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Licensing web-based nursing programs, courses, and course materials.

With the advent of the digital information age, schools of nursing are developing and using web-based programs, courses, and course materials to meet students' needs for access and high-quality learning experiences. In an attempt to maximize scant resources, including faculty, many schools are seeking grant funding, joining consortia, or forming partnerships that require sharing of web-based course materials. Entering such collaborative arrangements usually requires licensing agreements to transfer intellectual capital. This article explains licensing and the related concepts of intellectual property, copyright, and technology transfer. It also identifies the advantages and disadvantages of licensing and describes a licensing process.

Computer-Assisted Instruction↗

Effect of adenoviral early genes and the host immune system on in vivo pancreatic gene transfer in the mouse.

Gene transfer technology may provide a novel approach to treatment for pancreatic diseases. Recombinant adenovirus achieves efficient gene transfer in vivo. In this study, a murine model of adenoviral-mediated pancreatic gene transfer was developed, and the factors responsible for adenoviral elimination were investigated. Three days after direct pancreatic injection of a replication-defective adenovirus containing the lacZ transgene, a high proportion (76.8 +/- 6.7%) of pancreatic cells expressed beta-galactosidase, the gene product. Gene expression was absent by 28 days posttransduction. In immunodeficient mice, beta-galactosidase expression persisted with 20.0 +/- 6.0% of pancreatic cells staining positive 60 days after viral transduction. To test whether early viral proteins are the antigenic components responsible for the potent antiviral immune response, normal mice were injected with different adenoviral vectors containing early gene deletions. Vectors containing deletions in early region 2 or 4 expressed beta-galactosidase at 28 days. Presently available adenoviral vectors engineered to avoid this response offer minimal improvements in transgene duration. Further vector modifications or alternative strategies are needed to achieve stable pancreatic adenoviral transgene expression.

Adenoviridae↗

[Telemedicine in diagnosis and treatment of occupational skin diseases].

Advances of new data transfer technologies in medicine enable distant consultations for far places residents. Scandinavian countries, especially Sweden, have accumulated significant experience with using television medicine in dermatology. Applying television medicine technologies in occupational dermatology is the most topical item for Nizhny Novgorod region. In these cases transfer could cover not only images of diseased skin sites, but also text (history description and other medical information). International cooperation with foreign colleagues including Swedish doctors is considered prospective.

Humans↗

Genetic engineering of T cell specificity for immunotherapy of cancer.

The ultimate goal of immunotherapy of cancer is to make use of the immune system of patients to eliminate malignant cells. Research has mainly focused on the generation of effective antigen specific T-cell responses because of the general belief that T-cell immunity is essential in controlling tumor growth and protection against viral infections. However, the isolation of antigen specific T cells for therapeutic application is a laborious task and it is often impossible to derive autologous tumor specific T cells to be used for adoptive immunotherapy. Therefore, strategies were developed to genetically transfer tumor specific immune receptors into patients T cells. To this end, chimeric receptors were constructed that comprise antibody fragments specific for tumor associated antigens, linked to genes encoding signaling domains of the T-cell receptor (TCR) or Fc receptor. T cells expressing such chimeric antibody receptors recapitulate the immune specific responses mediated by the introduced receptor. Recently, we introduced chimeric TCR genes into primary human T lymphocytes and demonstrated that these T cell transductants acquired the exquisite major histocompatibility complex (MHC) restricted tumor specificity dictated by the introduced TCR. Importantly, the introduction of chimeric TCR bypasses problems associated with the introduction of nonmodified TCR genes, such as pairing of introduced TCR chains with endogenous TCR chains and unstable TCRalpha expression. A novel strategy which is completely independent of available tumor specific T-cell clones for cloning of the TCR genes was recently used to transfer MHC restricted tumor specificity to T cells. Human "TCR-like" Fab fragments obtained by in vitro selection of Fab phages on soluble peptide/MHC complexes were functionally expressed on human T lymphocytes, resulting in MHC restricted, tumor specific lysis and cytokine production. In addition, affinity maturation of the antibody fragment on Fab phages allows improvement of the tumor cell killing capacity of chimeric Fab receptor engrafted T cells. Developments in retroviral transfer technology now enables the generation of large numbers of antigen specific T cells that can be used for adoptive transfer to cancer patients. In this article we summarize the developments in adoptive T cell immunogenetic therapy and discuss the limitations and perspectives to improve this technology toward clinical application.

