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At least 325 records · Page 18Linked to original sources
PubMed2000

Contractile dysfunction in hypertrophic cardiomyopathy: elucidating primary defects of mutant contractile proteins by gene transfer.

Hypertrophic cardiomyopathy (HCM) is an inherited disorder of cardiac muscle that has been linked to mutations in the contractile proteins that make up the cardiac muscle sarcomere. Recent advances in cardiovascular molecular biology, including gene targeting and transgenesis in mice, and gene transfer technology to adult cardiac myocytes in primary culture, have provided new insights into how these mutations alter the structure-function of the cardiac muscle pump and the molecular mechanisms of HCM pathogenesis. In this review, we highlight the contributions of the application of gene transfer technology to adult cardiac myocytes in vitro that aim at sorting the primary effects of HCM mutant contractile proteins on the structure and function of cardiac muscle cells from the compensatory and secondary phenomenon that occur during HCM pathogenesis in vivo. The elucidation of the primary molecular mechanisms underlying the development of HCM forms a foundation by which to identify the key targets for disease treatment or prevention.

Animals↗
PubMed1991

Clinical considerations in the design of protocols for somatic gene therapy.

Despite two decades of investigating the potential for somatic gene therapy in curing human disease, few clinical trials are being proposed. This delay is due in part to limitations of existing methods for gene transfer and to the recognized need to proceed judiciously into this controversial arena. Delay is also caused by a disjunction between the traditional precedents and principles of clinical investigation and the procedures instituted to regulate somatic gene therapy. The premise of this report is twofold: first, that more extensive clinical investigation of gene transfer technologies would be beneficial to patients, medicine, and basic science and second, that clinical investigations could be expedited by appealing to the established experience in clinical investigation without compromising the scientific excellence and discipline essential for this highly public process. This report develops a clinical perspective on potential applications of existing gene transfer technologies and the issues involved in developing experimental protocols. The initiation of clinical trials should be a primary goal of gene therapy research programs.

Animals↗
PubMed1997

Application of NASA's advanced life support technologies in polar regions.

NASA's advanced life support technologies are being combined with Arctic science and engineering knowledge in the Advanced Life Systems for Extreme Environments (ALSEE) project. This project addresses treatment and reduction of waste, purification and recycling of water, and production of food in remote communities of Alaska. The project focus is a major issue in the state of Alaska and other areas of the Circumpolar North; the health and welfare of people, their lives and the subsistence lifestyle in remote communities, care for the environment, and economic opportunity through technology transfer. The challenge is to implement the technologies in a manner compatible with the social and economic structures of native communities, the state, and the commercial sector. NASA goals are technology selection, system design and methods development of regenerative life support systems for planetary and Lunar bases and other space exploration missions. The ALSEE project will provide similar advanced technologies to address the multiple problems facing the remote communities of Alaska and provide an extreme environment testbed for future space applications. These technologies have never been assembled for this purpose. They offer an integrated approach to solving pressing problems in remote communities.

Alaska↗
PubMed2004

Intellectual property conundrum for the biological sciences.

Policy regarding academically generated biomedical intellectual property (IP) has been shaped by two important events: the Vannevar Bush report to then President Roosevelt in 1945 and the Bayh-Dole Act of 1980. This policy, which vests the intellectual property produced from federally funded biomedical research from the government to the academic institution, was designed to promote technology transfer and thus promote the health of the U.S. economy. However, the policy has led to significant challenges, particularly in implementation. Here it is argued that the difficulties are due to differences in the structure of motivations between biomedical scientists, institutional officials, and private sector entrepreneurs. Understanding these differences may lead to a review of policy with the goal of enhancing technology transfer for the future.

Biological Science Disciplines↗
PubMed2003

Gene transfer in experimental medicine.

Gene transfer technology has many potential applications in medicine. Phase I and phase II gene-based clinical trials have been conducted for the treatment of cancer, monogenic disorders, some neurodegenerative illnesses, cardiopathies and infectious diseases. A phase I gene therapy clinical trial has recently been approved for the treatment of Parkinson's disease, while preclinical studies are in progress to develop gene-based interventions for the treatment of Alzheimer's disease and Huntington's disease, amyotrophic lateral sclerosis, spinal cord injury, and diabetes type 1 and type 2. A number of gene transfer models have been generated for gene therapy and genetic immunization programs. Vector design is addressing several pressing issues in the matter of gene delivery improvement, stabilization of transgene expression and safety. This is necessary in order to achieve efficient gene-based therapeutic interventions. Indeed, considerable progress has been reported in the field of vector design, which has produced some encouraging results in clinical trials and preclinical studies. However, vector design should be further developed to allow for the successful application of gene transfer technology in therapy. This review summarizes the latest achievements and controversies in clinical trials and preclinical studies in the field of gene therapy.

