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At least 451 records · Page 25Linked to original sources
PubMed1997

Sustainable helminth control of ruminants in developing countries.

Widespread anthelmintic resistance, at least amongst the important nematode parasites of small ruminants, threatens the sustainability of these livestock industries throughout both the developed and developing world. The exacerbation of this problem over the last decade or so, has provided the impetus for research into non-chemotherapeutic parasite control alternatives, such as host genetic resistance, grazing management, worm vaccines and biological control. Although some of these options provide practical benefits if currently adopted, or exciting prospects for the future, collectively they are unlikely to dispense with the need for the timely intervention of effective anthelmintic treatment. The issue of sustainability of helminth control practices therefore rests with the preservation of anthelmintic effectiveness through the implementation of principles of integrated pest management. Herein lies the difficulty-putting the principles into practice. Much of the research into sustainable nematode parasite control of ruminants has been done in the developed rather than the developing world, and the efforts to transfer this information to livestock owners has also been commensurately greater in the former. However the need for research and technology transfer is much more urgent in the developing world because of the lack of scientific and financial resources, the greater dependence on livestock industries and the much greater severity of the problem of anthelmintic resistance. This will require a major philosophical change in the affluent western world to the funding of national and international aid organisations who are largely responsible for these activities.

Animals↗
PubMedDate not supplied

Adenovirus mediated gene transduction of primarily isolated mouse islets.

Expansion of pancreatic islet cell populations, especially the beta cells, using a currently available ex vivo gene transfer technology is important to develop cell therapies to treat Type I diabetes. In this study, we evaluated adenovirus mediated gene transfer efficiency in primarily isolated mouse islet cells in two types of culture conditions: freshly isolated suspended islets and cultured islets with monolayer formation. A recombinant replication deficient adenovirus vector encoding a green fluorescence protein (GFP) cDNA, Ad/ CMV-GFP, was used in the present transduction experiments. Rat 804G derived extracellular matrix (804G-ECM) and 3-isobutyl-1-methylxanthine (IBMX) were used to facilitate monolayer formation of the isolated mouse pancreatic islets. Suspended islets were transfected with Ad/CMV-GFP at more than 95% efficiency. However, analysis of immunohistochemical stains for insulin and glucagon in thin sliced sections of the islets revealed that GFP expression was localized just in the outer cells of the islets, almost all of which were glucagon positive alpha-cells. The beta-cells existing at the inner area of the suspended islets were GFP negative. In contrast, under the condition of the islets in monolayer formation cultures, all of the islet cells including the beta-cells were efficiently infected with Ad/CMV-GFP. To achieve an efficient adenoviral gene transfer to the pancreatic beta-cells, monolayer formation of the islets is critical. Such culture conditions were facilitated by combining 804G-ECM with IBMX.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Gene therapy for the extension of vein graft patency: a review.

The mainstay of treatment for long-segment small-vessel chronic occlusive disease not amenable to endovascular intervention remains surgical bypass grafting using autologous vein. The procedure is largely successful and the immediate operative results almost always favorable. However, the lifespan of a given vein graft is highly variable, and less than 50% will remain primarily patent after 5 years. The slow process of graft malfunction is a result of the vein's chronic maladaptive response to the systemic arterial environment, its primary component being the uncontrolled proliferation of vascular smooth muscle cells (SMCs). It has recently been suggested that this response might be attenuated through pre-implantation genetic modification of the vein, so-called gene therapy for the extension of vein graft patency. Gene therapy seems particularly well suited for the prevention or postponement of vein graft failure since: (1) the stimulation of SMC proliferation appears to largely be an early and transient process, matching the kinetics of current gene transfer technology; (2) most veins are relatively normal and free of disease at the time of bypass allowing for effective gene transfer using a variety of systems; and (3) the target tissue is directly accessible during operation because manipulation and irrigation of the vein is part of the normal workflow of the surgical procedure. This review briefly summarizes the current knowledge of the incidence and basic mechanisms of vein graft failure, the vector systems and molecular targets that have been proposed as possible pre-treatments, the results of experimental genetic modification of vein grafts, and the few available clinical studies of gene therapy for vascular proliferative disorders.

Arterial Occlusive Diseases↗
PubMed2001

Recent advances in retrovirus vector-mediated gene therapy: teaching an old vector new tricks.

