Structure of phage protein BC1872 from Bacillus cereus, a singleton with new fold.
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Biomedical subjects
Publications and source records attributed to F Collart.
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L-proline is an amino acid that plays an important role in proteins uniquely contributing to protein folding, structure, and stability, and this amino acid serves as a sequence-recognition motif. Proline biosynthesis can occur via two pathways, one from glutamate and the other from arginine. In both pathways, the last step of biosynthesis, the conversion of delta1-pyrroline-5-carboxylate (P5C) to L-proline, is catalyzed by delta1-pyrroline-5-carboxylate reductase (P5CR) using NAD(P)H as a cofactor. We have determined the first crystal structure of P5CR from two human pathogens, Neisseria meningitides and Streptococcus pyogenes, at 2.0 angstroms and 2.15 angstroms resolution, respectively. The catalytic unit of P5CR is a dimer composed of two domains, but the biological unit seems to be species-specific. The N-terminal domain of P5CR is an alpha/beta/alpha sandwich, a Rossmann fold. The C-terminal dimerization domain is rich in alpha-helices and shows domain swapping. Comparison of the native structure of P5CR to structures complexed with L-proline and NADP+ in two quite different primary sequence backgrounds provides unique information about key functional features: the active site and the catalytic mechanism. The inhibitory L-proline has been observed in the crystal structure.
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OBJECTIVE: To review the perioperative anaesthetic management of pulmonary arterial hypertension. DATA SOURCES: Extraction from Pubmed database of French and English articles on the perioperative anaesthetic management of pulmonary hypertension for 9 years. DATA SELECTION: The collected articles were reviewed and selected according their quality and originality. The more recent data were selected. DATA SYNTHESIS: Pulmonary arterial hypertension is classically divided in primary and secondary. Primary pulmonary hypertension (familial and sporadic) is relatively severe and rare. Muscularization of the terminal portion of the pulmonary vascular arterial tree, caused by smooth muscle cell hyperplasia is the first change. Pulmonary arterial hypertension linked with disorders of the respiratory system and hypoxemia or pulmonary venous hypertension including mitral valve disease and chronic left ventricular dysfunction are often associated with high morbidity and mortality. The main consequence of pulmonary hypertension development is the occurrence of right-sided circulatory failure. A better understanding of disease pathophysiology will contribute to the development of new therapies increasing then the prognosis of these patients. The management of primary pulmonary hypertension or secondary pulmonary arterial hypertension is a challenge for the anaesthesiologist because the risk of right ventricular failure is markedly increased.
Despite progress with diagnostic criteria, the type and timing of laboratory tests used to diagnose infective endocarditis (IE) have not been standardized. This is especially true with serological testing. Patients with suspected IE were evaluated by a standard diagnostic protocol. This protocol mandated an evaluation of the patients according to the modified Duke criteria and used a battery of laboratory investigations, including three sets of blood cultures and systematic serological testing for Coxiella burnetii, Bartonella spp., Aspergillus spp., Legionella pneumophila, and rheumatoid factor. In addition, cardiac valvular materials obtained at surgery were subjected to a comprehensive diagnostic evaluation, including PCR aimed at documenting the presence of fastidious organisms. The study included 1,998 suspected cases of IE seen over a 9-year period from April 1994 to December 2004 in Marseilles, France. They were evaluated prospectively. A total of 427 (21.4%) patients were diagnosed as having definite endocarditis. Possible endocarditis was diagnosed in 261 (13%) cases. The etiologic diagnosis was established in 397 (93%) cases by blood cultures, serological tests, and examination of the materials obtained from cardiac valves, respectively, in 348 (81.5%), 34 (8%), and 15 (3.5%) definite cases of IE. Concomitant infection with streptococci and C. burnetii was seen in two cases. The results of serological and rheumatoid factor evaluation reclassified 38 (8.9%) possible cases of IE as definite cases. Systematic serological testing improved the performance of the modified Duke criteria and was instrumental in establishing the etiologic diagnosis in 8% (34/427) cases of IE.
A 46-year-old woman was monitored by bispectral index monitoring (BIS) during redo aortic and mitral valve replacement. On release of the aortic cross clamp there was a sudden, severe, unexplained, and sustained fall in the BIS value. Postoperatively, a CT scan was consistent with multiple ischaemic lesions. The lesions were presumed to be due to air embolism. This case suggests that a sudden unexplained and persistent fall in BIS may indicate cerebral ischaemia.
An apico-aortic shunt enables a reduction in the aortic transvalvular pressure gradient. It is recommended for patients with symptomatic severe stenosis when anatomical constraints contra-indicate valvular replacement. The authors report the case of a patient who underwent this uncommon procedure, which was indicated due to previous coronary bypass surgery using both mammary arteries, plus massive calcification of the ascending aorta. Angio-haemodynamic investigation and MRI performed three years and five years respectively following the procedure confirmed its efficiency. An analysis of the few reported series confirms the value of this special procedure.
