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At least 667 records · Page 37Linked to original sources
PubMed1998

Inhibition of pancreatic tumor cell growth in culture by p21WAF1 recombinant adenovirus.

New innovations are needed for the treatment of pancreatic cancer, as current treatments do not offer significant improvements in overall survival. p21WAF1--a tumor suppressor gene--acts as a downstream effector of p53 function and mediates G1 cell cycle arrest by inhibiting cyclin-dependent kinases, which promote cell growth. p21 expression has also been shown to increase more than 20-fold in senescent cells in culture. The replication-defective recombinant adenoviral system (rAd), a major innovation in gene transfer technology, has recently been used in gene therapy applications for various malignancies but not for pancreas cancer. In this study we used rAd-p21 in cell growth inhibition studies of pancreatic tumor cell lines in vitro to explore its potential as a prospective gene therapy for pancreatic adenocarcinoma. We studied two pancreatic cell lines in culture, HPAC and Hs766T. HPAC revealed higher endogenous levels of p21 gene expression at the protein and RNA levels compared to Hs766T. p21 induction was tested using different doses of rAd-p21 to establish an optimum dose for significant induction of p21 gene expression. Tumor cell growth in culture following rAd-p21 infection was also analyzed in both cell lines. HPAC and Hs766T cell lines showed a significant dose-dependent increase in p21 protein expression when infected with rAd-p21. Both cell lines showed significant growth arrest, but Hs766T showed less cell growth inhibition than HPAC cells. Flow cytometric cell cycle analysis of rAd-p21-infected cells showed a statistically significant increase in the number of cells in G0/G1 in HPAC cells. Similar results were also obtained in Hs766T cells, however, the data were not statistically significant. In conclusion, pancreatic tumor cell growth can be inhibited by rAd-p21 in vitro, with significant numbers of tumor cells reverting from S to G0/G1. Thus rAd-p21 may be effective as a candidate gene therapy for pancreatic cancer and should be further evaluated with in vivo studies.

Adenocarcinoma↗
PubMed2001

Hydroxychloroquine enhances the endocrine secretion of adenovirus-directed growth hormone from rat submandibular glands in vivo.

Use of gene transfer technology for treating single protein deficiency disorders requires delivery of therapeutic levels of the transgene product. We have suggested that salivary glands may provide a potentially valuable target site for certain systemic applications of gene therapeutics (He et al., Gene Ther. 1998;5:537-541). However, the ability of salivary glands to deliver therapeutic proteins to either the upper gastrointestinal tract via saliva or to the bloodstream, as required, must be carefully evaluated. In the anterior pituitary gland, human growth hormone (hGH) is secreted into the bloodstream via the regulated secretory pathway. However, when expressed from an adenoviral vector delivered to salivary glands, most hGH follows the regulated, tissue-specific, exocrine secretory pathway into saliva, where it is not therapeutically useful. We tested the hypothesis that the commonly used, FDA-approved drug hydroxychloroquine (HCQ) can divert adenovirus-directed hGH from this regulated secretory pathway in rat submandibular glands and enhance delivery into the bloodstream. In untreated rats, there was approximately 20-fold more vector-directed hGH in saliva than in serum. Administration of HCQ led to a shift of hGH secretion into the bloodstream. When delivered at doses of 1 or 10 mg/kg body weight, via intraperitoneal injection plus intraductal infusion, the saliva:serum hGH ratio was approximately 2:1. Such HCQ delivery did not significantly alter the total amount of hGH measured, but increased the serum level of hGH 5- to 6-fold. Also, HCQ had no significant effects on serum chemistries or hematological parameters. We conclude that HCQ is able to significantly enhance hGH secretion from salivary glands into the bloodstream and may be useful to facilitate clinical applications of gene therapeutics via salivary glands.

Adenoviridae↗
PubMed1993

Clinical psychopharmacologic practice. The need for developing a research base.

The advent of psychotropic drugs has enormously improved psychiatric care. Nonetheless, our practice is not optimum. Current knowledge is not regularly applied. It has been repeatedly shown that the majority of patients with psychiatric illness go undiagnosed, and even if diagnosed, they are inappropriately or ineffectively treated, both by clinical psychiatrists and by primary care practitioners. Improved care depends on practitioner education, often referred to as "technology transfer."

