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1.
Nature ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048819

RESUMEN

Biological membranes are partitioned into functional zones termed membrane microdomains, which contain specific lipids and proteins1-3. The composition and organization of membrane microdomains remain controversial because few techniques are available that allow the visualization of lipids in situ without disrupting their native behaviour3,4. The yeast eisosome, composed of the BAR-domain proteins Pil1 and Lsp1 (hereafter, Pil1/Lsp1), scaffolds a membrane compartment that senses and responds to mechanical stress by flattening and releasing sequestered factors5-9. Here we isolated near-native eisosomes as helical tubules made up of a lattice of Pil1/Lsp1 bound to plasma membrane lipids, and solved their structures by helical reconstruction. Our structures reveal a striking organization of membrane lipids, and, using in vitro reconstitutions and molecular dynamics simulations, we confirmed the positioning of individual PI(4,5)P2, phosphatidylserine and sterol molecules sequestered beneath the Pil1/Lsp1 coat. Three-dimensional variability analysis of the native-source eisosomes revealed a dynamic stretching of the Pil1/Lsp1 lattice that affects the sequestration of these lipids. Collectively, our results support a mechanism in which stretching of the Pil1/Lsp1 lattice liberates lipids that would otherwise be anchored by the Pil1/Lsp1 coat, and thus provide mechanistic insight into how eisosome BAR-domain proteins create a mechanosensitive membrane microdomain.

2.
J Biol Chem ; 293(13): 4818-4829, 2018 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-29425097

RESUMEN

Membrane phosphoinositides control organization and dynamics of the actin cytoskeleton by regulating the activities of several key actin-binding proteins. Twinfilin is an evolutionarily conserved protein that contributes to cytoskeletal dynamics by interacting with actin monomers, filaments, and the heterodimeric capping protein. Twinfilin also binds phosphoinositides, which inhibit its interactions with actin, but the underlying mechanism has remained unknown. Here, we show that the high-affinity binding site of twinfilin for phosphoinositides is located at the C-terminal tail region, whereas the two actin-depolymerizing factor (ADF)/cofilin-like ADF homology domains of twinfilin bind phosphoinositides only with low affinity. Mutagenesis and biochemical experiments combined with atomistic molecular dynamics simulations reveal that the C-terminal tail of twinfilin interacts with membranes through a multivalent electrostatic interaction with a preference toward phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), PI(4,5)P2, and PI(3,4,5)P3 This initial interaction places the actin-binding ADF homology domains of twinfilin in close proximity to the membrane and subsequently promotes their association with the membrane, thus leading to inhibition of the actin interactions. In support of this model, a twinfilin mutant lacking the C-terminal tail inhibits actin filament assembly in a phosphoinositide-insensitive manner. Our mutagenesis data also reveal that the phosphoinositide- and capping protein-binding sites overlap in the C-terminal tail of twinfilin, suggesting that phosphoinositide binding additionally inhibits the interactions of twinfilin with the heterodimeric capping protein. The results demonstrate that the conserved C-terminal tail of twinfilin is a multifunctional binding motif, which is crucial for interaction with the heterodimeric capping protein and for tethering twinfilin to phosphoinositide-rich membranes.


Asunto(s)
Proteínas de Microfilamentos/antagonistas & inhibidores , Proteínas de Microfilamentos/química , Modelos Químicos , Simulación de Dinámica Molecular , Fosfatidilinositoles/química , Secuencias de Aminoácidos , Animales , Ratones , Proteínas de Microfilamentos/metabolismo , Fosfatidilinositoles/metabolismo , Dominios Proteicos
3.
Blood ; 130(15): 1746-1756, 2017 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-28743718

