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1.
Artículo en Inglés | MEDLINE | ID: mdl-34751885

RESUMEN

Cardiovascular magnetic resonance imaging is one of the most important diagnostic modalities in the evaluation of cardiomyopathies. However, significant limitations are the complex and time-consuming workflows and the need of contrast agents. The aim of this multi-center retrospective study was to assess workflows and diagnostic value of a short, contrast agent-free cardiac magnetic resonance protocol. 160 patients from Heidelberg, Germany and 119 patients from Montreal, Canada with suspected cardiomyopathy and 20 healthy volunteers have been enrolled. Scans were performed at a 1.5Tesla or 3Tesla scanner in Heidelberg and at a 3Tesla scanner in Montreal. We used single-slice T1 map only. A stepwise analysis of images has been performed. The possible differential diagnosis after each step has been defined. T1-values and color-encoded T1 maps significantly contributed to the differential diagnosis in 54% of the cases (161/299); the final diagnosis has been done without late gadolinium enhancement images in 83% of healthy individuals, in 99% of patients with dilated cardiomyopathy, in 93% of amyloidosis patients, in 94% of patients with hypertrophic cardiomyopathy and in 85% of patients with hypertensive heart disease, respectively. Comparing the scan time with (48 ± 7 min) vs. without contrast agent (23 ± 5 min), significant time saving could be reached by the short protocol. Subgroup analysis showed the most additional diagnostic value of T1 maps in amyloidosis and hypertrophic cardiomyopathy or in confirmation of normal findings. In patients with unclear left ventricular hypertrophy, a short, non-contrast protocol can be used for diagnostic decision-making, if the quality of the T1 map is diagnostic, even if only one slice is available.

2.
Oncogene ; 35(50): 6416-6428, 2016 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-27375026

RESUMEN

The Wnt pathway has essential roles in cell proliferation, cell fate determination and tumorigenesis by regulating the expression of a wide range of target genes. As a core signaling cascade, the canonical Wnt pathway is regulated at different levels by numerous proteins. We have previously shown that carboxypeptidase E (CPE) is a novel regulator of the canonical Wnt signaling pathway. Here, we show that CPE and the Wnt3a ligand are co-secreted from cells. We show that although the C'-terminal Lys residue of Wnt3a is critical for its activity and is important for the effect of CPE on the Wnt pathway, CPE does not execute its effect by removing this Wnt3a residue. Interestingly, CPE through its N'-terminal sequence, forms aggregates with Wnt3a and possible endoplasmic reticulum (ER) stress leading to its loss of function. Together, our current results provide a mechanistic insight into the way CPE regulates the canonical Wnt signaling pathway.


Asunto(s)
Carboxipeptidasa H/fisiología , Proteína Wnt3A/metabolismo , Animales , Células COS , Chlorocebus aethiops , Estrés del Retículo Endoplásmico , Células HEK293 , Humanos , Agregado de Proteínas , Vía de Señalización Wnt
3.
J Med Case Rep ; 10: 94, 2016 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-27071931

RESUMEN

BACKGROUND: Primary cardiac tumors are rare and often asymptomatic or present with unspecific symptoms. Benign cardiac tumors of vascular origin are especially rare, with only few existing data in the literature. CASE PRESENTATION: A 35-year-old Caucasian female patient presented to our department with an asymptomatic giant intracardiac angioma infiltrating both ventricles. Evaluation of this tumor involved electrocardiography, echocardiography, cardiac magnetic resonance imaging, coronary angiography, an open myocardial biopsy, and histological examination of the resected specimen. Because our patient was asymptomatic, she was managed conservatively with regular follow-up. We discuss the treatment options available in comparison with similar cases. CONCLUSION: Diagnosis and therapy of benign cardiac tumors, especially of asymptomatic lesions, can be a challenge. There is no evidence available to help in the management of such patients. An extensive evaluation is needed with different imaging modalities, and case-specific decisions should be made that involve experts in cardiology, cardio-oncology, and heart surgery.