Clinical Competence↗
PubMed1994

The public health implications of AIDS research in Africa.

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic has led to greatly increased international collaboration for medical research, mainly epidemiologic in nature, in Africa. Greater understanding of HIV/AIDS has resulted, and considerable training and technology transfer have occurred. However, analytic and descriptive research in countries heavily affected by AIDS has been slow to turn to assessment of interventions, and practical benefits to those countries' public health and policies have lagged behind scientific knowledge. This article considers the public health implications of selected HIV/AIDS research in sub-Saharan Africa and discusses opportunities for interventions and more applied research. Topics covered include HIV testing and its role, surveillance, control of sexually transmitted diseases, the vulnerability of youth and women, tuberculosis, HIV/AIDS care, and the inadequacy of resources currently committed to HIV/AIDS prevention and control in resource-poor countries. Research on HIV/AIDS in Africa has yielded crucial information but now should prioritize interventions and their evaluation. Specific goals that might limit the effects of the HIV/AIDS epidemic in resource-poor countries are achievable given vision, commitment, and resources.

AIDS Serodiagnosis↗
PubMed1996

Automated slide preparation system for the clinical laboratory.

An automated device has been developed to prepare a wide variety of cytology preparations. Using the device, cells collected in suspension are mildly dispersed and transferred to a glass slide using filter-transfer technology. The cell density on the slide is controlled by the instrument. A companion product, the solution used in specimen transport and preparation, provides long-term preservation of diagnostic cells while lysing red blood cells. The overall process yields clean, uniform samples with better visualization of the diagnostic cells. The use of a disposable filter prevents sample-to-sample contamination. Collection of the sample in solution makes it possible to produce multiple slides from one sample.

Cell Biology↗
PubMed1998

Testing environment for single-gene disorders in U.S. reference laboratories.

Molecular diagnosis is the detection of pathogenic mutations in DNA and RNA samples prepared from at-risk patients. Principles underlying DNA-based diagnosis originate from localization and identification of genes responsible for human disease and the characterization of pathogenic mutations; new diagnostic tests are in constant development. Indications for testing include diagnosis, carrier risk revision, prenatal diagnosis, presymptomatic diagnosis, and population screening. The majority of DNA diagnoses are performed in a reference laboratory in which the referring physician, rather that the patient, is the client of the laboratory. Thus, the role of the genetic counselor in a reference laboratory is quite different from traditional clinical practice. As with all clinical laboratory tests, molecular diagnostics are interpreted within the context of the patient's overall clinical presentation and are overlaid with regulatory programs of quality assurance, quality improvement, and quality control. The greatest challenges facing the clinical laboratory are genetic heterogeneity, cost control, regulatory and patent compliance, technology transfer, and the genetic education of the referring physician.

Genetic Counseling↗
PubMed2000

Production of transgenic porcine blastocysts by nuclear transfer.

In this study the in vitro development of porcine nuclear transfer (NT) embryos was investigated. Transgenic fetal fibroblast cells that were frozen after 5 days of serum starvation were injected immediately after thawing into enucleated metaphase II (MII) oocytes. Reconstructed embryos were activated by incubation in 200 microM thimerosal followed by a 30-min treatment of 8 mM DTT. The embryos were subsequently cultured in NCSU23, supplemented with 4 mg/ml BSA for 7 days. The actual cleavage rate (embryos showing > or =2 nuclei) in 6 replicates was 33% (ranging from 15% to 50%). Three blastocysts with cell numbers of 14, 15, and 18 were obtained. The blastocyst rate was significantly lower for NT embryos as opposed to parthenogenetically activated embryos (1% vs. 5%; P<0.05). The neomycin-resistance gene was amplified by PCR in all three NT embryos, indicating their origin from the injected transgenic fibroblasts. Efforts are now being directed in improvements in the nuclear transfer technology, whereby viable fetuses or offspring can be produced from these NT-embryos.

Animals↗
PubMed1993

Dietary strategies for cancer prevention.

