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At least 1,603 records · Page 89Linked to original sources
PubMed2005

Hydroxyl stereochemistry and amine number within poly(glycoamidoamine)s affect intracellular DNA delivery.

Nucleic acid drugs have great potential to treat many devastating aliments, but their application has been hindered by the lack of efficacious and nontoxic delivery vehicles. Here, a new library of poly(glycoamidoamine)s (D1-D4, G1-G4, and M1-M4) has been synthesized by polycondensation of esterified d-glucaric acid (D), dimethyl-meso-galactarate (G), and d-mannaro-1,4:6,3-dilactone (M) with diethylenetriamine (1), triethylenetetramine (2), tetraethylenepentamine (3), and pentaethylenehexamine (4). The stereochemistry of the carbohydrate hydroxyl groups and the number of amine units have been systematically changed in an effort to examine how the polymer chemistry affects the plasmid DNA (pDNA) binding affinity, the compaction of pDNA into nanoparticles (polyplexes), the material cytotoxicity, and the efficacy of nucleic acid delivery. The polymers with four secondary amines (D4, G4, and M4) between the carbohydrates were found to have the highest pDNA binding affinity and the galactarate polymers generally yielded the smallest polyplexes. Delivery studies with pDNA containing the firefly luciferase or beta-galactosidase reporter genes in BHK-21, HeLa, and HepG2 cells demonstrated that all of the poly(glycoamidoamine)s deliver pDNA without cytotoxicity. Polymers D4, G4, and M4 displayed the highest delivery efficiency, where G4 was found to be a particularly effective delivery vehicle. Heparin competition assays indicated that this may be a result of the higher pDNA binding affinity displayed by G4 as compared to D4 and M4. Polyplexes formed by polymers with weaker pDNA affinities may dissociate at the cell surface due to interactions with negatively charged glycosaminoglycans, which would cause a decrease in the number of polyplexes that are endocytosed.

Carbohydrate Sequence↗
PubMedDate not supplied

Reproductive biotechnologies for endangered mammalian species.

Assisted reproductive techniques (gamete cryopreservation, artificial insemination, embryo transfer, and in vitro fertilization) allow to propagate small fragmented populations of wild endangered species or domestic breeds. There are the best way for producing several offspring from selected genitors in order to avoid inbreeding depression. However, few mammalian species have been well studied for their reproductive biology whereas huge differences have been observed between these species. Furthermore, materials, methods and experimental designs have to be adapted for each case and each limiting factor (wildness, poor quantity of biological material, disparate locations). Genome resource banking is currently arising and the most applied reproductive biotechnology remains artificial insemination. Assisted reproductive techniques currently developed in domestic species (intracytoplasmic sperm injection, nuclear transfer) may offer new opportunities for the propagation of endangered species.

Animals↗
PubMed2004

Microbial community structure in a thermophilic anaerobic hybrid reactor degrading terephthalate.

A thermophilic terephthalate-degrading methanogenic consortium was successfully enriched for 272 days in an anaerobic hybrid reactor, and the microbial structure was characterized using terminal RFLPs, clone libraries and fluorescence in-situ hybridization with rRNA-targeted oligonucleotide probes. All the results suggested that Methanothrix thermophila-related methanogens, Desulfotomaculum-related bacterial populations in the Gram-positive low-G + C group, and OP5-related populations were the key members responsible for terephthalate degradation under thermophilic methanogenic conditions except during periods when the reactor experienced heat shock and pump failure. These perturbations caused a significant shift in bacterial population structure in sludge samples taken from the sludge bed but not from the surface of the packing materials. After system recovery, many other bacterial populations emerged, which belonged mainly to the Gram-positive low-G + C group and Cytophaga-Flexibacter-Bacteroides, as well as beta-Proteobacteria, Planctomycetes and Nitrospira. These newly emerged populations were probably also capable of degrading terephthalate in the hybrid system, but were out-competed by those bacterial populations before perturbations.

Anaerobiosis↗
PubMed2005

The availability of references and the sponsorship of original research cited in pharmaceutical advertisements.