Asunto(s)
Neoplasias Cardíacas/diagnóstico , Hemangioma/diagnóstico , Adulto , Biopsia/métodos , Angiografía Coronaria , Ecocardiografía , Femenino , Ventrículos Cardíacos , Humanos , Hallazgos Incidentales , Angiografía por Resonancia Magnética , Imagen Multimodal , Miocardio/patología
4.
Int J Cardiol ; 167(2): 470-7, 2013 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-22357420

RESUMEN

AIMS: Vascular smooth muscle cell (VSMC) migration, proliferation and remodeling of the extracellular matrix contribute to lumen loss after arterial injury leading to restenosis. Several studies indicated the role of the cyclic guanosine monophosphate signaling in neointimal formation. Cinaciguat, the novel soluble guanylate cyclase activator, currently being in phase IIb clinical trial, has been shown to exert antiplatelet and anti-remodeling effects in animal models of vascular pathology. In this study we investigated the effects of cinaciguat on post-injury arterial stenosis. METHODS AND RESULTS: Male Sprague-Dawley rats (n=100) underwent endothelial denudation by wire injury of the right common carotid artery. Cinaciguat (10mg/kg/day orally) were administered to 50 rats (1-, 2-, 3-day and 1-, 3-week treatment time), while 50 rats received placebo. A 3-week treatment resulted in a significantly reduced vascular stenosis (17.53 ± 10.84% in the treatment group vs. 43.25 ± 30.83% in the control wire injury group) and neointima/media area ratio (0.45 ± 0.32 in the treatment group vs. 1.09 ± 0.69 in the control wire injury group). By using quantitative real-time PCR, Western blot and immunohistochemistry, matrix-metallopreoteinase-9 (MMP-9) was found to be upregulated in the control-injured carotids over the whole follow-up, and cinaciguat significantly decreased MMP-9 expression by 3 weeks. As assessed by protein immunoblot, injury-induced local decrease of soluble guanylate cyclase ß1 subunit could be recovered by cinaciguat. In vitro wound healing assay with VSMCs revealed dose-dependent antimigratory and antiproliferative effects of cinaciguat. Plasma level of cyclic guanosine monophosphate was significantly elevated after 3 weeks of treatment. CONCLUSION: Our results show that cinaciguat prevents injury-induced neointimal hyperplasia by decreasing VSMC migration and proliferation through the regulation of MMP-9.


Asunto(s)
Benzoatos/uso terapéutico , Traumatismos de las Arterias Carótidas/metabolismo , Movimiento Celular/fisiología , Metaloproteinasa 9 de la Matriz/biosíntesis , Músculo Liso Vascular/metabolismo , Neointima/metabolismo , Animales , Benzoatos/farmacología , Traumatismos de las Arterias Carótidas/tratamiento farmacológico , Traumatismos de las Arterias Carótidas/patología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Guanilato Ciclasa/metabolismo , Masculino , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Neointima/patología , Neointima/prevención & control , Ratas , Ratas Sprague-Dawley
5.
Eur J Vasc Endovasc Surg ; 40(2): 168-75, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20434373

