Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 38
Filter
1.
Infect Dis Now ; 51(3): 293-295, 2021 May.
Article in English | MEDLINE | ID: mdl-33934809

ABSTRACT

Saccharomyces cerevisiae fungemia: risk factors, outcome and links with S. boulardii-containing probiotic administration. OBJECTIVE: The aim of our study was to review cases of S. cerevisiae fungemia along with the corresponding risk factors (including S. boulardii probiotic intake), treatment and outcomes. PATIENTS AND METHODS: Retrospective study (2005-2017) of S. cerevisiae fungemia. All the data were extracted from medical files. RESULTS: We identified 10 patients with S. cerevisiae fungemia. Mean age was 59.4 years (range 21-88). Four fifths (80%) were on total parenteral or enteral nutrition, 70% had a central venous line, and 30% were admitted in an Intensive Care Unit (ICU). S. boulardii-containing probiotic prescription was identified in 6 subjects. Three patients with no risk factors such as ICU or central venous catheter were 80 years old or more. Mortality rate was 50%. CONCLUSION: S. cerevisiae fungemia is a rare but life-threatening infection, associated with intake of probiotics containing S. boulardii. Besides classical risk factors, older age should be a contraindication for these probiotics.


Subject(s)
Fungemia/drug therapy , Fungemia/microbiology , Probiotics/adverse effects , Saccharomyces boulardii/pathogenicity , Saccharomyces cerevisiae/pathogenicity , Adult , Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , Enteral Nutrition/adverse effects , Female , Fungemia/mortality , Humans , Intensive Care Units , Male , Middle Aged , Parenteral Nutrition/adverse effects , Probiotics/administration & dosage , Retrospective Studies , Risk Factors , Saccharomyces boulardii/isolation & purification , Saccharomyces cerevisiae/isolation & purification , Treatment Outcome , Young Adult
4.
Transpl Infect Dis ; 12(1): 23-30, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19744284

ABSTRACT

Cytomegalovirus (CMV) is a major cause of infectious complications following cardiac transplantation, severely affecting short- and long-term outcomes. A 12-month, multicenter, randomized, open-label study in de novo cardiac transplant patients was undertaken to compare the efficacy, renal function, and safety of everolimus plus reduced cyclosporine versus mycophenolate mofetil (MMF) plus standard cyclosporine (ClinicalTrials.gov NCT00150046). CMV-specific data was prospectively collected on infections, laboratory evidence, CMV syndrome, and CMV disease. In total, 176 patients were randomized (everolimus 92; MMF 84). Use of CMV prophylaxis was similar between groups (everolimus 20.8%; MMF 24.0%). Patients in the everolimus arm had a significantly lower incidence of any CMV event (8.8% versus 32.5% with MMF, P<0.001), CMV infection as an adverse event (4.4% versus 16.9%, P=0.011), laboratory evidence of CMV (antigenemia 7.7% versus 27.7%, P<0.001; polymerase chain reaction assay 2.2% versus 12.0%, P=0.015), and CMV syndrome (1.1% versus 8.4%, P=0.028). In the donor (D)+/recipient (R)+and D-/R+ subgroups, even after adjusting for use of prophylaxis, the CMV event rate remained significantly lower with everolimus than with MMF (P=0.0015 and P=0.0381, respectively). In conclusion, de novo cardiac transplant recipients experienced lower rates of CMV infection, CMV syndrome, or organ involvement on an everolimus-based immunosuppressant regimen compared with MMF.


Subject(s)
Cytomegalovirus Infections/epidemiology , Heart Transplantation/adverse effects , Immunosuppressive Agents , Mycophenolic Acid/analogs & derivatives , Sirolimus/analogs & derivatives , Adult , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Cytomegalovirus/drug effects , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/prevention & control , Drug Therapy, Combination , Everolimus , Female , Graft Rejection/epidemiology , Heart Transplantation/immunology , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Incidence , Kidney Function Tests , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Sirolimus/administration & dosage , Sirolimus/adverse effects , Sirolimus/therapeutic use , Treatment Outcome
5.
Ann Vasc Surg ; 23(5): 634-8, 2009.
Article in English | MEDLINE | ID: mdl-19467828

