The cytoplasmic amino-terminus of the Latent Membrane Protein-1 of Epstein-Barr Virus: relationship between transmembrane orientation and effector functions of the carboxy-terminus and transmembrane domain

The Latent Membrane Protein 1 (LMP-1) protein of Epstein-Barr virus (EBV) is localized in the plasma membrane of the infected cell. LMP-1 possesses a hydrophobic membrane spanning domain, and charged, intracellular amino- and carboxy-termini. Two models have been proposed for the contribution of the amino-terminus to LMP-1's function: (i) as an effector domain, interacting with cellular proteins, or (ii) as a structural domain dictating the correct orientation of transmembrane domains and thereby positioning LMP-1's critical effector domains (i.e. the carboxy-terminus). However, no studies to date have addressed directly the structural contributions of LMP-1's cytoplasmic amino-terminus to function. This study was designed to determine if LMP-1's cytoplasmic amino-terminus (N-terminus) encodes information required solely for maintenance of proper topological orientation. We have constructed LMP-1 chimeras in which the cytoplasmic N-terminus of LMP-1 is replaced with an unrelated domain of similar size and charge, but of different primary sequence. Retention of the charged amino-terminal (N-terminal) cytoplasmic domain and first predicted transmembrane domain was required for correct transmembrane topology. The absolute primary sequence of the cytoplasmic N-terminus was not critical for LMP-1's cytoskeletal association, turnover, plasma membrane patching, oligomerization, Tumor Necrosis Factor Receptor-associated factor (TRAF) binding, NF-kappaB activation, rodent cell transformation and cytostatic activity. Furthermore, our results point to the hydrophobic transmembrane domain, independent of the cytoplasmic domains, as the primary LMP-1 domain mediating oligomerization, patching and cytoskeletal association. The cytoplasmic amino-terminus provides the structural information whereby proper transmembrane orientation is achieved.     

Rotavirus vaccines: Current controversies and future directions

Rotaviruses are the most important cause of pediatric gastroenteritis worldwide. In August 1998, a new rotavirus vaccine was licensed for general use in the United States. However, 14 months later, the vaccine was withdrawn from the market because of serious gastrointestinal side effects. This paper discusses the need for a rotavirus vaccine, the development of the first rotavirus vaccine, and the safety issues that led to the recall of that vaccine.     

Place du ballon intragastrique avant une chirurgie bariatrique

An intragastric balloon is a temporary device designed to provide weight-loss in obese patients. It is placed and removed via upper digestive endoscopy and may well be useful as preoperative treatment for morbidly obese patients. The resulting weight-loss makes successful treatment of associated comorbidities possible. In such cases, use of an intragastric balloon can only be considered as part of a multidisciplinary approach involving surgeon, nutritionist and gastroenterologist.     

A clinicopathologic and immunohistochemical analysis of 53 cases of medulloblastoma with emphasis on synaptophysin expression

Synaptophysin (SYN) has been identified as an integral membrane glycoprotein of presynaptic vesicles in neurons and neuroendocrine cells, and as a marker for medulloblastoma and other neuronal tumors. SYN expression was studied with a monoclonal antibody (MAb) by the immunoperoxidase technique in 53 medulloblastomas. The expression of neuron-specific enolase (NSE), Leu-7 (LEU), S-100 protein (S100), glial fibrillary acidic protein (GFAP), neurofilament protein (NF), vimentin (VIM), cytokeratin (CKER), and desmin (DES) was also assessed with antisera and MAbs. SYN reactivity was present in 94% of tumors, whereas reactivity with other markers of neuronal differentiation was also observed: NSE (100%) and LEU (83%). Regarding the intermediate filament proteins, 38% of the cases were reactive for VIM, 21% for GFAP, and 9% for DES; none expressed NF or CKER. Eight percent were reactive for S100. Among the 53 cases, the male-female ratio was 1:3; 80% of DES-positive tumors occurred in females. The mean age was 10.5 yr, (60% diagnosed in the first decade; peak age incidence between 5 and 10 yr). Five tumors were discovered in patients older than 20 yr of age. Follow-up showed that 40% of patients developed a recurrence and 47% of patients died of tumor. No statistically significant relationship was demonstrated between patterns of immunoreactivity and prognosis. We conclude that SYN is a useful marker for medulloblastomas, indicating that this tumor is a primitive neuronal-neuroblastic neoplasm. However, it is but one of several immunophenotypic markers expressed by the medulloblastoma.     

Unruptured sinus of Valsalva aneurysm with right ventricular outflow obstruction diagnosed by two-dimensional and Doppler echocardiography

This report presents a case of an unusually large unruptured sinus of Valsalva aneurysm complicated by right ventricular outflow tract obstruction, right coronary artery occlusion and incomplete right bundle branch block. Two-dimensional and Doppler echocardiography were instrumental in preoperative diagnosis and postoperative follow-up.     

Linkage disequilibrium test implies a large effective population number for HIV in vivo

The effective size of the HIV population in vivo, although critically important for the prediction of appearance of drug-resistant variants, is currently unknown. To address this issue, we have developed a simple virus population model, within which the relative importance of stochastic factors and purifying selection for genetic evolution differs over, at least, three broad intervals of the effective population size, with approximate boundaries given by the inverse selection coefficient and the inverse mutation rate per base per cycle. Random drift and selection dominate the smallest (stochastic) and largest (deterministic) population intervals, respectively. In the intermediate (selection-drift) interval, random drift controls weakly diverse populations, whereas strongly diverse populations are controlled by selection. To estimate the effective size of the HIV population in vivo, we tested 200 pro sequences isolated from 11 HIV-infected patients for the presence of a linkage disequilibrium effect which must exist only in small populations. This analysis demonstrated a steady-state virus population of 10(5) infected cells or more, which is either in or at the border of the deterministic regime with respect to evolution of separate bases.