BACKGROUND: Two-thirds of cancer cases are associated with two lifestyle practices: 35% with the typical American diet, and 30% with tobacco use. In contrast to the field of tobacco control, research and resources dedicated to the field of nutrition have been limited, in part because dietary change has been considered controversial and requires a more complex set of interventions. METHODS: This series of papers reviews the science base underlying diet as a cancer control strategy, including research about diet-cancer relationships, current nutrition policy recommendations, American dietary trends, models of dietary behavior change, and diet in health care delivery. The history of technology transfer of new knowledge into widespread application will be compared and contrasted with other cancer control measures. RESULTS: There is scientific and policy agreement about three priority dietary goals for the year 2000: increase fruit and vegetable consumption to 5 or more servings every day, increase breads, cereals, and legumes to 6 or more servings daily, and decrease fat to no more than 30% of total calories. Current data do not indicate that these goals will be reached. As yet there is no organized effort, with clearly identified steps, to translate research into practice. The parallel with delays in implementing other cancer control measures, including Papanicolaou testing, mammography, and tobacco intervention, is striking. CONCLUSION: Without resources dedicated to dietary modification in the general population, it is not likely that the potential savings of more than 300,000 new cases, 160,000 deaths, and the $25 billion in associated costs will be realized in the foreseeable future.

American Cancer Society↗
PubMed1994

Clinical trials in the community. The community clinical oncology program experience.

In 1983, the National Cancer Institute initiated the community clinical oncology program (CCOP), the goal of which was to hasten the adoption of state-of-the-art cancer medicine in community-based institutions. The strategy adopted was to link community oncologists to major cancer centers and research bases for the conduct of clinical trials. Since the program was initiated, a significant amount of literature has been developed, providing insight into the operation and success of the program. These reports have been combined with experience of the author, a principal investigator of an established CCOP, in an effort to characterize the critical features of the program. Experience to date indicates that CCOPs have been successful in accruing patients to cancer-treatment clinical trials, contributing approximately one third of patients placed in investigational protocols. Since 1987, CCOPs have been required to participate in nontreatment-related research in cancer prevention, detection, and mitigation of cancer symptoms, or cancer control research. After a slow beginning, both the research bases and CCOPs have accumulated experience in the development of and accrual of patients in cancer control protocols. This review suggests that CCOPs, as they mature, will fulfill their goal as an important mechanism for the transfer of technology and the conduct of clinical research.

Clinical Trials as Topic↗
PubMed2000

Lipids, lipophilic drugs, and oral drug delivery-some emerging concepts.

Lipid-based dose forms, which encompass a wide variety of compositional and functional characteristics, can be advantageously utilized for the formulation of lipophilic drugs. There has been a traditional reluctance to develop lipid-based dose forms due to potential problems of chemical and physical instability, and a paucity of knowledge regarding formulation design algorithms and technology transfer issues. However, there is a current resurgence of interest in lipid-based dose forms due to potential commercial and pharmaceutical benefits, and the industry trend towards the discovery/development of increasingly hydrophobic (and potent) new chemical entities. This mini-review describes some emerging formulation and biopharmaceutic strategies that hold promise for better understanding how to design and evaluate lipid-based dose forms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Mitochondrial DNA in focal dystonia: a cybrid analysis.

The cause and pathophysiology of dystonia remain unknown. The recent identification of mitochondrial complex I deficiency in platelets from patients with sporadic focal dystonia suggests that a defect of energy metabolism may be relevant in a proportion of patients. We have addressed the possible contribution of mitochondrial DNA (mtDNA) to the complex I deficiency in dystonia by the use of genome transfer technology. Platelets from patients deficient for complex I were fused with A549 p0 (mtDNA-less) cells to form cybrids comprising the A549 nucleus and dystonia mtDNA. Mixed cybrid cell lines were analyzed for 9 controls and 9 dystonia patients, and clonal cybrid lines were generated for 2 control and 2 dystonia patients. Subsequent biochemical analysis showed that the dystonia complex I defect was complemented in both the mixed and the clonal cybrid lines. These results contrast with similar studies in mitochondrial myopathy and Parkinson's disease patients, in which the mitochondrial defect was maintained in at least a proportion of A549 cybrids, and suggest that the complex I defect in dystonia is not caused by an mtDNA mutation.

Blood Platelets↗
PubMed1995

Magnetic field exposure among utility workers.