Animals↗
PubMed1996

The basis for somatic gene therapy of cancer.

A decade of advances in understanding of the molecular basis of sporadic and familial cancers has combined with developments in mammalian gene transfer technology to stimulate intensive research into the potential applications of somatic gene therapy for cancer. Somatic gene immunotherapy is already in progress to stimulate and direct the natural targeting capabilities of the immune system against the threat of disseminated residual disease. The association of a plethora of mutated tumor suppressor genes (p53, p16 BRCA1, BRCA2) with diverse cancers has also highlighted the potential of somatic gene therapy with wild-type versions of suppressor genes as an anti-cancer therapeutic modality either in its own right or in synergistic association with traditional anti-cancer therapies. The methodologies for gene transfer technology range from direct intravenous injection of naked modified DNAs to intravenous injection of liposome-encapsulated DNAs or microsphere-bound DNAs. Recombinant retroviral and adenoviral vectors have natural transfection capabilities and display tropism for particular tissues that are of selective advantage against particular cancers. Liposomes display very high efficiencies of gene transfer with the advantages of successful transfer to a wide range of tissue types but their widespread systemic distribution offers problems in relation to selective targeting of tumor cells. The challenges to current gene transfer processes are much the same as that of other anti-cancer therapies: achieving selective targeting of cancer cells whilst optimizing dosages and minimizing the risk of collateral damage to healthy tissues.

Animals↗
PubMed1987

Making childhood asthma management education happen in the community: translating health behavioral research into local programs.

The public health benefits of research can be realized only if proven new techniques are translated into readily usable processes and materials and widely adopted by professionals and patients alike. To accomplish this, a systematic technology transfer process is needed. One recent outcome of health behavior research has been identification of the skills needed by children and parents to effectively manage childhood asthma. Methods for teaching these skills were tested on hundreds of families in a variety of health care settings. They were then packaged in program manuals that guide health professionals through the teaching process and provide all necessary materials for conducting sessions. The resulting four programs teach attack prevention and control skills. They also emphasize coping skills and help families come to terms with the behavioral factors that impinge on asthma management and affect compliance with medical advice. A technology transfer project for getting initial community adoption of these programs is described. The evolution of the project, including the development of the programs themselves, packaging considerations, establishment of a unique partnership for dissemination, development of a model workshop for stimulating health professionals, implementation of programs, and follow up and evaluation, is described. Successful elements are identified at each step.

Asthma↗
PubMed2005

Tyrosine hydroxylase replacement in experimental Parkinson's disease with transvascular gene therapy.

Transvascular gene therapy of Parkinson's disease (PD) is a new approach to the gene therapy of PD and involves the global distribution of a therapeutic gene to brain after an intravenous administration and transport across the blood-brain barrier (BBB). This is enabled with the development of a nonviral gene transfer technology that encapsulates plasmid DNA inside pegylated immunoliposomes or PILs. An 85- to 100-nm liposome carries the DNA inside the nanocontainer, and the liposome surface is conjugated with several thousand strands of 2000-Da polyethyleneglycol (PEG). This PEGylation of the liposome stabilizes the structure in the blood stream. The liposome is targeted across the BBB via attachment to the tips of 1-2% of the PEG strands of a receptor-specific monoclonal antibody (mAb) directed at a BBB receptor, such as the insulin receptor or transferrin receptor (TfR). Owing to the expression of the insulin receptor or the TfR on both the BBB and the neuronal plasma membrane, the PIL is able to reach the neuronal nuclear compartment from the circulation. Brain-specific expression is possible with the combined use of the PIL gene transfer technology and brain-specific gene promoters. In the 6-hydroxydopamine rat model of experimental PD, striatal tyrosine hydroxylase (TH) activity is completely normalized after an intravenous administration of TfRmAb-targeted PILs carrying a TH expression plasmid. A treatment for PD may be possible with dual gene therapy that seeks both to replace striatal TH gene expression with TH gene therapy, and to halt or reverse neurodegeneration of the nigro-striatal tract with neurotrophin gene therapy.