Antibodies, Neoplasm↗

The transfer of vaccine technology to developing countries. The Latin American experience.

Technological advances by developed countries are producing safer, more potent vaccines. In addition, the transfer of the technology of vaccine production to some developing countries has been taking place during the past five decades, thereby making possible the participation of developing countries in the production and supply of the essential biologicals that are required for immunization programs. Examples of successful transfers of technology, the decisive elements and factors that contribute to the transfers, and the major obstacles to such transfers are presented.

Caribbean Region↗

A review of gene therapy for haematological disorders.

Gene therapy aims to correct the disease process by restoring, modifying or enhancing cellular functions through the introduction of a functional gene into a target cell. Whilst the concept of gene therapy is simple, the practical reality of translating this new technology to the clinic has proven to be more difficult than first imagined. Recent progress in gene transfer technology has shown impressive clinical success in infants with immunodeficiency. However, two of these children have subsequently developed leukaemia as a result of insertional mutagenesis, thus, raising important questions about the safety of genetic therapeutics. This article reviews the current status of gene therapy and outlines the challenges faced by this emerging technology that holds so much promise for many suffering from catastrophic disorders.

Animals↗

Recent progress in mammalian cloning.

PURPOSE: Our purpose was to review recent progress in the use of nuclear transfer technology to produce genetically identical mammals. METHODS: A literature review was conducted. RESULTS: The reasons for cloning nonhuman mammals are manyfold including commercial, biomedical, and basic research applications. Individual steps in the nuclear transfer process are itemized, along with a detailed description of the specific approaches used in the production of Dolly, NETI, and DITTO. The potential application of nuclear transfer in the treatment of human infertility is also considered, along with bioethical concerns. Finally, insights are provided concerning the future application of cloning technology in rhesus macaques. CONCLUSIONS: The cloning of a lamb (Dolly) from an adult, mammary gland cell coupled with the successful production of rhesus monkeys (NETI and DITTO) by nuclear transfer of embryonic cells marks the beginning of a "Golden Age" in the development and application of somatic cell cloning technology in mammals.

Animals↗

Salivary glands as a model for craniofacial applications of gene transfer.

The potential applications of gene transfer technology to all branches of medicine are increasing. It is quite likely that within the next 10-20 years surgical practice routinely will utilize gene transfer, at least adjunctively. The purpose of this review is to familiarize the oral and maxillofacial surgeon with this technology. Studies performed with salivary glands in animal models are presented as examples of proof of concept.

Animals↗

Cell cycle analysis of cultured porcine mammary cells.

One of the major points of debate in determining the effectiveness of nuclear transfer technology has been the phase of the cell cycle of the donor cell at the time of nuclear transfer. Here, a primary mammary cell line has been isolated and various treatments for synchronization of the cell cycle have been tested. The cells were then simultaneously stained for DNA content and protein content and the percentages of cells in G1, G0, S, and G2 + M were estimated. In the first experiment, cells were either cycling, grown to confluence, or serum-starved for 5 days. Serum starvation increased (p < 0.05) the percentage of cells in G0 compared to confluent or cycling cells from 3% to 8% to 22%. By using forward scatter to determine the size of the cells it was determined that if small cells (7-15 microm) were selected from the serum-starved group 43.9% will be in G(0) as compared to 4.5% of cycling cells and 9.9% of confluent cells. Dimethyl sulfoxide (DMSO) treatment (0%, 0.5%, or 1.0%) for 72 hours (shown to synchronize some cell types in G0) had no effect on the percentage of cells in G0, G1, S, or G2 + M. Treatment with mimosine (0 microM, 0.4 microM, 0.8 microM or 1.2 microM), a compound that should synchronize the cells in G1, increased (p < 0.05) the percentage of cells in G1 from 66.7% (0 microM mimosine) to 79.0% to 82.0%. Finally, treatment with colchicine for 24 hours (shown to synchronize some cell types in G2 + M) increased (p < 0.05) the percentage of cells in G2 + M (0 microM colchicine) from 13.3% to 27.2% to 31.6%. It is concluded that many cell cycle synchronization techniques are effective in porcine mammary cell lines, but none of the techniques are 100% effective. Such results should help elucidate the mechanisms involved in nuclear transfer.

