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Biomedical subjects

R J Gregory

Publications and source records attributed to R J Gregory.

At least 37 records · Page 2Linked to original sources
PubMed1998

Neuro-talk: an intervention to enhance communication.

Neurologically impaired individuals, their family members, nurses, and physicians generally have few terms with which to describe neurological sensations and events. Neuro-talk is a made-up word to describe the unique language needs of persons affected by neurological conditions. Strategies to cope with neurological conditions vary, and most are less than successful. As a result, many individuals are unable to communicate effectively about their situation, and in return, others find it difficult to converse with them. This awkward impasse does not have to be, for communication patterns can be improved and enhanced. Nurses can teach people to use an enriched vocabulary, to explain their situation with metaphors and analogies, and to understand specifics about anatomy and physiology. This will offer nurses opportunities to interact productively and meaningfully with neurologically impaired individuals.

Adaptation, Psychological↗
PubMed1998

p53 gene therapy in a rat model of hepatocellular carcinoma: intra-arterial delivery of a recombinant adenovirus.

p53 tumor suppressor gene therapy has been proposed for cancers characterized by inactivation of p53 function, and successful therapy will require efficient strategies for gene delivery. To maximize transgene expression in tumors, a clinical strategy has been proposed to treat neoplasms in the liver via hepatic artery administration of a recombinant adenovirus encoding wild-type p53 (rAd-p53). We have developed a syngeneic rat model using a p53mut hepatocellular carcinoma cell line (McA-RH7777) that results in multifocal liver tumor nodules to provide experimental support for this strategy. Treatment of McA-RH7777 cells with rAd-p53 in vitro resulted in efficient transgene expression, growth suppression, and apoptosis. Intrahepatic artery dosing with rAd-p53 or an adenovirus encoding beta-galactosidase (rAd-betagal) increased transgene expression in tumor tissue and decreased systemic exposure when compared with i.v. dosing. Daily hepatic artery dosing of rAd-p53 suppressed tumor growth when compared with untreated rats or animals treated with rAd-betagal. These data demonstrate the potential for arterial gene delivery to tumors using recombinant adenoviruses, and support continued investigation of rAd-p53 gene therapy for liver malignancies.

Adenoviridae↗
PubMed1997

Engineered mutants of pRB with improved growth suppression potential.

We have constructed a panel of substitution mutants which affect one or more of the putative cdk target sites of the RB protein. We have examined the activity of these mutants relative to wild-type RB by both a transcriptional repression assay and by measuring growth suppression in vitro. We find that some phosphorylation site mutants of pRB can repress E2 transcription more strongly than wild-type RB. These mutants are partially resistant to phosphorylation by cdks and can arrest tumor cells in G1 in vitro. Our results indicate a functional correlation between the ability to repress E2F-dependent transcription and the ability to suppress tumor cell growth in vitro. In addition, we describe two classes of RB mutants: N-terminal truncated p56RB and a novel mutant of RB containing multiple substitutions near its nuclear localization signal. Both classes of RB mutants have greater activity than the wild-type protein. Because RB is a key regulator of cell cycle progression, expression of a more potent, phosphorylation resistant RB may have utility in both RB(-/-) and RB(+/+) tumors as well as in hyperproliferative disorders.

Amino Acid Substitution↗
PubMed1997

Analytical anion-exchange HPLC of recombinant type-5 adenoviral particles.

The expanding use of adenoviral vectors for gene therapy has brought about the need for new analytical tools. We have developed an anion-exchange high-performance liquid chromatography method to analyze recombinant adenovirus serotype 5 samples. Before this assay, available analytical methods consisted of either long-term biological assays or required highly purified test articles. These methods were inadequate for optimizing adenovirus production and purification. This assay can quantitate viral particles in either crude lysates or highly pure samples. It can be used to assess particles in both dilute and concentrated samples over a wide dynamic range. Moreover, the population of viral particles eluted in the peak contains most of the infectious virions. This assay is a sensitive technique that overcomes the limitations of previous methods. It provides an essential tool to accomplish process optimization.

Adenoviridae↗
PubMed1997

Reliability of fat-pad sign in radial head/neck fractures of the elbow.

