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At least 127 records · Page 7Linked to original sources
PubMed1986

Morphometric studies on wound healing after systemic administration of adriamycin and local application of fibrin sealant. Application of a new wound healing model using spongiosa implants.

For investigations on the development of regenerative granulation tissue in wound healing a new model using bone spongiosa ("Kieler Spongiosa") implants is presented. Particular attention was devoted to developing a model which permits studies on wound healing without disturbance by foreign body reaction and infections. Two test groups of rats received four blocks of "Kieler Spongiosa" each in a symmetrical fashion in a paramedian region underneath the dorsal skin. The spongiosa blocks had previously been treated with glutaraldehyde to achieve cross-linkage of the collagenous structures of the surfaces of the spongiosa trabeculae. After one week (group 1) and two weeks (group 2) the animals were sacrificed. The spongiosa blocks were removed, fixed and evaluated in layered serial sections after decalcification. Two blocks which had been removed randomly from the back and front served for morphometric determination of the total volume of bony substance and the developed granulation tissue. Moreover, the cellular composition of the granulation tissue was morphometrically examined with regard to its content of capillaries, granulation tissue cells and inflammatory cells. The two other blocks were examined for DNA and hydroxyproline content of granulation tissue. Comparison of the two experimental groups yielded marked differences in spongiosa space infiltrated by granulation tissue and its composition. Our model was used to assess the influence of systemic administration of adriamycin and/or local application of a fibrin sealant system on granulation tissue formation and its morphologic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Application of reproductive biotechnology in animals: implications and potentials. Applications of reproductive cloning.

The development of new methods of nuclear transfer in mammals is creating many new opportunities in research, medicine and agriculture. The method of cloning is repeatable and has been established in many laboratories worldwide. However, the present procedure is inefficient with fewer than 4% of embryos becoming viable offspring. A considerable improvement in efficiency is required before wide scale use for livestock improvement. The opportunity to introduce precise genetic changes to livestock is available for the first time through the use of gene targeting procedures in cultured cells that are used as nuclear donors. This has potential application in the production of organs for transplantation to humans, studies of human genetic disease and basic research in to the control of gene expression and function.

Agriculture↗
PubMed2000

Polar application of test substances in an organotypic environment and under continuous medium flow: a new tissue-based test concept for a broad range of applications in pharmacotoxicology.

We have established a new test concept for in vitro pharmacological trials. Our model employs tissue explants to test compounds for toxicity which arises with the metabolic interactions among different cell types. Microsurgical preparation of tissue explants avoids the destruction of the organ-specific tissue architecture. Explants were mounted in tissue carriers to improve nutrition and handling of the sample. To allow for the omission of serum supplementation of the culture medium, explants were cultured under continuous medium flow. Test substances are applied considering the polar architecture of most tissues in vivo, for example, covering the apical aspect of epithelia. In principal, all tissues obtained from any species, including man, can be used in this system. A trial application was performed with vitreous body substitutes, substances used in ophthalmology. One compound had passed cell culture tests, but caused massive blood vessel deterioration in vivo. Using our test system based on the developing renal vessel system, we could confirm, within 24 hours, severe vessel damage which resembles the injury suffered by the rabbit retina. We demonstrate that an improved tissue culture assay is a suitable tool for the detection of toxicity that remained unidentified in cell culture tests.

Animals↗
PubMedDate not supplied

Topical application of beta-radiation to reduce intimal hyperplasia after carotid artery balloon injury in rabbit. A possible application for brachytherapy in vascular surgery.