Oncoretrovirus-based vectors have been shown to be a safe and reliable vector system that can achieve permanent integration of delivered transgenes. Successful application of these vectors for gene therapy has proven difficult due to their relatively low transduction efficiency; however, cumulative improvements in methodology have recently yielded promising clinical results. Furthermore, significant improvements in basic retrovirus vector technology now promise to revitalize the field. This review focuses on these important recent developments in the field of retrovirus-mediated gene transfer technology and its application to human diseases.

Animals↗
PubMed2001

Development and application of ovine reproductive technologies: an Indian experience.

Sheep play an important role in the Indian economy by providing employment to a large population of marginal and landless farmers. The production from native breeds is relatively low due to their poor reproductive efficiency. Embryo transfer technology can be utilised for faster multiplication of elite animal to increase the genetic gain. A great deal of research is involved to overcome the constraints in the technology, i.e. expensive and complicated nature of the technology and low success rate. In order to avoid surgical involvement, procedures of laparoscope aided embryo collection and transfer have been developed. Although the use of FSH of ovine origin has given more consistent superovulatory response, but it is still too low to get sufficient numbers of progeny from a donor ewe. The progress made in cryopreservation of ram semen has opened the possibility for conservation and utilisation of frozen semen of elite rams in sheep improvement programme. The lambing rate obtained after laparoscope aided intrauterine artificial insemination with frozen semen is encouraging but the impetus is now to develop the non-invasive transcervical insemination technique.

Journal Article↗
PubMed2002

Apolipoprotein E-deficient mice created by systemic administration of antisense oligodeoxynucleotides: a new model for lipoprotein metabolism studies.

Atherosclerotic cardiovascular disease results from complex interactions among multiple genetic and environmental factors. Thus, it is important to elucidate the influence of each factor on cholesterol metabolism. For this purpose, transgenic/gene-targeting technology is a powerful tool for studying gene functions. However, this technology has several disadvantages such as being time consuming and expensive. Accordingly, we established new animal models using in vivo gene transfer technology. In this study, we examined the feasibility of the creation of a new animal model for the study of atherosclerosis. We hypothesized that apolipoprotein (apo) E-deficient mice can be created by systemic administration of antisense apo E oligodeoxynucleotides (ODN) coupled to the HVJ-liposome complex. Initially, we examined the localization and cellular fate of FITC-labeled antisense ODN administered intravenously. FITC-labeled ODN transfection by the HVJ-liposome method resulted in fluorescence in the liver, spleen and kidney, but not in other organs such as brain. Moreover, fluorescence with the HVJ-liposome method was sustained for up to 2 weeks after transfection, which resulted in a striking difference from transfection of ODN alone or ODN in liposomes without HVJ, which showed rapid disappearance of fluorescence (within 1 day). Given these unique characteristics of the HVJ-liposome method, we next examined transfection of antisense apo E ODN by intravenous administration. Transfection of antisense apo E ODN resulted in a marked reduction of apo E mRNA levels in the liver, but no change in apo B and beta-actin mRNA levels. In mice fed a normal diet, a transient increase in cholesterol and triglyceride levels was observed in the antisense apo E-treated group, but they returned to normal levels by 6 days after transfection. Similar findings were also found in mice fed a high cholesterol diet. Neither scrambled nor mismatched ODN resulted in any increase in cholesterol. To make chronic hypercholesterolemic mice, we therefore performed repeated injections of apo E antisense ODN. Whenever antisense apo E ODN were injected, mice showed a transient increase in cholesterol and triglyceride. Cumulative administration of antisense apo E ODN resulted in a sustained increase in cholesterol for up to 3 weeks after the last transfection. Finally, mice treated with repeated injections of antisense apo E every week developed sustained hypercholesterolemia and hypertriglyceridemia until withdrawal of injections. Apolipoprotein-deficient mice created by intravenous administration of antisense ODN are a promising new animal model to help understand the role of apolipoprotein in vivo and develop a new drug therapy targeting apolipoprotein.

Animals↗
PubMedDate not supplied

Embryo transfer and related technologies in sheep reproduction.

