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At least 865 records · Page 48Linked to original sources
PubMed1995

[Copper-induced liver cirrhosis in a 13-month old boy].

A micronodular liver cirrhosis with a massive accumulation of copper in hepatocytes was found in a 13-months old boy. The causal factor was due to the increased copper concentration within the drinking water, which caused liver disease of the boy who had been completely weaned at the age of four weeks. The cooper concentration found in the drinking water exceeded 12 mg/l after a twelve hour stagnation time; after several days of stagnation the highest measured concentration was 28.6 mg/l. This increase is caused by the combined effect of copper pipes and acidulous well water.

Biopsy↗
PubMed1998

Gastrointestinal upsets and new copper plumbing--is there a connection?

This article summarizes two investigations that examine the health effects of prolonged exposure to copper-contaminated drinking water. The first study was initiated after elevated copper levels were detected in several homes that were either newly constructed or recently remodeled. All of these homes were served by the same municipal water supplier. The second case involved illnesses and water-quality problems that were reported by several residents of a mobile home park shortly after a new water distribution system was installed. Findings from these investigations suggest that copper-contaminated drinking water may be a fairly common cause of nausea, diarrhea, abdominal cramps, and headaches-especially among residents of new or recently-remodeled homes, and in areas where water supplies are naturally corrosive.

Adolescent↗
PubMed2005

Surrogate data--a secure way to share corporate data.

The privacy of chemical structure is of paramount importance for the industrial sector, in particular for the pharmaceutical industry. At the same time, companies handle large amounts of physico-chemical and biological data that could be shared in order to improve our molecular understanding of pharmacokinetic and toxicological properties, which could lead to improved predictivity and shorten the development time for drugs, in particular in the early phases of drug discovery. The current study provides some theoretical limits on the information required to produce reverse engineering of molecules from generated descriptors and demonstrates that the information content of molecules can be as low as less than one bit per atom. Thus theoretically just one descriptor can be used to completely disclose the molecular structure. Instead of sharing descriptors, we propose to share surrogate data. The sharing of surrogate data is nothing else but sharing of reliably predicted molecules. The use of surrogate data can provide the same information as the original set. We consider the practical application of this idea to predict lipophilicity of chemical compounds and we demonstrate that surrogate and real (original) data provides similar prediction ability. Thus, our proposed strategy makes it possible not only to share descriptors, but also complete collections of surrogate molecules without the danger of disclosing the underlying molecular structures.

Chemical Engineering↗
PubMed2006

Physical controls on directed virus assembly at nanoscale chemical templates.

Viruses are attractive building blocks for nanoscale heterostructures, but little is understood about the physical principles governing their directed assembly. In situ force microscopy was used to investigate organization of Cowpea Mosaic Virus engineered to bind specifically and reversibly at nanoscale chemical templates with sub-30 nm features. Morphological evolution and assembly kinetics were measured as virus flux and inter-viral potential were varied. The resulting morphologies were similar to those of atomic-scale epitaxial systems, but the underlying thermodynamics was analogous to that of colloidal systems in confined geometries. The 1D templates biased the location of initial cluster formation, introduced asymmetric sticking probabilities, and drove 1D and 2D condensation at sub-critical volume fractions. The growth kinetics followed a t(1/2) law controlled by the slow diffusion of viruses. The ability of poly(ethylene glycol) (PEG) to induce the lateral expansion of virus clusters away from the 1D templates suggests a significant role for weak interactions.

Comovirus↗
PubMedDate not supplied

Occupational chemical exposures in artificial organic fiber industries.

This review discusses artificial organic fibers that are produced from materials of natural origin such as rayons, cellulose triacetates and proteins; or made from polymerised chemicals such as polyamides, polyesters, polyvinyls, modacrylics, carbon fibers, polyolefins, polyurethane and polytetrafluoroethylene. Chemicals involved include monomers, solvents, flame retardants, pigments and other additives. Occupational exposure to chemicals in the production stages are discussed and also the potential health hazards involved are reviewed. Current exposure levels, engineering controls and work practices for some of the chemicals used in the Ontario artificial fiber industry are discussed. Recommendations are made for areas that need further study and/or investigation.

Acrylic Resins↗
PubMed2002

Engineering the surface properties of synthetic gene delivery vectors.

Synthetic gene delivery vehicles are a highly promising approach to gene delivery; however, several problems must still be overcome before they can begin to enjoy dinical success. A number of these problems can be addressed by engineering and optimizing the properties of the vector surface, the component of the particle that interacts and "communicates" with tissues and cells during the delivery process. Surfaces must be engineered to satisfy two ostensibly conflicting constraints: the ability to interact specifically with a target cell while avoiding nonspecific protein interactions, particularly with components of the immune system. We summarize progress that has been made in both these areas and discuss several approaches where the intersection of biological and chemical solutions promises to significantly advance the engineering of synthetic vehicles.

Animals↗
PubMed1998

Principles of tissue engineering applied to programmable osteogenesis.