BACKGROUND: Procalcitonin (PCT) blood concentrations are known to be an appropriate marker of severe systemic inflammatory response syndrome (SIRS) induced by coronary artery surgery with and without cardiopulmonary bypass. Pro-brain natriuretic peptide (N-BNP) is a newly described cardiac hormone considered to be an effective marker of severity and prognosis of acute coronary syndromes and congestive heart failure. We evaluated the perioperative time courses of PCT and N-BNP and investigated their role as early markers of severe SIRS (SIRS with cardiovascular dysfunction) induced by off-pump coronary artery bypass (OPCAB). METHODS: Sixty-three patients were prospectively included. The American College of Chest Physicians Classification was used to diagnose SIRS and organ system failure to define severe SIRS. Serum concentrations of PCT and N-BNP were determined before, during and after surgery. Receiver operating characteristic curves and cut-off values were used to assess the ability of these markers to predict postoperative severe SIRS. RESULTS: SIRS occurred in 25 (39%) patients. Nine of them (14%) showed severe SIRS. Significantly higher serum concentrations of N-BNP and PCT were found in patients with severe SIRS with peak concentrations respectively at 8887 pg ml(-1) (range 2940-29372 pg ml(-1)) for N-BNP and 9.50 ng ml(-1) (range 1-65 ng ml(-1)) for PCT. The area under the curve using N-BNP to detect postoperative severe SIRS was 0.799 before surgery (0.408 for PCT; P<0.01) and 0.824 at the end of surgery (0.762 for PCT; P<0.05). CONCLUSIONS: N-BNP may be an appropriate marker indicating the early development of non-infectious postoperative severe SIRS after OPCAB.
OBJECTIVE: To compare N-terminal pro-brain natriuretic peptide (NT-pro-BNP), procalcitonin (PCT), and troponin I (Tn I) concentrations during and after coronary artery surgery in patients with or without cardiovascular complications. DESIGN AND SETTING: Prospective, comparative study of 12 months in the cardiovascular intensive care unit in a university hospital. PATIENTS: 60 adult patients undergoing coronary artery bypass grafting with the off-pump technique. MEASUREMENTS AND RESULTS: Plasma NT-pro-BNP, PCT, and Tn I levels were measured before and immediately after the end of operation and on PODs 1, and 2 and 3. We defined complicated postoperative course as myocardial infarction, cardiogenic shock, arrhythmias, congestive heart failure, and death occurring after the fourth postoperative hour. Receiver operating characteristic (ROC) curve cutoff values were used to assess the ability of the three markers to predict future cardiac events. The area under ROC curve (AUC) using NT-pro-BNP to detect a cardiovascular complicated course was 0.780 at the preoperative time and 0.850 at the end of surgery. A preoperative NT-pro-BNP value of 397 pg/ml had a sensitivity of 76%, specificity of 67%, and accuracy of 74% for predicting a subsequent cardiovascular complication. An immediate postoperative NT-pro-BNP value of 430 pg/ml had a sensitivity of 80%, specificity of 77%, and accuracy of 76%. Patients with preoperative NT-pro-BNP levels less than 275 pg/ml had an excellent postoperative prognosis. Other two markers were less appropriate. CONCLUSIONS: NT-pro-BNP levels measured before and immediately after off-pump coronary artery bypass seem to be predictive of postoperative cardiac events.
The crystal structure of the YckF protein from Bacillus subtilis was determined with MAD phasing and refined at 1.95A resolution. YckF forms a tight tetramer both in crystals and in solution. Conservation of such oligomerization in other phosphate sugar isomerases indicates that the crystallographically observed tetramer is physiologically relevant. The structure of YckF was compared to with its ortholog from Methanococcus jannaschii, MJ1247. Both of these proteins have phosphate hexulose isomerase activity, although neither of the organisms can utilize methane or methanol as source of energy and/or carbon. Extensive sequence and structural similarities with MJ1247 and with the isomerase domain of glucosamine-6-phosphate synthase from Escherichia coli allowed us to group residues contributing to substrate binding or catalysis. Few notable differences among these structures suggest possible cooperativity of the four active sites of the tetramer. Phylogenetic relationships between obligatory and facultative methylotrophs along with B. subtilis and E. coli provide clues about the possible evolution of genes as they loose their physiological importance.
