The major histocompatibility complex class II Ea promoter requires TFIID binding to an initiator sequence.

The major histocompatibility complex (MHC) class II Ea promoter is dependent on the presence of conserved upstream X and Y boxes and of initiator (Inr) sequences. In vitro transcription analysis of the Inr region with linker-scanning mutants pinpoints a functionally essential element that shows homology to the terminal deoxynucleotidyltransferase (TdT) Inr; contrary to the TdT Inr and other Inrs identified so far, the key sequence, between positions +5 and +12, is located within a transcribed area. Swapping the TdT sequence into the corresponding Ea position leads to a fivefold increase in transcription rate, without altering start site selection. Inr-binding proteins LBP-1/CP2 and TIP--a TdT Inr-binding protein unrelated to YY1--recognize the Ea Inr; they interact with overlapping yet distinct sequences around the Cap site, but their binding does not coincide with Ea Inr activity. A good correlation is, rather, found with binding of immunopurified holo-TFIID to this element. TFIID interacts both with Ea TATA-like and Inr sequences, but only the latter is functionally relevant. Unlike TBP, TFIID binds in the absence of TFIIA, indicating a stabilizing role for TBP-associated factors in Ea promoter recognition. Sequence comparison with other mouse and human MHC class II promoters suggests a common mechanism of start site(s) selection for the MHC class II gene family.

[Perception and understanding chronic heart failure by the patient. The impact of therapeutic education on the level of knowledge of patients. About 350 cases]. / Perception et compréhension de l'insuffisance cardiaque chronique par le patient. Impact d'une formation éducative sur les connaissances des patients. Etude médico-infirmière à propos de 35 cas.

UNLABELLED: Heart failure is a severe disease with a poor prognosis despite major therapeutic progresses achieved recently. A key factor is the high number of hospitalizations for heart failure, considered as being avoidable, since they are related to a lack of adequate management of the patients. Several therapeutic education programs focused on heart failure are in progress. Even though these programs aim at making patients an active agent managing the disease, data on patient's level of knowledge and experience regarding heart failure are scarce. The aim of our study was to analyze the patient's perception of the disease and his/her practices about this disease, as well as the treatments used. METHODS: we included 350 consecutive patients and analyzed their level of knowledge and experience using a questionnaire, as well as interviews performed by nurses and physicians. This initial assessment was followed by a second assessment after an 8-hours course in 2 days, made by the multidisciplinary education team of R. Dubos hospital (including physicians, nurses, physiotherapists, dietician). RESULTS: in contrast to tests assessing the knowledge on the disease, which were in overall satisfactory, the results on the level of knowledge on treatments and heart failure pathways were poor. The courses improve significantly the level of knowledge in all domains, whatever would the age and the level of patient's demand for information be. The analysis of the patient's conception of his/her own disease reveals the lack of knowledge on the severity of heart failure. Frequently, the effect of treatments is considered as poorly efficient, and a substantial fraction of these patients have underlying depressive moods. CONCLUSION: the understanding of the level of knowledge and the perception of the patient regarding his/her disease is primordial for setting educational structures and programs. However, the patient's conception of the disease is different from care providers. It is therefore essential to assess the patient's conception by an educational diagnosis prior to implement adapted education programs, in order to improve durably the patient's knowledge, at every age.

Down-regulation of cyclin B1 gene transcription in terminally differentiated skeletal muscle cells is associated with loss of functional CCAAT-binding NF-Y complex.

The observation that cyclin B1 protein and mRNAs are down-regulated in terminally differentiated (TD) C2C12 cells, suggested us to investigate the transcriptional regulation of the cyclin B1 gene in these cells. Transfections of cyclin B1 promoter constructs indicate that two CCAAT boxes support cyclin B1 promoter activity in proliferating cells. EMSAs demonstrate that both CCAAT boxes are recognized by the trimeric NF-Y complex in proliferating but not in TD cells. Transfecting a dominant-negative mutant of NF-YA we provide evidence that NF-Y is required for maximal promoter activity. Addition of recombinant NF-YA to TD C2C12 nuclear extracts restores binding activity in vitro, thus indicating that the loss of NF-YA in TD cells is responsible for the lack of the NF-Y binding to the CCAAT boxes. Consistent with this, we found that the NF-YA protein is absent in TD C2C12 cells. In conclusion, our data demonstrate that NF-Y is required for cyclin B1 promoter activity. We also demonstrate that cyclin B1 expression is regulated at the transcriptional level in TD C2C12 cells and that the switch-off of cyclin B1 promoter activity in differentiated cells depends upon the loss of a functional NF-Y complex. In particular the loss of NF-YA protein is most likely responsible for its inactivation.