Animals↗
PubMed1994

[Strategies of general anesthesia for cleft palate surgery in Cambodia].

Hare lip and cleft palate surgery team activities in Cambodia were launched in 1989 by a non-governmental Japanese organization, Operations Unies. The objectives of the project are to provide appropriate surgical treatment and safe general anesthesia for local patients and also to conduct technology transfer of general anesthesia and surgery to the local medical staffs. From June 1991 to January 1993, a surgery/anesthesia team was dispatched 4 times and a total of 130 patients received surgical treatments under general anesthesia. Anesthesia techniques employed included total intravenous anesthesia in 70 patients (54%) and intravenous anesthesia with 0.3-0.7% of halothane in 60 patients (46%). There were no major complications, such as airway obstruction and apnea, in the recovery room and in the ward. The reasons why we chose intravenous agents are difficulty in obtaining inhaled agents in Cambodia and lack of scavenging system in a operating room. Although halothane anesthesia with spontaneous breathing has been recommended in developing countries, total intravenous anesthesia could be one of the applicable techniques in these countries. In Cambodia, shortage of medical doctors and the absence of anesthesiologist constitute a major barrier to technology transfer in clinical anesthesia.

Anesthesia, General↗
PubMed1990

Transfer of technology. Cancer education.

Advances in research are transmitted to practicing physicians through a variety of continuing medical education approaches. Physicians are sophisticated managers of their learning and use group and self-instruction methods. Local hospitals and professional societies along with reading are major sources of continuing education. Cancer education to transmit the latest advances draws on all methods of continuing medical education. A study of practicing physicians' interests and preferences in cancer education provides guidance about tailoring continuing medical education to physician needs. The use of personal computers may be important in bringing information directly to the physician in the practice setting. The challenge is to provide educational opportunities in a variety of ways to meet the diverse needs of the practicing medical community.

American Cancer Society↗
PubMed1994

The introduction of Cyclofem into national family planning programmes: experience from studies in Indonesia, Jamaica, Mexico, Thailand and Tunisia. Task Force on Research on Introduction and Transfer of Technologies for Fertility Regulation, Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland.

Studies on the introduction of Cyclofem into family planning programmes have been undertaken in Indonesia, Jamaica, Mexico, Thailand and Tunisia. Cyclofem is a once-a-month injectable contraceptive containing 25mg medroxyprogesterone acetate and 5mg estradiol cypionate. A total of 7927 subjects were followed in close to routine service delivery conditions in primary and secondary family planning outlets. The studies confirmed the high efficacy of the method with 12-month pregnancy rates ranging from 0 to 0.7%. Major differences were seen in reasons and rates of discontinuation between countries, the overall 12-month life table discontinuation rates ranging from 33.5% in Indonesia to 71.8% in Tunisia. The reasons for discontinuation in each of the five countries are described, differences between countries contrasted, and service delivery issues which should be addressed further, raised.

Adolescent↗
PubMed2000

The ability of pea transformation technology to transfer genes into peas adapted to western Canadian growing conditions.

Transgenic pea plants can be produced by Agrobacterium-mediated transformation of thin slices from developing embryo axes. To determine if the method is effective for different pea genotypes, seven pea breeding lines adapted to western Canadian growing conditions were tested, using three different Agrobacterium tumefaciens transformation vectors. All vectors contained the gus (uidA) gene coding for the beta-glucuronidase (GUS) protein, but with different chemical selection genes. In total, 323 transgenic plants were recovered from 39 independent transformation events. Transgenic plants were recovered from each genotype and each selection system, but not from all combinations. GUS-positive explants were obtained from seeds harvested between 24 and 31 days after flowering. The mean time from Agrobacterium treatment to planting into soil averaged 186 days. Based on the initial number of seeds used, the transformation frequency was 0.6% (i.e. six independent transgenic events per 1000 axes sliced). The inserted genes were functional and inherited in a Mendelian fashion. Although more plants were recovered by selection on chlorsulfuron, GUS activity was generally greater in plants selected on kanamycin. GUS activity in the leaves of the original plants varied, but GUS activity in the second generation was correlated with that of the original transformants.

Journal Article↗