In a prospective study at a single centre between August 1995 and March 1996, 193 patients with elbow injuries were studied. Standard radiographs of the elbows were taken. A total of 181 X-rays were reported by one person concerning the presence or absence of fractures and fat-pad signs. The radiographs were analysed and positive predictive values were calculated for the presence of the fat-pad sign with radial head/neck fractures. The sensitivity for radial head/neck fracture is 85.4 per cent, while the specificity is only 50 per cent. The fat-pad sign must be used cautiously as an indicator of radial head/neck fractures; its absence is a more reliable indicator of the absence of a radial head/ neck fracture.

Adolescent↗
PubMed1997

Antibody to CD40 ligand inhibits both humoral and cellular immune responses to adenoviral vectors and facilitates repeated administration to mouse airway.

Adenoviral vectors have been used successfully to transfer the human CFTR cDNA to respiratory epithelium in animal models and to CF patients in vivo. However, studies done primarily in mice, indicate that present vector systems have limitations. Among other things, transgene expression in the lung is transient and the production of neutralizing antibodies against adenovirus correlates with a reduced ability to readminister a vector of the same serotype. Here we demonstrate that in mice, a transient blockade of costimulation between activated T cells and B cells/antigen presenting cells using a monoclonal antibody (MR1) against murine CD40 ligand inhibits the development of neutralizing antibodies to adenoviral (Ad) vector. MR1 also decreased the cellular immune response to Ad vector and allowed an increase in persistence of transgene expression. Furthermore, when administered with a second dose of Ad vector to mice preimmunized against vector, MR1 was able to interfere with the development of a secondary antibody response and allowed for high levels of transgene expression upon a third administration of vector to the airway.

Adenoviridae↗
PubMed1997

Effect of the E4 region on the persistence of transgene expression from adenovirus vectors.

The utility of adenovirus vectors for gene therapy is limited by the transience of expression that has been observed in various in vivo models. Immunological responses to viral targets can eliminate transduced cells and cause the loss of transgene expression. We previously described the characterization of an E4 modified adenovirus, Ad2E4ORF6, which is replication defective in cotton rats. We reasoned that gene transfer vectors based on Ad2E4ORF6 would have a reduced potential for viral gene expression in vivo which might be beneficial for achieving persistence of transgene expression. E1 replacement vectors expressing the cystic fibrosis transmembrane regulator or beta-galactosidase were constructed as series of vectors that differed with respect to the E4 region. Vectors containing a wild-type E4 region, E4 open reading frame 6, or a complete E4 deletion were compared in the lungs of BALB/c mice for persistence of expression. Results obtained with nude mice indicate that nonimmunological factors have a major influence on the longevity of transgene expression. Expression was transient from the E1a promoter with all vectors but persisted from the cytomegalovirus promoter only with a vector containing a wild-type E4 region. Transience of expression did not correlate with the disappearance of vector DNA, suggesting that promoter down-regulation may be involved. Coinfection studies indicate an E4 product(s) could be supplied in trans to allow persistent expression from the cytomegalovirus promoter. In summary, the choice of promoter is important for achieving persistence of expression; in addition, some promoters are highly influenced by the context of the vector backbone.

Adenoviridae↗
PubMed1997

The limits to health care and rehabilitation.

Customary in the field of health care and rehabilitation, a spirit of optimism pervades the work and attitudes held by most practitioners. Professionals have many reasons and excellent track records in working with individual clients to support optimistic beliefs. At the same time, substantial social, economic, and political limits determine what can be undertaken and accomplished. Some of these constraints are global in character; others are organizational. Definitions of these limits and awareness about their causes can lead to higher quality research and action on sociological, political, economic, and/or systems-level approaches. Eventually, this awareness and the responses to the limits may lead to greater resources and better outcomes. Such results would support rather than limit effective action at the individual level. New Zealand provides an interesting case study, given the prevailing economic hard times.

Decision Making, Organizational↗
PubMed1996

Adenovirus-mediated p53 gene transfer suppresses growth of human glioblastoma cells in vitro and in vivo.