ABSTRACT

BACKGROUND: We evaluated midterm results of endovascular management of traumatic aortic isthmic ruptures. METHODS: Between 2001 and 2008, 10 patients (seven males, mean age 38 years) underwent endovascular treatment of an acute aortic rupture. Eight procedures were emergent, with four cases of hemodynamic instability with Glasgow scores of 3, 5, and 7. Associated traumas were severe brain, liver, and pelvic bone injuries. All procedures were performed with transoesophageal echocardiography monitoring. We used two AneuRx and nine Medtronic Talent or Valiant stent grafts. RESULTS: All patients survived their traumatic isthmic rupture. In nine patients, stent-graft deployment was successful. One patient experienced a distal migration needing a laparotomy and deployment of an additional new thoracic stent graft. The mean intensive care unit stay was 48 hr (range 24-168). The mean hospital stay was 11 days (range 8-43). All patients were controlled clinically and by contrast computed tomography (CT) according to the EUROSTAR protocol. There were no endoleaks, stent graft-related complications, or late deaths during a mean follow-up of 49 months. The control CT showed a lack of apposition of the proximal part of the stent graft at the inner curve of the aortic arch in three patients. CONCLUSION: The midterm results of endovascular treatment of acute traumatic aortic isthmic rupture are encouraging and compare favorably to the surgical approach. Late follow-up is required to exclude possible stent-graft complications, especially in young patients with angulated aortic arches.


Subject(s)
Aortic Rupture/surgery , Blood Vessel Prosthesis Implantation , Acute Disease , Adolescent , Adult , Aortic Rupture/diagnostic imaging , Aortic Rupture/physiopathology , Aortography/methods , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Critical Care , Echocardiography, Transesophageal , Female , Foreign-Body Migration/etiology , Foreign-Body Migration/surgery , Hemodynamics , Humans , Length of Stay , Male , Middle Aged , Prosthesis Design , Reoperation , Retrospective Studies , Severity of Illness Index , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonography, Interventional , Young Adult
7.
Ann Vasc Surg ; 21(3): 312-7, 2007 May.
Article in English | MEDLINE | ID: mdl-17484967

ABSTRACT

The aim of this study is to compare measurement of stump pressure (SP) and somatosensory evoked potentials (SSEP) made during carotid surgery as criteria upon which to base the decision whether or not to use a shunt. We included 288 patients who underwent for carotid surgery under general anaesthesia. We performed 247 endarterectomies with patch closure (85.7%), 25 carotid transsection with reimplantation (8.7%), and 16 carotid bypasses (5.6%). SSEP monitoring showed no modification in 225/288 patients (78.1%), moderate modification in 32/288 patients (11.1%), and severe modification in 31/288 patients (10.8%). Shunt was used if there was moderate or severe SSEP modification in response to carotid clamping, which represents 63 patients in our series. A shunt was used in 47/288 patients (16.3%). In 16 patients, despite SSEP modifications, the shunt was not used because these SSEP modifications occurred only in the last minutes of the procedure just before off clamping the carotid. The mean SP for all patients was 51 mm Hg. In the shunted patients, the mean SP was 33 mm Hg. Variation of SP was correlated with the SSEP modifications. There was just one perioperative stroke in this series (1/288 = 0.3%). We concluded that the threshold of SP below which shunting is indicated in our study was 44 mm Hg with 81% sensibility and 68% specificity.


Subject(s)
Arteriovenous Shunt, Surgical , Blood Pressure , Endarterectomy, Carotid/methods , Evoked Potentials, Somatosensory , Monitoring, Intraoperative , Aged , Analysis of Variance , Blood Vessel Prosthesis Implantation/methods , Carotid Artery, Common/physiopathology , Carotid Artery, Common/surgery , Carotid Stenosis/physiopathology , Carotid Stenosis/surgery , Cerebrovascular Circulation , Female , Graft Occlusion, Vascular/prevention & control , Humans , Male , Middle Aged , Predictive Value of Tests , Saphenous Vein/surgery , Sensitivity and Specificity , Severity of Illness Index , Survival Analysis , Treatment Outcome
8.
Transplant Proc ; 39(1): 311-3, 2007.
Article in English | MEDLINE | ID: mdl-17275532

ABSTRACT

Bacillary angiomatosis is an infection caused by Bartonella, which has first been described in human immunodeficiency virus (HIV)-infected patients. We report an unusually located lesion, in a totally asymptomatic kidney transplant recipient. The diagnosis was strongly suggested based on the iconography and our histological analysis, but was not confirmed using polymerase chain reaction (PCR) and immunohistochemical studies. We illustrate our difficult way to the diagnosis as well as the course of the disease and our therapeutic strategy.


