Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.     

Release of soluble transferrin receptor from the surface of human leukemic HL60 cells

Information regarding transferrin (Tf) receptor degradation is largely incomplete. HL60 cells were shown to release to their growth medium a Tf-binding protein which could be immunoprecipitated by anti-Tf receptor monoclonal antibodies (MoAbs) B3/25 and OKT9. Soluble Tf receptor was detected in the medium within one hour of replating of cells, and its release was inhibited at 4 degrees C. The affinity of Tf for the soluble receptor released by cells (kd = 2.3 x 10(-10) mol/L) was slightly lower than its affinity for the detergent-solubilized cellular receptor (kd = 1.2 x 10(-10) mol/L). 125I-Tf internalized and released by cells subsequently bound to Tf receptor released by the same cells, and soluble Tf receptor in the conditioned medium (CM) inhibited 125I-Tf binding to intact cells. The soluble Tf receptor isolated from the CM was smaller (78,000 daltons) than the cell surface receptor (94,000 daltons) when analyzed by gel electrophoresis under reducing conditions. Isolated cell membranes readily released soluble receptor; however, this release could be blocked by protease inhibitors. The soluble Tf receptor may represent the extracytoplasmic domain of the cellular Tf receptor released from the surface of HL60 cells through proteolytic cleavage by a membrane-based protease.     

Thrombosis and thrombolysis in unstable angina

Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures.     

Dual activity maps in primate visual cortex produced by different temporal patterns of zif268 mRNA and protein expression

The inducible nature of the immediate-early genes (IEGs) c-fos and zif268 allows their products to be used as activity markers in the brain. The utility of such markers in general is restricted because they can resolve only neurons activated by a single stimulus. To overcome this limitation, we have developed a double-label technique that exploits the dissimilar time course of zif268 mRNA and protein induction, allowing them to be separately induced by two different stimuli and independently stained to provide a visual display of neurons that are responsive to each stimulus. Two powerful features of this new imaging technique—the possibility of staining separate populations of activated neurons and the ability to visualize them at the cellular level—should extend IEG applications in biological activity mapping.     

Partial abnormal pulmonary venous return. An underestimated and unknown association in Turner-Ullrich syndrome. Presentation of an original case]

The authors report the case of a 59-year-old woman with a complex cardiac lesion consisting of degenerative major mitral insufficiency masking partial abnormal pulmonary venous return. These cardiac abnormalities fell within a context of genetic disease since the patient had Turner's syndrome, confirmed at the age of 58 by a 45 x 0 karyotype. They detail the originality of the clinical manifestations of partial abnormal pulmonary venous return and review the literature concerning cardiac malformations in Turner's syndrome.