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At least 595 records · Page 33Linked to original sources
PubMed1993

Report on the evaluation of the VA/Seattle below-knee prosthesis.

The Department of Veterans Affairs (VA), Rehabilitation Research and Development (Rehab R&D) Service, Technology Transfer Section (TTS) with collaboration from the Prosthetic and Sensory Aids Service (PSAS) managed clinical trials to evaluate the VA/Seattle Below-Knee (BK) Prosthetic System. The clinical trials were held at the Prosthetic Treatment Center (PTC), VA Medical Center, Hines, Illinois. Five other VA medical centers participated in the outreach program of the trials as satellite stations, with PTC Hines as the central fabrication facility. The VA/Seattle BK system is the first complete prosthetic system designed and developed by the Department of Veterans Affairs. It consists of a socket designed and fabricated using computer-aided, automated technology, and off-the-shelf modular components: a lightweight pylon and an ankle unit, and a lightweight, energy-storing foot. The computer-based socket design software, the modular components, and the prosthetic foot were developed with funds from the VA Rehab R&D Service. The evaluation trials were conducted to determine the efficacy of the VA/Seattle prosthesis, its reliability, and acceptance by veterans. The clinical trials began in April 1991 and were completed in August 1992. Forty-six BK amputee veterans were fitted with the VA/Seattle prosthesis. Their progress with the prosthesis was followed for a period of 6 months and data were gathered at intervals of 2 weeks, 3 months, and 6 months. Forty sets of subject data instruments were collected. In order to maintain the accuracy of the results, TTS used the 22 sets that were complete for data analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Perspectives on nutrition needs for the new millennium for South Asian regions.

South Asia is the most populated region of the world with several nutritional challenges. Though per capita food energy supply, child survival and life expectancy have improved, and even today large segments of the population are below the poverty line with high infant and maternal mortality rates. It is important to recognize the crucial role of nutrition throughout the life cycle-from conception to old age. It is very necessary now to move from food security to nutrition security and improve the quality of foods both in macro- and micronutrients in order to break the transgenerational effects of malnutrition. The key solutions to the problems should address the issue of social development, population stabilization, environmental degradation and inadequate health and nutritional services. Strategies for empowering women and actuating community participation as sustainable programmes for human development, measures to reduce underweight and stunting in children and prevention of micronutrient malnutrition across the population are required. Enhancing food and nutrition security through innovative diversified agriculture and dietary practices, prevention and control of infection, promotion of food safety and fortification of staples with appropriate attention on emerging chronic disorders are essential. Population control measures to stabilize the fertility rates, biotechnological approaches for genetically modified foods, nutrition surveillance based on assessment, analysis and action to address the logistic, technical and compliance issues with emphasis on promotion of breast feeding and complementary foods with adequate attention on the reproductive needs of adolescent girls, pregnant mothers and lactating women would eliminate low birth weight, stunting, and chronic energy deficiency in vulnerable groups. Focused studies on bioavailability of micronutrients and its enhancement, innovative horticulture interventions, fortifications, social marketing strategies would promote the intake of micronutrient and phytonutrient rich foods. In-depth epidemiological research, an insight into foetal origins of adult disease and nutrition-genes interaction and life style alterations will avert the emerging epidemic of chronic diet related disorders. An investment in preventing foetal malnutrition improves nutrition of women in reproductive age, infant and child nutrition and prevents the onset of chronic disease in adult life. Human resource development, IEC measures, technology transfer, operational and logistic research, building of databases, integrated, intersectoral, multidisciplinary plans and sound management information system and surveillance with net working and experience sharing in the region will help to overcome the common challenges and lay the foundation for a better scenario in these regions in the near future.

Adolescent↗
PubMed2006

Endothelial nitric oxide synthase keeps erection regulatory function balance in the penis.