This paper reviews the status of embryo transfer and the major technologies applied to preimplantation of embryos in sheep. Embryo production from superovulated ewes is hindered by an unpredictable response to hormonal treatment. Progress in this area should be expected by an appropriated control of follicular development with gonadotropin-releasing hormone (GnRH) agonist or antagonist prior to gonadotrophin administration. Simple protocols for the cryopreservation of sheep embryos by vitrification are already available and the development of frozen-thawed blastocysts to term is close to the fresh ones. Further research is required to identify factors able to promote the maturation in vitro of oocytes, namely those obtained from prepubertal animals. Semen and embryo sexing procedures are available in cattle although much less attention was paid to their application to sheep. Among all the reproductive technologies, cloning with embryonic and foetal cells has progressed dramatically in sheep and nuclear transfer has been used to produce transgenic animals as an alternative to pronuclear injection. The production of the first lamb cloned from a somatic cell opened new opportunities in animal breeding as well as exciting lines of basic research. The overall conclusions are that, apart from superovulation, the application of in vitro technologies is likely to evolve rapidly and once applied, a great impact on traditional and new animal productions should be expected. However, a better understanding of the changes in gene expression, induced in embryos by different in vitro manipulation procedures, is necessary to prevent abnormal foetal development.

Animals↗
PubMed2000

Tissue engineering via local gene delivery.

The first goal of this review is to describe a local plasmid gene transfer technology known as the gene activated matrix (GAM). GAM was the first gene therapy designed specifically for tissue engineering applications, and the mechanism of action of plasmid gene transfer is closely tied to the normal sequence of events associated with wound healing. The normal sequence of wound healing events is stereotyped for most tissues, and one assumption has been that GAM could serve as a platform technology for local gene delivery in various tissues and organs. This hypothesis essentially has been proved: animal studies over the past 6 years have established that plasmid genes can be delivered to acutely injured tendon, ligament, bone, muscle, skin, and nerve. The second goal of the review is to describe the most likely "first use" of the technology in man, namely, treatment of osteoporotic hip fracture in the elderly. Although not universally appreciated, interest in osteoporotic fracture should grow because of epidemiological, surgical, and societal considerations. These considerations, plus the unmet clinical need associated with the current standard of fracture care, justify efforts to develop novel therapies for bone regeneration and repair in the elderly.

Animals↗
PubMed1994

Nervous system modification by transplants and gene transfer.

New possibilities to modify function and direct repair in the central nervous system (CNS) have been established by the merger of gene transfer technology with neural transplantation. Rapid advances in viral-mediated DNA-delivery procedures permit the study of novel gene expression in neurons and glial cells. Foreign genes, transferred by a virus vector, can be used to generate new cell lines, identify transplanted cells, and express growth factors or enzymes for neurotransmitter synthesis. In addition to CNS cell types, non-neural cells are also being studied with transgene technology in the nervous system. Functional effects have been obtained with grafts of genetically modified cells in animal models of several nervous system disorders, and the recent results set the stage for potential application of these techniques to human CNS gene therapy.

Adenoviruses, Human↗
PubMed2003

Improved in vitro development rates of sheep somatic nuclear transfer embryos by using a reverse-order zona-free cloning method.

This paper describes a modified zona-free cloning protocol for examining the effects of short-term exposure of donor nuclei to maternal chromosomal components and associated factors. In vitro matured zona-free sheep oocytes were enucleated by micromanipulator-assisted aspiration either before or after fusion with adult fibroblast or granulosa donor cells. Subsequent kinetics of donor nuclei and maternal chromatin as well as in vitro embryo development rates were recorded. The effect of an additional activation stimulus in connection with the reverse-order cloning (fusion before enucleation) and the feasibility of manual enucleation by metal blade were also studied. As a result of the simultaneous fusion and activation, most donor nuclei remained in interphase but swelled in size. Maternal chromosomes reached anaphase II-telophase II stages within 1-2 h of activation, effectively facilitating telophase enucleation with both the micromanipulator-assisted aspiration and manual bisection. A significantly higher development rate to the blastocyst stage was achieved with the reverse-order protocol, suggesting further investigation into the possible role of oocyte nucleus-associated factors in reprogramming is warranted. Overall, the reverse-order zona-free cloning method was efficient in the production of transferable cloned sheep blastocysts and may offer yet another choice of methodology in the practical application of nuclear transfer technology.

Animals↗
PubMed1993

Nuclear transfer in cattle: effect of nuclear donor cells, cytoplast age, co-culture, and embryo transfer.

