Biomedical subjects

Judith Stein

Publications and source records attributed to Judith Stein.

8 recordsLinked to original sources

PubMed2006

Biodistribution of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar, without integration, despite differing plasmid backbones or gene inserts.

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidly they would clear. In the course of these studies, it has been observed that regardless of the gene insert (expressing the vaccine immunogen or cytokine adjuvant) and regardless of the promoter used to drive expression of the gene insert in the plasmid backbone, the plasmid vaccines do not biodistribute widely and remain essentially in the site of injection, in the muscle and overlying subcutis. Even though approximately 10(14) molecules are inoculated in the studies in rabbits, by day 8 or 9 ( approximately 1 week postinoculation), already all but on the order of 10(4)-10(6) molecules per microgram of DNA extracted from tissue have been cleared at the injection site. Over the course of 2 months, the plasmid clears from the site of injection with only a small percentage of animals (generally 10-20%) retaining a small number of copies (generally around 100 copies) in the muscle at the injection site. This pattern of biodistribution (confined to the injection site) and clearance (within 2 months) is consistent regardless of differences in the promoter in the plasmid backbone or differences in the gene insert being expressed by the plasmid vaccine. In addition, integration has not been observed with plasmid vaccine candidates inoculated i.m. by Biojector 2000 or by needle and syringe. These data build on the repeated-dose toxicology studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar despite differing plasmid backbones or gene-inserts.

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). All treatment-related toxicities identified in these repeated-dose toxicology studies have been confined primarily to the sites of injection and seem to be the result of both the delivery method (as they are seen in both control and treated animals) and the intended immune response to the vaccine (as they occur with greater frequency and severity in treated animals). Reactogenicity at the site of injection is generally seen to be reversible as the frequency and severity diminished between doses and between the immediate and recovery termination time points. This observation also correlated with the biodistribution data reported in the companion article (Sheets et al., 2006), in which DNA plasmid vaccine was shown to remain at the site of injection, rather than biodistributing widely, and to clear over time. The results of these safety studies have been submitted to the Food and Drug Administration to support the safety of initiating clinical studies with these and related DNA plasmid vaccines. Thus far, standard repeated-dose toxicology studies have not identified any target organs for toxicity (other than the injection site) for our DNA plasmid vaccines at doses up to 8 mg per immunization, regardless of disease indication (i.e., expressed gene-insert) and despite differences (strengths) in the promoters used to drive this expression. As clinical data accumulate with these products, it will be possible to retrospectively compare the safety profiles of the products in the clinic to the results of the repeated-dose toxicology studies, in order to determine the utility of such toxicology studies for signaling potential immunotoxicities or intrinsic toxicities from DNA vaccines. These data build on the biodistribution studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Contact angle anomalies indicate that surface-active eluates from silicone coatings inhibit the adhesive mechanisms of fouling organisms.

Silicone coatings with critical surface tensions (CST) between 20 and 30 mN m-1 more easily release diverse types of biofouling than do materials of higher and lower CST. Oils added to these coatings selectively further diminish the attachment strengths of different marine fouling organisms, without significantly modifying the initial CST. In a search for the mechanisms of this improved biofouling resistance, the interfacial instabilities of four silicone coatings were characterised by comprehensive contact angle analyses, using up to 12 different diagnostic fluids selected to mimic the side chain chemistries of the common amino acids of bioadhesive proteins. The surfaces of painted steel test panels were characterised both before and after exposure to freshwater, brackish water, and seawater over periods ranging from 9 months to nearly 4 years. Contact angle measurements demonstrated significant surface activity of the oil-amended coatings both before and after long-term underwater exposure. The surface activity of the control (coating without oil) increased as a result of underwater exposure, consistent with mild surface chain scission and hydrolysis imparting a self-surfactancy to the coating and providing a weak boundary layer promoting continuing easy release of attaching foulants. Coatings with additives that most effectively reduced biofouling showed both initial and persistent contact angle anomalies for the test liquid, thiodiglycol, suggesting lower-shear biofouling release mechanisms based upon diminished bioadhesive crosslinking by interfering with hydrogen- and sulfhydryl bonds. Swelling of the silicone elastomeric coatings by hydrocarbon fluids was observed for all four coatings, before and after immersion.