OBJECTIVES: We evaluated the regulatory influence of endothelial nitric oxide (NO) on the basal functional states of the NO and RhoA/Rho-kinase signaling pathways in the penis using endothelial NO synthase (eNOS) mutant mice and eNOS gene transfer technology. METHODS: Four groups of mice were used: wild type (WT), eNOS gene deleted (eNOS-/-), eNOS and neuronal NOS gene deleted (dNOS-/-), and eNOS-/- mutant mice transfected intracavernosally with eNOS. Cyclic guanosine monophosphate (cGMP) concentration, protein kinase G (PKG) activity, activated RhoA, and Rho-kinase activity were determined in penes of WT and both mutant mouse groups. Constitutive NOS and PKG activities, RhoA, Rho-kinase-alpha and -beta isoforms, and phosphorylated myosin light-chain phosphatase target subunit (p-MYPT-1) expressions and Rho-kinase activity were determined in penes of eNOS-/- mice after eNOS gene transfer. RESULTS: Compared with results in the WT penis, eNOS-/- and dNOS-/- mutant mouse penes had significant reductions in NOS activity, cGMP concentration, PKG activity, Rho-kinase activity, and p-MYPT-1 expression (p<0.05) with no significant changes in activated RhoA or in RhoA and Rho-kinase-alpha and -beta protein expressions. After eNOS gene transfer to penes of eNOS-/- mice, Rho-kinase-beta and p-MYPT-1 expressions and total Rho-kinase activity were significantly increased from baseline levels (p<0.05). CONCLUSIONS: These data suggest that endothelial NO has a role in the penis as a regulator of the basal signaling functions of the NO and RhoA/Rho-kinase erection mediatory pathways. These data offer new insight into the homeostasis of erection regulatory biology.

Analysis of Variance↗
PubMed2004

Salivary glands: novel target sites for gene therapeutics.

Directing the local or systemic expression of therapeutic proteins is a potentially important clinical application of gene transfer technology. Gene-based therapeutics theoretically offer many advantages over protein therapeutics. Numerous tissues have been evaluated for this purpose in animal models, most commonly the liver and skeletal muscle. Based on pre-clinical studies, we suggest that salivary glands are a valuable, yet under-appreciated, target tissue for both systemic and upper gastrointestinal tract gene therapeutic applications.

Animals↗
PubMed1994

[Research in gene therapy--its status in Germany].

Progress in mammalian molecular biology and in the analysis of the human genome has allowed to identify the causes of an increasing number of human diseases in recent years. Newly developed gene transfer techniques were reason to implement new therapeutic concepts. By means of viral vectors or other transfer vehicles genes can be introduced into cells of the human body in order to replace a deficient function (in inherited diseases) or to play a role in defending the body (against cancer or, in the cardiovascular field, eventually by preventing restenosis). Despite considerable achievements of current DNA transfer technologies it seems premature to qualify gene therapy already as a new medical practice. The development in Germany is characterized by a late start in this field of research. The number of projects is correspondingly small. However, it may be expected that newly initiated governmental support of gene therapy research will lead to an expansion of the activities in this area.

Animals↗
PubMed1999

Genetically modified tumour vaccines--where we are today.

Tumour vaccines are based on weakly immunogenic specific tumour antigens admixed with adjutants in order to elicit, restore or augment antitumour immune responses against residual or metastatic tumour cells. Cellular cytotoxicity is considered to play a major role in eliminating tumour cells. Activation of cellular toxicity requires at least three synergistic signals: presentation of specific tumour antigen, constimulatory signal (B7 molecules) and propagation signal (cytokines). Recently several HLA-restricted specific tumour antigens recognized by cytotoxic T-cells have been characterized. Antibody defined antigens, heat shock proteins and viral antigens are also discussed. First generation vaccines made of whole cancer cells or tumour-cell lysates together with non-specific adjutants produced about 20% of clinical responses and are currently tested in prospective clinical trials. Novel second generation of tumour vaccines employ genetically modified tumour cells, antigen presenting cells (dendritic cells) or recombinant tumour antigens. Tumour cells are modified with genes encoding molecules providing signals for cytotoxic T-cells required for recognition and killing of cancer cells such as B7 constimulatory molecules, HLA proteins and genes of different cytokines. Dendritic cells are modified with genes of specific tumour antigens in order to activate both helper and cytotoxic T-cells. Novel vaccines produce specific immune responses and objective clinical responses with minimal toxicity in phase I/II trials. Advances in gene transfer technology, tumour immunology and better methods of monitoring specific antitumour immune responses allow the hope that tumour vaccines will be introduced into the clinic, at least in some malignancies resistant to systemic therapy so far such as melanoma and renal cell carcinoma.