This article presents a strategy for design, engineering, and fabrication of a bioresorbable, manufactured bone graft substitute (BGS) device. The approach is based on established precepts of osteogenesis, molecular biology of hyaluronic acid and osteoinductive proteins, and theoretical preformance criteria for such a device collated from the literature of 1991 to 1996. Application of this design and engineering strategy results in a composite device consisting of a D,D-L,L-polylactic acid macrostructure optimized to the architecture of cancellous bone, a microstructure composed of a filamentous velour of hyaluronan and a recombinant human bone morphogenetic protein 2 (rhBMP-2). The performance of this construct was tested in vivo in the dog, intertransverse process, spinal fusion model and in a critical sized defect of the rabbit radius. Data from these studies are used to illustrate principle points of the design and engineering concept.

Animals↗
PubMed2003

Chemical complementation: small-molecule-based genetic selection in yeast.

Protein and metabolic engineering would greatly benefit from a general system linking the presence of a small molecule to the power of genetic selection. We use nuclear receptors to link the survival of Saccharomyces cerevisiae to the presence of small molecules through genetic selection, extending classical genetic complementation to a new "chemical complementation." In this system the Gal4 DNA-binding domain is fused to ligand-binding domains from two nuclear receptors, expressed in the strain PJ69-4A, and grown on plates containing known ligands for the receptors. Yeast survive on selective plates only in the presence of a nuclear receptor and the corresponding ligand. Mutagenesis can increase the sensitivity of chemical complementation. This system may be extended to engineer nuclear receptors for practically any small molecule through directed evolution coupled to genetic selection, and for performing metabolic engineering in yeast.

Antineoplastic Agents↗
PubMed2004

DNA display III. Solid-phase organic synthesis on unprotected DNA.

DNA-directed synthesis represents a powerful new tool for molecular discovery. Its ultimate utility, however, hinges upon the diversity of chemical reactions that can be executed in the presence of unprotected DNA. We present a solid-phase reaction format that makes possible the use of standard organic reaction conditions and common reagents to facilitate chemical transformations on unprotected DNA supports. We demonstrate the feasibility of this strategy by comprehensively adapting solid-phase 9-fluorenylmethyoxycarbonyl-based peptide synthesis to be DNA-compatible, and we describe a set of tools for the adaptation of other chemistries. Efficient peptide coupling to DNA was observed for all 33 amino acids tested, and polypeptides as long as 12 amino acids were synthesized on DNA supports. Beyond the direct implications for synthesis of peptide-DNA conjugates, the methods described offer a general strategy for organic synthesis on unprotected DNA. Their employment can facilitate the generation of chemically diverse DNA-encoded molecular populations amenable to in vitro evolution and genetic manipulation.

Chromatography, High Pressure Liquid↗
PubMed1992

Alteration of enzyme specificity and catalysis.

In the past year, site-directed mutagenesis and other forms of protein engineering have been used to reverse the substrate specificity of several pairs of enzymes, including disulphide oxidoreductases, proteases, sugar-processing enzymes, and nucleases, as well as the specificity of hormones and their receptors. Mutations have been found that affect rate-determining steps, allowing normally transient intermediates to accumulate. Other mutations endow enzymes with totally new chemical reactions, and even novel biological functions. A combination of molecular genetics and chemical modification has been used for protein engineering.

Animals↗
PubMed1991

Quantitative structure-activity relationships for chemical toxicity to environmental bacteria.

Quantitative structure-activity relationships (QSARs) were developed for nonreactive chemical toxicity to each of four groups of bacteria of importance in environmental engineering: aerobic heterotrophs, methanogens, Nitrosomonas, and Microtox. The QSARs were based on chemicals covering a range of structures and including important environmental pollutants (i.e., chlorinated and other substituted benzenes, phenols, and aliphatic hydrocarbons). QSARs were developed for each chemical class and for combinations of chemical classes. Three QSAR methods (groups of chemical describing parameters) were evaluated for their accuracy and ease of use: log P, linear solvation energy relationships (LSER), and molecular connectivity. Successful QSARs were found for each group of bacteria and by each method, with correlation coefficients (adjusted r2) between 0.79 and 0.95. LSER QSARs incorporated the widest range of chemicals with the greatest accuracy. Log P and molecular connectivity QSARs are easier to use because their parameters are readily available. Outliers from the QSARs likely due to reactive toxicity included acryls, low pKa compounds, and aldehydes. Nitro compounds and chlorinated aliphatic hydrocarbons and alcohols showed enhanced toxicity to the methanogens only. Chemicals with low IC50 concentrations (log IC50 mumol/liter less than 1.5) were often outliers for Nitrosomonas. QSARs were validated statistically and with literature data. A suggested method is provided for use of the QSARs.

Bacteria↗
PubMed2003

Engineering of secondary metabolite pathways.

Nature produces an astonishing wealth of secondary metabolites with important biological functions. To access this diversity of structurally complex chemical compounds for industrial and biomedical applications, cells have been engineered to produce higher levels and/or novel compounds that were previously inaccessible. Recent examples of metabolic and combinatorial engineering illustrate different strategies for the production of secondary metabolites in microbial cells.

Biopolymers↗
PubMed2002

Solid acids for green chemistry.