NF-Y histone fold alpha1 helices help impart CCAAT specificity.

NF-Y is a conserved trimeric transcriptional activator with an extremely high specificity for CCAAT boxes. The NF-YB and NF-YC subunits have histone fold motifs with a high degree of homology to NC2alpha/beta, a TBP-binding repressor. The histone fold is composed of three alpha helices, alpha1, alpha2, alpha3, separated by short loops. Structural data on core histones showed that alpha1 are involved in DNA-binding. To understand the molecular basis of NF-Y sequence-specificity, we constructed deletion and swapping mutants, in which the alpha1 of NC2 and archeal HMfB, a bona fide histonic protein, was placed in NF-YB and NF-YC. Our analysis indicates that (i) subunit interactions are normal; (ii) NF-YB-NF-YC and NC2alpha/beta do not form heterodimers and NC2 cannot associate NF-YA. (iii) None of the NF-Y swaps can complex with TBP on a TATA box. (iv) Specific residues, R47 and K49 in NF-YC and N61 in NF-YB, are crucial for CCAAT-binding. We conclude that specificity of the NF-Y trimer is not due to NF-YA only, but stems in part from the contribution of the histone fold alpha1, particularly that of NF-YB.

Cloning and expression of human NF-YC.

The CCAAT box is an important element in eukaryotic promoters and NF-Y (CBF) is a conserved heterotrimeric protein binding to it. Two subunits, NF-YB and NF-YC, contain a histone-like motif. We cloned the complete cDNA coding for the human NF-YC gene. The ORF codes for a 335 aa protein that shows virtual identity to the rat sequence, confirming the stunning invariance of NF-Y genes across species. We expressed and purified the yeast homology domain of NF-YC in bacteria and performed EMSA together with the corresponding conserved domains of NF-YA and NF-YB, obtaining a CCAAT-binding mini-NF-Y. We evaluated the expression of NF-YC and found that mRNA levels are similar in different human tissues except in testis.

Bedside B-type natriuretic peptide and functional capacity in chronic heart failure.

OBJECTIVES: To determine if B-type natriuretic peptide (BNP) measurement could be useful in determination of functional capacity in patients suffering from chronic heart failure. BACKGROUND: Evaluating functional capacity is a crucial factor in the follow-up of patients with chronic heart failure. There are numerous methods for measuring functional capacity and their relative merits remain under discussion. Clinical classifications are very subjective and other methods are difficult to use in clinical practice. METHODS: We evaluated functional capacity in 151 consecutive patients using the 6-min walk test. All patients were clinically classified using the New York Heart Association (NYHA) classification. We measured BNP plasma levels using a bedside BNP test. RESULTS: Six minute walk test performance decreased through NYHA classes 1 to 4 (469+/-87, 411+/-82, 325+/-83 and 196+/-63 m, respectively, P<0.01) and BNP levels increased through NYHA classes 1 to 4 (26.3+/-7.2, 73+/-13, 401+/-74 and 924+/-84 pg/ml, respectively, P<0.001). There was a significant correlation between 6-min walk test performance and BNP plasma levels (R=0.69 P<0.001) and a weaker correlation between BNP and left ventricular ejection fraction (R=0.45 P<0.04). In some patients there was a mismatch between NYHA classification and 6-min walk test performance. In all cases BNP could correct the clinical estimation of functional capacity. When we divided the patients into three sub-groups within each NYHA class, we showed that using BNP could better define functional capacity in patients suffering from chronic heart failure in NYHA classes I to III. CONCLUSION: The measurement of BNP levels thus usefully supplements the clinical examination. The existence of bedside BNP testing methods facilitates its use in routine clinical practice. It also permits easier follow-up of patients with chronic heart failure.

Short-term effects of sinus rhythm restoration in patients with lone atrial fibrillation: a hormonal study.

