Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complex Mixtures”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1988

The Urtica dioica Agglutinin Is a Complex Mixture of Isolectins.

Rhizomes of stinging nettle (Urtica dioica) contain a complex mixture of isolectins. Ion exchange chromatography with a high resolution fast protein liquid chromatography system revealed six isoforms which exhibit identical agglutination properties and carbohydrate-binding specificity and in addition have the same molecular structure and virtually identical biochemical properties. However, since the U. dioica agglutinin isolectins differ definitely with respect to their amino acid composition, it is likely that at least some of them are different polypeptides coded for by different genes.

Journal Article↗
PubMed1990

Analytical tools and biomonitoring for carcinogens in complex mixtures.

Two approaches are described for the analysis and biomonitoring of complex mixtures: (a) activity-guided fractionation of pyrolysed opium followed by spectroscopic determination of molecular structure and (b) trapping of possibly genotoxic metabolites by a series of microencapsulated, recoverable, synthetic macromolecular targets within the milieu of the gastrointestinal tract. Opium pyrolysis was shown to produce (principally from morphine) a series of hydroxyphenanthrenes of novel structure having activity not only in the S. typhimurium used as a guide, but also in a variety of in vitro and in vivo test systems. Many analytical tools were used together for separation, structure determination and activity monitoring, and their relative merits and overall strategy are discussed. The microcapsules have been shown to trap carcinogens, nitrosating agents, cross-linking agents and aldehydes. Their trapping of a model carcinogen in vivo is modulated by components of human diets. Development of these microcapsules for detecting endogenous carcinogens and their sources is discussed with reference to the type of target and analytical tools that may be appropriate.

Carcinogens, Environmental↗
PubMed1995

High-resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical identification of the 2X and embryonic myosin heavy chains in complex mixtures of isomyosins.

In mammals myosin heavy chains (MHC) are polypeptides with a molecular mass of about 200 kDa whose isoforms can be identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunochemistry. Electrophoretic analysis is the only method for quantitating MHC profiles in single myofibers and/or cryostat sections of biopsied muscle. We present a method for SDS-PAGE of adult rat skeletal muscle which resolves MHC into four bands: 1, 2B, 2X, and 2A from the faster to the slower migrating band. Furthermore, embryonic MHC can be also resolved in a complex mixture of isomyosins, e.g. developing or regenerating muscles. The method does not involve preparation of gradient gels or electrophoresis at low temperature. Improved reproducibility is obtained by: (i) modification of the sample buffer; (ii) use of 7% polyacrylamide in the separating gel; (iii) control of pH of running buffer by recirculation or change of the buffer during the run; and (iv) a 24 h run. The procedure is compatible with Coomassie Brilliant Blue, silver and immunoblot staining. Resolution is sufficient to permit transblotting of separated MHC after SDS-PAGE. The different isoforms are easily identified with monoclonal antibodies. The technique provides an improved method to separate MHC and quantitate MHC2X and MHCemb in complex mixtures of MHC from a few cryostat sections of normal and diseased muscle.

Animals↗
PubMed1989

Complex mixture effects on the dermal absorption of benzo[a]pyrene and other polycyclic aromatic hydrocarbons from mouse skin.

To study the dermal penetration of benzo[a]pyrene (BAP) in relation to other polycyclic aromatic hydrocarbons (PAHs), a complex mixture of PAHs was applied to the backs of CD-1 mice, and the dermal residence times of BAP and eleven other PAHs were determined using gas chromatography. The dermal penetration of BAP was found to be representative of the other PAHs studied, with a dermal half-life of 6.7 h. Half-lives of the other eleven PAHs ranged from 5.0 to 8.8 h. The dermal half-life of BAP applied in a volatile organic solvent, rather than a PAH mixture, was 3.0 h. The effects of five complex organic mixtures, with boiling points ranging from 300-700 degrees F to greater than 850 degrees F, on the dermal residence time of BAP was studied by adding radiolabeled BAP to the mixtures, and applying them to the backs of mice. All of the mixtures studied increased the dermal residence time of BAP by amounts ranging from 1.8-fold to 6.9-fold.