RESUMEN

Regulated reorganization of the actin cytoskeleton is a prerequisite for proper platelet production and function. Consequently, defects in proteins controlling actin dynamics have been associated with platelet disorders in humans and mice. Twinfilin 2a (Twf2a) is a small actin-binding protein that inhibits actin filament assembly by sequestering actin monomers and capping filament barbed ends. Moreover, Twf2a binds heterodimeric capping proteins, but the role of this interaction in cytoskeletal dynamics has remained elusive. Even though Twf2a has pronounced effects on actin dynamics in vitro, only little is known about its function in vivo. Here, we report that constitutive Twf2a-deficient mice (Twf2a-/-) display mild macrothrombocytopenia due to a markedly accelerated platelet clearance in the spleen. Twf2a-/- platelets showed enhanced integrin activation and α-granule release in response to stimulation of (hem) immunoreceptor tyrosine-based activation motif (ITAM) and G-protein-coupled receptors, increased adhesion and aggregate formation on collagen I under flow, and accelerated clot retraction and spreading on fibrinogen. In vivo, Twf2a deficiency resulted in shortened tail bleeding times and faster occlusive arterial thrombus formation. The hyperreactivity of Twf2a-/- platelets was attributed to enhanced actin dynamics, characterized by an increased activity of n-cofilin and profilin 1, leading to a thickened cortical cytoskeleton and hence sustained integrin activation by limiting calpain-mediated integrin inactivation. In summary, our results reveal the first in vivo functions of mammalian Twf2a and demonstrate that Twf2a-controlled actin rearrangements dampen platelet activation responses in a n-cofilin- and profilin 1-dependent manner, thereby indirectly regulating platelet reactivity and half-life in mice.


Asunto(s)
Plaquetas/metabolismo , Proteínas de Microfilamentos/metabolismo , Citoesqueleto de Actina/metabolismo , Animales , Apoptosis , Arterias/patología , Integrinas/metabolismo , Ratones , Trombocitopenia/metabolismo , Trombocitopenia/patología , Trombosis/patología
4.
Handb Exp Pharmacol ; 235: 123-152, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27469496

RESUMEN

Cell migration is necessary for several developmental processes in multicellular organisms. Furthermore, many physiological processes such as wound healing and immunological events in adult animals are dependent on cell migration. Consequently, defects in cell migration are linked to various diseases including immunological disorders as well as cancer progression and metastasis formation. Cell migration is driven by specific protrusive and contractile actin filament structures, but the types and relative contributions of these actin filament arrays vary depending on the cell type and the environment of the cell. In this chapter, we introduce the most important actin filament structures that contribute to mesenchymal and amoeboid cell migration modes and discuss the mechanisms by which the assembly and turnover of these structures are controlled by various actin-binding proteins.


Asunto(s)
Citoesqueleto de Actina/química , Movimiento Celular , Citoesqueleto de Actina/fisiología , Animales , Humanos , Miosinas/química , Seudópodos/fisiología , Fibras de Estrés/química , Fibras de Estrés/fisiología
5.
Mol Biol Cell ; 35(2): br6, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38088874

RESUMEN

The capping of barbed filament ends is a fundamental mechanism for actin regulation. Capping protein controls filament growth and actin turnover in cells by binding to the barbed ends of the filaments with high affinity and slow off-rate. The interaction between capping protein and actin is regulated by capping protein interaction (CPI) motif proteins. We identified a novel CPI motif protein, Bsp1, which is involved in cytokinesis and endocytosis in budding yeast. We demonstrate that Bsp1 is an actin binding protein with a high affinity for capping protein via its CPI motif. In cells, Bsp1 regulates capping protein at endocytic sites and is a major recruiter of capping protein to the cytokinetic actin ring. Lastly, we define Bsp1-related proteins as a distinct fungi-specific CPI protein group. Our results suggest that Bsp1 promotes actin filament capping by the capping protein. This study establishes Bsp1 as a new capping protein regulator and promising candidate to regulate actin networks in fungi.


Asunto(s)
Actinas , Citocinesis , Actinas/metabolismo , Citoesqueleto de Actina/metabolismo , Proteínas de Microfilamentos/metabolismo , Endocitosis , Proteínas de Capping de la Actina/metabolismo
6.
Acta Orthop ; 84(4): 331-7, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23992137