It is well known that atrial fibrillation can lead to heart failure, and is attributed to rapid ventricular rate (tachycardia-induced cardiomyopathy). Some recent studies suggest the possible existence of an intrinsic left-ventricular factor related to atrial fibrillation, irrespective of other elements. In order to demonstrate the implication of this factor, we measured B-type Natriuretic Peptide, known as a functional marker of left-ventricular dysfunction, in 40 consecutive patients with chronic non-valvular atrial fibrillation, with low ventricular rate and absence of clinical heart failure or echocardiographic left-ventricular dysfunction. In all patients, Brain Natriuretic Peptide (BNP) plasma level was high and dramatically decreased 24 h after external electrical cardioversion (61.4 pg/ml before cardioversion, 23.5 pg/ml 1 day after cardioversion, P<0.002). Our study demonstrates that atrial fibrillation, in absence of high ventricular rate, induces an asymptomatic cardiac alteration that is not detectable by echocardiography.

Myocardial contractile reserve under low doses of dobutamine and improvement of left ventricular ejection fraction with treatment by carvedilol.

To examine the ability of myocardial contractile reserve (MCR) assessment to predict the improvement of left ventricular ejection fraction with treatment by carvedilol, a prospective study was undertaken in 85 patients with chronic heart failure and left ventricular ejection fraction < 45%. Low dose dobutamine echocardiography (DSE), a 6-min walk test and measured brain natriuretic peptide (BNP) were assessed in all the patients. Patients were separated into two groups. Group A were patients without any myocardial reserve and group B patients with a myocardial contractile reserve defined as an increment of more than 20% of the resting left ventricular ejection fraction during dobutamine infusion. The two groups differed for percentage of ischemic cardiomyopathy (67.8 in group A vs. 29.7% in group B P = 0.028), 6-min walk test performance (respectively, 343 vs. 415 meters P < 0.05) and BNP plasma levels (respectively, 184.5 vs. 70.1 P < 0.02) but not for left ventricular ejection fraction or NYHA class. During DSE, MCR and heart rate variation was higher in group B than in group A. At the end of the follow up, LVEF increased and NYHA class decreased in group B but not in group A. In multivariate analysis the existence of MCR could predict the improvement of LVEF with treatment by carvedilol. In our study, studying MCR could help to predict patients who will improve their LVEF with carvedilol prior to the administration of the treatment.

Thallium gated SPECT: relation between immediate post-stress evolution of ejection fraction and severity of perfusion pattern.

BACKGROUND AND AIMS: A significant decrease of left ventricular ejection fraction (LVEF) at stress has been reported with 99Tc(m) gated single-photon emission computed tomography (gSPECT) in severe myocardial stunning up to 1 h after exercise. This study was designed to show whether 201Tl gSPECT can measure LVEF evolution from rest to stress in routine examination and give additional information to perfusion interpretation since acquisition starts immediately after stress test. METHODS: Post-exercise and rest 201Tl gSPECT were performed in 187 patients with suspected coronary artery disease. Myocardial perfusion was quantified by 20-segment analysis. Patients were divided into four groups according to their summed perfusion score, reversibility rate and electrocardiographic findings, i.e. in order of severity: I = normal perfusion, II = fixed defect owing to a myocardial infarction, III = full reversible ischaemia, and IV = partial reversible ischaemia. LVEF was calculated by Germano's automatic algorithm. RESULTS: Normal subjects (n = 29) and infarcted patients (n = 34) showed a significant LVEF increase between rest and stress, +7 +/- 9% and +5 +/- 7% respectively. In full reversible ischaemic patients (n = 46), stress LVEF showed no increase (+1 +/- 8%) and this group was statistically different from both group I and group II. Furthermore, when ischaemia was partially reversible (n = 31), LVEF decreased significantly (-3 +/- 8%), particularly when exercise tests were abnormal (-4 +/- 8%). Group IV was statistically different from groups I and II. CONCLUSIONS: Good agreement exists between the severity of ischaemic perfusion pattern and LVEF degradation at stress, which is consistent with previously published data using 99Tc(m) gSPECT. Additionally, the use of 201Tl for immediate post-exercise imaging allows the observation of a physiological LVEF increase in normal and infarcted patients.

[Recurrent bronchogenic cyst with rupture into the pericardium. A case report]. / Kyste bronchogénique récidivant rompu dans le péricarde. A propos d'un cas.

A case of tamponnade due to intrapericardial rupture of a recurrent bronchogenic cyst, presenting as pericarditis, is described. This case is unique because it demonstrates the possibility of rupture of a bronchogenic cyst into the pericardium and by the unusual mode of presentation. It also shows that bronchogenic cysts may recur many years after incomplete ablation. Bronchogenic cysts are benign dysembrioplasic formations characterised by their respiratory epithelial lining. The usual presentation in the adult is by haemorrhage or infection, but our case shows that recurrent pericarditis without an obvious cause may be due to bronchogenic cyst, which should be systematically excluded. The diagnosis suspected after medical imaging (chest X-ray, scanner, magnetic resonance imaging) is confirmed by histology. Total surgical ablation is the treatment of choice and may be curative.