RESUMEN

OBJECTIVE: Reactive oxygen and nitrogen species (e.g., peroxynitrite) may trigger neointima formation leading to restenosis. In a rat carotid endarterectomy (CEA) model, we investigated the effects of the manganese(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP), a superoxide dismutase (SOD) mimetic and peroxynitrite scavenger on neointima formation. METHODS: CEA was performed in male Sprague-Dawley rats. Animals received either vehicle (control group; n=15) or 15 mg kg(-1) day(-1) MnTBAP intraperitoneally for 3 weeks (treatment group; n=13). Four groups of carotids were analysed: the left, uninjured carotids (sham) and the right, injured carotids (control CEA) from the control group, the right, injured carotids from the treatment group (CEA+MnTBAP) and an additional group of carotids that were harvested 1h following endarterectomy. The analysis of carotid arteries was performed by histology, immunohistochemistry and real-time polymerase chain reaction (PCR). Plasma malondialdehyde (MDA) levels were measured by lipid hydroperoxidase assay. RESULTS: Stenosis rate (10.5+/-8.1% vs. 45.4+/-28.3%), the percentage of proliferating cell nuclear antigen-positive cells (13.4+/-7.1% vs. 23.3+/-11.0%) and nitrotyrosine immunoreactivity (5.8+/-1.9 vs. 8.0+/-2.0) were significantly reduced in the vascular wall of the CEA+MnTBAP group compared with control CEA group. Ratio of Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL)-positive nuclei was significantly lower after antioxidant therapy (41.7+/-26.7% vs. 64.9+/-18.5%). Plasma MDA levels increased after endarterectomy (11.7+/-4.8 vs. 4.1+/-2.0 micromol l(-1)) and reduced in the treatment group (3.2+/-2.1 micromol l(-1)). No significant gene regulation after MnTBAP treatment could be noted. CONCLUSIONS: MnTBAP decreased neointima formation, which was associated with reduced vascular smooth muscle cell proliferation and attenuated local and systemic nitro-oxidative stress.


Asunto(s)
Estenosis Carotídea/metabolismo , Endarterectomía Carotidea , Radicales Libres/farmacología , Metaloporfirinas/farmacología , Estrés Oxidativo/fisiología , Animales , Estenosis Carotídea/prevención & control , Estenosis Carotídea/cirugía , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Hiperplasia , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Peroxidación de Lípido , Masculino , Estrés Oxidativo/efectos de los fármacos , Ácido Peroxinitroso/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Depuradores de Clase E , Prevención Secundaria , Túnica Íntima/patología
6.
Eur J Vasc Endovasc Surg ; 40(1): 35-43, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20435490

RESUMEN

PURPOSE: To assess primary success and safety of percutaneous transluminal angioplasty and/or stenting of innominate artery lesions and to compare its 30-day stroke/mortality level with the literature data. METHODS: A total of 72 patients (77 stenoses, five recurrent, 58 symptomatic and 39 female) with seven innominate vessel occlusions, nine subocclusive lesions and 61 significant (>60%) stenoses of innominate artery treated between 2000 and 2009 were retrospectively reviewed. With the exception of seven, all procedures were performed using a transfemoral approach. A stent was implanted in 49 (63.6%) cases. Follow-up included neurological examination, carotid duplex scan and office/telephone interview. RESULTS: Primary technical success was 93.5% (72/77). There was neither periprocedural (<48 h) death, nor major neurological complication. Minor periprocedural neurological complications consisted of 2/72 (2.6%) ipsilateral TIAs. Access site complications included 4 (5.2%) access site bleedings. Follow-up was achieved in 65/72 (90.3%) of all patients and 68 (88.3%) of all procedures for a mean of 42.3 months and revealed neither major neurological complication, nor additional TIA. The cumulative primary patency rate was 100% at 12 months, 98+/-1.6% at 24 months, and 69.9+/-8.5% at 96 months. The cumulative secondary patency rate was 100% at 12 and at 24 months, and 81.5+/-7.7% at 96 months. Log-rank test showed no significant difference (p=0.79) in primary cumulative patencies between PTA alone (n=28) or PTA/stent (n=49). CONCLUSION: Transfemoral PTA with or without stent appears to be a safe treatment option for innominate artery lesions.


Asunto(s)
Angioplastia de Balón , Arteriopatías Oclusivas/terapia , Tronco Braquiocefálico , Adulto , Anciano , Anciano de 80 o más Años , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/instrumentación , Angioplastia de Balón/mortalidad , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/mortalidad , Arteriopatías Oclusivas/fisiopatología , Tronco Braquiocefálico/diagnóstico por imagen , Tronco Braquiocefálico/fisiopatología , Constricción Patológica , Femenino , Humanos , Hungría , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Examen Neurológico , Radiografía , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Stents , Accidente Cerebrovascular/etiología , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex , Grado de Desobstrucción Vascular
7.
Thorac Cardiovasc Surg ; 58(2): 86-92, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20333570

