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Biomedical subjects

Ronald W Bordens

Publications and source records attributed to Ronald W Bordens.

4 recordsLinked to original sources

Use of an automated image processing program to quantify recombinant adenovirus particles.

Electron microscopy has a pivotal role as an analytical tool in pharmaceutical research. However, digital image data have proven to be too large for efficient quantitative analysis. We describe here the development and application of an automated image processing (AIP) program that rapidly quantifies shape measurements of recombinant adenovirus (rAd) obtained from digitized field emission scanning electron microscope (FESEM) images. The program was written using the macro-recording features within Image-Pro Plus software. The macro program, which is linked to a Microsoft Excel spreadsheet, consists of a series of subroutines designed to automatically measure rAd vector objects from the FESEM images. The application and utility of this macro program has enabled us to rapidly and efficiently analyze very large data sets of rAd samples while minimizing operator time.

Adenoviridae↗

Pegylated IFNs for chronic hepatitis C: an update.

For over a decade, IFN-alpha(2) has been the standard treatment for chronic hepatitis C. However, the drug's rapid clearance and short half-life have led to low rates of sustained virological response. Pegylation is a well-established method of modifying the pharmacological properties of IFNs, causing significant improvements in pharmacokinetics, which in turn lead to improved efficacy. Two pegylated forms of IFN-alpha(2) have been developed: PEG-IFN-alpha(2b) and PEG-IFN-alpha(2a), and their efficacy has been established in randomised, controlled trials. However, the two differ significantly in structure, in vitro activity and pharmacological properties, and this may translate into -differences in clinical efficacy. Comparative trials have been initiated that will provide insight into relative importance of pharmacokinetics, bioactivity and dosing regimen.

Animals↗

The use of field emission scanning electron microscopy to assess recombinant adenovirus stability.

A field emission scanning electron microscopy (FESEM) method was developed to assess the stability of a recombinant adenovirus (rAd). This method was designed to simultaneously sort, count, and size the total number of rAd viral species observed within an image field. To test the method, a preparation of p53 transgene-expressing recombinant adenovirus (rAd/p53) was incubated at 37 degrees C and the viral particles were evaluated by number, structure, and degree of aggregation as a function of time. Transmission electron microscopy (TEM) was also used to obtain ultrastructural detail. In addition, the infectious activity of the incubated rAd/p53 samples was determined using flow cytometry. FESEM image-analysis revealed that incubation at 37 degrees C resulted in a time-dependent decrease in the total number of detectable single rAd/p53 virus particles and an increase in apparent aggregates composed of more than three adenovirus particles. There was also an observed decrease in both the diameter and perimeter of the single rAd/p53 viral particles. TEM further revealed the accumulation of damaged single particles with time at 37 degrees C. The results of this study demonstrate that FESEM, coupled with sophisticated image analysis, may be an important tool in quantifying the distribution of aggregated species and assessing the overall stability of rAd samples.

Adenoviruses, Human↗

Interferon-alpha as an immunotherapeutic protein.

Interferon-alpha (IFN-alpha) has proven to be a clinically effective antiviral and antineoplastic therapeutic drug for more than 16 years. During this time, evidence from in vitro laboratory studies and the clinical arena has supported the concept that IFN-alpha is an immunotherapeutic drug. By regulating a diverse set of cytokines and their receptors, IFN-alpha is uniquely positioned to prime the host immune response and provide an effective antineoplastic- and antiviral-immune response. IFN-alpha stimulates the innate cell-mediated response and then participates in the transition of the initial host innate response into an effective adaptive-immune response. IFN-alpha also drives the adaptive cell-mediated CD8+ T-cell response and helps to maintain a CD4+ Th1-cell population balance for an effective antineoplastic and antiviral host defense. This review will describe the current state of knowledge of IFN-alpha as an immunoregulatory protein and address specific issues of IFN-alpha as an immunotherapeutic for antineoplastic and antiviral diseases.

Antineoplastic Agents↗