Subject(s)
Angiomatosis/diagnosis , Anti-Bacterial Agents/therapeutic use , Kidney Transplantation , Postoperative Complications/surgery , Thoracic Neoplasms/surgery , Bartonella/genetics , Bartonella/isolation & purification , Bartonella Infections/diagnosis , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Necrosis , Polymerase Chain Reaction , Radiography, Thoracic , Treatment Outcome
9.
Acta Chir Belg ; 106(4): 423-6, 2006.
Article in English | MEDLINE | ID: mdl-17017698

ABSTRACT

Osteosarcomas of the cranial bones need a large surgical radical resection. The best option to reconstruct mandible defect after resection is the free fibula flap. In our patient an acute ischaemic leg occurred just after the free fibula flap harvest for mandible reconstruction. The abnormal distribution of the calf arteries leads to catastrophic consequences. The peroneal artery could be the main dominant artery of the leg in a small number of patients. We reported an extremely rare case of "peronea magna", described in less than 0.2% of the global population. A careful pre-operative workup of the calf vessels is required in all the patients who need free fibula flap harvest.


Subject(s)
Bone Transplantation , Fibula/surgery , Intraoperative Complications , Ischemia/etiology , Leg/blood supply , Mandible/surgery , Plastic Surgery Procedures , Tissue and Organ Harvesting/adverse effects , Adult , Female , Fibula/blood supply , Follow-Up Studies , Graft Survival , Humans , Mandibular Neoplasms/surgery , Necrosis , Osteosarcoma/surgery , Popliteal Artery/abnormalities , Tibial Arteries/abnormalities
10.
J Cardiovasc Surg (Torino) ; 47(4): 477-9, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16953169

ABSTRACT

Dextrocardia with complete situs inversus is a rare condition that occurs approximately in 2/10,000 live births. Coronary revascularization management in this setting differs in the technical considerations imposed by the malposition of the heart itself. We report here a case of complete arterial revascularization using both internal thoracic arteries and the left (homologous vessel to the right) gastroepiploic artery in an adult patient with triple-vessel disease and situs inversus totalis. Strategies for the choice of conduits and anastomoses as well as technical details are discussed.


Subject(s)
Coronary Artery Bypass/methods , Coronary Disease/complications , Dextrocardia/complications , Coronary Disease/surgery , Follow-Up Studies , Humans , Male , Middle Aged
11.
Rev Mal Respir ; 22(1 Pt 1): 103-12, 2005 Feb.
Article in French | MEDLINE | ID: mdl-15968763

ABSTRACT

INTRODUCTION: An air leak following pulmonary resection is generally defined as persistent, or prolonged, if it fails to resolve within the first post-operative week. The precise definition has varied from study to study. STATE OF ART: Persistent air leak represents the most frequent complication in patients undergoing general thoracic procedures. The groups most at risk are elderly patients, patients with chronic obstructive pulmonary disease (COPD), and those who have general risk factors such as diabetes mellitus or who are taking oral steroids. The surgical procedures most commonly affected are upper lobectomies and lung volume reduction surgery for end-stage emphysema. PERSPECTIVES: Technically, performing a pleural tent at the time of an upper lobectomy may decrease the incidence of prolonged air leak. Reinforcement or buttressing of the staple line has been shown to decrease both the incidence and the duration of air leaks, but this increases costs and should thus be reserved for patients with lung parenchyma at the highest risk. The use of biological glues can be helpful in reducing the duration of chest tube drainage when applied intraoperatively for moderate and/or severe parenchymal air leaks, however, their systematic use in not recommended. The management of chest tube drainage after pulmonary resection varies widely from one institution to another. Most recent reports have favoured early discontinuation of negative pressure drainage and a move to underwater seal drainage (from the second post-operative day), however, no large scale randomised study is yet available to compare this with a more conservative approach. CONCLUSIONS: The management of persistent air leak following surgery requires identification of risk factors, good surgical technique and appropriate chest tube management.