PURPOSE: Endovascular brachytherapy for the prevention of intimal hyperplasia (IH) and restenosis after balloon/stent angioplasty has proven effective both in animal preparations and clinical trials. A variety of beta-emitting isotopes and catheter-based devices have been developed for the delivery of low-dose radiation in clinical coronary and peripheral trials. No platform, however, has yet been developed for brachytherapy in concert with vascular surgical operations. The purpose of this study was to evaluate the vascular histopathologic response following balloon injury to rabbit carotid arteries with and without topically applied low-dose beta-radiation. METHODS: The beta-emitting isotope strontium-90 (Sr-90) was conjugated onto the matrix of polypropylene (PLYP) mesh. Rabbit carotid arteries were balloon-injured with a #2 embolectomy catheter. Six carotid arteries were wrapped with nonradioactive PLYP mesh (controls) and Sr-90 ( approximately 90 microCi) PLYP mesh in order to deliver low-dose radiation to the vessel wall from the external (adventitial) surface. Tissue was harvested at 6 weeks and processed for histologic examination. RESULTS: There was consistent blockade of fibrocellular neointima formation with virtually no neointima present in all treated segments, compared to moderate neointima formation in controls. Medial thinning and smooth muscle cell (SMC) necrosis were also associated with topical brachytherapy. CONCLUSION: beta-Radiation applied by an externally wrapped PLYP mesh labeled with Sr-90 markedly suppressed neointima formation in an animal vascular surgical injury model. Further studies, however, are necessary to determine a suitable isotope and dosage for clinical application.

Administration, Topical↗
PubMed1999

New 4-point pharmacophore method for molecular similarity and diversity applications: overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures.

A new 4-point pharmacophore method for molecular similarity and diversity that rapidly calculates all potential pharmacophores/pharmacophoric shapes for a molecule or a protein site is described. The method, an extension to the ChemDiverse/Chem-X software (Oxford Molecular, Oxford, England), has also been customized to enable a new internally referenced measure of pharmacophore diversity. The "privileged" substructure concept for the design of high-affinity ligands is presented, and an example of this new method is described for the design of combinatorial libraries for 7-transmembrane G-protein-coupled receptor targets, where "privileged" substructures are used as special features to internally reference the pharmacophoric shapes. Up to 7 features and 15 distance ranges are considered, giving up to 350 million potential 4-point 3D pharmacophores/molecule. The resultant pharmacophore "key" ("fingerprint") serves as a powerful measure for diversity or similarity, calculable for both a ligand and a protein site, and provides a consistent frame of reference for comparing molecules, sets of molecules, and protein sites. Explicit "on-the-fly" conformational sampling is performed for a molecule to enable the calculation of all geometries accessible for all combinations of four features (i.e., 4-point pharmacophores) at any desired sampling resolution. For a protein site, complementary site points to groups displayed in the site are generated and all combinations of four site points are considered. In this paper we report (i) the details of our customized implementation of the method and its modification to systematically measure 4-point pharmacophores relative to a "special" substructure of interest present in the molecules under study; (ii) comparisons of 3- and 4-point pharmacophore methods, highlighting the much increased resolution of the 4-point method; (iii) applications of the 4-point potential pharmacophore descriptors as a new measure of molecular similarity and diversity and for the design of focused/biased combinatorial libraries.

Binding Sites↗
PubMed2003

The application of new software tools to quantitative protein profiling via isotope-coded affinity tag (ICAT) and tandem mass spectrometry: II. Evaluation of tandem mass spectrometry methodologies for large-scale protein analysis, and the application of statistical tools for data analysis and interpretation.