[Comparison of segmental wall motion in electrocardiogram-gated myocardial scintigraphy and transthoracic echocardiography]. / Comparaison de la cinétique segmentaire entre la tomoscintigraphie myocardique couplée à l'électrocardiogramme et l'échocardiographie transthoracique.

ECG-gated myocardial scintigraphy (Gspect) is a recent method of assessing myocardial perfusion, left ventricular ejection fraction and regional wall motion in a single investigation. It reduces the time required for the evaluation of coronary patients by radionucleide cardiology. Many reports have validated the measurement of the left ventricular ejection fraction compared with other methods. However, there are fewer series reporting the results of regional wall motion. The authors compared segmental wall motion by Gspect after injecting Thallium or Mibi and by transthoracic echocardiography in 47 patients or 423 myocardial segments. The concordance of score (normal, hypokinetic, akinetic, dyskinetic) was 75% (Kappa = 0.538). If analysis was limited to a normal-abnormal differentiation (binary analysis) it increased to 83%. When perfusion was taken into consideration, it was 81% (normal perfusion), 63% (mild hypoperfusion) and 70% (moderate and severe hypoperfusion). This concordance improved in binary analysis respectively to 85, 74 and 86% respectively. When the typs of segment was taken into consideration, concordance varied from 57 to 100%. The concordances were 74% for Thallium and 78% for Mibi scintigraphy, improving to 82% and 85% respectively in binary analysis. Thus, analysis of LV regional wall motion by Gspect is comparable to transthoracic echocardiography. This result, completed by measurement of LV ejection fraction and of myocardial perfusion, provides a method of evaluation of coronary patients in a single investigation.

[Anaphylactic shock and myocytic necrosis after treatment with Artotec]. / Réaction anaphylactique et nécrose myocytaire consécutives à la prise d'Artotec.

Treatment with non-steroid anti-inflammatory drugs associated with a prostaglandin analogue is common, but the potential cardiovascular effects are largely unknown. The authors report a case of myocardial necrosis and anaphylactic shock due to treatment with diclofenac and misoprostol. The reintroduction of the treatment in hospital led to the recurrence of the initial cutaneous and cardiac symptoms in this patient.

[Cardiobacterium hominis on a aortic valve prosthesis]. / Endocardite à Cardiobacterium hominis sur prothèse valvulaire aortique.

A new case of late bacterial endocarditis caused by Cardiobacterium hominis is reported. The infection developed on an aortic valve prosthesis and responded favourably to medical treatment. The main characteristics of the micro-organism and of the oslerian graft are reviewed in the light of published data. The problem of endocarditis with negative blood cultures is discussed since C. hominis is reputed difficult to cultivate, although this was not the case in our patient.

[Recurrent syncope during deglutition. An uncommon form of sinusal dysfunction]. / Syncopes itératives lors de la déglutition. Une forme rare de dysfonction sinusale.

The authors report the case of a 69 year old man with a 16 year history of syncope occurring only while swallowing liquids. Two episodes were observed during a hospital admission to the intensive care unit for unstable angina and allowed documentation of prolonged sinus arrest (7 sec) causing syncope. In the light of this case and a review of the literature, the physiopathological role of deglutition in the genesis of cardiac conduction defects and arrhythmias is discussed and the new classification of sinus node dysfunction proposed by Bashour in 1985 is recalled.

[Single coronary artery arising from the right coronary sinus. Report of two cases]. / Artère coronaire unique naissant du sinus coronaire droit. A propos de deux cas.

The authors report two cases of single coronary artery arising from the right coronary sinus. Both patients had angina with reversible myocardial ischaemia on exercise Thallium scintigraphy. Coronary angiography showed single coronary artery arising from the right coronary sinus in both cases with severe stenosis of the right coronary artery in the first and occlusion of the right coronary artery in the second patient. Both underwent surgical revascularisation with a good result. Single coronary artery is a rare congenital abnormality (approximately 0.36 per 1,000) diagnosed at autopsy until 1963, and thereafter at coronary angiography. A review of the literature shows that an equal number of single coronary arteries arise from the right as from the left coronary sinus: there does not seem to be an increased risk of complication when a branch runs between the aorta and pulmonary artery. On the other hand, single coronary arteries arising from the right coronary sinus seem to be more commonly associated with atherosclerosis than a network with two coronary arteries, but when the lesions are proximal, the risk is high. Revascularisation is indicated only when myocardial ischaemia has been documented.