BACKGROUND: The primary goal of pharmaceutical advertisements is to convince physicians to prescribe the manufacturer's product. We sought to determine what materials are cited in support of claims in pharmaceutical ads and medical research articles, and whether health care professionals seeking to verify the claims could obtain these references. METHODS: We reviewed 438 unique ads from the 1999 issues of 10 American medical journals, and a random sample of 400 references in medical research articles selected from the same journals. We classified references as journal article, data on file, meeting abstract or presentation, book or monograph, marketing report, prescribing information, government document or Internet site. We attempted to confirm or obtain each reference through library and Internet searches or by direct request from the manufacturer. The main outcome we sought to determine was the availability of the reference to a clinician. We also ascertained the source of funding for original research cited in the ads and the research articles. RESULTS: In the 438 ads with medical claims, 126 contained no references and 312 contained 721 unique references. Of these ad references, 55% (396/721) cited journal articles and 19% (135/721) cited data on file. In contrast, in the sample of research article references, 88% (351/400) cited journal articles and 8% (33/400) cited books. Overall, 84% of the citations from the ads were available: 98% of journal articles, 86% of books, 71% of meeting abstracts or presentations and 20% of data-on-file references. In all, 99% of the sample of research article references were available. We determined that 58% of the original research cited in the pharmaceutical ads was sponsored by or had an author affiliated with the product's manufacturer, as compared with 8% of the articles cited in the research articles. INTERPRETATION: Many pharmaceutical ads contain no references for medical claims. Although references to journal articles were usually obtainable, other published sources were not as easily acquired. The majority of unpublished data-on-file references were not available, and the majority of original research cited to substantiate claims in the pharmaceutical ads was funded by or had authors affiliated with the product's manufacturer.

Advertising↗
PubMed2006

Protonic and temperature modulation of constituent expression by component selection in a dynamic combinatorial library of imines.

The constitutional recomposition of a dynamic library of imines displays a complex behavior under the effect of two parameters, acidity and temperature. A qualitative analysis of the quantitative data is presented. The results illustrate the response of such a dynamic system to a physical stimulus (temperature) and a chemical effector (H+), thus demonstrating its adaptive behavior under the pressure of external factors. They also point to the possibility of modulating a given functional property (optical, electronic, ionic) by constitutional recomposition induced by a specific trigger. Such features are of great interest for the development of stimuli-responsive, functional dynamic materials.

Journal Article↗
PubMed2001

Semenogelin II gene is replaced by a truncated line 1 repeat in the cotton-top tamarin.

The human seminal vesicles secrete two proteins, semenogelin I and semenogelin II, at very high concentrations. It has previously been shown that the cotton-top tamarin (Sanguinus oedipus), a New World monkey, is lacking the semenogelin II gene. We have now determined the nucleotide sequence of DNA located 5--13 kilobases (kb) downstream of the tamarin semenogelin I gene---a region that in man is occupied by the semenogelin II gene. Two regions with homology to the human semenogelin II gene were identified in the tamarin DNA. The first region, of 3.5 kb, is homologous to DNA upstream of the human gene, and the second region, of 0.6 kb, is mainly derived from the second intron. Between these regions, equivalent to 594 base pairs (bp) upstream of the transcription initiation site to 12 bp downstream of the stop codon in the human semenogelin II gene, the cotton-top tamarin DNA carries a truncated LINE1 repeat. In another set of experiments, the tamarin DNA hybridizing to the mouse semenoclotin gene was investigated. It was concluded that hybridization is with the second intron of the semenoclotin gene, but very likely, the material does not represent a cotton-top tamarin semenoclotin gene. Thus, a mammalian ancestor probably carried a single gene that in the rodent lineage developed into the semenoclotin gene and in the primate lineage into a progenitor of the semenogelin genes.

Base Sequence↗
PubMed2001

Combinatorial array-based enzymatic polyester synthesis.

A combinatorial strategy for biocatalytic polymer synthesis is demonstrated. A library of polymers was synthesized in 96 deep-well plates using AA-BB polycondensations of acyl donors and acceptors. The library was based on four straight-chain diesters as acyl donors (C(3)-C(10)) with aliphatic/aromatic diols as well as more diverse structures including carbohydrates, nucleic acids, and a natural steroid diol used as acyl acceptors. The lipase from Candida antarctica was active in acetonitrile and was capable of catalyzing the polycondensation of the aforementioned monomers to polymers with M(w)'s reaching as high as 20,000 Da, including the preparation of novel sugar-containing polyesters. The combinatorial approach to biocatalytic polymer synthesis described herein serves as a foundation for polymeric materials discovery by demonstrating that polymer arrays can be produced from structurally complex monomers.

Catalysis↗
PubMed2006

Determination of the initial beam parameters in Monte Carlo linac simulation.

