESUMO

INTRODUCTION: Pain is the main problem in patients suffering from cerebral palsy, particularly in adults. The upper limbs are affected in 25% of cases. Here, we report the case of a patient with Kienböck's disease. METHOD: Clinical case and literature review. A 28-year-old man suffering from dystonic quadriplegia consulted for progressively worsening pain in the right wrist. Kienböck's disease was diagnosed and conservative treatment with botulinum toxin in the flexor carpi radialis recommended. A good result was obtained with a decrease in pain. This result was still present two years later. DISCUSSION: Although few references are made to it in literature, Kienböck's disease in cerebral palsy is probably underestimated. Maintenance of the wrist in a permanent flexed position and muscular hypertonia may be risk factors. Knowledge of this particular clinical picture will enable it to be detected promptly and thus enable conservative treatment to be organised with a maximum chance of therapeutic success, preventing the need for surgery.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Paralisia Cerebral/complicações , Osso Semilunar/patologia , Osteonecrose/tratamento farmacológico , Dor/etiologia , Punho , Adulto , Analgésicos/uso terapêutico , Terapia Combinada , Humanos , Imobilização , Osso Semilunar/diagnóstico por imagem , Masculino , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Osteonecrose/diagnóstico por imagem , Osteonecrose/etiologia , Osteonecrose/terapia , Quadriplegia/etiologia , Radiografia , Contenções , Ulna/patologia
20.
Proc Natl Acad Sci U S A ; 97(18): 9913-8, 2000 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-10954741

RESUMO

Sec7 domains (Sec7d) catalyze the exchange of guanine nucleotide on ARFs. Recent studies indicated that brefeldin A (BFA) inhibits Sec7d-catalyzed nucleotide exchange on ARF1 in an uncompetitive manner by trapping an early intermediate of the reaction: a complex between GDP-bound ARF1 and Sec7d. Using (3)H-labeled BFA, we show that BFA binds to neither isolated Sec7d nor isolated ARF1-GDP, but binds to the transitory Sec7d-ARF1-GDP complex and stabilizes it. Two pairs of residues at positions 190-191 and 198-208 (Arno numbering) in Sec7d contribute equally to the stability of BFA binding, which is also sensitive to mutation of H80 in ARF1. The catalytic glutamic (E156) residue of Sec7d is not necessary for BFA binding. In contrast, BFA does not bind to the intermediate catalytic complex between nucleotide-free ARF1 and Sec7d. These results suggest that, on initial docking steps between ARF1-GDP and Sec7d, BFA inserts like a wedge between the switch II region of ARF1-GDP and a surface encompassing residues 190-208, at the border of the characteristic hydrophobic groove of Sec7d. Bound BFA would prevent the switch regions of ARF1-GDP from reorganizing and forming tighter contacts with Sec7d and thereby would maintain the bound GDP of ARF1 at a distance from the catalytic glutamic finger of Sec7d.


Assuntos
Fator 1 de Ribosilação do ADP/química , Fator 1 de Ribosilação do ADP/metabolismo , Brefeldina A/farmacocinética , Fatores de Troca do Nucleotídeo Guanina , Proteínas/química , Proteínas/metabolismo , Sítios de Ligação , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Cinética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Mutação Puntual , Conformação Proteica , Estrutura Secundária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Deleção de Sequência
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