Adjuvants, Immunologic↗
PubMed2002

Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning.

The presence of galactose alpha-1,3-galactose residues on the surface of pig cells is a major obstacle to successful xenotransplantation. Here, we report the production of four live pigs in which one allele of the alpha-1,3-galactosyltransferase locus has been knocked out. These pigs were produced by nuclear transfer technology; clonal fetal fibroblast cell lines were used as nuclear donors for embryos reconstructed with enucleated pig oocytes.

Alleles↗
PubMed2002

[Transgenic cattle constitute a breakthrough in production of innovative medicine. From milk to medicine].

The continuously increasing demand for biomolecules, e.g. human proteins, for applications in human health care, is one of the main driving forces for the development of safe, large-scale production systems. One very promising approach is the production of biomolecules in the milk of transgenic cattle. By using nuclear transfer technology, transgenic cattle can be generated in a very safe and efficient manner, thereby offering a significant time reduction when compared to conventional breeding methods. As a result, that the transgenic cattle platform offers an efficient, safe and cost-effective method for producing large amounts of biopharmaceuticals, which is essential to the development of innovative health care products.

Animal Husbandry↗
PubMed2006

[Gene therapy in orthopaedic surgery].

Gene therapy in orthopaedic surgery is being intensively studied in the context of different genetic and nonmendelian diseases. Experimental progress in this area is characterized by the complexity of gene vector selection and production, gene transfer technology, application routes, choice of animal models, and evaluation of its efficacy using structural and functional parameters. The first clinical studies for gene therapy of rheumatoid arthritis already demonstrated their practical feasibility. Current data indicate that gene-based therapies are effective in promoting the repair of articular cartilage, and bone defects. Such strategies may lead to the development of novel molecular therapies treatments in orthopaedic surgery.

Bone Diseases↗
PubMed1999

BAPS Prize--1997. Fetal gene therapy: efficacy, toxicity, and immunologic effects of early gestation recombinant adenovirus. British Association of Paediatric Surgeons.

BACKGROUND/PURPOSE: Advancements in gene transfer technology and prenatal diagnosis have allowed investigators to consider an in utero gene therapy approach for fatal genetic diseases. The authors sought to develop fetoscopic techniques for gene delivery and investigate the efficacy and safety of recombinant adenoviral vectors in the fetus. METHODS: Fetal sheep between 60 and 130 days' gestation (dGA) underwent either fetoscopic intratracheal injection or umbilical vein (UV) injection of recombinant adenovirus, AdCMVlacZ. At death, fetal organs were examined for beta-galactosidase expression, histopathology, and CD45 immunostaining. Fetal serum was compared with preimmune serum for transaminase levels and the presence of antiadenoviral neutralizing antibodies. RESULTS: Fetoscopic intratracheal delivery of AdCMVlacZ in late-gestation sheep fetuses resulted in efficient alveolar gene transfer, but, antiadenoviral immunologic reactions limited the longevity of transgene expression to 14 days. This prompted an examination of whether early gestational exposure could induce tolerance in the fetus to adenoviral and transgene antigens. AdCMVlacZ (1 x 10(11) particles) was injected via UV into fetuses at 60 dGA. Within 3 days, beta-galactosidase expression was localized to the fetal liver, adrenal glands, kidneys, and endocardium. Although adrenal expression was nearly constant over 28 days, expression in fetal liver disappeared within 14 to 28 days. Loss of hepatic expression did not appear to be immune mediated because there was no evidence of hepatic inflammation or appearance of antiadenoviral neutralizing antibodies. Fetuses injected with AdCMVlacZ at 60 dGA were reinjected with 1 x 10(13) particles at 125 dGA and antiadenoviral humoral immune responses were recorded. Despite early-gestation adenovirus injection, fetuses still responded to the late-gestation adenoviral exposure, developing antiadenoviral neutralizing antibodies similar to control fetuses. CONCLUSIONS: The authors developed fetoscopic access for pulmonary adenovirus delivery in late-gestation sheep. Although initial alveolar transduction was highly efficient, antiadenoviral immune responses limited the duration of transgene expression. In contrast, early-gestation adenoviral delivery did not elicit antiadenoviral immune responses despite achieving efficient transduction of many fetal tissues. Furthermore, early-gestation adenovirus delivery did not affect late-gestation antiadenoviral immune responses. These findings suggest that the early-gestation sheep fetus is not amenable to adenoviral tolerance induction by UV injection and that it is incompetent of immunologic response to adenovirus. For the purposes of in utero gene therapy, recombinant adenovirus may be applied optimally to genetic diseases requiring transient in utero expression.