The Electric and Magnetic Field Measurement Project for Utilities--the Electric Power Research Institute (EPRI) Electric and Magnetic Field Digital Exposure (EMDEX) Project (the EPRI EMDEX Project)--was a multifaceted project that entailed technology transfer, measurement protocol design, data management, and exposure assessment analyses. This paper addresses one specific objective of the project: the collection, analysis, and documentation of power-frequency magnetic field exposures for a diverse population of utility workers. Field exposure data measured by an EMDEX system were collected by volunteer utility employees at 59 sites in four countries between September, 1988, and September, 1989. Specially designed sampling procedures and data collection protocols were used to ensure uniform implementation across sites. Volunteers within 13 job classifications recorded which of eight work or three nonwork environments they occupied while wearing an EMDEX meter. Approximately 50,000 hours of magnetic field exposure records taken at 10 s intervals were obtained, about 70% of which were from work environments. Exposures and time spent in environments were analyzed by primary work environment, by occupied environment, and by job classification. Generally, for utility-specific job classifications related to the generation, transmission, and distribution of electricity, the field and exposure measurements in terms of workday mean field were higher than in more general occupations. The job classifications with the highest (median workday mean) exposure were substation operators (0.7 microT) and electricians (0.5 microT). Total variance also tended to be largest for utility-specific job classifications. For these workers, the contributions of between-worker and within-worker variances to total variance were about the same. Measurements in utility-specific environments were higher than in more general environments. Estimates of time-integrated exposure indicated that utility-specific job classifications received about one-half or more of their total exposure on the job. The nonwork field and exposure distributions for workers in all job categories were comparable with median nonworkday means of about 0.09 microT.

Documentation↗
PubMed2004

Detection of single nucleotide variations by a hybridization proximity assay based on molecular beacons and luminescence resonance energy transfer.

A powerful combination of molecular beacon and luminescence resonance energy transfer technology reveals alterations in nucleic acid structure by as little as a single nucleotide in a novel hybridization proximity assay. The assay measures the length of a single-stranded target when a terbium chelate-labeled molecular beacon hybridizes to one side of the nucleic acid segment to be measured and an acceptor probe carrying a convention fluorophore hybridizes to the opposite end of the target. Using a test sequence shortened incrementally by deleting single nucleotides, this assay reports a nearly linear relationship between sequence length and the distance separating acceptor and donor probes. Consequently, this assay can be used to detect alternative splicing, allele types, rearrangements, insertion, and deletion events by measuring separation distances within a predefined region. Furthermore, the use of terbium chelates in molecular beacons can produce exceptionally high signal-to-background ratios compared to the use of conventional fluorophores. Principles of optimal probe design are investigated experimentally and by computational simulations of plausible molecular beacon folding. Some molecular beacon designs form dimers that reduce their maximal response to target sequences. A simple assay to detect such dimers is reported as a tool to help improve the design of molecular beacons. Optimally designed molecular beacons with terbium chelates and hybridization proximity assays are expected to expand their applications in the analysis and screening of genetic diseases.

Base Sequence↗
PubMed2003

Bidirectional expression units enable streptogramin-adjustable gene expression in mammalian cells.

Serious initiatives in gene therapy and tissue engineering require a sophisticated molecular toolbox combining DNA transfer technologies, human-compatible transcription control systems, as well as compact and robust expression configurations. We have designed several versatile bidirectional expression cassettes that enable coadjustable expression of two desired transgenes in response to clinically licensed antibiotics of the streptogramin class (pristinamycin, Pyostacin, Synercid). The bidirectional expression modules consist of a central operator (PIR) that is specific for the pristinamycin-dependent transactivator (PIT). Streptogramin-adjustable binding of PIT to PIR transactivates two divergently oriented promoters and initiates transcription of the desired transgenes. The bidirectional expression module can be equipped with different minimal promoters and configured for expression of (1) two functional effector genes, (2) one effector gene and a reporter gene, (3) PIT and an effector gene to form a highly compact one-vector expression arrangement. We have validated the streptogramin-adjustable bidirectional expression technology in different basic and autoregulated expression configurations in a variety of mammalian and human cell lines.