There are many factors affecting the efficiency of nuclear transfer technology. Some are evaluated here using our novel approach by enucleating oocytes at 20-22 hr after in vitro maturation (IVM), culturing the enucleated oocytes (cytoplasts) for 8-10 hr or 18-20 hr to gain activation competence and then conducting nuclear transfer. In the first experiment, we demonstrated that cumulus cell (CC) monolayer can support some cloned embryos to develop into morulae or blastocysts. Co-culture with CC and bovine oviduct epithelial cell (BOEC) monolayers resulted in no differences (P > 0.05) in supporting the development of cloned embryos (Experiment 2). When in vitro matured oocytes were enucleated at 22 hr after IVM followed by nuclear transfer 18-20 hr later, cleavage and morula or blastocyst development of the cloned embryos were similar to those resulting from the enucleated oocytes which had been matured in vivo (Experiment 3). Frozen embryos as nuclear donor cells worked equally well as fresh embryos for cloning in embryo development which was superior to IVF embryos (Experiment 4). However, fresh embryos resulted in a higher proportion (P < 0.05) of blastomere recovery than did frozen of IVF embryos. Finally, embryo transfer of cloned embryos from our procedure produced a viable calf, demonstrating the commercial value of this novel approach of the technology.

Animals↗
PubMedDate not supplied

DNA transfection of macaque and murine respiratory tissue is greatly enhanced by use of a nuclease inhibitor.

BACKGROUND: Nuclease activity present within respiratory tissues contributes to the rapid clearance of injected DNA and therefore may reduce the transfection activity of directly injected transgenes. Most gene transfer technologies transduce or transfect murine tissues more efficiently than corresponding primate tissues. Therefore, it is prudent to assess the utility of novel gene transfer strategies in both rodent and primate models before proceeding with further development. METHODS: This study analyzed the effects of ATA (a nuclease inhibitor) on the direct transfection of macaque and murine lung tissue; compared the levels of DNase activity in murine, primate, and human lung fluids; and tested the inhibitory activity of ATA on the DNase activity present in these samples. Fluorescent microspheres were used to detect areas of transfection in lung. RESULTS: Intratracheal administration of a nuclease inhibitor (ATA) with naked DNA (0.5 microg ATA/g body weight) enhanced direct transfection efficacy in macaque lung by over 86-fold and by over 54-fold in mouse lung. Hematoxylin and eosin staining showed no apparent tissue toxicity. Moreover, macaque, human, and mouse lung fluids were found to possess similar levels of DNase activity and this activity was inhibited by similar concentrations of ATA. The authors also successfully pioneered the use of carboxylate-modified microsphere tracers to identify areas of transfection and/or treatment. CONCLUSION: This work provides evidence that using direct nuclease inhibitors will enhance lung transfection and that nuclease activity is present in all lung fluids tested, which can be inhibited by the use of direct DNase inhibitors.

Animals↗
PubMed1998

Prospects for gene therapy of insulin-dependent diabetes mellitus.

The application of gene therapy to Type I (insulin-dependent) diabetes mellitus awaits improvements in gene transfer technologies and the development of better tools for accurate diagnosis of pre-diabetic people. Identification of the most promising candidate genes for gene transfer requires further elucidation of the molecular events involved in beta-cell autoimmune destruction, islet ontogeny and differentiation, and beta-cell function. This review outlines a number of possible targets for gene therapy in Type I diabetes, which could help prevent the autoimmune damage to islets, induce islet regeneration, and restore insulin production through engineering of self non-beta cells or beta-cell transplantation. It also evaluates their potential merits and drawbacks.

Autoimmune Diseases↗
PubMed2004

Nuclear transplantation, embryonic stem cells and the potential for cell therapy.

Nuclear transfer experiments in mammals have shown that the nucleus of an adult cell has the ability to direct the development of an entire organism, id est its genome is totipotent. However, these experiments did not conclusively demonstrate that the nuclei of terminally differentiated adult cells remain totipotent. It is possible that rare adult stem cells served as donors for the few surviving clones. To address this question, we have generated monoclonal mice from terminally differentiated lymphocytes that carry a single antigen receptor rearrangement in all tissues. Nuclear transfer technology may provide a powerful method for obtaining autologous cells for replacement therapy. We have demonstrated the feasibility of this concept by combining nuclear transfer with gene and cell therapy to treat the immune deficiency of Rag2 mutant mice, thus establishing a paradigm for 'therapeutic cloning'. Moreover, we will discuss the potential use of nuclear transfer to study the role of reversible genomic (epigenetic) modifications during tumorigenesis.

Animals↗
PubMed2001

[Adenovirus vectors and their clinical application in gene therapy].