Alterations in the p53 tumor-suppressor gene occur in 35-60% of human glioblastomas, and re-introduction of p53 can suppress neoplastic growth. To evaluate the potential for p53 gene therapy of glioblastoma, we have analyzed the response of human glioblastoma cell lines in vitro and in vivo to experimental therapy with replication-deficient recombinant adenoviruses encoding wild-type p53 (rAd-p53). Western blot analyses showed high-level expression of p53 protein after treatment with rAd-p53, and transgene expression was dependent on promoter strength. A p53-specific dose-dependent inhibition of in vitro cellular proliferation was observed in 5 of 6 cell lines, and growth inhibition corresponded to adenovirus-mediated gene transfer and expression. p53-specific cell death was quantitated by release of the lactate dehydrogenase enzyme. Fragmentation of DNA into nucleosomal oligomers and the occurrence of a hypodiploid cell population detected by flow cytometry provided evidence for apoptosis. Studies in nude mice demonstrated that ex vivo infection with rAd-p53 suppressed the tumorigenic potential of human glioblastoma cells. Furthermore, direct injection of rAd-p53 into established s.c. xenografts inhibited tumor growth. Our observations suggest that re-introduction of wild-type p53 may have potential clinical utility for gene therapy of glioblastoma.

Adenoviridae↗
PubMed1996

Inhalant use patterns among Eskimo school children in western Alaska.

An inhalant use survey was administered to 376 school children in 14 isolated villages. Questions in the survey elicited gender and ethnic distribution, frequency and duration of use, age of onset, reasons for using and inhalant of choice. These characteristics were further examined by dividing users into 2 groups based on use frequency and duration, i.e., Light Users and Heavy Users. Lifetime prevalence was 48%. Most inhalant use appeared to be sporadic, transient and occurring in social context. Heavy Users differed from Light Users in that they were more likely to be male, have an earlier age of onset, have different ethnic distribution and use inhalants in response to affect. These children may represent an inhalant dependent subgroup. This finding of user heterogeneity has important implications for the development of effective prevention and treatment programs.

Adhesives↗
PubMed1996

Information exchange as empowerment: a case study.

In July 1994 a newspaper was created to share information in and among the community of people with disabilities in Palmerston North, New Zealand. The project became, in only a few months, not only economically viable, but extremely successful as a social and community experiment, and an endeavour by people with disabilities to inform each other and the larger community. This article describes the origin, design and development, and the current status of the newspaper, and advances the recommendation that people with disability elsewhere, and those professionally employed in the rehabilitation field, consider similar initiatives to inform, and thereby empower, people with disabilities.

Consumer Advocacy↗
PubMed1996

Rehabilitation interventions: ideas based on a South Pacific example.

The South Pacific represents a unique area of the world where people with disabilities do need and want rehabilitation interventions. Cross-cultural work, however, carries inherent misunderstandings. Some ideas and examples illustrate how rehabilitation interventions can take place if and when deeper insight into cultural differences is available.

Adult↗
PubMed1995

Characterization of an adenovirus gene transfer vector containing an E4 deletion.

We describe the construction and characterization of an adenovirus type 2 vector, Ad2E4ORF6, which has been modified in the E4 region to contain only open reading frame 6. When assayed in cultured cells, Ad2E4ORF6 virus replication is slightly delayed but viral DNA synthesis, host-cell protein synthesis shut-off, and virus yield are indistinguishable from wild type. Late protein synthesis is normal with the exception of fiber synthesis, which is reduced approximately 10-fold. Despite the reduced fiber synthesis, Ad2E4ORF6 viral particles appear to contain a full complement of fiber protein. Virus replication in cotton rats indicates that Ad2E4ORF6 is replication defective in vivo. This may have safety implications for the development adenovirus vectors in that virus arising by recombination in the E1 region of an Ad2E4ORF6-based vector would be defective for growth in vivo. The deletion of E4 open reading frames that are not required for virus growth in vitro increases the cloning capacity of adenovirus vectors by 1.9 kb and may be generally useful for the construction of adenovirus vectors containing large cDNA inserts and/or regulatory elements. We describe the inclusion of the A2E4ORF6 modification in a recombinant adenovirus vector, Ad2/CFTR-2, for gene transfer of the human cystic fibrosis transmembrane regulator (CFTR).

Adenoviridae↗