High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.     

A morphometric study of the inferior orbital fissure using three‐dimensional anatomical landmarks: Application to orbital surgery

The inferior orbital fissure (IOF) is an important structure during orbital surgery, however, neither its anatomical features nor the procedures necessary to expose the IOF have been examined in detail. A morphometric analysis of the IOF was performed on 232 orbits using computer software. The longest and shortest borders of the IOF were 18.2 ± 4.9 and 1.9 ± 1.3 mm, respectively. The outer and the inner angles were 138.9 ± 32.7° and 38.4 ± 24.7°, respectively. The perimeter of the IOF was 50.6 ± 13.5 mm and its area was 61.3 ± 39.1 mm². Eight types of IOF were observed. Type 1 IOF was observed in 42.2% and the Type 2 IOF was identified in 15.9%. A statistically significant relation was found between the longest edge and area and the widest edge and area of the IOF. The findings of our study suggest that the removal of the lateral wall should begin inferiorly, just lateral to the IOF and extended superolaterally. These data may be useful during surgical approaches to the orbit. Clin. Anat. 22:649–654, 2009. © 2009 Wiley‐Liss, Inc.     

Robot-assisted catheter manipulation for intracardiac navigation

Objective  Manual navigation of intracardiac steerable catheters is inaccurate, requires dexterity for efficient manipulation of the catheter, and exposes the interventionalist to ionizing radiation. The objective of this research is to develop a system that replaces the interventionalists’s hands in catheter manipulation for accurate and semi-automatic tele-navigation of catheters. Methods  Based on a proposed kinematic model for the distal shaft of the catheter, a system has been developed for assisted navigation of intracardiac catheters. When the distal shaft of the catheter lies inside a cardiac chamber, a robotic apparatus is utilized for automatic steering of the catheter tip to reach designated targets within the chamber. Results  The catheter modeling was validated through the experiments on three swine. The robotic system could navigate the catheter tip to designated targets with a mean distance of 6.53 mm from the target. Conclusion  Preliminary in vivo studies demonstrate the feasible application of the system in catheter navigation and the validity of catheter modeling and control strategies.     

Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury

We measured the effect of treatment of traumatic brain injury (TBI) in the rat with human umbilical cord blood (HUCB) administered i.v.. HUCB cells were injected into the tail vein 24 h after TBI and the rats were sacrificed at day 28 after the treatment. The Rotarod test and the neurological severity score (NSS) were used to evaluate neurological function. The distribution of the donor cells in the brain, heart, lung, kidney, liver, spleen, bone marrow, and muscle were analyzed in recipient rats using immunohistochemical staining and laser confocal microscopy. HUCB cells injected i.v. significantly reduced motor and neurological deficits compared with control groups by day 28 after the treatment. The cells preferentially entered the brain and migrated into the parenchyma of the injured brain and expressed the neuronal markers, NeuN and MAP-2, and the astrocytic marker, GFAP. Some HUCB cells integrated into the vascular walls within the boundary zone of the injured area. Our data suggest that i.v. administration of HUCB may be useful in the treatment of TBI.     

Active amino acids of the Kell blood group protein and model of the ectodomain based on the structure of neutral endopeptidase 24.11

In addition to its importance in transfusion, Kell protein is a member of the M13 family of zinc endopeptidases and functions as an endothelin-3-converting enzyme. To obtain information on the structure of Kell protein we built a model based on the crystal structure of the ectodomain of neutral endopeptidase 24.11 (NEP). Similar to NEP, the Kell protein has 2 globular domains consisting mostly of alpha-helical segments. The domain situated closest to the membrane contains both the N- and C-terminal sequences and the enzyme-active site. The outer domain contains all of the amino acids whose substitutions lead to different Kell blood group phenotypes. In the model, the zinc peptidase inhibitor, phosphoramidon, was docked in the active site. Site-directed mutagenesis of amino acids in the active site was performed and the enzymatic activities of expressed mutant Kell proteins analyzed and compared with NEP. Our studies indicate that Kell and NEP use the same homologous amino acids in the coordination of zinc and in peptide hydrolysis. However, Kell uses different amino acids than NEP in substrate binding and appears to have more flexibility in the composition of amino acids allowed in the active site.     

Dietary components and human platelet activity

Platelet hyperactivity is one of the most important factors responsible for the incidence of cardiovascular disease. There are many nutritive and non-nutritive compounds present in the diet which may affect platelet function in various ways. Recent discovery of anti-platelet factors in plants, vegetables and fruits provides a new dietary means for a long-term strategy to favorably modify human blood platelet activity. This review summarises the effects of these dietary components on human platelet function both in vitro and in vivo.