Solid acids and especially those based on micelle-templated silicas and other mesoporous high surface area support materials are beginning to play a significant role in the greening of fine and specialty chemicals manufacturing processes. A wide range of important organic reactions can be efficiently catalyzed by these materials, which can be designed to provide different types of acidity as well as high degrees of reaction selectivity. The solid acids generally have high turnover numbers and can be easily separated from the organic components. The combination of this chemistry with innovative reaction engineering offers exciting opportunities for innovative green chemical manufacturing in the future.

Acids↗
PubMed2003

[Protein splicing and its application].

Protein splicing is a newly discovered posttranslational editing process that removes an internal protein fragment from the protein precursor. During the splicing process the internal protein fragment, intein, triggered the self-excision from the precursor protein and the concomitant ligation of the flanking protein fragments, exteins. The self-catalysis requires neither auxiliary enzymes nor cofactors and only involves four intramolecular reactions. A number of key catalytic residues in inteins and flanking fragments have been identified, which led to the development of the protein splicing process as a protein engineering tool. Controllable cleavage of the peptide bond at either the N or the C terminus of an intein has allowed the design of novel strategies for manipulation of protein and peptides. Affinity purification of recombinant proteins can be facilitated by fusion the target protein with an intein. The fusion also creates C-terminal thioester, which expands the scope of chemical ligation in protein. Inteins can be engineered in a "split and inverted" configuration to form a cyclic polypeptide consisting of the sequence linking two intein subdomains. This article summarizes the recent advance in the mechanism of protein splicing and its applications in protein purification, protein ligation and protein cyclization.

Inteins↗
PubMed2003

Cancer incidence among marine engineers, a population-based study (Iceland).

OBJECTIVES: Marine engineers are in their occupation exposed to different chemicals, organic solvents, exhaust gases, oils, and petroleum products, and were formerly exposed to asbestos. The aim was to study the cancer pattern, with particular attention to lung and bladder cancer, in an Icelandic cohort of marine engineers, indirectly controlling for their smoking habits. METHODS: A cohort of 6603 male marine engineers was followed up from 1955 to 1998, a total of 167,715 person-years. The cohort was record linked by the engineers' personal identification numbers to population-based registers containing the vital and emigration status and cancer diagnosis. Standardized incidence ratios (SIRs) were calculated for all cancers and different cancer sites in relation to different lag time and year of graduation. Information on smoking habits was obtained by administering a questionnaire to a sample of the cohort (n = 1,501). RESULTS: In the total cohort 810 cancers were observed, whereas 794 were expected (SIR 1.0, 95% CI 1.0-1.1), and significantly increased risk of stomach cancer (SIR 1.3, 95% CI 1.0-1.5) and lung cancer (SIR 1.2, 95% CI 1.0-1.5) was found. Increased risk of all cancers (SIR 1.2, 95% CI 1.1-1.3), stomach cancer (SIR 1.5, 95% CI 1.1-1.9), lung cancer (SIR 1.4, 95% CI 1.2-1.8), pleural mesothelioma (SIR 4.8, 95% CI 1.3-12.3), and urinary bladder cancer (SIR 1.3, 95% CI 1.0-1.8) were observed when a 40-year lag time was applied. The engineers' smoking habits were similar to those in a sample of the general population. The predictive value for lung cancer was 1.03. CONCLUSIONS: The increased risk for mesothelioma is possibly attributable to the previous asbestos exposure. The excess of lung cancer could also be related to asbestos exposure. The high incidence of stomach cancer, lung cancer, and bladder cancer may be related to exposure to chemical risk factors, such as oils and petroleum products, as confounding due to smoking seems to be ruled out. In the light of the limited exposure information in the present study the importance of the different occupational exposures needs to be evaluated in further studies.

Adult↗
PubMed2001

Structural determination of zinc dithiophosphates in lubricating oils by gas chromatography-mass spectrometry with electron impact and electron-capture negative ion chemical ionization.

Pentafluorobenzyl ester derivatives were used to identify zinc dialkyldithiophosphates and diaryldithiophosphates antiwear engine oil additives by GC-electron impact ionization (EI) MS and GC-electron-capture negative ion chemical ionization (ECNCI) MS analysis. GC-EI-MS of the dialkyldithiophosphate-pentafluorobenzyl derivatives afforded characteristic fragment ions corresponding to the cleavage of one and two alkyl radicals. In most cases, information was only obtained on one alkyl chain. Additional and complete information was obtained with retention time indices using synthetic derivatives and with GC-ECNCI-MS analysis. ECNCI afforded characteristic dithiophosphate anions which allowed the determination of the total number of carbon atoms in the alkyl radicals. The diastereoisomer mixtures of 2-hydroxy-sec.-alkyl radicals were completely separated on GC analysis.

Gas Chromatography-Mass Spectrometry↗
PubMed2002

Towards novel processes for the fine-chemical and pharmaceutical industries.

In response to the need in the pharmaceutical industry for more complex, chiral molecules, fine-chemical companies are embracing new manufacturing technologies to produce compounds of these specifications. In particular, recent developments in biocatalysis combined with novel process engineering are providing improved methods for the production of valuable chemical intermediates.

Catalysis↗