Case Western Reserve University

About: Case Western Reserve University is a education organization based out in Cleveland, Ohio, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 54617 authors who have published 106568 publications receiving 5071613 citations. The organization is also known as: Case & Case Western.

A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation.

Abstract: The action potential model presented in our accompanying article in this journal is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as described below Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both the Na(+)-Ca2+ exchanger (INaCa) and a nonspecific Ca(2+)-activated current (Ins(Ca)) The relative contributions of INaCa and of Ins(Ca) to the generation of DADs are different under different degrees of Ca2+ overload Early afterdepolarizations (EADs) can be categorized into two types: (1) plateau EADs, resulting from a secondary activation of the L-type Ca2+ current during the plateau of an action potential, and (2) phase-3 EADs, resulting from activation of INaCa and Ins(Ca) by increased [Ca2+]i due to spontaneous Ca2+ release from the SR during the late repolarization phase Spontaneous rhythmic activity and triggered activity are caused by spontaneous Ca2+ release from the SR under conditions of Ca2+ overload Postextrasystolic potentiation reflects the time delay associated with translocation of Ca2+ from network SR to junctional SR The cell is paced at high frequencies to investigate the long-term effects on the intracellular ionic concentrations

Stem cell technology and bioceramics: From cell to gene engineering

Abstract: Mesenchymal stem cells reside in bone marrow and, when these cells are incorporated into porous ceramics, the composites exhibit osteo-chondrogenic phenotypic expression in ectopic (subcutaneous and intramuscular) or orthotopic sites. The expressional cascade is dependent upon the material properties of the delivery vehicle. Bioactive ceramics provide a suitable substrate for the attachment of the cells. This is followed by osteogenic differentiation directly on the surface of the ceramic, which results in bone bonding. Nonbioactive materials show neither surface-dependent cell differentiation nor bone bonding. The number of mesenchymal stem cells in fresh adult bone marrow is small, about one per one-hundred-thousand nucleated cells, and decreases with donor age. In vitro cell culture technology can be used to mitotically expand these cells without the loss of their developmental potency regardless of donor age. The implanted composite of porous ceramic and culture-expanded mesenchymal stem cells exhibits in vivo osteo-chondrogenic differentiation. In certain culture conditions, these stem cells differentiate into osteoblasts, which make bone matrix on the ceramic surface. Such in vitro prefabricated bone within the ceramic provides immediate new bone-forming capability after in vivo implantation. Prior to loading of the cultured, marrow-derived mesenchymal stem cells into the porous ceramics, exogenous genes can be introduced into these cells in culture. Combining in vitro manipulated mesenchymal stem cells with porous ceramics can be expected to effect sufficient new bone-forming capability, which can thereby provide tissue engineering approaches to patients with skeletal defects in order to regenerate skeletal tissues.

DNA Replication Precedes Neuronal Cell Death in Alzheimer's Disease

Abstract: Alzheimer's disease (AD) is a devastating dementia of late life that is correlated with a region-specific neuronal cell loss. Despite progress in uncovering many of the factors that contribute to the etiology of the disease, the cause of the nerve cell death remains unknown. One promising theory is that the neurons degenerate because they reenter a lethal cell cycle. This theory receives support from immunocytochemical evidence for the reexpression of several cell cycle-related proteins. Direct proof for DNA replication, however, has been lacking. We report here the use of fluorescent in situ hybridization to examine the chromosomal complement of interphase neuronal nuclei in the adult human brain. We demonstrate that a significant fraction of the hippocampal pyramidal and basal forebrain neurons in AD have fully or partially replicated four separate genetic loci on three different chromosomes. Cells in unaffected regions of the AD brain or in the hippocampus of nondemented age-matched controls show no such anomalies. We conclude that the AD neurons complete a nearly full S phase, but because mitosis is not initiated, the cells remain tetraploid. Quantitative analysis indicates that the genetic imbalance persists for many months before the cells die, and we propose that this imbalance is the direct cause of the neuronal loss in Alzheimer's disease.