RESUMEN

BACKGROUND AND PURPOSE: Drug-based treatment of rheumatoid arthritis (RA) has evolved markedly over the past 2 decades. Using nationwide register data, we studied how this has affected the rates of hip, knee, shoulder, and elbow replacement from 1995 to 2010. METHODS: The number of primary joint replacements was obtained from the Finnish Arthroplasty Register. To test the hypothesis that improvements in medical treatment of RA reduce the need for joint replacements, we also collected data about purchases of different disease-modifying anti-rheumatic agents (DMARDs) and biological drugs from the nationwide drug registers. RESULTS: The annual incidence of primary joint replacements for RA declined from 19 per 10(5) in 1995 to 11 per 10(5) in 2010. The decline was greater for upper-limb operations than for lower-limb operations. At the same time, the numbers of individuals using methotrexate, hydroxychloroquine, and sulfasalazine (the most commonly used DMARDs) increased 2- to 4-fold. INTERPRETATION: Our results are in accordance with observations from other countries, and indicate that the use of joint replacements in RA has decreased dramatically. Our data suggest that effective medical therapy is the most likely explanation for this favorable development.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artroplastia de Reemplazo/estadística & datos numéricos , Antirreumáticos/administración & dosificación , Artritis Reumatoide/cirugía , Femenino , Finlandia/epidemiología , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Sistema de Registros , Sulfasalazina/administración & dosificación , Sulfasalazina/uso terapéutico
7.
J Cell Biol ; 222(7)2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-37338934

RESUMEN

Conserved protein complexes called ESCRTs (endosomal sorting complexes in retrograde transport) exert diverse membrane remodeling and repair functions in cells. Hakala and Roux discuss a novel type of ESCRT-III structure found by Stempels et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202205130) in migrating macrophages and dendritic cells, suggesting a novel, cell type-specific function for this complex.


Asunto(s)
Complejos de Clasificación Endosomal Requeridos para el Transporte , Endosomas , Transporte Biológico , Adhesión Celular , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Endosomas/metabolismo , Transporte de Proteínas , Macrófagos , Células Dendríticas
8.
Clin Exp Rheumatol ; 29(1): 65-71, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21345294

RESUMEN

OBJECTIVES: To assess long-term impact of RA on the HR-QoL in a cohort of working-age patients with early disease treated by a multidisciplinary team including early and active use of disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Fifty-five consecutive patients with RA who were naïve to DMARDs and glucocorticoids were assessed at baseline and at 6 months, 1, 2, 5 and 10 years. HR-QoL, disease activity, function, and joint destruction of hands and feet were assessed by using the Nottingham Health Profile (NHP) instrument, the 28-joint based Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), and the Larsen scores, respectively. GEE (generalised estimation equations)-method was used to evaluate longitudinal relationships between the HR-QoL changes and other variables. RESULTS: All NHP dimensions except social isolation improved significantly during the first six months and remained favourable up to 10 years. The most prominent improvements were seen in the dimensions for pain and emotional reaction (p<0.001). In longitudinal evaluation statistically significant associations (p<0.001) were found between the DAS28 and the NHP dimensions for pain, energy and emotional reaction, and between the HAQ and the NHP dimensions for pain, energy and mobility. The extent of joint damage had no statistically significant associations to the six dimensions of the NHP instrument. CONCLUSIONS: Early improvements in HR-QoL carried over the ten-year follow-up in patients with recent-onset RA treated with a multidisciplinary strategy including early and active DMARD therapy. HR-QoL changes were longitudinally associated especially with disease activity and function.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/psicología , Calidad de Vida/psicología , Artritis Reumatoide/fisiopatología , Artrografía , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Articulaciones/fisiopatología , Masculino , Persona de Mediana Edad , Recuperación de la Función , Índice de Severidad de la Enfermedad
9.
Nat Cell Biol ; 23(2): 147-159, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33558729

RESUMEN

Coordinated polymerization of actin filaments provides force for cell migration, morphogenesis and endocytosis. Capping protein (CP) is a central regulator of actin dynamics in all eukaryotes. It binds to actin filament (F-actin) barbed ends with high affinity and slow dissociation kinetics to prevent filament polymerization and depolymerization. However, in cells, CP displays remarkably rapid dynamics within F-actin networks, but the underlying mechanism remains unclear. Here, we report that the conserved cytoskeletal regulator twinfilin is responsible for CP's rapid dynamics and specific localization in cells. Depletion of twinfilin led to stable association between CP and cellular F-actin arrays, as well as to its retrograde movement throughout leading-edge lamellipodia. These were accompanied by diminished F-actin turnover rates. In vitro single-filament imaging approaches revealed that twinfilin directly promotes dissociation of CP from filament barbed ends, while enabling subsequent filament depolymerization. These results uncover a bipartite mechanism that controls how actin cytoskeleton-mediated forces are generated in cells.