RESUMEN

BACKGROUND: We tested the hypothesis that pharmacological preconditioning with a newly developed, potent non-adenosine analogue A1AdoR agonist (BR-4935) improves biventricular cardiac and endothelial function after cardiopulmonary bypass. METHODS: Twelve anesthetized dogs underwent cardiopulmonary bypass. Dogs were divided into two groups: group 1 (n = 6) received saline vehicle, group 2 (n = 6) received BR-4935 before cardiopulmonary bypass. Biventricular hemodynamic variables were measured using a combined pressure-volume conductance catheter. Coronary blood flow, ATP content, malondialdehyde and myeloperoxidase levels and vasodilatative responses to acetylcholine and sodium nitroprusside were also determined. RESULTS: Administration of the A1AdoR agonist led to a significantly better recovery of left and right ventricular systolic function after 60 minutes of reperfusion. Although the vasodilatative response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly greater increase in coronary blood flow in the BR-4935 group. In addition, the ATP content was significantly higher in the same group. Furthermore, malondialdehyde and myeloperoxidase levels significantly decreased in the A1AdoR group. CONCLUSION: Pharmacological preconditioning with a new, potent non-adenosine analogue A1AdoR agonist improves biventricular function recovery and endothelial function after hypothermic cardiac arrest.


Asunto(s)
Agonistas del Receptor de Adenosina A1 , Aminopirina/análogos & derivados , Puente Cardiopulmonar/efectos adversos , Cardiotónicos/farmacología , Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Función Ventricular Izquierda/efectos de los fármacos , Función Ventricular Derecha/efectos de los fármacos , Acetilcolina/farmacología , Adenosina Trifosfato/metabolismo , Aminopirina/farmacología , Animales , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Perros , Endotelio Vascular/fisiopatología , Malondialdehído/metabolismo , Contracción Miocárdica/efectos de los fármacos , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Nitroprusiato/farmacología , Peroxidasa/metabolismo , Recuperación de la Función , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología
8.
J Cardiovasc Surg (Torino) ; 50(5): 655-63, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19339958

RESUMEN

AIM: The aim of our study was to compare the early restenosis rate between patients undergoing carotid artery stenting (CAS) and carotid endarterectomy (CEA) at a single cardiovascular institution. METHODS: In 2004, 368 carotid endarterectomies were carried out on 347 patients and 144 internal carotid artery stentings were performed on 140 patients. The mean follow-up time was 18.4 months (range 6-38 months). Restenosis rates were calculated with the Kaplan-Meyer method and the two groups were compared by using log-rank test. Perioperative outcome was also evaluated and the groups were compared with chi-square test. RESULTS: Significantly more perioperative complications occurred in the CAS group, mainly transient neurological (7.60% vs 2.20% in the CEA group, P<0.05) and cardiovascular symptoms (4.10% vs 1.10% in the CEA group, P<0.05). Moderate restenosis (50-69%) occurred in 11.41% (42/368) of CEA cases and in 4.86% (7/144) of CAS cases (P<0.05). Severe (70%) restenosis rates were 10.05 % in the CEA group and 3.47% in the CAS group (P<0.05). CONCLUSIONS: Incidence of restenosis after carotid artery stening was less common than after carotid endarterectomy. On the other hand, perioperative complications were recorded more often after CAS than following CEA.


