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At least 1,135 records · Page 63Linked to original sources
PubMed2003

[Chalcones (1,3-diarylpropen-1-ones) and their analogs as potential therapeutic agents in cardiovascular system diseases].

At the beginning of a new millennium, several important questions have come to the fore connected with the utilization of natural resources for the investigation of new medicaments (necessity of cooperation of both highly developed and developing countries in the protection of natural resources, necessity to justly evaluate and reward the contributions of the individual cultures in the case that a knowledge of traditional medicine was employed in the development of a new medicament, necessity to achieve the maximal chemical variety of real and virtual libraries of substances from which potential drugs are selected for screening tests). The research of chalcones and its analogues which are relatively easily available not only by isolation from natural material, but also by the methods of classical and combinatorial synthesis should not be substantially affected by the above-described changes. The present communication links up with previous papers (Opletalová, V., Sedivý, D.: Ces. slov. Farm. 48, 252 (1999); Opletalová, V.: Ces. slov. Farm. 49, 278 (2000); Opletalová, V. et al.: Folia Pharm. Univ. Carol. 25, 21 (2000)) and is devoted to the stabilizing action of chalcones on the vascular wall, vasodilating and anti-aggregating effects, and a favourable effect of their antioxidative activity on the functions of the cardiovascular system. The introduction also briefly discusses the nomenclature of this group of compounds.

Animals↗
PubMed1992

[Screening and distinguishing heavy chain variable region genes of McAb against encephalitis type B virus].

In order to prepare human-mouse chimeric antibody against encephalitis type B virus, hybridoma 51-8 cells secreting monoclonal antibody against the virus were used as material for isolating heavy-chain variable region gene of the McAb. High molecular weight DNA of the hybridoma cell was partially digested by BamHI, and then constructed a gene library containing 2 x 10(7) pfu with lambda EMBL-3 as vector. With cDNA of heavy-chain variable region of the monoclonal antibody as probe, nine positive plaques were screened from 360,000 plaques, which have been proven that they contained a fragment of heavy-chain variable region genes by dot hybridization and Southern hybridization. Four recombinants among the nine positive plaques were further distinguished with J11 probe containing J3, J4 and heavy-chain enhancer. After cutting by EcoR1, there was a 3.8 kb fragment in three recombinants as similar to that in liver cell and Sp2/0 cell, but not in the fourth recombinant (lambda 8a4) which contained a 4.5 kb fragment that did not present in liver cell and Sp2/0 cell. The results showed that the inserts in former 3 recombinants were non-rearranged fragment of heavy-chain variable region genes, but the insert in lambda 8a4 contained a rearranged functional variable region gene. The 4.5 kb fragment could not be hybridized with a probe containing J1 and J2, but contained VH, J3 or/and J4 and enhancer, that further proved it was a functional variable region gene. Therefore, the 4.5 kb fragment was isolated and subcloned in pUC 19, and its physical map was made.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[XX male syndrome: a study model of the genetic determination of the male sex].

Using Y-specific probes, issued from a library of the human Y chromosome, DNA from about 30 XX men has been studied by the Southern technique. Two groups of patients could be distinguished: one with Y genetic material, the second, without Y DNA. Among XX males with Y sequences there was a genetic heterogeneity with a variable amount of Y DNA sequences. These Y DNA sequences come from the short arm of the Y chromosome and are probably translocated to the paternal X. Concerning the other group, in which no Y sequence could be detected, either Y DNA was present but was not detected, or the mechanism of maleness was Y-independent.

Base Sequence↗
PubMedDate not supplied

Common RNA polymerase I, II, and III upstream elements in mouse 7SK gene locus revealed by the inverse polymerase chain reaction.

7SK RNA in mammalian cells is derived from a gene or genes belonging to a middle-repetitive family in the genome. Standard library search techniques applied to isolating such genes are complicated by the finding of multiple truncated or otherwise modified versions of the sequence, whereas the true gene loci can sometimes be eliminated from amplified libraries. After an unsuccessful search for the 7SK RNA gene in four mouse genomic libraries, we used the inverse polymerase chain reaction (IPCR) on fractionated genomic DNA to characterize sequences containing complete copies of 7SK plus flanking regions for analysis of putative transcription regulatory sequences. Direct sequence of IPCR-amplified material allowed for selection of upstream and downstream primers which could then be used for direct PCR, sequencing, and characterization of the mouse 7SK gene locus. So far, we found only one complete copy of the canonical 7SK gene that differed from the human sequence in only 4 bases. The gene is flanked by a very well-conserved upstream control region that includes a TATA motif, two direct repeats, and a proximal sequence element common to mammalian genes transcribed by all three RNA polymerases. The 3' region contains multiple stretches of T residues, typical of class III terminators.

Animals↗
PubMed2005

Comparison of thermal neutron distributions within shield materials obtained by experiments, SN and Monte Carlo code calculations.