Animals↗

Approaches to gene transfer in keratinocytes.

The introduction and expression of exogenous genetic material in cultured cells has provided a powerful tool for studying gene function and regulation. Immortalized cell lines have been useful for establishing gene transfer methodologies that are generally inefficient. For investigators of epidermal and mucosal biology, wishing to make use of the tissue architecture produced by primary keratinocytes in vitro, the limited life span of these cells presents a host of unique problems. Primary cells require the use of gene transfer methods that are highly efficient and will not significantly alter the cell's normal differentiation pathway. The purpose of this review is to evaluate gene transfer technology as it applies to keratinocytes.

Epithelial Cells↗

Gene therapy for carcinoma of the breast: Genetic immunotherapy.

Advances in gene transfer technology have greatly expanded the opportunities for developing immunotherapy strategies for breast carcinoma. Genetic immunotherapy approaches include the transfer of genes encoding cytokines and costimulatory molecules to modulate immune function, as well as genetic immunization strategies which rely on the delivery of cloned tumor antigens. Improved gene transfer vectors, coupled with a better understanding of the processes that are necessary to elicit an immune response and an expanding number of target breast tumor antigens, have led to renewed enthusiasm that effective immunotherapy may be achieved. It is likely that immunotherapeutic interventions will find their greatest clinical application as adjuvants to traditional first-line therapies, targeting micrometastatic disease and thereby reducing the risk of cancer recurrence.

Antigens, Neoplasm↗

Progress and challenges in viral vector-mediated gene transfer to the brain.

Gene transfer into the brain allows the manipulation of transgene expression in both time and space. Recently developed gene transfer technologies allow transgenes to be expressed in any anatomically, biochemically or functionally distinct group of brain cells. Gene transfer has been used to alter the expression of neurotransmitter receptors, ion channels, signaling proteins, neuronal growth, differentiation and survival factors, and thus to modify brain anatomy, neuron physiology, behavior and pathology. However, challenges remain in making gene therapy a more widespread tool for the treatment of neurological disease. We have identified the following as areas needing development: access and delivery of viral vectors to the brain; diffusion of viral vectors and transgenes throughout large areas of brain tissue; viral vector side effects and toxicity, inflammatory and immune responses to vectors; long-term stable transgene expression; cell type-specific expression of transgenes; and the ability of the experimenter or physician to switch transgene expression 'on' and 'off' at will. In the last year, neuro-gene therapy has shown that brain defects in experimental disease models can be prevented and corrected, and that viral vectors and encoded transgenes can be made to diffuse over larger brain areas. In addition, the cause of vector-induced inflammation and immune responses have begun to be elucidated, so that rational approaches can be developed to avoid these complications. Further improvements in viral vectors will facilitate clinical trials in the near future.

Adenoviridae↗

Cloning: can it be good for us? An overview of cloning technology and its moral implications.

Adequate answers to moral questions about cloning require a working knowledge of the science and technology involved, both present and anticipated. This essay presents an overview of the current state of somatic cell nuclear transfer technology (SCNT), the type of cloning that now permits whole organism reproduction from adult DNA. This essay explains the basic science and technology of SCNT and explores its potential uses. Next, this essay notes remaining scientific obstacles and unanswered moral questions that must be resolved before SCNT can be used for human reproduction. Attention is given to aspects related to cloning for therapeutic and research purposes.