Asunto(s)
Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Proteínas de Microfilamentos/metabolismo , Seudópodos/metabolismo , Adenosina Difosfato/metabolismo , Animales , Recuperación de Fluorescencia tras Fotoblanqueo , Proteínas Fluorescentes Verdes/metabolismo , Ratones , Ratones Noqueados , Proteínas de Microfilamentos/genética , Mutación/genética , Polimerizacion
10.
Biophys J ; 98(10): 2327-36, 2010 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-20483342

RESUMEN

Actin-depolymerizing-factor (ADF)/cofilins have emerged as key regulators of cytoskeletal dynamics in cell motility, morphogenesis, endocytosis, and cytokinesis. The activities of ADF/cofilins are regulated by membrane phospholipid PI(4,5)P(2) in vitro and in cells, but the mechanism of the ADF/cofilin-PI(4,5)P(2) interaction has remained controversial. Recent studies suggested that ADF/cofilins interact with PI(4,5)P(2) through a specific binding pocket, and that this interaction is dependent on pH. Here, we combined systematic mutagenesis with biochemical and spectroscopic methods to elucidate the phosphoinositide-binding mechanism of ADF/cofilins. Our analysis revealed that cofilin does not harbor a specific PI(4,5)P(2)-binding pocket, but instead interacts with PI(4,5)P(2) through a large, positively charged surface of the molecule. Cofilin interacts simultaneously with multiple PI(4,5)P(2) headgroups in a cooperative manner. Consequently, interactions of cofilin with membranes and actin exhibit sharp sensitivity to PI(4,5)P(2) density. Finally, we show that cofilin binding to PI(4,5)P(2) is not sensitive to changes in the pH at physiological salt concentration, although the PI(4,5)P(2)-clustering activity of cofilin is moderately inhibited at elevated pH. Collectively, our data demonstrate that ADF/cofilins bind PI(4,5)P(2) headgroups through a multivalent, cooperative mechanism, and suggest that the actin filament disassembly activity of ADF/cofilin can be accurately regulated by small changes in the PI(4,5)P(2) density at cellular membranes.


Asunto(s)
Citoesqueleto de Actina/fisiología , Factores Despolimerizantes de la Actina/fisiología , Movimiento Celular/fisiología , Citocinesis/fisiología , Destrina/fisiología , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfatidilinositoles/metabolismo , Sitios de Unión/fisiología , Evolución Molecular , Homología de Secuencia de Aminoácido
11.
Duodecim ; 126(11): 1317-21, 2010.
Artículo en Fi | MEDLINE | ID: mdl-20681355

RESUMEN

With the exception of a previous history of pulmonary sarcoidosis, a previously healthy 38-year old man developed a sudden unilateral metatarsal pain and gradually progressing osteoporotic, partly lytic metatarsal bone lesions. The patient received a bisphosphonate treatment. Clinical and radiological situation began to improve during the follow-up observation. The diagnosis was based on clinical picture.


Asunto(s)
Huesos Metatarsianos/diagnóstico por imagen , Osteoporosis/diagnóstico por imagen , Dolor/diagnóstico por imagen , Adulto , Difosfonatos/uso terapéutico , Humanos , Masculino , Osteoporosis/tratamiento farmacológico , Dolor/etiología , Radiografía
12.
Duodecim ; 125(19): 2131-2, 2009.
Artículo en Fi | MEDLINE | ID: mdl-19938416

RESUMEN

Anti-citrulline antibodies are highly specific to rheumatoid arthritis (RA) and are thus helpful in differential diagnosis. Early and aggressive disease modifying anti-rheumatic drug (DMARD) therapy is essential for a positive treatment result in cases of RA. Remission during the 1st year of treatment predicts permanent remission, milder joint damage and better functional ability. It is recommended that patients with an unsatisfactory response to DMARDs, including methotrexate and a combination of DMARDs, should be treated primarily with TNF blockers, and non-responders with rituximab or abatacept. RA is an independent risk factor for cardiovascular diseases. The assessment of cardiovascular risk must not be forgotten in daily practice.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/inmunología , Biomarcadores/análisis , Enfermedades Cardiovasculares/etiología , Citrulina/inmunología , Diagnóstico Diferencial , Humanos
13.
Duodecim ; 125(5): 563-4, 2009.
Artículo en Fi | MEDLINE | ID: mdl-19385345