[Value of type B natriuretic peptide in the emergency management of patients with suspected cardiac failure. Report of 125 cases]. / Apports du peptide natriurétique de type B dans la prise en charge aux urgences des patients suspects d'insuffisance cardiaque. A propos de 125 patients.

Shortness of breath is a common cause of consultation in the emergency unit. Therefore, it is essential to diagnose cases of cardiac failure. This may be difficult in some cases. The authors set out to assess the value of measuring brain natiuretic peptide in this context. Brain natiuretic peptide (BNP) was measured by an ultrafast method (Biosite/BMD) on arrival of 125 patients to the emergency unit. The results were then compared with the diagnoses made in the emergency unit and those of the hospital discharge summary. Nearly 18% of patients were wrongly classified in the emergency room; 1/3 were falsely diagnosed as cardiac failure and 2/3 were not recognised initially as having cardiac failure. In 90% of patients, in particular in the group wrongly considered as not having cardiac failure, BNP measurement could have helped correct the mistake. The optimal threshold value of BNP for diagnosis of cardiac failure in this study was 300 pg/mL, with positive and negative predictive values of 92.4 and 90.2%, respectively.

[Isolated left ventricular muscular diverticulum in an adult. Value of non-invasive examinations]. / Diverticule musculaire isolé du ventricule gauche chez l'adulte. Intérêt des explorations non invasives.

The authors report a case of ventriculum in a 45 year old women investigated for chest pain. This was a congenital muscular left ventricular diverticulum confirmed by a complete imaging series including echocardiography, magnetic resonance imaging, angio-scintigraphy and conventional angiography. This diverticulum was unusual due to the fact that there was no associated congenital disease and that it was discovered in an adult. The authors review the literature and discuss the value of non-invasive imaging procedures.

[Citalopram and Torsades de Pointes. A case report]. / Citalopram et torsades de pointes. A propos d'un cas.

Inhibitors of serotonin uptake are drugs prescribed without recognised cardiovascular risk. The authors report a case of torsades de pointes following Citalopram ingestion. In this patient, the proof of reintroduction in a hospital environment resulted in prolongation of the QT interval. Screening of patients for acquired or congenital long QT intervals is therefore necessary before starting treatment with Citalopram.

[Stress ultrasonography under low doses of dobutamine, contractile reserve and dilated cardiomyopathy]. / Echographie de stress sous faibles doses de dobutamine, réserve contractile et cardiomyopathies dilatées.

The demonstration of a myocardial contractile reserve with low dose dobutamine is an emerging imaging technique in patients with dilated cardiomyopathy. This contractile reserve is correlated with a better prognosis and enables identification of subgroups of patients who could increase their left ventricular ejection fractions under carvedilol. A review of the published literature shows that the method does not expose patients to major risk, providing patients are selected and carefully monitored during the procedure. Complementary studies of larger numbers of patients are required to confirm its value as a prognostic and therapeutic marker in patients with dilated cardiomyopathy.

[Optimal myocardial revascularization by coronary bypass and complementary angioplasty. Study of 100 patients]. / Revascularisation myocardique optimale par pontages coronaires et angioplasties complémentaires. Etude chez 100 patients.

One hundred patients underwent early coronary angiography (average 20.5 days) after coronary bypass surgery between 1994 and 1996. The indications in clinically asymptomatic patients were: study of double mammary grafts, non respect of the preoperative plan (grafts not available, technical difficulties), and/or postoperative ECG changes. 12.1% of internal mammary grafts and 18.2% of the saphenous vein grafts were considered to be non-fractional: due to occlusion in 3 and 11.9%, due to poor implantation site (persistence of a distal stenosis): 3 and 0.8% respectively. After investigations to detect ischaemia in the region concerned or persistence of a critical lesion on a non-revascularised main artery, 26 complementary angioplasties were performed: 3 on internal mammary grafts, 4 on saphenous vein grafts and 19 on the native vessels. Surgery alone resulted in complete revascularisation in 70% and its association with cardiological interventional techniques increased the value to 85%. The association of coronary bypass surgery and transluminal angioplasty may therefore result in optimal revascularisation. This should reduce the morbidity rate, the number of hospital admissions (recurrent ischaemia and reoperation) and improve survival. However, the exact modalities of this combined revascularisation remain to be defined.