Animals↗
PubMed2002

Thyroid toxicity due to subchronic exposure to a complex mixture of 16 organochlorines, lead, and cadmium.

The human population in the industrialized world is ubiquitously exposed to complex mixtures of persistent pollutants that contaminate food, water, and air. A large number of these contaminants have been shown to cause significant toxicity to the hypothalamic-pituitary-thyroid (HPT) axis in laboratory animal studies, through a variety of mechanisms, although these effects occur at levels of exposure greatly in excess of common human exposure. While many of the mechanisms of thyroid toxicity of these substances are potentially complementary, little is known of the degree of interaction of common persistent contaminants on responses of the HPT axis. To investigate the potential effects of a complex, environmentally relevant mixture on the HPT axis, sexually mature male rats were administered a mixture of 16 common organochlorines (dichlorodiphenoxytrichloroethane [DDT], p,p'-dichlorodiphenoxydichloroethylene [p,p'-DDE], hexachlorobenzene [HCB], tetrachlorodibenzo-p-dioxin [TCDD], polychlorinated biphenyls [PCBs], methoxychlor, endosulfan, heptachlor, hexachlorocyclohexane, dieldrin, aldrin, mirex, and several chlorinated benzenes, and metal contaminants [lead, cadmium]). The doses of the mixture that were administered were related to minimum risk levels or tolerable daily intakes of these substances, as derived by risk assessment with the 1x, 10x, 100x, and 1000x groups receiving mixture components at doses equivalent to 1x, 10x, 100x, or 1000x the minimum risk level (or tolerable daily intake, reference dose), respectively. After 70 daily treatments by gavage, endpoints related to circulating thyroid hormone (serum thyroxine [T(4)], triiodothyronine [T(3)], thyroid stimulating hormone [TSH], and serum T(3) uptake [T(3)-up]), thyroid gland histomorphology (thyroid follicle cross sectional area, epithelial height, follicle roundness or aspect ratio, colloid/epithelial ratio) and hepatic metabolism of thyroid hormone (UDP-glucuronyl transferase [UGT] and outer-ring deiodinase [ORD]) were assessed. All examined endpoints were significantly altered by the mixture albeit with great variability between endpoints in the sensitivity. While most endpoints examined did not show significant changes at mixture doses below 1000x, 2 endpoints, TSH and hepatic outer ring deiodinase activity, were significantly increased and decreased, respectively, by 1x dose and showed dose-related increases in severity with increasing dose. Median thyroid follicle cross sectional area was also increased by the lowest dose of the mixture but decreased with subsequent increases in dose until, at the highest dose, this parameter was significantly reduced relative to control. The relative sensitivity of endpoints of thyroid function in detecting toxicity of the mixture was TSH = ORD = median follicle area >> T(3) > all other endpoints. These results demonstrate that low doses of ubiquitous environmental contaminants can alter HPT physiology in sexually mature males.

Animals↗
PubMed2006

Mass measurement accuracy in analyses of highly complex mixtures based upon multidimensional recalibration.

Mass spectrometry combined with a range of on-line separation techniques has become a powerful tool for characterization of complex mixtures, including protein digests in proteomics studies. Accurate mass measurements can be compromised due to variations that occur in the course of an on-line separation, e.g., due to excessive space charge in an ion trap, temperature changes, or other sources of instrument "drift". We have developed a multidimensional recalibration approach that utilizes existing information on the likely mixture composition, taking into account variable conditions of mass measurements, and that corrects the mass calibration for sets of individual peaks binned by, for example, the total ion count for the mass spectrum, the individual peak abundance, m/z value, and liquid chromatography separation time. The multidimensional recalibration approach uses a statistical matching of measured masses in such measurements, often exceeding 105, to a significant number of putative known species likely to be present in the mixture (i.e., having known accurate masses), to identify a subset of the detected species that serve as effective calibrants. The recalibration procedure involves optimization of the mass accuracy distribution (histogram), to provide a more confident distinction between true and false identifications. We report the mass accuracy improvement obtained for data acquired using a TOF and several FTICR mass spectrometers. We show that the multidimensional recalibration better compensates for systematic mass measurement errors and also significantly reduces the mass error spread: i.e., both the accuracy and precision of mass measurements are improved. The mass measurement improvement is found to be virtually independent of the initial instrument calibration, allowing, for example, less frequent calibration. We show that this recalibration can provide sub-ppm mass measurement accuracy for measurements of a complex fungal proteome tryptic digest and provide improved confidence or numbers of peptide identifications.