Adult↗

Genetically augmented tissue engineering of the musculoskeletal system.

Recent advances in gene transfer technology permit the design of strategies to improve the outcome of orthopaedic tissue engineering by genetic means. Using ex vivo and in vivo strategies, genes have been transferred successfully to, and expressed within, numerous tissues of the musculoskeletal system, including articular cartilage, meniscus, intervertebral disc, bone, tendon, ligament, synovium, and muscle. With these technologies, various genes encoding modulatory species of ribonucleic acid or proteins such as growth factors, receptors, and transcription factors could be used in the context of genetically augmented tissue engineering. Proof of principle has been established in numerous animal models, and a human protocol for the transfer of genes to synovium already is underway. Progress so far permits cautious optimism of a successful outcome to these pursuits.

Animals↗

Current status and perspectives for the generation of transgenic pigs for xenotransplantation.

Xenotransplantation implies transplantation of organs between discordant, e.g. non-related species. This procedure usually is associated with a hyperacute rejection response (HAR) which destroys the transplanted organ within minutes. To overcome the growing shortage of human organs, transgenic pigs have been generated that express human complement regulatory genes. This approach enables to overcome the HAR as shown by an extended average survival rate of 40-90 days of the immunosuppressed primate recipient of a transgenic porcine heart. It is expected that transgenic pigs will be available as organ donors within the next 5-7 years. A major prerequisite is the prevention of the potential transfer of pathogenic microorganisms, in particular porcine endogenous retroviruses (PERV). Transgenic livestock has been generated predominantly via microinjection of DNA-constructs into pronuclei of zygotes. However, efficiency is low and only 1-3% transgenic offspring are to be obtained. Integration of the transgene occurs at random and expression is independent from the number of integrated copies but can be affected by the integration site. Improvements of the efficiency in the generation of transgenic pigs will be achieved by the use of genetically modified donor cells in nuclear transfer technology (cloning).

Animals↗

Clinical application of somatic gene therapy in inborn errors of metabolism.

Rapid advances in recombinant DNA and gene transfer technologies provide the potential for somatic gene therapy of inborn errors of metabolism in which the genetically defective function will be restored by transfer of a normal gene into somatic cells. The therapeutic potential and safety of gene therapy has been explored in cultured cells and experimental animals, but therapeutic clinical trials have not yet been proposed or performed. The technologies which may make somatic gene replacement therapy feasible need to be considered and criticised from a clinical perspective. Clinical trials will be necessary to determine the efficacy of somatic gene therapy and address concerns about safety.

Animals↗

Gene therapy in lung cancer.

The poor overall survival rates associated with non- small-cell lung cancer despite advances in chemotherapy, radiotherapy, and surgery mandate the search for novel approaches. Advances in gene transfer technology have allowed gene therapy strategies to develop that act in such a way as to stimulate the immune system, transfer "suicide" genes, inactivate oncogenes, replace tumor suppressor genes, and transfer pro-apoptotic genes. Clinical trials evaluating these possibilities have begun, and findings indicate that the transfer of tumor sup- pressor genes (wild-type p53) is feasible and has low overall toxicity. Subsequent clinical trials have begun to evaluate the clinical potential of these approaches in non-small-cell lung cancer.

Apoptosis↗

Altering behavior with gene transfer in the limbic system.

There is now sufficient knowledge of the workings of the limbic system to allow experimental manipulation of behaviors anchored in limbic function. While such manipulations have traditionally involved lesions, stimulation or pharmacological approaches, it has become plausible to use gene transfer technology to alter patterns of gene expression in the nervous system. In this review, I consider ways in which gene transfer has been used to alter limbic function. These involve altering (a) cognition, (b) the rewarding properties of addictive substances, (c) patterns of social affiliation, and (d) responses to stress.

Animals↗