Asunto(s)
Angioplastia de Balón/instrumentación , Estenosis Carotídea/terapia , Endarterectomía Carotidea , Stents , Anciano , Angioplastia de Balón/efectos adversos , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Distribución de Chi-Cuadrado , Endarterectomía Carotidea/efectos adversos , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía
9.
Anticancer Res ; 24(3a): 1657-63, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15274337

RESUMEN

BACKGROUND: A human neuroblastoma cell line (Paju) was induced by retinoic acid (RA) to differentiate into neuron-like cells. MATERIALS AND METHODS: We studied the expression and the possible role of histamine receptors H1 and H2 in retinoic-acid mediated differentiation by semiquantitative RT-PCR. We studied the effect of exogeneously added RA on the morphological change of the human neuroblastoma cell line and the differentiation was followed by vimentine, glial fibrillary acidic protein (GFAP) and neurofilament (NF) immunostaining. We monitored the change of the histidine decarboxylase (HDC) expression and the histamine content during the RA treatment by immunoblot and flow cytometry methods. RESULTS: Our data showed that H1 and H2 histamine receptors are present on Paju cells. Ten nM RA markedly increased the H1 receptor expression of these cells, while the H2 expression was unchanged. CONCLUSION: In the RA-treated Paju cells, the histamine content increased compared to the untreated cells, suggesting that neuroblastoma-derived histamine is involved in the regulation of RA-induced in vitro differentiation by H1 receptors.


Asunto(s)
Histamina/biosíntesis , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/metabolismo , Tretinoina/farmacología , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular Tumoral , Histidina Descarboxilasa/biosíntesis , Histidina Descarboxilasa/genética , Humanos , Filamentos Intermedios/efectos de los fármacos , Filamentos Intermedios/metabolismo , Neuroblastoma/patología , Neuronas/citología , Neuronas/metabolismo , ARN Mensajero/genética , Receptores Histamínicos H1/biosíntesis , Receptores Histamínicos H1/genética , Receptores Histamínicos H2/biosíntesis , Receptores Histamínicos H2/genética
10.
J Cell Biol ; 155(4): 557-70, 2001 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-11706049

RESUMEN

The Golgi apparatus comprises an enormous array of components that generate its unique architecture and function within cells. Here, we use quantitative fluorescence imaging techniques and ultrastructural analysis to address whether the Golgi apparatus is a steady-state or a stable organelle. We found that all classes of Golgi components are dynamically associated with this organelle, contrary to the prediction of the stable organelle model. Enzymes and recycling components are continuously exiting and reentering the Golgi apparatus by membrane trafficking pathways to and from the ER, whereas Golgi matrix proteins and coatomer undergo constant, rapid exchange between membrane and cytoplasm. When ER to Golgi transport is inhibited without disrupting COPII-dependent ER export machinery (by brefeldin A treatment or expression of Arf1[T31N]), the Golgi structure disassembles, leaving no residual Golgi membranes. Rather, all Golgi components redistribute into the ER, the cytoplasm, or to ER exit sites still active for recruitment of selective membrane-bound and peripherally associated cargos. A similar phenomenon is induced by the constitutively active Sar1[H79G] mutant, which has the additional effect of causing COPII-associated membranes to cluster to a juxtanuclear region. In cells expressing Sar1[T39N], a constitutively inactive form of Sar1 that completely disrupts ER exit sites, Golgi glycosylation enzymes, matrix, and itinerant proteins all redistribute to the ER. These results argue against the hypothesis that the Golgi apparatus contains stable components that can serve as a template for its biogenesis. Instead, they suggest that the Golgi complex is a dynamic, steady-state system, whose membranes can be nucleated and are maintained by the activities of the Sar1-COPII and Arf1-coatomer systems.


Asunto(s)
Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Proteínas de Saccharomyces cerevisiae , Factor 1 de Ribosilacion-ADP/metabolismo , Brefeldino A/metabolismo , Brefeldino A/farmacología , Vesículas Cubiertas por Proteínas de Revestimiento/metabolismo , Aparato de Golgi/efectos de los fármacos , Aparato de Golgi/fisiología , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Membranas Intracelulares/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Unión al GTP Monoméricas/metabolismo , Transporte de Proteínas , Proteínas de Transporte Vesicular
11.
J Cell Biol ; 153(3): 529-41, 2001 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-11331304