Alkaline Phosphatase↗
PubMed2006

Determination and pharmacokinetic study of syringin and chlorogenic acid in rat plasma after administration of Aidi lyophilizer.

A high-performance liquid chromatographic (HPLC) method was developed for the first time to simultaneously quantify syringin and chlorogenic acid in rat plasma using wavelength-transfer technology. The analysis was performed on a Diamonsil C(18) column (200 x 4.6 mm i.d., 5 microm particle size) with isocratic mobile phase consisting of acetonitrile-0.05% phosphoric acid (12:88, v/v). The linear ranges were 0.20-10 and 0.25-30 microg/mL, respectively. The lower limits of quantification were 0.20 and 0.25 microg/mL, respectively. The method was shown to be reproducible and reliable with intraday precision below 8.5 and 6.1%, interday precision below 7.1 and 5.5%, accuracy within +/-7.1 and +/-8.6%, and mean extraction recovery excess of 92.1 and 80.9%, respectively, which were all calculated from the blank plasma sample spiked with syringin and chlorogenic acid at three concentrations of 0.20, 1.0 and 6.0 microg/mL for syringin and 0.25, 2.0 and 20 microg/mL for chlorogenic acid. This method was validated for specificity, accuracy and precision and was successfully applied to the pharmacokinetic study of syringin and chlorogenic acid in rat plasma after intravenous administration of Aidi lyophilizer.

Animals↗
PubMed1994

Symbiosis of biotechnology and biomaterials: applications in tissue engineering of bone and cartilage.

The three ingredients for the successful tissue engineering of bone and cartilage are regulatory signals, cells, and extracellular matrix. Recent advances in cellular and molecular biology of the growth and differentiation factors have set the stage for a symbiosis of biotechnology and biomaterials. Recent advances permit one to enunciate the rules of architecture for tissue engineering of bone and cartilage. The purification and cloning of bone morphogenetic proteins (BMPs) and growth factors such as platelet derived growth factors (PDGF), transforming growth factor-beta (TGF-beta), and insulin-like growth factors (IGF-I) will allow the design of an optimal combination of signals to initiate and promote development of skeletal stem cells into cartilage and bone. Successful and optimal bone and cartilage formation is a synergy of inductive and conductive strategies governed by biomechanics, optimal load bearing, and motion. BMPs function as inductive signals. Biomaterials (both natural and synthetic) mimic the extracellular matrix and play a role in conduction of bone and cartilage. Examples of biomaterials include hydroxyapatite, polyanhydrides, polyphosphoesters, polylactic acid, and polyglycolic acid. The prospects for novel biomaterials are immense, and they likely will be a fertile growth industry. Cooperative ventures between academia and industry and technology transfer from the federal government augur well for an exciting future for clinical applications.

Animals↗
PubMed2002

Practice-informed research and research-informed psychotherapy.

The information processing demands of planning and conducting psychotherapy and the types of information that clinicians value potentially can inform research that is likely to be useful to clinicians. Four approaches to conducting research on psychotherapy issues-technology transfer studies, quasi-experimental single-case designs, mental health services research, and case-focused patient profiling-have the potential to inform the practicing therapist. These approaches generally are either treatment focused or patient focused, and can vary in their relevance to the individual case.

Decision Making↗
PubMed1993

Software for quantitative immunogold and in situ hybridization.

A well-deserved criticism of stereology is that it is often too difficult to understand and use. Nevertheless, it is rapidly becoming one of the most effective ways of collecting and interpreting structural data in experimental biology. Recent breakthroughs in theory have produced a remarkable set of tools that can be used to engineer new methods. The dilemma remains, however, in that some of these new methods continue to be too difficult to understand and use. One solution to this growing problem of technology transfer might be to simplify the methods with computer software. To test this idea, programs were written for quantitative immunogold and in situ hybridization. Simulators were used to develop and test new experimental designs, which, in turn, were translated into step-by-step laboratory tool kits. This paper shows how these tool kits can turn two-dimensional section data into estimates for the number of labeled molecules in three-dimensional organelles, cells, tissues, and organs. The results indicate that software can identify the key data of an experiment and reduce the computational requirements of a new stereological method to entering constants and variables into data entry forms.

Animals↗