Benchmark experiments of thermal neutron distributions within the shield materials, graphite pile and pure water, were performed by using 252Cf fission neutrons and gold foil activation detectors, and, to these results, the estimates obtained by using the discrete ordinate code ANISN and the Monte Carlo code MCNP5 with two different cross-section libraries, ENDF/B-VI and the Japanese new version of JENDL-3.3, were compared. The results revealed that the MCNP5 calculations with the two libraries closely agree with the experiments and that there are slight differences between the MCNP5 and the ANISN calculations. The differences are caused mainly by the overestimation of the thermal neutron absorption cross sections constructed in NJOY99. The ANISN calculations with the modified absorption cross sections reproduced the results of the MCNP5 fairly well.

Computer Simulation↗
PubMed2002

Solution-phase preparation of a 560-compound library of individual pure mappicine analogues by fluorous mixture synthesis.

Solution-phase mixture synthesis has efficiency advantages and favorable reaction kinetics. Applications of this technique, however, have been discouraged by the difficulty in obtaining individual, pure final products by using conventional separation and identification processes. Introduced here is a new strategy for mixture synthesis that addresses the separation and identification problems. Members of a series of organic substrates are paired with a series of fluorous tags of different chain lengths. The tagged starting materials are then mixed and taken through a multistep reaction process. Fluorous chromatography is used to demix the tagged product mixtures on the basis of the fluorine content of the tags to provide the individual pure components of the mixture, which are detagged to release the final products. The utility of fluorous mixture synthesis is demonstrated by the preparation of a 560-membered library of analogues of the natural product mappicine. A seven-component mixture is carried through a four-step mixture synthesis (two one-pot and two parallel steps) to incorporate two additional points of diversity onto the tetracyclic core. Methods for analysis and purification of the intermediates are established for the quality control of the mixture synthesis.

Alkaloids↗
PubMed2003

Microbead display of proteins by cell-free expression of anchored DNA.

Gene expression technologies where nucleic acid sequences remain physically linked to their corresponding gene products are important tools for selection and identification of rare variants in large protein libraries. Here, we describe a gene expression system, which combines the potential of bead-based suspension array technology (SAT) with gene expression and clonal identification. Using streptavidin-coated polystyrene micrometer-sized beads as solid supports for anchored PCR products, we have investigated conditions for cell-free expression and bioaffinity technology to provide clonal co-anchoring of corresponding gene products. Experiments showed that coupled transcription and translation of PCR product expression cassettes resulted in display of affinity-anchored proteins whose binding characteristics could be analyzed via direct and selective interaction with a fluorescently labeled target protein. Interestingly, experiments performed with differently biotinylated PCR products showed that the efficiency of display was dependent on the directionality of the expression cassette relative to the bead surface. In spiked systems, using small immunoglobulin binding proteins as models, we demonstrate efficient flow cytometric sorting of beads corresponding to the target interacting clones, verified by post-sorting analysis and clonal identification at DNA level. The use of this technology, including alternative formats, for different proteomics applications is discussed.

Adsorption↗
PubMed1991

Characterization of somatic cell hybrids by bivariate flow karyotyping and fluorescence in situ hybridization.

We report on the use of flow karyotyping and fluorescence in situ hybridization (FISH) to characterize the human chromosomes in somatic cell hybrids. The identity, DNA content, and relative frequency of human chromosomes are derived from flow karyotypes, i.e., measurements of Hoechst and chromomycin fluorescence intensities of chromosomes by dual beam flow cytometry. Chromosome integrity is assessed by comparing the peak position of a human chromosome in the flow karyotypes of a hybrid cell line and its human donor. When human donor cells are unavailable, the peak position of a human chromosome in a hybrid line is compared to the range of peak positions among normal individuals. The relative frequency of human chromosomes in subclones or hybrids grown in culture is monitored using the volumes of peaks in flow karyotypes. FISH with biotinylated human genomic DNA or chromosome-specific repeat sequence as probe is used in conjunction with flow karyotyping to confirm the number of human chromosomes in hybrids. Some small rearrangements are detected by flow karyotyping and not by FISH. On the other hand, translocations between human and rodent chromosomes are detected by FISH and not always by flow karyotyping. Flow karyotyping and FISH were used to characterize over 100 hybrid lines donated by other laboratories. A hybrid set useful for the construction of chromosome-enriched gene libraries is presented. In this set, each of the 24 human chromosome types is present and intact, as judged by these techniques, in a line containing little or no other human material.

Animals↗
PubMedDate not supplied

Expression-cloning and sequence of a cDNA encoding human growth hormone-releasing factor.