RESUMEN

The endocytic itineraries of lipid raft markers, such as glycosyl phosphatidylinositol (GPI)-anchored proteins and glycosphingolipids, are incompletely understood. Here we show that different GPI-anchored proteins have different intracellular distributions; some (such as the folate receptor) accumulate in transferrin-containing compartments, others (such as CD59 and GPI-linked green fluorescent protein [GFP]) accumulate in the Golgi apparatus. Selective photobleaching shows that the Golgi pool of both GPI-GFP and CD59-GFP constantly and rapidly exchanges with the pool of these proteins found on the plasma membrane (PM). We visualized intermediates carrying GPI-GFP from the Golgi apparatus to the PM and separate structures delivering GPI-GFP to the Golgi apparatus.GPI-GFP does not accumulate within endocytic compartments containing transferrin, although it is detected in intracellular structures which are endosomes by the criteria of accessibility to a fluid phase marker and to cholera and shiga toxin B subunits (CTxB and STxB, which are also found in rafts). GPI-GFP and a proportion of the total CTxB and STxB taken up into cells are endocytosed independently of clathrin-associated machinery and are delivered to the Golgi complex via indistinguishable mechanisms. Hence, they enter the Golgi complex in the same intermediates, get there independently of both clathrin and rab5 function, and are excluded from it at 20 degrees C and under conditions of cholesterol sequestration. The PM-Golgi cycling pathway followed by GPI-GFP could serve to regulate lipid raft distribution and function within cells.


Asunto(s)
Membrana Celular/metabolismo , Aparato de Golgi/metabolismo , Microdominios de Membrana/metabolismo , Transporte Biológico , Antígenos CD59/metabolismo , Compartimento Celular , Toxina del Cólera/metabolismo , Colesterol , Clatrina/metabolismo , Exocitosis , Glicosilfosfatidilinositoles/metabolismo , Proteínas Fluorescentes Verdes , Proteínas Luminiscentes/metabolismo , Microscopía Fluorescente , Fotomicrografía , Toxinas Shiga/metabolismo , Transferrina/metabolismo
13.
Annu Rev Cell Dev Biol ; 16: 557-89, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11031247

RESUMEN

Green fluorescent protein chimerae acting as reporters for protein localization and trafficking within the secretory membrane system of living cells have been used in a wide variety of applications, including time-lapse imaging, double-labeling, energy transfer, quantitation, and photobleaching experiments. Results from this work are clarifying the steps involved in the formation, translocation, and fusion of transport intermediates; the organization and biogenesis of organelles; and the mechanisms of protein retention, sorting, and recycling in the secretory pathway. In so doing, they are broadening our thinking about the temporal and spatial relationships among secretory organelles and the membrane trafficking pathways that operate between them.


Asunto(s)
Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Proteínas/metabolismo , Animales , Transporte Biológico , Membrana Celular/metabolismo , Células , Retículo Endoplásmico/fisiología , Cinética , Orgánulos
14.
Cell ; 99(6): 589-601, 1999 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-10612395

RESUMEN

Quantitative imaging and photobleaching were used to measure ER/Golgi recycling of GFP-tagged Golgi proteins in interphase cells and to monitor the dissolution and reformation of the Golgi during mitosis. In interphase, recycling occurred every 1.5 hr, and blocking ER egress trapped cycling Golgi enzymes in the ER with loss of Golgi structure. In mitosis, when ER export stops, Golgi proteins redistributed into the ER as shown by quantitative imaging in vivo and immuno-EM. Comparison of the mobilities of Golgi proteins and lipids ruled out the persistence of a separate mitotic Golgi vesicle population and supported the idea that all Golgi components are absorbed into the ER. Moreover, reassembly of the Golgi complex after mitosis failed to occur when ER export was blocked. These results demonstrate that in mitosis the Golgi disperses and reforms through the intermediary of the ER, exploiting constitutive recycling pathways. They thus define a novel paradigm for Golgi genesis and inheritance.


