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Biomedical subjects

R E Oakley

Publications and source records attributed to R E Oakley.

7 recordsLinked to original sources
PubMed2001

Overexpression of connexin 43 in skeletal myoblasts: Relevance to cell transplantation to the heart.

OBJECTIVE: Skeletal myoblast transplantation is a promising strategy for treating end-stage heart failure. One potential problem in the development of functional, synchronously contracting grafts is the degree of intercellular communication between grafted myoblasts and host cardiomyocytes. Thus it is expected that enhancement of intercellular gap junction formation would result in improved efficiency of skeletal myoblast transplantation. In this study we investigated whether myoblasts overexpressing connexin 43, a major cardiac gap junction protein, would enhance this intercellular communication. METHODS AND RESULTS: L6 rat skeletal myoblast cell lines overexpressing connexin 43 were generated by means of gene transfection and clonal selection. Connexin 43 overexpression of these myoblasts, which continued both in undifferentiated and differentiated states (up to 17-fold greater protein level in comparison with control-transfected myoblasts, as measured with Western blotting), was observed on cell surfaces where gap junctions should exist. Both dye microinjection and scrape loading with fluorescent dyes showed enhancement in intercellular dye transfer between connexin 43-transfected myoblasts compared with that found in control-transfected cells. Morphologically, these myoblasts fused and differentiated into multinucleated myotubes more rapidly, demonstrating a higher level of cellular creatine kinase activity as a marker of myogenic differentiation throughout the culture period compared with that of control-transfected myoblasts. CONCLUSIONS: We have generated connexin 43-overexpressing skeletal myoblast cell lines that resulted in improved formation of functional intercellular gap junctions, which could be relevant to synchronous contraction of grafted myoblasts in the heart. In addition, these cells demonstrated more rapid differentiation, which would also be advantageous in a graft for transplantation to the heart.

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PubMed1999

In vivo transfer of bacterial marker genes results in differing levels of gene expression and tumor progression in immunocompetent and immunodeficient mice.

To optimize gene delivery for the treatment of malignant mesothelioma, expression of the beta-galactosidase marker gene was examined in a murine model of intraperitoneal malignant mesothelioma. The beta-galactosidase gene was delivered to the peritoneal cavity of tumor-bearing mice by various plasmid-liposome complexes or by replication-incompetent retrovirus, used alone or complexed to liposomes. In tumor samples from immunodeficient nude mice, moderate levels of gene expression were achieved by liposome-complexed plasmids. Retroviral gene delivery was more effective, and was increased nearly 10-fold by complexing the retrovirus to liposomes. In contrast, in tumor samples from immunocompetent CBA mice treated with the same vectors, no marker gene expression was detected. In immunodeficient mice, tumor growth was not affected by beta-galactosidase gene transfer. However, immunocompetent mice showed a significant decrease in tumor size and increase in survival time after beta-galactosidase delivery. Induction of cytotoxic T cells capable of lysing beta-Gal-transfected tumor cells suggests that tumor cells transduced with the bacterial beta-galactosidase gene may be eliminated in immunocompetent hosts. Our findings also indicate that plasmid-liposome complexes, which achieve a low level of gene expression, and retrovirus-liposome complexes, which result in nearly 100 times higher levels of gene expression in tumor cells in vivo, are similarly effective in inducing an antitumor immune response.

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PubMed1999

External coaptation.

The goal of any method of fracture repair should be the early return of total limb function and the prevention of fracture disease. This can be accomplished through adhering to the basic principles of good patient and fracture assessment, choosing the correct method of fracture repair, and appropriate patient care. The complications of external coaptation can be minimized by appropriate patient and fracture assessment as well as correct cast and splint application. Choosing external coaptation as a method of fracture repair can be rewarding as long as the appropriate steps are taken to ensure success.

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PubMed1996

Inherited and congenital diseases of the feline lower urinary tract.

Congenital urinary tract disorders of young cats may result from heritable (genetic) or acquired disease processes that affect differentiation and growth of the developing urinary tract, or from similar disease processes that eventually affect the structure or function of the mature urinary system. Although congenital diseases of the feline lower urinary tract are uncommon, clinical signs associated with these anomalies may be indistinguishable from those of other acquired causes of lower urinary tract disease. Early detection and proper management of congenital disorders may result in restoration of urinary bladder and urethral function and/or progressive urinary tract dysfunction.

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PubMedDate not supplied

Experimental evaluation of central venous pressure monitoring in the dog.

The measurement of central venous pressure (CVP) will provide objective information about intravascular blood volume. Limitations exist with direct and indirect methods of measuring CVP; however, the purpose of this study was to determine if such factors as catheter size, patient position, or measurements taken with either a water manometer or a strain-gauge transducer would affect the accuracy of CVP measurements. The study population consisted of six adult, mixed-breed dogs. Catheter sizes evaluated were 16- and 19-gauge. Patient positions evaluated were right and left lateral recumbencies. Right atrial pressures (RAPs) were used as the reference standards for CVP measurements. Measurements of RAP and CVP were obtained with a water manometer and a strain-gauge transducer. No significant differences were observed in measured CVPs for the effects of catheter size and right versus left lateral recumbency. A 2.7-mmHg difference in water manometry was demonstrated when compared to strain-gauge transducer measurements. Also, strain-gauge transducer measurements had less precision compared to water manometer measurements.

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