Subject(s)
Pneumonectomy/adverse effects , Air , Humans , Respiration Disorders/etiology , Respiration Disorders/physiopathology
12.
Curr Opin Cardiol ; 20(2): 115-21, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15711197

ABSTRACT

PURPOSE OF REVIEW: Patients with aortic root pathology may benefit from 'valve-conservation' surgery although application of this philosophy is limited by a lack of 'standardized' surgical techniques. A functional classification of aortic root and valvular abnormalities has been developed in 260 patients and correlated with the etiology of the pathologic process and the surgical procedure performed. Early outcome was assessed using hospital records and medium-term follow-up by cardiological review. RECENT FINDINGS: From January 1995 until March 2001, 260 patients were operated on for aortic root pathology using valve-conserving surgical techniques. Hospital mortality was 2%; intra-operative echocardiography showed residual aortic regurgitation (Grade 1-2) in 11%, none in the remaining patients. Follow-up at a mean of 20 months (87% of patients) showed trivial or Grade 1 aortic regurgitation in 80%. SUMMARY: Application of a simple functional classification for aortic root pathology and aortic valve disease allows the logical application of 'valve-conserving' surgical procedures with excellent early and medium-term results.


Subject(s)
Aorta/physiopathology , Aortic Valve Insufficiency/surgery , Aortic Valve/physiopathology , Cardiac Surgical Procedures/methods , Aorta/abnormalities , Aorta/surgery , Aortic Valve/abnormalities , Aortic Valve/surgery , Aortic Valve Insufficiency/classification , Aortic Valve Insufficiency/etiology , Humans
13.
Eur J Cardiothorac Surg ; 26(3): 628-33, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15302061

ABSTRACT

OBJECTIVES: In regurgitant tricuspid aortic valves, cusp prolapse may be isolated or associated with dilatation of the proximal aorta. Newly appearing cusp prolapse can also appear after an aortic valve sparing operation (AVSO) and be responsible for residual aortic regurgitation. In this report, we describe our experience in repairing prolapsing aortic cusps in 44 patients with aortic regurgitation. METHODS: Between 1996 and 2003, 260 patients had aortic valve repair or valve sparing procedures in our department. All patients had peri-operative TEE. Prolapse of one or more of the aortic cusps was identified by TEE and confirmed by careful surgical inspection before and after valve sparing surgery. Forty-four patients with cusp prolapse were identified. Fifteen had an isolated prolapse, with a normal root (group I), 18 had cusp prolapse associated with dilatation of the proximal aorta (group IIa), and 11 had a newly appearing prolapse after AVSO (group IIb). Correction of the prolapsing cusp was achieved by either free edge plication, triangular resection or resuspension with PTFE. This procedure was associated with an aortic annuloplasty in group I, and with AVSO in groups II and III. RESULTS: Post-operative TEE showed AR trivial or grade I regurgitation. At a mean of 23 months follow-up, one patient with recurrent regurgitation required an aortic valve replacement with a homograft. All remaining patients were in NYHA class I or II. Echocardiography confirmed the durability of the valve repair. CONCLUSIONS: Among the common causes of aortic regurgitation, isolated cusp prolapse is frequent and is amenable to surgical repair with excellent mid-term results. In particular, in patents who are potential candidates for AVSO, identification and correction of an associated prolapse, either pre-existing or secondary to the AVSO procedure, may further extend the indications for this technique, increase its success rates and improve its long-term outcome.


Subject(s)
Aortic Valve Prolapse/surgery , Aortic Valve/surgery , Aortic Valve/pathology , Aortic Valve Prolapse/diagnostic imaging , Aortic Valve Prolapse/pathology , Cardiopulmonary Bypass , Echocardiography, Transesophageal , Follow-Up Studies , Humans , Middle Aged , Reoperation
15.
Ann Chir Plast Esthet ; 48(2): 99-114, 2003 Apr.
Article in French | MEDLINE | ID: mdl-12801550

ABSTRACT

Because of their rich blood supply and of their original detersive and filling properties, the muscular pedicled flaps harvested from the trunk or the omental flap elevated from the abdomen may be very usefull to treat large defects or major septic problems in pleural, pericardic or mediastinal cavities. We here describe the main principles to be followed in such intrathoracic reconstructions performed in order to control severe mediastinites, aortic prosthetic infections, pleural empyemas and broncho-pleural, tracheo-esophageal or broncho-esophageal fistulas. In all these circumstances, the muscular or omental flaps which are transferred into the chest are selected according to the recipient field and to their respective access to the upper, middle and lower portions of the pleural space or mediastinum. Twelve different flaps so appear available to achieve the adequate reconstruction, filling or coverage of nine distinct topographic sites. Their rational use, based on various anatomical guidelines, allows to prevent or to cure efficiently 90% of the infectious or fistular complications frequently observed in the postoperative course of aggressive, functional or oncological, intrathoracic surgical procedures.