Asunto(s)
Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Mitosis/fisiología , Proteínas de Saccharomyces cerevisiae , Animales , Línea Celular , Citocinas/metabolismo , Retículo Endoplásmico/ultraestructura , Técnica del Anticuerpo Fluorescente , Galactosiltransferasas/genética , Aparato de Golgi/ultraestructura , Proteínas Fluorescentes Verdes , Humanos , Interfase/fisiología , Membranas Intracelulares/metabolismo , Proteínas Luminiscentes/genética , Metafase/fisiología , Microscopía Electrónica , Proteínas de Unión al GTP Monoméricas/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas de Transporte Vesicular
18.
J Cell Biol ; 143(6): 1485-503, 1998 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-9852146

RESUMEN

Quantitative time-lapse imaging data of single cells expressing the transmembrane protein, vesicular stomatitis virus ts045 G protein fused to green fluorescent protein (VSVG-GFP), were used for kinetic modeling of protein traffic through the various compartments of the secretory pathway. A series of first order rate laws was sufficient to accurately describe VSVG-GFP transport, and provided compartment residence times and rate constants for transport into and out of the Golgi complex and delivery to the plasma membrane. For ER to Golgi transport the mean rate constant (i.e., the fraction of VSVG-GFP moved per unit of time) was 2.8% per min, for Golgi to plasma membrane transport it was 3.0% per min, and for transport from the plasma membrane to a degradative site it was 0.25% per min. Because these rate constants did not change as the concentration of VSVG-GFP in different compartments went from high (early in the experiment) to low (late in the experiment), secretory transport machinery was never saturated during the experiments. The processes of budding, translocation, and fusion of post-Golgi transport intermediates carrying VSVG- GFP to the plasma membrane were also analyzed using quantitative imaging techniques. Large pleiomorphic tubular structures, rather than small vesicles, were found to be the primary vehicles for Golgi to plasma membrane transport of VSVG-GFP. These structures budded as entire domains from the Golgi complex and underwent dynamic shape changes as they moved along microtubule tracks to the cell periphery. They carried up to 10,000 VSVG-GFP molecules and had a mean life time in COS cells of 3.8 min. In addition, they fused with the plasma membrane without intersecting other membrane transport pathways in the cell. These properties suggest that the post-Golgi intermediates represent a unique transport organelle for conveying large quantities of protein cargo from the Golgi complex directly to the plasma membrane.


Asunto(s)
Membrana Celular/metabolismo , Aparato de Golgi/metabolismo , Glicoproteínas de Membrana , Proteínas del Envoltorio Viral/metabolismo , Compuestos de Aluminio/farmacología , Animales , Transporte Biológico , Células COS , Membrana Celular/efectos de los fármacos , Membrana Celular/ultraestructura , Citocalasina B/farmacología , Fluoruros/farmacología , Aparato de Golgi/efectos de los fármacos , Aparato de Golgi/ultraestructura , Proteínas Fluorescentes Verdes , Cinética , Proteínas Luminiscentes/metabolismo , Modelos Biológicos , Nocodazol/farmacología , Proteínas Recombinantes de Fusión/metabolismo , Factores de Tiempo , Transfección , Virus de la Estomatitis Vesicular Indiana/genética , Proteínas del Envoltorio Viral/genética
20.
Appl Radiat Isot ; 49(3): 259-64, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9451779

RESUMEN

The Radiation Health Section of the Health Department of Western Australia has been a repository for unwanted radioactive sources for many years. They had been placed in the radioactive store located on the Queen Elizabeth II Medical Centre Campus. After a collection period of more than 20 years the storage facilities of the Radiation Health Section were nearing capacity. A decision was made to relocate these sources into a permanent near surface burial facility. Following extensive community consultation and site investigations, waste originating in Western Australia was disposed of at Mt Walton (East), 80 km North East of Koolyanobbing, Western Australia in November 1992.


Asunto(s)
Residuos Radiactivos , Eliminación de Residuos/métodos , Monitoreo del Ambiente , Arquitectura y Construcción de Instituciones de Salud , Fenómenos Geológicos , Geología , Humanos , Australia Occidental
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