Adenoviridae↗
PubMed2004

Gene expression imaging with radiolabeled peptides.

An approach to image radiolabeled peptide localization at tumor sites by inducing tumor cells to synthesize membrane expressed human somatostatin receptor subtype 2 (hSSTr2) with a high affinity for radiolabeled somatostatin analogues is described. The use of gene transfer technology to induce expression of high affinity membrane hSSTr2 can enhance the specificity and degree of radiolabeled peptide localization in tumors. Employing this strategy, induction of high levels of hSSTr2 expression with selective tumor uptake of radiolabeled peptides was achieved in both subcutaneous non-small cell lung cancer and intraperitoneal ovarian cancer mouse human tumor xenograft models. The features of this genetic transduction imaging approach are: (1) constitutive expression of a tumor-associated receptor is not required; (2) tumor cells are altered to express a new target receptor or increased quantities of a constitutive receptor at levels which may significantly increase tumor targeting of radiolabeled peptides compared to uptake in normal tissues; (3) gene transfer can be accomplished by local or regional injection of adenoviral vectors; (4) it is feasible to target adenovirus vectors to tumor cells by modifying adenoviral tropism (binding) or by the use of tumor-specific promoters such that the hSSTr2 will be specifically expressed in the desired tumor; and (5) this technique can be used to image expression of a second therapeutic gene.

Animals↗
PubMed2004

Prepubertal propagation of transgenic cloned goats by laparoscopic ovum pick-up and in vitro embryo production.

The use of laparoscopic ovum pick-up (LOPU) followed by in vitro embryo production was evaluated in the early propagation of cloned goats. Ten kinder goats produced by somatic cell nuclear transfer technology were used as oocyte donors. Half of the donor animals were subjected to LOPU at 2-3 months of age (prior to induction of lactation), whereas the other five goats were subjected to LOPU at 6-7 months of age (following induction to lactation). They were stimulated with 80 mg NIH-FSH-P1 (Folltropin, Vetrepharm, Canada) together with 300 IU eCG (Novormon, Vetrepharm, Canada) administered intramuscularly 36 h prior to LOPU. The number of follicles aspirated and oocytes recovered was higher in the younger group of donors (57 +/- 7 and 41 +/- 4 vs. 28 +/- 2 and 25.8 +/- 2, p < 0.05), however, oocytes from animals in the late prepubertal age showed higher developmental capacity resulting in higher transferable embryo yield (81.4% vs. 67.8%, p < 0.01), pregnancy rate (80% vs. 40%, p < 0.05) and total kids born (27 vs. 15, p < 0.01). In conclusion, LOPU in combination with in vitro embryo production techniques is an efficient method for the early propagation of valuable goats produced by somatic cell nuclear transfer.

Animals↗
PubMed2001

Staff beliefs about addiction treatment.

In 1999, the National Institute on Drug Abuse established a researcher/provider partnership designed to test the effectiveness of research-based innovations in community-based treatment settings and facilitate the transfer of those innovations throughout the national treatment system. As a preliminary step in developing their local Clinical Trials Network, researchers and treatment providers within the Delaware Valley Node surveyed 317 staff members concerning their beliefs about addiction treatment. More than 80% of respondents supported increased use of research-based innovations, 12-step/traditional approaches, and spirituality in addiction treatment, while only 39% and 34%, respectively, endorsed the increased use of naltrexone and methadone maintenance. Also, 35% of respondents indicated that confrontation should be used more, and 46% agreed with discharging noncompliant patients. Individuals with more formal training tended to be less supportive of confrontation and more supportive of the increased use of medications. Implications for the clinical trials and technology transfer are discussed.

Alcoholics Anonymous↗
PubMed1997

Establishing chemoresistance in hematopoietic progenitor cells.