Proteomic approaches to biological research that will prove the most useful and productive require robust, sensitive, and reproducible technologies for both the qualitative and quantitative analysis of complex protein mixtures. Here we applied the isotope-coded affinity tag (ICAT) approach to quantitative protein profiling, in this case proteins that copurified with lipid raft plasma membrane domains isolated from control and stimulated Jurkat human T cells. With the ICAT approach, cysteine residues of the two related protein isolates were covalently labeled with isotopically normal and heavy versions of the same reagent, respectively. Following proteolytic cleavage of combined labeled proteins, peptides were fractionated by multidimensional chromatography and subsequently analyzed via automated tandem mass spectrometry. Individual tandem mass spectrometry spectra were searched against a human sequence database, and a variety of recently developed, publicly available software applications were used to sort, filter, analyze, and compare the results of two repetitions of the same experiment. In particular, robust statistical modeling algorithms were used to assign measures of confidence to both peptide sequences and the proteins from which they were likely derived, identified via the database searches. We show that by applying such statistical tools to the identification of T cell lipid raft-associated proteins, we were able to estimate the accuracy of peptide and protein identifications made. These tools also allow for determination of the false positive rate as a function of user-defined data filtering parameters, thus giving the user significant control over and information about the final output of large-scale proteomic experiments. With the ability to assign probabilities to all identifications, the need for manual verification of results is substantially reduced, thus making the rapid evaluation of large proteomic datasets possible. Finally, by repeating the experiment, information relating to the general reproducibility and validity of this approach to large-scale proteomic analyses was also obtained.

Amino Acid Sequence↗
PubMed2000

Chromatographic properties of the ion-exclusion column IonPac ICE-AS6 and its application in environmental analysis, Part II: application in environmental analysis

Biological processes, geochemical reactions, anthropogenic emissions, and transformation reactions of xenobiotics are responsible for the widespread occurrence of aliphatic carboxylic acids in the environment. To study the performance of the ion-exclusion chromatography column IonPac ICE-AS6 in the analysis of environmental and environmental-technical samples, organic acids are investigated in composting seepage, silage effluents, aqueous extracts of sewage sludge, molasses hydrolysate, and alkaline cellulose hydrolysates. With respect to the diverse sample matrix and composition, different chromatographic conditions are applied. It is possible to determine various volatile fatty acids, dicarboxylic acids, (poly)hydroxy acids, and keto acids as main and trace components in samples with very high and low dissolved organic carbon content. Low baseline noise allows the determination of malic and succinic acid in the concentration range of approximately 1 microM/L in the presence of higher concentrations of fully ionized compounds. The applicability of the column in environmental analysis may be limited by the poor retardation of strong organic acids, insufficient separation of some relevant substance combinations (i.e., citric and isocitric acid), and very strong hydrophobic interactions with straight-chain monocarboxylic acids containing four or more carbon atoms.

Journal Article↗
PubMed1999

Evaluation of application techniques of fibrin sealant to prevent cerebrospinal fluid leakage: a new device for the application of aerosolized fibrin glue.

OBJECTIVE: This report evaluates the sealing effects of fibrin sealant applied on the dura mater using different techniques. METHODS: Three application methods were studied: a sequential layer method, a simultaneous method using a cannula, and a spray method using a newly developed spray device. The sealing effects of these methods were compared using in vitro histological analysis and a pressure resistance test. The clinical efficacy of the fibrin sealant to prevent water leakage through the dura mater was retrospectively analyzed in a total of 509 patients. The process of absorption of a clinically applied fibrin clot in vivo was examined using surgical specimens. RESULTS: The fibrin plate made using the spray method withstood a hydrostatic pressure greater than 200 cm H2O. A scanning electron microscopic study of the fibrin clots showed that the sequential and simultaneous methods produced a fibrin fiber network; in contrast, our spray method formed a dense fibrin tissue in which the fibrin molecules fused together forming stratified laminae. Of the 295 supratentorial craniotomies during which spraying was used, postsurgical cerebrospinal fluid leakage occurred in 9 cases (3.1%), whereas of the 214 craniotomies during which spraying was not used, cerebrospinal fluid leakage occurred in 19 cases (8.9%). Histological examinations of 10 surgical specimens obtained during second craniotomies revealed that the spray-made fibrin clots had been gradually replaced by mature granulation composed of collagenous connective tissue. CONCLUSION: The optimal technique for applying fibrin sealant is the spray method that aerosolizes fibrin glue and produces a tough fibrin plate.

Administration, Topical↗
PubMedDate not supplied

Application of Rasch analysis in the development and application of quality of life instruments.