Subject(s)
Omentum/surgery , Plastic Surgery Procedures/methods , Surgical Flaps , Thoracic Surgical Procedures/methods , Abdomen/surgery , Decision Making , Fistula/prevention & control , Humans , Mediastinum/pathology , Mediastinum/surgery , Omentum/pathology , Prosthesis Implantation , Surgical Wound Infection/prevention & control , Thorax/pathology
16.
Bull Mem Acad R Med Belg ; 158(5-6): 315-20, 2003.
Article in French | MEDLINE | ID: mdl-15025273

ABSTRACT

Autologuous stem cell transplantation within regional infarcted or ischemic myocardium is currently a focus of experimental research world-wide, and could provide a unique way to ensure myocardial functional recovery. In order to benefit from immediate access to bone marrow stromal cells at the time of myocardial injury, and thus avoid the delay rendered necessary by autologuous harvesting and clonal expansion, the use of allogeneic stem cell could be of major interest. This experimental work is based on a unique mini-swine model in which the histocompatibility antigens are known, and perfectly controlled, through inbreeding and investigate the survival and the induction of an immune tolerance to allogeneic stem cells injected into the infarcted myocardium with the use of transient immunosuppression (12 days).


Subject(s)
Cardiomyoplasty , Myocardial Infarction/therapy , Stem Cell Transplantation , Animals , Combined Modality Therapy , Disease Models, Animal , Immunosuppression Therapy/methods , Swine , Swine, Miniature
18.
Eur J Cardiothorac Surg ; 20(3): 468-74; discussion 474-5, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11509265

ABSTRACT

OBJECTIVE: To assess the effectiveness of positron emission tomography with radiolabeled [18F]-2-fluoro-deoxy-D-glucose (PET-FDG) imaging in mediastinal lymph node (LN) staging for non-small cell lung carcinoma (NSCLC) and to compare it to conventional clinical and surgical staging. METHODS: From June 1998 to February 2000, we enrolled 64 potentially resectable NSCLC patients in a prospective study of PET-FDG imaging of the mediastinum to assess LN involvement. Results of this technique were compared to conventional clinical and surgical staging. Diagnostic efficacy was determined by calculating sensitivity, specificity, overall accuracy, and positive and negative predictive values for each method. RESULTS: PET-FDG imaging correctly identified nodal stage (N0-N1 vs. N2) in 50 out of 61 patients (82%), overstaging occurred in eight patients (13%), and understaging in three patients (4.9%). The sensitivity, specificity, accuracy, and positive and negative predictive values for PET-FDG scan imaging were 67, 85, 82, 43, and 93.6%, respectively. Conventional staging correctly identified nodal stage (N0-N1 vs. N2) in 51 out of 62 patients (82%), overstaging occurred in five patients (8.1%), and understaging in six patients (9.7%). The sensitivity, specificity, accuracy, and positive and negative predictive values for conventional staging were 33, 90.6, 82, 37, and 89%, respectively. With regard to N2 disease, conventional staging showed a poor sensitivity (33%). Indeed, six out of 64 patients were understaged for mediastinal LN involvement. Even though the improvement was not statistically significant (McNemar P=0.08), the combined use of PET-FDG scan and computerized tomography (CT) scan allowed a two-fold increase in the sensitivity of our clinical preoperative staging. Moreover, relying on the PET-scan high negative predictive value might have contributed to a three-fold decrease in the number of required surgical staging procedures. CONCLUSIONS: Our study shows that the PET-FDG imaging strength lies in its very high negative predictive value and increased sensitivity. In this study, the overall accuracy of PET-FDG scan (82%) was lower than previously reported. Combined with chest CT-scan preoperatively, it may alleviate the need for surgical staging when PET-FDG studies of the mediastinum are negative. However, with a positive PET-FDG scan result, further diagnostic procedures should be pursued in order to avoid overstaging and allow better surgical patient selection.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Fluorodeoxyglucose F18 , Lung Neoplasms/diagnostic imaging , Radiopharmaceuticals , Tomography, Emission-Computed , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis , Male , Mediastinoscopy , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed
19.
Eur J Cardiothorac Surg ; 20(3): 481-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11509267