RESUMEN

Pain medication should be based on patient's needs and risk profile. Age > 65 years, prior ulcer, co-morbidities, large daily dose, Helicobacter pylori infection, concurrent use of glucocorticoids, serotonin re-uptake inhibitors, or warfarin increase the risk of upper gastrointestinal bleeds. As a preventive strategy the use of concurrent proton pump inhibitors with non-selective NSAIDs is recommended. It is also possible to use COX-2 selective NSAIDs but they are contraindicated for persons with atherosclerotic diseases and special consideration is required for persons with risk factors of heart diseases. Paracetamol is the drug of choice for pain.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Dolor/tratamiento farmacológico , Acetaminofén/uso terapéutico , Anciano , Interacciones Farmacológicas , Humanos , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico
15.
Clin Rheumatol ; 25(3): 309-13, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16217592

RESUMEN

Aortic valve lesions are often found in patients with rheumatic diseases, but their clinical significance has not been properly evaluated. In the present study, the echocardiographic files of the cardiology unit of the Oulu University Hospital were screened for a diagnosis of aortic insufficiency (AI). The aetiology of the valve disease and specific details of the rheumatic disease were evaluated in 160 patients. Twenty-eight patients (18%) had a history of rheumatic fever. Rheumatic disease was found in 14 patients (8.8%) with AI, which is significantly more than the prevalence of rheumatic diseases (1.8%) in the corresponding age group (35-100 years) in Finland. Rheumatoid arthritis or juvenile rheumatoid arthritis was found in seven patients (4.4%), whereas ankylosing spondylitis or seronegative spondylarthropathy were found in four patients (2.5%). Other rheumatic diseases included Takayasu's arteritis (two patients) and scleroderma (one patient). When 38 patients with pure AI without other possible aetiology were analysed, rheumatic disease was found in five patients (13%). Patients with rheumatic disease as a potential aetiology of AI often had symptomatic valve disease, which required surgical treatment, although great differences between different aetiologies were not found.


Asunto(s)
Insuficiencia de la Válvula Aórtica/etiología , Enfermedades Reumáticas/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Insuficiencia de la Válvula Aórtica/diagnóstico , Insuficiencia de la Válvula Aórtica/fisiopatología , Enfermedad Crónica , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/fisiopatología
16.
Clin Rheumatol ; 25(6): 882-4, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16552464

RESUMEN

The aim of this study was to evaluate the effectiveness of IL-1 inhibition in rheumatic disease using real-life, observational methods. We analyzed data from 47 patients collected from the national ROB-FIN for rheumatic disease. Commonly used, validated measures of efficacy and adverse effects were documented and analyzed. The series contains 47/1,135 patients (mean age 47+/-11 years, range 25-73, females 83%) on anakinra of whom 39 patients suffered from rheumatoid arthritis (RA), two presented with psoriatic arthritis, and four with juvenile RA. At 3 months (26/40), 46% reached American College of Rheumatology (ACR) 20 and 27% ACR 50. In patients naive to biological drugs, the response rate at 3 months was 60% for ACR 20 and 20% for ACR 50. At follow-up of the total series, ACR responses at 6 and 12 months were 69/56% for ACR 20 and 23/22% for ACR 50. These data give room for IL-1 suppression when treating patient with rheumatic disease. Careful selection of patients, together with combining anakinra with disease-modifying antirheumatic drugs, perhaps adds effectiveness. For treating clinicians in Finland, these results are encouraging, as reimbursed treatment alternatives for patients refractory to all other therapies are still few.


