If a strong and stable association can be firmly established between cognitive and MR variables in appropriate subsets of MS patients, it might aid in the investigation of interventions to enhance cognition and modify the course of the disease.

An automatic method has been developed for segmentation of abdominal computed tomography (CT) images for virtual colonoscopy obtained after a bowel preparation of a low-residue diet with ingested contrast solutions to enhance the image intensities of residual colonic materials. Removal of the enhanced materials was performed electronically by a computer algorithm. The method is a multistage approach that employs a modified self-adaptive on-line vector quantization technique for a low-level image classification and utilizes a region-growing strategy for a high-level feature extraction. The low-level classification labels each voxel based on statistical analysis of its three-dimensional intensity vectors consisting of nearby voxels. The high-level processing extracts the labeled stool, fluid and air voxels within the colon, and eliminates bone and lung voxels which have similar image intensities as the enhanced materials and air, but are physically separated from the colon. This method was evaluated by volunteer studies based on both objective and subjective criteria. The validation demonstrated that the method has a high reproducibility and repeatability and a small error due to partial volume effect. As a result of this electronic colon cleansing, routine physical bowel cleansing prior to virtual colonoscopy may not be necessary.

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We examined whether coupling of a ventricular myocyte to a non-myocyte cell expressing HCN2 could create a two-cell syncytium capable of generating sustained pacing. Three non-myocyte cell types were transfected with the mHCN2 gene and used as sources of mHCN2-induced currents. They were human mesenchymal stem cells and HEK293 cells, both of which express connexin43 (Cx43), and HeLa cells transfected with Cx43. Cell-cell coupling between heterologous pairs increased with time in co-culture, and hyperpolarization of the myocyte induced HCN2 currents, indicating current transfer from the mHCN2-expressing cell to the myocyte via gap junctions. The magnitude of the HCN2 currents recorded in myocytes increased with increasing junctional conductance. Once a critical level of electrical cell-cell coupling between myocytes and mHCN2 transfected cells was exceeded spontaneous action potentials were generated at frequencies of ∼0.6 to 1.7 Hz (1.09 ± 0.05 Hz). Addition of carbenoxolone (200 μm), a gap junction channel blocker, to the media stopped spontaneous activity in heterologous cell pairs. Carbenoxolone washout restored activity. Blockade of HCN2 currents by 100 μm 9-amino-1,2,3,4-tetrahydroacridine (THA) stopped spontaneous activity and subsequent washout restored it. Neither THA nor carbenoxolone affected electrically stimulated action potentials in isolated single myocytes. In summary, the inward current evoked in the genetically engineered (HCN2-expressing) cell was delivered to the cardiac myocyte via gap junctions and generated action potentials such that the cell pair could function as a pacemaker unit. This finding lays the groundwork for understanding cell-based biological pacemakers in vivo once an understanding of delivery and target cell geometry is defined.

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