This paper discusses recent advances that have been made in the field of psychometrics, specifically, the application of Rasch analysis to the instrument development process. It emphasizes the importance of assessing the fundamental scaling properties of an instrument prior to consideration of traditional psychometric indicators. The paper introduces Rasch analysis and shows how it has been applied in the development of needs-based measures in order to ensure that they provide unidimensional measurement. By ensuring that scales are based on the same measurement model and that they fit the Rasch model it is possible for QoL scores to be compared across diseases by means of cocalibration and item banking.

Health Services Needs and Demand↗
PubMedDate not supplied

Application of the dyadic Green's function method to calculate the heat generated by a direct contact applicator.

A rigorous formalism using the dyadic Green's function to determine the relative heating pattern in a two-layer fat-muscle medium of a dipole-corner reflector applicator in direct contact with the finite fat layer is described. The results are compared with the earlier approximate calculations of Guy and Lehmann. Though the two theories give identical results for the relative heat produced in the muscle layer, the relative heating patterns predicted by the present theory in the fat layer are different.

Adipose Tissue↗
PubMed2000

Urea biosensors and their application in hemodialysis--perspective of EnFET application.

Parameters such as blood urea nitrogen concentration, normalized protein catabolic rate and Kt/V that are utilized for urea concentration measurements in blood and dialysate for the optimization of the hemodialysis process are reviewed in the paper. Basic methods of urea concentration measurement are described. Urea biosensors of the EnFET type based on the pH-sensitive Si3N4 gate FET and pNH4-sensitive FET with a Siloprene membrane containing nonactine, both of our own construction, are presented. Application of these biosensors for urea concentration measurement in blood and dialysate is described. An experimental microdialysis system with urease in detector solution and a pH-ISFET detector are described. A comparison of two dialysis procedures, with a commercial dialysate an initial of pH 5.6 and with pH kept lowered during the dialysis process applied to rats, is given.

Animals↗
PubMed1993

Synthesis and application of new microcarriers for animal cell culture. Part II: Application of polystyrene microcarriers.

In this work (Part II) the application of new polystyrene based microcarriers in cell culture technology is demonstrated. Carriers with a variety of surface modifications were tested as a growth support for cell line BHK 21. The growth behavior of the cells and cell to surface attachment were compared to Cytodex 3 (Pharmacia), which was used as a reference carrier. To select carriers with growth supporting surfaces, broad screening in petri dish experiments was carried out. Candidates with the highest growth rates were investigated in spinner flash experiments in further detail. Polystyrene carrier with a surface modification like triethylamine, maltamine or N-methylglucosamine were able to support growth as good or better as the reference carrier Cytodex 3. Economies of ingredients and ease in laboratory handling could make amine-modified polystyrenes a competitive alternative to currently commercially available microcarrier types.

Animals↗
PubMed1997

Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid oligomers: Part II. Biodegradation and drug delivery application.

Previously synthesized lactic/glycolic acid (PLGA) oligomers with different compositions (i.e. different ratio of lactic to glycolic acid in the oligomers) were further studied regarding their biodegradation and drug delivery application. The PLGA oligomers have fast biodegradation characteristics. They degrade to water soluble substances, i.e. lactic and glycolic acids, at a rate of 31.43-40.68 mg day-1 in a medium of constant pH and 28.04-37.87 mg day-1 in a medium of non-constant pH. The biodegradation rate is affected by the composition of the PLGA oligomers and the pH of the incubating medium. The higher the content of glycolic acid moiety in the oligomer, the faster the biodegradation rate. The lower the pH of the incubating medium, the slower the biodegradation of PLGA oligomers. A sustained-release drug delivery system based on the PLGA oligomers was fabricated as injectable microgranules by thermal blending of the PLGA oligomers and drug. Aspirin was used as a model drug. The oligomeric microgranules have advantages of easy fabrication, high drug loading efficiency, easy administration, and fast biodegradation. This thermal blending preparation method has a high loading efficiency of more than 90%. The PLGA oligomeric microgranules can release drug from 9 to 13 days depending on the oligomer composition. Both drug release rate and release duration are influenced by composition of the oligomers. The PLGA oligomeric matrix has the capability of protecting aspirin from hydrolysis. The lactic/glycolic acid oligomeric microgranules have potential use for sustained-release drug delivery.