Adhesiveness↗

PubMed2005

Development of a risk assessment tool for women with a family history of breast cancer.

BACKGROUND: Innovative technologies that enable the collection of family history information and the assessment of breast cancer risk have a potential to enhance the quality of preventive care. We developed a computerized tool that supports stratification of breast cancer risk, genetic risk assessment in the clinical environment (GRACE). METHODS: In a preliminary evaluation of the tool's impact, we randomized women with a family history of breast cancer (n=72) to either use the GRACE tool or undergo risk counseling by a nurse specialist. RESULTS: There was no statistically significant differences between the GRACE and nurse counselling groups in risk perceptions (F=.03, P>.05) and cancer-related worries (F=.80, P>.05). However, patients reported more positive attitudes toward working with the nurse. CONCLUSION: It was feasible to use GRACE in a Clinic. Additional research is required to identify solutions for providing emotional support in conjunction with the tool.

Adolescent↗

PubMed2003

Silicone foul release coatings: effect of the interaction of oil and coating functionalities on the magnitude of macrofouling attachment strengths.

Silicone biofouling release coatings have been shown to be an effective method of combating fouling. Nearly all silicone foul release coatings are augmented with an oil additive to decrease macrofouling attachment strength. This paper addresses the effect of the type of oil that is incorporated into the silicone coating and the type of silicone coating itself (silica vs calcium carbonate filled) on macrofouling adhesion strengths to the coating. It was found that not only are the main effects of oil type and silicone coating type important in determining the magnitude of the attachment strength of the organism, but the interaction term (oil type crossed with coating type) is highly significant for all organisms studied, except oysters at the University of Hawaii test site (Oahu, Hawaii) which has a significance level of alpha = 0.1. Each of the organisms exhibited a unique response to the various silicone fouling release coatings. Thus, in order to predict the effectives of foul release coatings, the composition variables of the coatings and the type of target organisms must be considered.

Adhesiveness↗

PubMed2003

Structure-property relationships of silicone biofouling-release coatings: effect of silicone network architecture on pseudobarnacle attachment strengths.

Model silicone foul-release coatings with controlled molecular architecture were evaluated to determine the effect of compositional variables such as filler loading and crosslink density on pseudobarnacle attachment strength. Pseudobarnacle adhesion values correlated with filler loadings in both condensation and hydrosilylation-cured silicones. Variation of crosslink density of hydrosilylation-cured silicones had an insignificant effect on attachment strength. X-ray photoelectron spectroscopy (XPS) indicated that the mode of failure upon detachment of the pseudobarnacle was dependent upon the crosslink density; samples with high crosslink density failed cohesively within the silicone.

Adhesiveness↗

PubMed2003

The effects of silicone fluid additives and silicone elastomer matrices on barnacle adhesion strength.

Barnacle adhesion strength was used to screen seventy-seven polydimethylsiloxane elastomeric coatings for fouling-release properties. The test coatings were designed to investigate the effect on barnacle adhesion strength of silicone fluid additive type, additive location, additive molecular weight, additive loading level, mixtures of additives, coating matrix type and coating fillers. The type of silicone fluid additive was the primary controlling factor in barnacle fouling-release. The type of silicone matrix in which the fluid resided was found to alter the effect on fouling-release. Two PDMS fluids, DMSC15 and DBE224, significantly reduced the adhesion strength of barnacles compared to unmodified elastomers. Optimum fouling-release performance was dependent on the interaction of fluid type and elastomeric matrix.

Adhesiveness↗

PubMed2003

Medicare and long-term care.

While Medicare coverage of long-term care services (nursing facility care and home health care) is not comprehensive, it can be an important source of coverage for Medicare beneficiaries who need skilled care. In this brief, we provide an overview of these benefits--including information about what services are covered, when they are covered, and how much your clients will pay for this care.

Aged↗