Growth hormone-releasing factor (GRF) is believed to mediate both neural and hormonal control of the release and perhaps synthesis of growth hormone (GH) from the anterior pituitary. Its presence in only minute quantities in the hypothalamus hampered for many years efforts to determine its structure. Recently, two groups independently characterized a peptide from two human pancreatic tumours that possessed GH-releasing activity. Antibodies to this peptide have revealed immunoreactive material in the hypothalamus of several primate species. Furthermore, an apparently identical peptide has now been isolated directly from human hypothalamus. Using both oligonucleotide and antibody screening of a cDNA expression library, we have isolated a recombinant clone encoding human pancreatic GRF (hpGRF) within a larger precursor protein. The nucleotide sequence predicts that processing of GRF from the precursor should generate two additional peptides of unknown function. Restriction analysis of genomic DNA indicates that there is probably a single human GRF gene and suggests that the pancreatic tumour and hypothalamic proteins are encoded by an identical mRNA.

Amino Acid Sequence↗
PubMed1997

Characterization of SV40-transformed xeroderma pigmentosum cell lines for their usability in HPRT mutation studies.

We have characterized six SV40-transformed xeroderma pigmentosum cell lines (XP20S and XP12BE derived from female donors, XP12RO-SV, XP3BR/12SV, XP4PA-SV and XP8CAC-SV from male donors) for their usability in HPRT mutation studies. All cell lines exhibit hypersensitivity, compared with MRC5CV1 cells, towards the cytotoxic action of UV-irradiation. They were all shown to be heteronuclear and hyperdiploid with pronounced variability in chromosome number. Fluorescence in situ hybridization (FISH) with an X-chromosomal library (X-chromosome painting) and BrdUrd-labelling of late-replicating X-chromosomes demonstrated the presence of variable numbers of X-chromosomes and additional X-chromosomal material and suggested the presence of more than one genetically active HPRT allele in the majority of cells of five cell lines. The cell line XP8CAC-SV (complementation group C) seemed to be most suitable for HPRT mutation studies due to its near-diploid karyotype with only one X-chromosome in the majority of cells. From this cell line, a clonal subline was established (XP8CAC-SV-C1) which revealed the same UV-hypersensitivity as the parental cell line and a near-diploid karyotype with one X-chromosome in 94% of the metaphases. Molecular analysis of the HPRT gene gave a normal PCR amplification pattern for all exons and the normal wild-type sequence of the cDNA. HPRT tests with (+)-anti-benzo[a]pyrene-7,8-diol-9,10-oxide [(+)-anti-BPDE] showed a reproducible, concentration related increase in mutant frequencies. Compared with results with MRC5CV1 cells, the obtained data indicate spontaneous and (+)-anti-BPDE-induced hypermutability of the XP line. XP8CAC-SV-C1 thus represents a permanent XP cell line with characteristic cellular XP features which is convenient for studying the influence of deficient excision repair on HPRT mutant frequencies and mutation spectra.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2000

James Jackson an American physician in London, 1799-1800.

James Jackson (1777-1867) was a prominent physician in Massachusetts during the first half of the nineteenth century. Early in his career, he had traveled to London to complete his medical studies. A search of libraries and archives on both sides of the Alantic has uncovered hitherto unpublished and little known information about his experiences on his journey and while abroad (1799-1800). Presentation of this material not only serves to supplement what is already known about Jackson but in addition heightens our understanding and awareness of contemporary medical issues of his day.

History, 18th Century↗
PubMedDate not supplied

Identification by suppression subtractive hybridization of p21 as a radio-inducible gene in human glioma cells.

BACKGROUND: Radio-gene therapy involves the delivery, to tumor cells, of a therapeutic transgene whose expression is controlled by irradiation. MATERIALS AND METHODS: Here, we sought to identify novel radio-inducible transcripts in U87MG human malignant glioma cells using suppression subtractive hybridization (SSH). RESULTS: Of 998 clones from a subtracted library of irradiated U87MG cells, 24 candidate clones were identified by dot blot and 3 clones were confirmed as having been induced by irradiation by Northern blot analysis. All three clones showed 99-100% homology to the cyclin-dependent kinase (cdk) inhibitor, p21(Waf/Cip1). A screening of 12 human malignant glioma cell lines revealed that irradiation increased p21 mRNA expression and p21 protein levels levels in all of the five cell lines retaining p53 wild-type activity in a p53 reporter assay, but in none of seven p53 reporter-negative cell lines. CONCLUSION: Irradiation induces p21 mRNA expression in a strictly p53-dependent manner and may only enhance the expression of a limited number of genes in glioma cells. We conclude that the identification of radio-inducible genomic sequences suitable for radio-gene therapy may turn out to be difficult.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMedDate not supplied

Combinatorial search for advanced luminescence materials.