For Monte Carlo linac simulations and patient dose calculations, it is important to accurately determine the phase space parameters of the initial electron beam incident on the target. These parameters, such as mean energy and radial intensity distribution, have traditionally been determined by matching the calculated dose distributions with the measured dose distributions through a trial and error process. This process is very time consuming and requires a lot of Monte Carlo simulation experience and computational resources. In this paper, we propose an easy, efficient, and accurate method for the determination of the initial beam parameters. We hypothesize that (1) for one type of linacs, the geometry and material of major components of the treatment head are the same; the only difference is the phase space parameters of the initial electron beam incident on the target, and (2) most linacs belong to a limited number of linac types. For each type of linacs, Monte Carlo treatment planning system (MC-TPS) vendors simulate the treatment head and calculate the three-dimensional (3D) dose distribution in water phantom for a grid of initial beam energies and radii. The simulation results (phase space files and dose distribution files) are then stored in a data library. When a MC-TPS user tries to model their linac which belongs to the same type, a standard set of measured dose data is submitted and compared with the calculated dose distributions to determine the optimal combination of initial beam energy and radius. We have applied this method to the 6 MV beam of a Varian 21EX linac. The linac was simulated using EGSNRC/BEAM code and the dose in water phantom was calculated using EGSNRC/DOSXYZ. We have also studied issues related to the proposed method. Several common cost functions were tested for comparing measured and calculated dose distributions, including chi2, mean absolute error, dose difference at the penumbra edge point, slope of the dose difference of the lateral profile, and the newly proposed Kappaalpha factor (defined as the fraction of the voxels with absolute dose difference less than alpha%). It was found that the use of the slope of the lateral profile difference or the difference of the penumbra edge points may lead to inaccurate determination of the initial beam parameters. We also found that in general the cost function value is very sensitive to the simulation statistical uncertainty, and there is a tradeoff between uncertainty and specificity. Due to the existence of statistical uncertainty in simulated dose distributions, it is practically impossible to determine the best energy/radius combination; we have to accept a group of energy/radius combinations. We have also investigated the minimum required data set for accurate determination of the initial beam parameters. We found that the percent depth dose curves along or only a lateral profile at certain depth for a large field size is not sufficient and the minimum data set should include several lateral profiles at various depths as well as the central axis percent depth dose curve for a large field size.

Body Burden↗
PubMed1983

Isolation of recombinant bacteriophage containing male-specific mouse DNA.

The mammalian Y chromosome is an isolated piece of genetic material that directs sexual determination and gametogenesis. Very little is understood about the mechanism whereby the Y chromosome carries out these functions. Also, there is a severe lack of genetic markers on this chromosome. In order to understand the structure and function of the Y chromosome at the level of its DNA sequences and to provide genetic markers, we are isolating clones of DNA whose sequences are found primarily in DNA from male mice. To this end, we have developed a procedure for the identification of such clones. Application of this screening procedure to a lambda library derived from mouse sperm DNA has yielded 12 distinct clones, part of whose sequences are present predominantly in male DNA. Besides this DNA, they also contain other sequences that are shared with female DNA. These clones are either derived from the Y chromosome or they represent autosomal sequences specifically amplified during male development.

Animals↗
PubMed2006

Travellers' diarrhoea: contemporary approaches to therapy and prevention.

Travellers' diarrhoea remains a major public health problem, contributing to significant morbidity and disability. Because bacterial enteropathogens cause a majority of this form of diarrhoea, antibacterial drugs are effective when used in chemoprophylaxis or for empirical treatment.A review of the MEDLINE listings for travellers' diarrhoea for the past 4 years was conducted; a library of >1,000 scientific articles on the topic was also considered in developing this review. Persons who travel from industrialised countries to developing countries of the tropical and semi-tropical world are the individuals who experience travellers' diarrhoea. While diarrhoea occurs with reduced frequency among persons travelling to low-risk areas from other low- or other high-risk areas, and there remain areas of intermediate risk, this review looks primarily at the illness occurring in persons from industrialised regions visiting high-risk regions of Latin America, Africa and Southern Asia. The material reviewed deals with the high frequency of acquiring diarrhoea during international travel to high-risk areas, seen in approximately 40%, and the expected bacterial causes of illness, of which diarrhoeagenic Escherichia coli is the most important. The host risk factors associated with increased susceptibility to diarrhoea include young age, lack of previous travel to high-risk regions in the past 6 months, indiscriminate food and beverage selection patterns, and host genetics. It appears feasible to decrease the rate of illness among the travelling public by careful food and beverage selection or through chemoprophylaxis with nonabsorbed rifaximin. Chemoprophylaxis with rifaximin should help to reduce the occurrence of travellers' diarrhoea and hopefully prevent post-diarrhoea complications, including irritable bowel syndrome. Early empirical therapy with antibacterial drugs, including rifaximin, a fluoroquinolone or azithromycin, will decrease the duration of illness and return travellers more quickly to their planned activities.With collaboration between local governments and public health researchers, it may be possible to improve hygiene in areas to be visited, which may translate into reduced rates of illness. More liberal use of rifaximin prophylaxis is likely to reduce the occurrence of illness and complications of disease. Vaccines and immunoprophylactic products may be beneficial for prevention of a subset of individuals otherwise developing diarrhoea.