Aspirin↗
PubMed1982

Applications of immunocolloids in light microscopy. Preparation of protein A-silver and protein A-gold complexes and their application for localization of single and multiple antigens in paraffin sections.

The protein A-gold (pAg) complex, a useful reagent for electron microscopic localization of antigens in thin sections, is tested for its suitability as second step reagent in light microscopic immunohistochemistry. In addition, the preparation of colloidal silver, its complex formation with staphylococcal protein A and the application of the protein A-silver complex for antigen localization in paraffin sections is reported. The antigens were visualized in a two-step technique with specific antisera in the first incubation step and pAg or pA-silver as a general second step reagent. The pAg complex gives a red coloration of antigenic sites, whereas the pA-silver stained yellow. The contrasting color provided by the two immunocolloids allowed localization of two antigens in the same section. No color mixing occurred, showing that removal of the antibodies of the first staining sequence is unnecessary. Staining is virtually permanent with the light microscopic immunocolloid method. It is concluded that pAg and pA-silver complexes are useful as general second step reagents for the localization of a variety of antigens in paraffin sections.

Animals↗
PubMed2004

Exploring the portability of informatics capabilities from a clinical application to a bioscience application.

This report describes XDesc (eXperiment Description), a pilot project that serves as a case study exploring the degree to which an informatics capability developed in a clinical application can be ported for use in the biosciences. In particular, XDesc uses the Entity-Attribute-Value database implementation (including a great deal of metadata-based functionality) developed in TrialDB, a clinical research database, for use in describing the samples used in microarray experiments stored in the Yale Microarray Database (YMD). XDesc was linked successfully to both TrialDB and YMD, and was used to describe the data in three different microarray research projects involving Drosophila. In the process, a number of new desirable capabilities were identified in the bioscience domain. These were implemented on a pilot basis in XDesc, and subsequently "folded back" into TrialDB itself, enhancing its capabilities for dealing with clinical data. This case study provides a concrete example of how informatics research and development in clinical and bioscience domains has the potential for synergy and for cross-fertilization.

Clinical Medicine↗
PubMed2006

Clinical applications of whole-genome association studies: future applications at the bedside.

Until now, performing whole-genome association studies has been an unattainable, but highly desirable, goal for geneticists. With the recent advent of high-throughput genotyping platforms, this goal is now a reality for geneticists today and for clinicians in the not-so-distant future. This review will cover a broad range of topics to provide an overview of this emerging branch of genetics, and will provide references to more specific sources. Specifically, this review will cover the technologies available today and in the near future, the specific types of whole-genome association studies, the benefits and limitations of these studies, the applications to complex disease-gene interactions, diagnostic devices, therapeutics, and finally, we will describe the 5-year perspective and key issues.

Alleles↗
PubMed1987

The ICIDH: format, application in different settings, and distinction between disability and handicap. A critique of papers on the application of the International Classification of Impairments, Disabilities, and Handicaps.

Recent papers on the ICIDH generally agree about the need for and the usefulness of the ICIDH, although inevitably some difficulties are reported in applying it. Some of these stem from the context and professional purpose of the assessments (on the whole the rehabilitation setting was found to be less problematic than community surveys), and others from the application to particular sub-groups, such as children, the elderly, the mentally ill, or those with milder or fluctuating disability. Most problems concerned the nature of the relationship between disability and handicap and the distinction between these concepts. This review suggests an alternative formulation of the disablement model which shows handicap as arising out of an interaction between impairment and disability and the environment in which the individual lives, the resources available, and the social and cultural setting. While on the whole optimistic, the papers reviewed indicate that there is still more work required both on a practical and conceptual level.

Disability Evaluation↗