ABSTRACT

OBJECTIVE: To determine the presence of occult micrometastasis (OM) in a selected population of surgically resectable patients presenting with non-small cell lung carcinoma (NSCLC) and to evaluate its prognostic value on relapses and survival. METHODS: From February 1996 to December 1999, 99 patients undergoing surgical treatment for NSCLC were prospectively investigated for the presence of occult bone marrow micrometastasis. Tumor cells were detected with monoclonal primary antibodies directed against low molecular weight cytokeratins. RESULTS: Median follow-up time was 14.3 months (range 0.2-45.6 months). Overall prevalence of OM was 22.2% (22 out of 99). The presence of OM was not correlated to pathology, T status, or N status. In survival analysis, the only independent predictors of overall survival were N0 status and Stage I (P=0.016 and 0.004, respectively), while T1 was a predictor of disease-free survival (P=0.044). Metastasis and loco-regional recurrence were observed at follow-up in 18.2 (four out of 22) and 9% (two out of 22) of patients OM(+) and in 14.3 (11 out of 77) and 7.8% (six out of 77) of patients OM(-), respectively (P=not significant). OM was a predictor neither of overall survival nor of disease-free survival (P=0.52 and 0.97, respectively). In Stage I patients, 1-year overall survival and 1-year disease-free survival were 89 and 98% for OM(-) patients and 88 and 90% for OM(+) patients, respectively (P=0.57 and P=0.75). CONCLUSIONS: OM was present in >20% of surgically treated NSCLC patients and did not correlate to pathological variables. In contrast to previous published data, in this study the presence of OM had no influence on overall or disease-free survival.


Subject(s)
Bone Marrow Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/mortality , Aged , Aged, 80 and over , Bone Marrow Neoplasms/diagnosis , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Prognosis , Prospective Studies , Survival Analysis , Survival Rate
20.
J Biol Chem ; 276(10): 6983-92, 2001 Mar 09.
Article in English | MEDLINE | ID: mdl-11114293

ABSTRACT

The mechanism(s) by which Smads mediate and modulate the transforming growth factor (TGF)-beta signal transduction pathway in fibrogenesis are not well characterized. We previously showed that Smad3 promotes alpha2(I) collagen gene (COL1A2) activation in human glomerular mesangial cells, potentially contributing to glomerulosclerosis. Here, we report that Sp1 binding is necessary for TGF-beta1-induced type I collagen mRNA expression. Deletion of three Sp1 sites (GC box) between -376 and -268 or mutation of a CAGA box at -268/-260 inhibited TGF-beta1-induced alpha2(I) collagen promoter activity. TGF-beta1 inducibility was also blocked by a Smad3 dominant negative mutant. Chemical inhibition of Sp1 binding with mithramycin A, or deletion of the GC boxes, inhibited COL1A2 activation by Smad3, suggesting cooperation between Smad3 and Sp1 in the TGF-beta1 response. Electrophoretic mobility shift assay showed that Sp1 and Smads form complexes with -283/-250 promoter sequences. Coimmunoprecipitation experiments demonstrate that endogenous Sp1, Smad3, and Smad4 form complexes in mesangial cells. In a Gal4-LUC reporter assay system, Sp1 stimulated the TGF-beta1-induced transcriptional activity of Gal4-Smad3, Gal4-Smad4 (266), or both. Using the transactivation domain B of Sp1 fused to the Gal4 DNA binding domain, we show that, in our system, the transcriptional activity of this Sp1 domain is not regulated by TGF-beta1, but it becomes responsive to this factor when Smad3 is coexpressed. Finally, combined Sp1 and Smad3 overexpression induces marked ligand-independent and ligand-dependent promoter activity of COL1A2. Thus, Sp1 and Smad proteins form complexes and their synergy plays an important role in mediating TGF-beta1-induced alpha2(I) collagen expression in human mesangial cells.


Subject(s)
Collagen/biosynthesis , DNA-Binding Proteins/metabolism , Glomerular Mesangium/cytology , Plicamycin/analogs & derivatives , Sp1 Transcription Factor/metabolism , Trans-Activators/metabolism , Transforming Growth Factor beta/metabolism , Base Sequence , Blotting, Northern , Cell Line , Cell Nucleus/metabolism , Collagen Type I , Gene Deletion , Genes, Reporter , Humans , Ligands , Luciferases/metabolism , Molecular Sequence Data , Plicamycin/pharmacology , Precipitin Tests , Promoter Regions, Genetic , Protein Binding , Protein Structure, Tertiary , RNA, Messenger/metabolism , Smad3 Protein , Smad4 Protein , Time Factors , Transcriptional Activation , Transfection , Transforming Growth Factor beta1
SELECTION OF CITATIONS
SEARCH DETAIL
...