An attractive approach to circumvent chemotherapy-induced myelosuppression is the use of gene-transfer technology to introduce new genetic material into hematopoietic cells. Several pre-clinical studies have demonstrated that increasing the expression of genes encoding proteins that modulate drug resistance in hematopoietic cells provides significant protection against chemotherapy-induced myelosuppression both in vitro and in vivo. Most work in this area has focused on the use of recombinant retroviruses as vectors for the delivery of DNA sequences into hematopoietic stem cells and progenitor cells. Based on these studies, clinical trials are now under way to evaluate the potential use of two gene sequences-multidrug resistance gene 1 and O6-methylguanine DNA methyltransferase. Reducing chemotherapy-induced myelosuppression by increasing the expression of genes that modulate drug resistance via gene transfer into bone marrow cells might allow dose-intensification of chemotherapy, which might result in an improvement in the clinical outcome of patients with high-risk tumors.

Aldehyde Dehydrogenase↗
PubMed2000

Options for tissue engineering to address challenges of the aging skeleton.

There will be more than 52 million Americans over the age of 65 by the year 2020 (U.S. Census Bureau). Regenerating form and function to bone defects in an elderly, osteoporotic population of this magnitude will be a daunting challenge. Tissue engineering options must be considered to answer this challenge. Options can include gene transfer technology, stem cell therapy, and recombinant signaling molecules. An additional component will be a carrier that localizes, protects, predictably releases cues and cells, as well as establishes an environment for restoring osseous form and function. The purposes of this article are to present an overview of the bone regenerating decrement affecting osteoporotic, elderly patients and to highlight some tissue engineering options that could offset this decrement.

Aged↗
PubMed1989

Strategies for developing innovative programs in international medical education. Identification of educational needs.

A U.S. medical educator noted that the needs of developing countries are not necessarily addressed by traditional methods of medical education in the United States, involving high-technology education, technology transfer, development of academic personnel, and the like. In many developing nations, where there may be a surplus of doctors and many unemployed doctors, there is also a vast population of underserved people. Many of the physicians may have been trained inappropriately, or they were not comfortable in certain environments. In order to have an impact on the vast population, that kind of anachronism must be addressed. He inquired whether there is a role for the United States in addressing the health of communities rather than the sickness of individuals. It was observed that the health needs of developing countries are often thought to relate to the issues of hygiene, sanitation, and prevention and that these needs are homogeneous. The needs for interventional technology and preventive primary care should be differentiated, and the requirements at both levels of assistance should be heeded, be it at a primary and preventive level or at the level of specialist-oriented technological intervention. There was discussion about the dichotomy that exists between schools of public health in the United States and the medical schools with which they are associated. They were referred to as "two separate cultures." Thus, some suggested that U.S. physicians involved in curative medicine need to be exposed to community-based medicine in other countries, and many questioned whether other countries should seek to model their systems after those in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)

Allied Health Personnel↗
PubMed1998

In vivo use of adenoviral vectors: effects on salivary gland structure.

Recently there has been considerable progress in the development of in vivo gene transfer technology. By this means, new genetic information may be introduced directly to cells, while the cells remain in their natural milieu. The ability to express exogenous proteins makes it possible to explore the functions of native or altered proteins and thereby develop new insights into cell function and dysfunction. We have demonstrated that the major salivary glands are efficiently infected by recombinant adenovirus vectors. These vectors are capable of expressing transgenes in both acinar and ductal cell types. Recently, we have developed vectors that contain cell-specific promoters so that proteins may be expressed in selected subpopulations of salivary cells. Early generations of adenoviral vectors elicited potent immune responses in vivo. However, modified vectors and adjunctive measures have improved the safety of gene transfer to salivary glands. Future studies will aim to increase the duration of adenovirus-based gene expression and to produce vector systems that are not toxic to the host.

Adenoviridae↗
PubMed2004

Current status and prospects for gene therapy.

Gene therapy is a new and exciting therapeutic concept that offers the promise of cure for an array of inherited, malignant and infectious disorders. After years of failure, substantial progress in the efficiency of gene-transfer technology has recently resulted in impressive clinical success in infants with immunodeficiency. Two of these children have, however, subsequently developed leukaemia as a result of insertional mutagenesis, raising concerns about the safety of genetic therapeutics. The purpose of this article is to review the current status of gene therapy in light of recent successes and tragedies, and to consider the challenges faced by this relatively new field.

Child↗