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Biomedical subjects

V Person

Publications and source records attributed to V Person.

7 recordsLinked to original sources
PubMed2001

Time course of the apoptotic cascade and effects of caspase inhibitors in adult rat ventricular cardiomyocytes.

K. Suzuki, S. Kostin, V. Person, A. Elsässer and J. Schaper. Time Course of the Apoptotic Cascade and Effects of Caspase Inhibitors in Adult Rat Ventricular Cardiomyocytes. Journal of Molecular and Cellular Cardiology (2001) 33, 983-994. Interpretation of the rate of apoptosis in diseased hearts is hampered by the fact that the time course of the apoptotic cascade in adult cardiomyocytes is largely unknown. Therefore, we established a standardized in vitro system, relevant to the in vivo situation of heart failure, using adult de- and redifferentiating cardiomyocytes to determine the time intervals necessary for the different steps of the apoptotic cascade to occur. Apoptosis was induced with 0.1 mmol/l H(2)O(2)in adult rat cardiomyocytes 10 days in culture. Dosages >0.5 mmol/l H(2)O(2)produced necrosis. Disruption of the mitochondrial membrane potential (Deltapsim) was the earliest sign of apoptosis and occurred at 2 h after H(2)O(2)exposure. The number of annexin V (translocation of phosphatidylserine) and PhiPhiLux (activation of caspase-3) positive cells significantly increased after 4 h and remained constant thereafter. Bcl-2 levels decreased. At 9 h, Bax expression was significantly elevated resulting in a reduced Bcl-2/Bax ratio. DNA fragmentation detected by TUNEL and ssDNA peaked at 14 h, parallel to the appearance of apoptotic ultrastructural changes. Although DNA fragmentation was inhibited by zVAD-fmk, Ac-DEVD-CHO, zLEVD-fmk, these caspase inhibitors failed to inhibit disruption of Deltapsim and increased the number of necrotic cells. Catalase inhibited both apoptosis and necrosis. Our results indicate that the occurrence of the different steps of the apoptotic cascade is time-dependent and tightly regulated. Caspase inhibitors reduce apoptosis but increase the rate of necrosis, suggesting that the cells are destined to die upstream of the caspase step, i.e. by mitochondrial damage. These data provide the basis for the critical evaluation and interpretation of the occurrence of apoptosis in failing hearts.

Animals↗
PubMed2000

Antisense oligonucleotide experiments elucidate the essential role of titin in sarcomerogenesis in adult rat cardiomyocytes in long-term culture.

An essential role of titin as a molecular ruler in sarcomerogenesis has been frequently discussed. In this study, we tested the hypothesis that the expression of titin is a prerequisite for thick filament incorporation into sarcomeres by using an antisense oligonucleotide approach to interfere with titin translation in the de-/redifferentiation model of adult rat cardiomyocytes (ARC) in long-term culture. As a first step, the growth pattern ranging from rod shape to round and later to spreading cells and the cell surface area of ARC were quantitatively evaluated and standardized. This represents the basis for experiments interfering with sarcomere formation using three different antisense phosphorothioate oligonucleotides (S-ODN) at a dosage of 10 microM specific for titin mRNA. Presence of fluorescein labeled S-ODN in ARC indicated cellular uptake and both, antisense and random S-ODN, induced a significant increase in cell size as compared with control untreated ARC. At days 12 and 16 in culture, antisense S-ODN treatment resulted in reduced expression of titin and disturbance of myosin incorporation into sarcomeres, evident by diffuse myosin labeling and a significantly decreased area of regular myosin cross-striation (control 75%, day 12 S-ODN 20%, day 16 14%) shown by laser scanning confocal microscopy. Cellular integrity indicated by presence of alpha-actinin was not disturbed. These findings provide evidence for the role of titin as a template for myosin incorporation and therefore as a prerequisite for sarcomerogenesis.

Animals↗
PubMed2000

Telelearning in a partnership between a university faculty and a regional health authority: benefits, challenges and strategies.

The University of Calgary's Faculty of Medicine and the Calgary Regional Health Authority understand that telehealth is an evolving field requiring both academic enquiry and operational readiness. Both parties are committed to quality educational programmes--the Faculty through its commitment to excellence and the Authority with its charge to maintain and enhance such programmes. There are shared applications, multi-learner user groups, shared strategies to overcome distances and shared infrastructure--technologies, communication pathways and resources. Having embarked on a joint telelearning venture, we have learned a number of lessons. Central to progress has been an appreciation and respect for unique mandates, a spirit of trust and flexibility, an agreement on a set of principles, ongoing communication between and participation from the users and, at times, redirection. Questions being answered include the following. How well is this collaborative model working? How functional is it at this time of health reform and restructuring? Can one meet complementary telelearning goals within a faculty-health authority relationship? These all have implications for future success.

Canada↗