A close association between human herpesvirus-8 (HHV-8) and Kaposi's sarcoma (KS) has been shown in transplant recipients, but donor-to-recipient transmission of HHV-8 is uncommon. Herein we report a case of a heart transplant recipient who had a fatal visceral KS in association with HHV-8 seroconversion at 18 months after transplantation with a donor having positive serology discovered after transplantation.
The surgical treatment of mitral regurgitation has been completely revamped in the last years. The development of reproducible and durable plasty techniques has made mitral valve replacement less and less frequent. The virtual disappearance of rheumatic valve disease in developed countries has made degenerative disease the most frequent etiology of mitral insufficiency. Furthermore the outlook of this pathology has been modified by the early surgical treatment. The following article presents the surgical techniques available today and their indications in the different types of mitral insufficiency.
OBJECTIVE: To review the perioperative anaesthetic management of ventricular assist devices. DATA SOURCES: Extraction from Pubmed database of french and english articles on the perioperative anaesthetic management of ventricular assist devices for 15 years. DATA SELECTION: The collected articles were reviewed and selected according to their quality and originality. The more recent data were selected. DATA SYNTHESIS: Cardiac transplantation is an effective treatment for patients in end stage cardiac failure, but the average waiting time of 17 months, associated with the lack of organs (357 out of 832 candidates were transplanted in 1996) results in a high number of deaths in patients awaiting transplantation. The appearance in the 1980's, of the first ventricular assist device (VAD) provided a new possibility for the management of patients with end-stage cardiac failure awaiting transplantation ("bridge to transplant"). The perioperative anaesthetic management of these patients is complex. End stage cardiac failure, poorly responsive to pharmacological interventions, results rapidly in secondary organ dysfunctions. VADs produce a rapid improvement in haemodynamic, renal, hepatic and neuro-endocrine functions over a 2 months period, allowing transplantation to take place under optimal conditions. However VADs are not without complications (1 year mortality of 20%), of which the major are: infections (40%), perioperative haemorrhage (30%) and thrombo-embolic sequelae (30%). A best knowledge of pathophysiology of these complications is necessary to an optimal management of patients with ventricular assist devices.
We report the case of a female patient of 76 years old admitted to our hospital for a pre-operative assessment of a symptomatic mitral regurgitation (MR) whose transthoracic echocardiography revealed only a trivial regurgitation. The occurrence during hospital stay of an acute pulmonary edema contemporary to the occurrence of a huge MR permitted to suspect the diagnosis of a paroxystic ischemic MR. Angiographic and hemodynamic evaluation revealed only a non-significant atheromateous plaque located in the distal LAD. The infusion of Methylergometrine triggered a severe spasm at the site of that plaque, associated with a huge MR visualized by TTE with restricted movements of both leaflets, responsible for an acute pulmonary edema occurring on the table of the catheterization laboratory. Recovery was quickly obtained after intravenous injection of Nitroglycerin, which removed the spasm and valvular regurgitation. The diagnosis of paroxystic ischemic mitral regurgitation was confirmed and a treatment based on high dosage of calcium-blocker was decided. After a follow-up of more than one year, the patient remains asymptomatic and the regurgitation has never occurred.
We report the case of a young patient native of the Ivory Coast who suffered from homozygous hemoglobin C disease. He presented with the usual findings of this hemoglobinopathy: a moderate hemolytic anemia and a massive, painful and even disabling splenomegaly. Pain completely disappeared following splenectomy. However, postoperative course was complicated by portal venous thrombosis, which was medically treated. No deficiency of natural coagulation inhibitors could be demonstrated, so splenectomy was the only factor predisposing to thrombosis. We consider that in only very few cases of hemoglobin C disease, splenectomy (preceded by prophylactic antipneumococcic vaccine) may be indicated from pain and risk of spontaneous splenic rupture.
ACE inhibitors and ARA are for the nephrologist two completely unique classes of antihypertensive agents as they offer the opportunity to control microalbuminuria, proteinuria and slow the progression of renal diseases. These properties have mainly been studied in type 1 and type 2 diabetics but can be extended to a wide range of renal diseases. The renal effects of the two classes of compounds differ but the clinical significance of these differences remains to be ascertained.
The automation of protein structure determination is an essential component for high-throughput structural analysis in protein X-ray crystallography and is a key element in structural genomics. This highly challenging undertaking relies at present on the availability of high-quality native and derivatized protein crystals diffracting to high or moderate resolution, respectively. Obtaining such crystals often requires significant effort. The present study demonstrates that phases obtained at low resolution (>3.0 A) from crystals of SeMet-labeled protein can be successfully used for automated structure determination. The crystal structure of acetate CoA-transferase alpha-subunit was solved using 3.4 A multi-wavelength anomalous dispersion data collected from a crystal containing SeMet-substituted protein and 1.9 A data collected from a native protein crystal.
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