Cardiovascular and abdominal motor responses evoked by intravenous neurotensin in guinea pigs

Developing T cells in the thymus are subject to a screening process, through interactions with thymic stromal cells, from which T cells with appropriate T-cell receptors are selected. The recent generation of T-cell receptor transgenic mice and mice homozygous for disrupted T-cell receptor genes have now supplied tools that improve the prospect for a better understanding of the molecular mechanisms of this thymic selection process. In addition these model systems appear to indicate a role for a, not yet fully characterized, pre-T cell receptor complex in survival and further differentiation of pre-T cells.     

Paroxysmal atrial fibrillation

Paroxysmal atrial fibrillation is the most frequent of cardiac arrhythmias and its frequency increases with age. Its diagnosis is difficult since the symptoms are often absent or misleading. It is based on electrocardiogram performed during the attack, and this has been made easier by the Holter technique or by sequential recordings triggered by the patient himself. It is only in special cases, when percritical recordings could not be made that intracavitary electrophysiological study is used to obtain indirect arguments in favour of the diagnosis. All heart diseases can be attended by this cardiac rhythm disorder which usually marks an unfavourable turn in the course of the disease, with an increased risk of sudden death in the end. But in most cases the only disorder found is a common arterial hypertension. Atrial fibrillation carries a risk of peripheral, and in particular cerebral, embolism evaluated at 5% per annum. This risk is high in patients with cardiopathy, but it also exists even with a normal heart. The value of anticoagulants has been demonstrated by large controlled studies, but it is important to know that a very strong anticoagulant treatment is unnecessary to reduce the risk of embolism. Only antiarrhythmic agents can maintain the patients in sinus rhythm for as long as possible before the passage to permanent fibrillation. Although no beneficial effect on mortality has been proved, these drugs are indicated for patients who have very marked symptoms or a major cardiopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Common migraine ("migraine without aura"): localization of the initial pain of attack

The importance of maximal versus submaximal exercise testing and the significance of heart failure on the prognostic value of exercise-provoked ST-segment depression > or = 0.1 mV was studied in 143 patients recovering from acute myocardial infarction. Patients were exercise tested prior to discharge and follow up lasted for up to 18 months (mean 17 months). End-point was first major event (i.e. first non-fatal reinfarction or death). A symptom-limited exercise test was superior to a heart-rate-limited test in detecting ST-segment depressions (27% vs. 20%: P < 0.5), and patients with ST-segment depression at lower heart rates did not have an increased risk of subsequent events compared with patients with ST-segment depression at higher heart rates (14% vs. 27%; NS). Heart failure surpassed ST-segment depression as a risk predictor (34% vs. 18%). Based on a meta-analysis including 13 studies (1987 patients) exercise-provoked ST-segment depression possessed an increased risk of subsequent major events (P < 0.0001; risk ratio = 1.90; 95% confidence limits 1.43,2.51). Thus, ST-segment depression provoked by a symptom-limited test selects patients with an increased risk of subsequent major events. In patients with a history of heart failure exercise-provoked ST-segment depression is of limited value.     

Epidemiology of hepatitis C and G in sporadic and familial porphyria cutanea tarda

From 1995 to 1997, we prospectively evaluated the prevalence of hepatitis C virus (HCV) RNA in 124 patients with porphyria cutanea tarda (PCT) from Northern France (83 sporadic and 41 familial PCT). Serum samples were analyzed for ferritin, transaminases, HCV antibodies, and HCV RNA. In addition, genotyping of HCV and searches for HCV infection risk factors (blood transfusion, iv drug abuse, and surgical intervention) were performed. Twenty-six of 124 patients (21%; 95% CI: 13.9-28) were positive for serum HCV antibodies. All of them were also positive for HCV RNA. The prevalence of HCV infection was higher in the sporadic PCT group (26.5%, 22 out of 83) than in the familial PCT group (9.7%, 4 out of 41). Risk factors for hepatitis C infection were found to be significantly increased in the HCV-positive group when compared with the HCV-negative PCT group. In all HCV-positive patients with a risk factor, the suspected date of exposure to the virus always preceded the clinical onset of PCT. The HCV genotype pattern in PCT patients was similar to that observed in nonporphyric HCV patients in western European countries. Serum ferritin level was increased in both HCV-positive and HCV-negative porphyric patients. Transaminase levels were significantly higher in HCV-infected PCT patients. Sixty-seven out of 124 patients were retrospectively studied for hepatitis G virus (HGV) infection. Six of these 67 patients (8.9%; 95% CI: 2.1-15.8) were positive for HGV RNA. None of the six HGV-infected patients were positive for HCV RNA. The HGV-infected patients did not differ statistically from those without HGV infection with regard to age, ferritin, transaminase levels, and PCT treatment. These results support the view that sporadic cases of HGV infection may occur frequently. This study of a large cohort of HCV and PCT patients further documents an increasing gradient in HCV prevalence from northern to southern Europe, and shows that HCV infection acts as a triggering factor of PCT. Finally, the HGV prevalence found in the PCT patients was comparable with that found in French blood donors, suggesting that HGV is not a PCT triggering factor.     

Interleukin 8 (IL-8) induces the expression of kinin B1 receptor in human lung fibroblasts

Near-haploidy is a rare cytogenetic finding in childhood acute lymphoblastic leukaemia (ALL) and is associated with a poor prognosis. A second hyperdiploid line, occurring presumably by endoreduplication of the near-haploid stemline, is often observed. We present a case of common ALL in relapse characterized morphologically by a dual population of small and large lymphoblasts. Cytogenetic analysis supplemented with fluorescence in-situ hybridization (FISH) studies localized near-haploidy and hyperdiploidy to the small and large blast population respectively. DNA ploidy determination confirmed two abnormal clones with near-haploidy as the predominant one. A novel t(9;12)(q11;q13) was present in the near-haploid clone and was duplicated in the hyperdiploid clone. This finding identified cells bearing near-haploidy to be the clonogenic population following malignant transformation and confirmed endoreduplication as the mechanism for the presence of associated hyperdiploidy.     

Molecular structure and stereoelectronic properties of sarmazenil--a weak inverse agonist at the omega modulatory sites (benzodiazepine receptors): comparison with bretazenil and flumazenil

X-ray diffraction and ab initio MO theoretical calculations were used in order to investigate the structural and electronic properties of sarmazenil, a weak inverse agonist at the omega modulatory sites (benzodiazepine receptors). This compound was compared to bretazenil, a partial agonist, and to the antagonist flumazenil on the basis of structural and electronic data. The conformational and theoretical properties (interatomic pi overlap populations, molecular electrostatic potential (MEP), the topology of frontier orbitals, and proton affinity) of these three imidazobenzodiazepinones were determined in order to analyse the stereoelectronic properties in relation with their distinct intrinsic efficacies at the omega modulatory sites.