Calibration↗
PubMed2007

Modeling self-assembly and phase behavior in complex mixtures.

Using a variety of computational techniques, I investigate how the self-assembly of complex mixtures can be guided by surfaces or external stimuli to form spatially regular or temporally periodic patterns. Focusing on mixtures in confined geometries, I examine how thermodynamic and hydrodynamic effects can be exploited to create regular arrays of nanowires or monodisperse, particle-filled droplets. I also show that an applied light source and chemical reaction can be harnessed to create hierarchically ordered patterns in ternary, phase-separating mixtures. Finally, I consider the combined effects of confining walls and a chemical reaction to demonstrate that a swollen polymer gel can be driven to form dynamically periodic structures. In addition to illustrating the effectiveness of external factors in directing the self-organization of multicomponent mixtures, the selected examples illustrate how coarse-grained models can be used to capture both the equilibrium phase behavior and the dynamics of these complex systems.

Journal Article↗
PubMed2001

Effects of subchronic exposure to complex mixtures of dioxin-like and non-dioxin-like polyhalogenated aromatic compounds on thyroid hormone and vitamin A levels in female Sprague-Dawley rats.

The aim of this study was to determine the effects of subchronic exposure to complex mixtures of polyhalogenated aromatic hydrocarbons (PHAHs) on the thyroid hormone and retinoid status in female Sprague-Dawley rats and to investigate the predictability of these effects by the toxic equivalency factor (TEF) concept. In the first experiment, the focus was on a complex dioxin-like PHAH mixture, which covered > 90% of the total toxic equivalents (TEQ) present in Baltic herring. In the second experiment, the contribution of non-dioxin-like polychlorinated biphenyls (PCBs) was investigated by testing the commercial PCB mixture Aroclor 1260, its 0-1 ortho and 2-4 ortho fractions and the reconstituted 0-4 ortho fraction. Hepatic retinoid levels were severely decreased ( approximately 70%) after treatment with the dioxin-like PHAH mixture, similar to the effect of a TEQ equivalent dose of 1 microg 2,3,7,8-TCDD/kg bw/week. However, the TEF concept failed to predict the effect on plasma retinol; a decrease (21%) was observed after treatment with the PHAH mixture, whereas an increase (21%) was found after treatment with TCDD. A more severe decrease of total thyroid hormone in plasma was observed after exposure to the PHAH mixture compared to treatment with TCDD ( approximately 60% vs. 38%). The discrepancy found between the predicted and observed effects for plasma retinol and thyroid hormone is possibly due to an additional effect of hydroxylated PCBs, formed from metabolizable PCBs present in the PHAH mixture. Aroclor 1260 and its fractions did not significantly alter the retinoid and thyroid hormone status at the dose levels tested, indicating that in case of exposure to complex PCB mixtures at environmental levels, no effects, or at best, only marginal effects can be expected on the retinoid and thyroid hormone status.

Animals↗
PubMed2004

Determining the relative amounts of positional isomers in complex mixtures of triglycerides using reversed-phase high-performance liquid chromatography-tandem mass spectrometry.