Phosphors are key materials in fluorescent lighting, displays, x-ray scintillation, etc. The rapid development of modern photonic technologies, e.g., mercury-free lamps, flat panel displays, CT-detector array, etc., demands timely discovery of advanced phosphors. To this end, a combinatorial approach has been developed and applied to accelerated experimental search of advanced phosphors and scintillators. Phosphor libraries can be made in both thin film and powder form, using masking strategies and liquid dispensing systems, respectively. High-density libraries with 100 to 1000 discrete phosphor compositions on a 1"-square substrate can be made routinely. Both compositions and synthesis temperatures can be screened in a high-throughput mode. In this article, details on the existing methods of combinatorial synthesis and screening of phosphors will be reported with examples. These methods are generic tools for application of combinatorial chemistry in the discovery of other solid state materials. A few highly efficient phosphors discovered with combinatorial methods have been reproduced in bulk form and their luminescent properties measured.

Combinatorial Chemistry Techniques↗
PubMed2005

Distance learning in toxicology: Australia's RMIT program.

RMIT University was the first to offer a comprehensive Masters of Toxicology in Australasia 19 years ago. In 2001 the program was transformed into two stages, leading to a Graduate Diploma and Master of Applied Science in Toxicology. Now, these programs are fully online and suitable for graduates living and working anywhere in the world. The modular distance-learning courses are specifically designed to equip students with essential skills for entering fields such as chemical and drug evaluation; risk assessment of chemicals in the workplace; environmental and food toxicology. RMIT's online course delivery system has made it possible to deliver the toxicology programs, both nationally and internationally. The learning material and interactive activities (tests and quizzes, discussion boards, chat sessions) use Blackboard and WebBoard, each with a different educational function. Students log in to a Learning Hub to access their courses. The Learning Hub enables students to extend their learning beyond the classroom to the home, workplace, library and any other location with Internet access. The teaching staff log in to the Learning Hub to maintain and administer the online programs and courses which they have developed and/or which they teach. The Learning Hub is also a communication tool for students and staff, providing access to email, a diary and announcements. The early experience of delivering a full toxicology program online is very positive. However this mode of teaching continues to present many interesting technical, educational and cultural challenges, including: the design and presentation of the material; copyright issues; internationalization of content; interactive participation; and the assessment procedures.

Australia↗
PubMed1995

The organization of the digital library.

As digital information proliferates and the difficulties of managing it threaten to overwhelm traditional publication and information delivery processes, new visions of a digital library are forming. Exactly what a digital library is and how it is to be organized have not yet been determined, and bibliographic organization of digital information has not been sufficiently addressed. Bibliography is the systematic description or classification of writings or publications considered as material objects. In today's digital world, such material objects may no longer be relevant, but the need for systematic description remains. The important issue is not whether digital bibliography is needed but, instead, whether or not existing bibliographic techniques are appropriate for this new media. A second issue is the location of the responsibility for a new digital bibliography. Does it rest with medical informaticians, often the producers of this new digital information, or with librarians, traditionally the classifiers of information? Developments in both medical informatics and medical librarianship indicate a need for greater collaboration between these specialties in order to achieve their common purpose--the creation, classification, and dissemination of scholarly information.

Bibliography of Medicine↗
PubMed2003

Parallel synthesis and biophysical characterization of a degradable polymer library for gene delivery.

We recently reported the parallel synthesis of 140 degradable poly(beta-amino esters) via the conjugate addition of 20 primary or secondary amine monomers to seven different diacrylate monomers. To explore possible structure/function relationships and further characterize this class of materials, we investigated the ability of each DNA-complexing polymer to overcome important cellular barriers to gene transfer. The majority of vectors were found to be uptake-limited, but complexes formed from polymers B14 and G5 displayed high levels of internalization relative to "naked" DNA (18x and 32x, respectively). Effective diameter and zeta potential measurements indicated that, in general, small particle size and positive surface charge led to higher internalization rates. Of the 10 DNA/polymer complexes with the highest uptake levels, all had effective diameters less than 250 nm and nine had positive zeta potentials. Lysosomal trafficking was investigated by measuring the pH environment of delivered DNA. Complexes prepared with polymers G5, G10, A13, B13, A14, and B14 were found to have near neutral pH measurements, suggesting that they were able to successfully avoid trafficking to acidic lysosomes. This work highlights the value of parallel synthesis and screening approaches for the discovery of new polymers for gene delivery and the elucidation of structure/function relationships for this important class of materials.

3T3 Cells↗
PubMed2006

Viruses: making friends with old foes.

The study of viruses has traditionally focused on their roles as infectious agents and as tools for understanding cell biology. Viruses are now finding a new expanded role as nanoplatforms with applications in materials science and medicine. Viruses form highly symmetrical monodisperse architectures and are ideal templates for engineering multifunctionality, including multivalent display of surface ligands and encapsulation of inorganic and organic materials. These developments assure that viruses will find applications as versatile nanoscale materials.

Binding Sites↗