Anti-Bacterial Agents↗
PubMed2002

Dental concepts in the Unified Medical Language System.

OBJECTIVE: Currently, no comprehensive, controlled vocabulary for dentistry is available. The objective of this study was to determine how well the Unified Medical Language System, the largest repository of concepts and terms in biomedicine, represents dental concepts. METHOD AND MATERIALS: The dental subset of concepts was extracted from Unified Medical Language System using the software program APEX (APplication for the EXtraction of domain-specific concepts). The relationships contained in the Unified Medical Language System Metathesaurus were used to locate the concepts related to 12 seed terms. The Encyclopédie Médico-Chirurgicale (513 dental terms) and the Diagnostic Codes developed by Leake et al (124 terms) were compared to the dental subset. Terms were classified as exact match, related term, or no match. The resultant matching characteristics were compared to those determined by the National Library of Medicine/Agency for Health Care Policy and Research Large Scale Vocabulary Test. RESULTS: The dental subset of Unified Medical Language System contained 948 concepts. The Encyclopédie Médico-Chirurgicale and the Diagnostic Codes exhibited similar matching characteristics for exact match (61.6% and 58.9%, respectively) and related term (38.0% and 32.2%, respectively). For no match, the matching frequencies were significantly different (P < .001). CONCLUSION: The Unified Medical Language System may be a comprehensive source of terms suitable for various representation requirements in dentistry.

Chi-Square Distribution↗
PubMed1970

Manuscripts and oral history: common interests and problems in the history of medicine.

The acceptance of the tape-recorded interview as a research tool and historical record in the history of medicine suggests some problems both for the researcher with respect to resource materials and for the repository. A direct relationship exists between manuscript collections and the oral history product, and it would be in the interest of the oral historian, the curator of manuscripts, and the repository if a unified conceptual approach were taken in the acquisition and preservation of manuscript records and oral history interviews.

History, Modern 1601-↗
PubMed1989

Multiple copies of the coding regions for the light-harvesting B800-850 alpha- and beta-polypeptides are present in the Rhodopseudomonas palustris genome.

A reverse-phase HPLC System for isolation of the water insoluble alpha- and beta-polypeptides of the light-harvesting complex II (LH II) of Rhodopseudomonas (Rps.) palustris without employment of any detergent was developed. The material obtained was of high purity and suitable for direct microsequence analysis. Chromatographic analysis could resolve at least two major beta-polypeptides, beta a and beta b, two major alpha-polypeptides, alpha a and alpha b, and two additional minor polypeptides. N-terminal amino acid sequencing shows that the resolved peaks correspond to different polypeptide species and that the minor species have an N-terminal sequence identical to that of the alpha b polypeptide. An oligonucleotide derived from the amino terminal sequence of the alpha a polypeptide was utilized to screen a genomic library from Rps.palustris. Several independent clones have been characterized by Southern blot and nucleotide sequence analysis. We show that Rps.palustris contains at least four different clusters of beta and alpha genes. Two clones contain sequences potentially coding for beta a-alpha a and beta b-alpha b polypeptides; and two additional clones potentially coding for beta and alpha peptides which we named beta c-alpha c and beta d-alpha d, which did not correspond to the major purified polypeptides. In addition to the protein chemistry data, the conservation at the amino acid level and the presence of canonical ribosomal binding sites upstream of each of the identified genes strongly suggest that all four coding regions are expressed.

Amino Acid Sequence↗
PubMed1999

A murine model for juvenile NCL: gene targeting of mouse Cln3.

JNCL is a neurodegenerative disease of childhood caused by mutations in the CLN3 gene. A mouse model for JNCL was created by disrupting exons 1-6 of Cln3, resulting in a null allele. Cln3 null mice appear clinically normal at 5 months of age; however, like JNCL patients, they exhibit intracellular accumulation of autofluorescent material. A second approach will generate mice in which exons 7 and 8 of Cln3 are deleted, mimicking the common mutation in JNCL patients.

Animals↗
PubMed2006

Design and modular parallel synthesis of a MCR derived alpha-helix mimetic protein-protein interaction inhibitor scaffold.

A terphenyl alpha-helix mimetic scaffold recognized to be capable of disrupting protein-protein interactions was structurally morphed into an easily amenable and versatile multicomponent reaction (MCR) backbone. The design, modular in-parallel library synthesis, initial cell based biological data, and preliminary in vitro screening for the disruption of the Bcl-w/Bak protein-protein interaction by representatives of the MCR derived scaffold are presented.