Asunto(s)
Artritis Juvenil/tratamiento farmacológico , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Juvenil/fisiopatología , Artritis Psoriásica/fisiopatología , Artritis Reumatoide/fisiopatología , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Sistema de Registros , Retratamiento , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
17.
Artículo en Inglés | MEDLINE | ID: mdl-17065120

RESUMEN

Our aim was to evaluate the incidence and degree of osteolysis in a prospective series of patients with rheumatoid arthritis operated on with Sutter implants. Eighty-seven of the 110 operated hands (104 patients) with 282 implants were evaluated after a mean of 5.7 years (2.1-7.4). Osteolytic changes were present in 142 (50%) of the metacarpal and 152 (54%) of the phalangeal bones. Twenty-six of the metacarpal (9%) and 36 of the proximal phalangeal (13%) bones had osteolytic changes that did not affect the cortical bone. Cortical invasion was recorded in 100 (35%) of the metacarpal and 103 (37%) of the proximal phalangeal bones. The cortex was perforated in both bones in 14 (5%). Osteolytic changes were related to fractures of implants and to the dominant hand, but not to pain. Surgeons who operate on patients with rheumatoid diseases should note that silicone rubber implants often cause osteolytic changes.


Asunto(s)
Artroplastia para la Sustitución de Dedos , Prótesis Articulares/efectos adversos , Articulación Metacarpofalángica/cirugía , Osteólisis/etiología , Elastómeros de Silicona , Artritis Reumatoide/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteólisis/diagnóstico por imagen , Estudios Prospectivos , Diseño de Prótesis , Radiografía , Reoperación
18.
Artículo en Inglés | MEDLINE | ID: mdl-16428214

RESUMEN

We compared the survival, fracture, and deformation rates of Swanson and Sutter implants in a prospective series of 53 patients with rheumatoid arthritis (RA). Fifty-eight hands were operated on with 215 silastic implants. The Swanson group comprised 25 hands and 89 implants, and the Sutter group 33 and 126, respectively. Follow up was 58 (37-80) months. During a period of 48 months the survival of Swanson and Sutter prostheses did not differ significantly: 92% (95% CI 84% to 96%) and 97% (95% CI 92% to 99%), respectively. The fracture rate was high in both groups: 26 (34%) in the Swanson and 25 (26%) in the Sutter group. There was no significant difference between the groups in definite fracture rates of implants. The Sutter prosthesis appears to be at least as durable an implant in rheumatoid patients' metacarpophalangeal arthroplasty as the Swanson.


Asunto(s)
Artritis Reumatoide/cirugía , Artroplastia de Reemplazo/efectos adversos , Fracturas Óseas/etiología , Prótesis Articulares/efectos adversos , Articulación Metacarpofalángica/cirugía , Adulto , Anciano , Artroplastia de Reemplazo/instrumentación , Materiales Biocompatibles/uso terapéutico , Dimetilpolisiloxanos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Falla de Prótesis , Infecciones Relacionadas con Prótesis/etiología , Reoperación , Siliconas/uso terapéutico
20.
Curr Biol ; 24(21): 2533-40, 2014 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-25308079

RESUMEN

Lamellipodia are dynamic actin-rich cellular extensions that drive advancement of the leading edge during cell migration. Lamellipodia undergo periodic extension and retraction cycles, but the molecular mechanisms underlying these dynamics and their role in cell migration have remained obscure. We show that glia-maturation factor (GMF), which is an Arp2/3 complex inhibitor and actin filament debranching factor, regulates lamellipodial protrusion dynamics in living cells. In cultured S2R(+) cells, GMF silencing resulted in an increase in the width of lamellipodial actin filament arrays. Importantly, live-cell imaging of mutant Drosophila egg chambers revealed that the dynamics of actin-rich protrusions in migrating border cells is diminished in the absence of GMF. Consequently, velocity of border cell clusters undergoing guided migration was reduced in GMF mutant flies. Furthermore, genetic studies demonstrated that GMF cooperates with the Drosophila homolog of Aip1 (flare) in promoting disassembly of Arp2/3-nucleated actin filament networks and driving border cell migration. These data suggest that GMF functions in vivo to promote the disassembly of Arp2/3-nucleated actin filament arrays, making an important contribution to cell migration within a 3D tissue environment.


Asunto(s)
Movimiento Celular/fisiología , Drosophila/metabolismo , Factor de Maduración de la Glia/fisiología , Seudópodos/fisiología , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Animales , Drosophila/citología , Drosophila/ultraestructura , Proteínas de Drosophila/metabolismo , Factor de Maduración de la Glia/genética , Factor de Maduración de la Glia/metabolismo , Proteínas de Microfilamentos/metabolismo , Seudópodos/ultraestructura
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