The potential therapeutic application of the gene transfer technology with adenovirus vectors seems to be enormous. Adenovirus vectors offer several advantages over other vectors, but several important limitations of adenovirus mediated gene transfer are also known. Great number of studies in inherited diseases and in different cancer therapy clinical trials have provided information of critical importance for design of efficient clinical protocols. Clinical trials have been extended to the treatment of many other diseases, too. There are about thirty currently active gene therapy protocols for the treatment only of HIV-1 infection in the USA. These programs aim to confer protective immunity against HIV-1 transmission to individuals who are in risk of infection, to develop preventive or therapeutic vaccines for patients with AIDS and other infectious diseases. Gene therapy represents one of the most important developments in oncology, however, before this can be realised as standard treatment the technical problems of gene delivery and higher safety must be overcome. The early--first and second generation--adenovirus vectors are now likely to be phased out for most diseases, and further experiments seem to be necessary. It might be change to the third generation or other, more modern vector application in clinical trials, as the helper dependent vectors. Almost all transcriptional unit is removed from the DNA of these vectors ("gutless vectors"), therefore they cannot reproduce, give higher gene expression and far less inflammatory. Despite the latest achievement reported in vector design it is not possible to predict yet to what extent and when gene therapy will be effective.

Adenoviridae↗
PubMed2002

[Continuing medical education as an "event"--innovative use of satellite technology during information transfer].

While it is true that satellite technology has for some time allowed experts that are physically far apart to congregate through their telepresences in--as a rule--one auditorium, nevertheless, the expenditure of effort involved is rarely worth the attention generated by the medium. Therefore by using innovative and appropriately timed satellite technology a multimedia concept with both the character of an "event" and the lasting quality of an "experience" was developed. This concept is based among other things on the complex interconnecting of four experts in four separate halls delivering four lectures (with ensuing discussions) as well as technically speaking on a live television outside broadcast standard including professional presentation and direction. The implementation of the concept was tested and optimised in the course of two information transfer events. Besides confirming the exceptional quality and motivational benefit of the concept the participants' evaluation also underscored the importance of the professional production with its use of specific forms of presentation (such as interviews).

Education, Medical, Continuing↗
PubMed1999

Nonsurgical collection and nonsurgical transfer of preimplantation embryos in the domestic rabbit (Oryctolagus cuniculus) and domestic ferret (Mustela putorius furo).

The objective of this study was to develop nonsurgical methods of embryo collection and transfer in domestic rabbits (Oryctolagus cuniculus) and domestic ferrets (Mustela putorius furo) to serve as models for use in mammals in which surgical procedures are the usual means for applying embryo transfer technology. Specially designed transcervical catheters were used together with a fibre optic endoscope to visualize and then catheterize the rabbit and ferret cervices. Five consecutive transcervical uterine flushes in each of eight superovulated female rabbits 78-89 h after an ovulatory injection of LH resulted in the retrieval of 187 embryos, for an average of 23 embryos per rabbit. A total of 116 embryos were nonsurgically transferred to the uteri of ten recipients, and resulted in 23 young (20%). Eight rabbits (80%) produced young with an average litter size of 2.88 (range 1-7). Ten consecutive transcervical uterine flushes in each of 37 female ferrets 145-178 h after an ovulatory injection of hCG resulted in the retrieval of 324 embryos, an average of 8.76 embryos per ferret. A total of 251 embryos from 27 donors were nonsurgically transferred to the uteri of 31 recipients, and resulted in 65 young (26%). Twenty-eight of the recipients (90%) were initially pregnant, as indicated by postpartum necropsies, and twenty-two ferrets (71%) produced young. The average litter size was 2.95 (range 1-7). This is the first report of live births resulting from the nonsurgical collection of embryos from a donor followed by nonsurgical transfer of those same embryos to a synchronous recipient. The methods reported here can serve as models for use in other mammals in which direct visualization and manipulation of the cervix are not possible, and will be particularly useful in endangered species.

Animals↗
PubMed2002

Gene therapy of severe combined immunodeficiencies.

The concept that the outcome of a devastating disease can be modified by inserting a transgene into abnormal cells is appealing. However, the gene-transfer technologies that are available at present have limited the success of gene therapy so far. Nevertheless, severe combined immunodeficiencies are a useful model, because gene transfer can confer a selective advantage to transduced cells. In this way, a proof of concept for gene therapy has been provided.

Adenosine Deaminase↗