Apoptosis↗
PubMed1992

An archipelago of CpG islands in Xq28: identification and fine mapping of 20 new CpG islands of the human X chromosome.

19 probes for CpG islands, mapping to Xq28, have been used as probes to construct a physical map of genes of this band of the human X chromosome. A total of 22 CpG islands have been precisely mapped in respect to known loci along the 9-10 Mb of Xq28. The fine mapping of such a large number of CpG islands has demonstrated that also in gene rich Giemsa light bands, like Xq28, gene distribution is non uniform: the CpG islands are clustered in the distal portion of the band in a 2 Mb region between the G6PD gene and the DXS15 locus. Moreover, 16 CpG islands were found between the G6PD and the RCP/GCP genes, a region of DNA of only about 300 kb. If this structural organization has a biological function it has yet to be determined. However, the isolation of large genomic regions enriched in gene sequences and the availability of cosmid or YAC contigs will provide the means to test the significance of such gene organization, as well as the material for large sequencing projects and gene search, for the identification of candidate genes for inherited disorders mapped to Xq28 and for comparative mapping.

Animals↗
PubMed1998

Solid Phase Synthesis of beta-Peptoids: N-Substituted beta-Aminopropionic Acid Oligomers.

A solid-phase organic synthesis method has been developed for the preparation of N-substituted-beta-aminopropionic acid oligomers or beta-peptoids 1. Treatment of polymer-bound 4-(benzyloxy)benzyl acrylate 2 with primary amines afforded N-substituted beta-alanines 3. Polymer loadings and product conversions were determined by direct cleavage of resin-bound materials and measurement by (1)H NMR with an internal standard. The NMR method was used to establish loading of all resin-bound intermediates including acrylic acid. Acylation with acryloyl chloride followed by Michael addition of primary amines to the acrylamide allowed preparation of di-beta-peptoids. By a linear set of seven reactions, trimeric N-benzyl-beta-aminopropionic acid was prepared in 67% overall yield. Single-bead FT-IR microspectroscopy was used to acquire spectra of the resin bound mono-beta-peptoids, di-beta-peptoids, and acrylamide intermediates. A combinatorial library of defined mixtures of tri-beta-peptoids was prepared by mixing equimolar amounts of the mono-beta-peptoid resins and carrying them through two sequences of the acylation-Michael addition. The identity of a sample mixture was determined by LC-MS analysis of the cleavage product.

Journal Article↗
PubMedDate not supplied

Collagen-binding matrix proteins from elastomeric extraorganismic byssal fibers.

The byssal threads of marine mussels represent a peculiar case of extraorganismic extracellular material. The threads consist of fibrous chimeric collagens such as preCol-P (with collagenous, elastin-like and histidine-rich domains) embedded in a microfibrillar matrix. We report here on the extraction, purification, and characterization of water-soluble proximal thread matrix protein 1 (PTMP1), which is preferentially located in the proximal portion of each byssal thread and decreases in a proximal to distal direction. PTMP1 has a mass of about 50 kDa as determined by matrix-assisted laser desorption-ionization with time-of-flight (MALDI-TOF) mass spectrometry. Glycine is the most common residue at 12.2 mol %, followed by asparagine/aspartic acid and glutamine/glutamic acid at 11.4 and 9.9 mol %, respectively. Glycosylation has been detected by Western blotting with biotinylated concanavalin A and neutral sugar analysis. With degenerate primers designed from the N-terminal sequence and an additional internal peptide derived by Lys-C endopeptidase digestion, a complete cDNA sequence for this protein was obtained by polymerase chain reaction (PCR) amplification of a Mytilus edulis foot cDNA library. Two variants with minor sequence differences limited to the N-terminus were found. The cDNA-deduced protein sequence reveals two symmetric internal repeats that together account for >85% of the protein. Sequence and epitope similarity of PTMP1 to the A domains of von Willebrand factor and integrin alpha(1)I suggest a capacity for collagen binding. Enzyme-linked immunosorbent assay (ELISA)-based measurement of PTMP1 binding to immobilized type I collagen shows high affinity (apparent K(D) = 0.25 microM), but the binding exhibits no dependence on metals. Using primers designed from M. edulis, we also found a PTMP1-like cDNA in a related species, M. galloprovincialis, with a deduced protein sequence having 97% identity with one M. edulis variant and 99% identity with the other. The corresponding cDNA sequences have 94% and 96% identity, respectively.

Animals↗