A reversed-phase HPLC-tandem mass spectrometry (RP-HPLC-MS-MS) method was refined for the positional analysis of complex mixtures of TAG. This method has the advantages of speed, ease of automation, and specificity over traditional digestion-based methods for the positional analysis of TAG. Collision-induced dissociation (CID) of ammoniated TAG in an ion-trap mass spectrometer produced spectra that were dependent on the FA position. Dominant DAG fragments were formed from the loss of a FA moiety from the ammoniated TAG species. The loss of FA in the outer positions was favored over their loss in the central position. The combination of RP-HPLC and CID produced spectra that were free of the isotope effects that can complicate spectral interpretation in existing methods. The combination also provided selectivity based on the chromatographic fractionation of TAG, in addition to the selectivity inherent in the CID process. Proof-of-concept experiments were performed with binary mixtures of TAG from the SOS/SSO, OSO/OOS, and the PSO/POS/SPO positional isomer systems (where S is 18:0, stearic acid; O is 18:1 (cis-9), oleic acid; and P is 16:0, palmitic acid). Plots of fractional DAG fragment intensities vs. fractional composition of the binary mixtures were linear. These plots were used to determine the fractional composition of each of these isomeric systems in a variety of vegetable oils and animal fats. Current limitations, future developments, and applications of this method are discussed.

Chromatography, High Pressure Liquid↗
PubMed1994

Mutation spectra in Salmonella of complex mixtures: comparison of urban air to benzo[a]pyrene.

We used an ion-exchange procedure coupled to the Salmonella assay to fractionate the dichloromethane-extractable particulate organics from an urban air sample collected in Boise, Idaho. A resulting base/neutral fraction contained 81% of the mutagenic activity but only 36% of the mass of the unfractionated sample. Chemical analysis showed that polycyclic aromatic hydrocarbons (PAHs) accounted for much of the mutagenic activity of the air sample. Colony probe hybridization, PCR, and DNA sequence analysis were then used to determine the mutations induced by the complex mixtures and a model PAH, benzo[a]pyrene (BAP) in approximately 900 revertants of the frameshift hisD3052 allele and approximately 400 revertants of the base-substitution hisG46 allele. The majority (93-94%) of the mutations induced at the frameshift allele in strain TA98 by the whole or base/neutral fraction of the urban air sample was a hotspot 2-base deletion of a CG or GC within the sequence CGCGCGCG. The remaining mutations were complex frameshifts that consisted of -2 or +1 frameshifts associated with a flanking base substitution. BAP induced a somewhat similar pattern of mutations, with 70% being the hotspot mutation, 23% being complex frameshifts, and the remaining being deletions. The inferred base-substitution specificity associated with the complex frameshifts at the hisD3052 allele (primarily G.C-->T.A transversions) was consistent with the observation that this same transversion was the primary mutation induced by the whole urban air sample and BAP at the base-substitution allele in strain TA100. At the frameshift allele, adducts that promote correct incorporation/slippage could account for hotspot mutations, whereas those that promote misincorporation/slippage could account for complex frameshifts. At the base-substitution allele, a mixture of adducts or of adducts with multiple conformations could account for the observed proportion of transitions and transversions. Combined with the bioassay-directed chemical analysis, these results from the first mutation spectra of a complex mixture suggest that such spectra reflect the dominance of particular classes of chemical mutagens within the mixture.

Air Pollutants↗
PubMed1984

Computerised gas chromatographic-mass spectrometric analysis of complex mixtures of alkyl porphyrins.

Computerised capillary gas chromatography-mass spectrometry (GC-MS) analysis of complex mixtures of alkyl porphyrins, as their bis-(trimethylsiloxy)silicon(IV) and bis(tert.-butyldimethylsiloxy)silicon(IV) derivatives, is described. The latter derivative is more suitable for routine GC-MS analysis. This computerised GC-MS approach, when applied to the alkyl porphyrins of two geological samples, a bitumen (Gilsonite, Eocene age, UT, U.S.A.) and a crude oil (Boscan, Cretaceous age, West Venezuela), has revealed the highly complex compositions of these fractions. Computer-aided data processing, using relative retention index (RRI) calculations, facilitated the classification of the chromatographic peaks according to structural type and membership of pseudo-homologous series. Computerised GC-MS is compared with, and contrasted to high-performance liquid chromatography as a means of petroporphyrin analysis.

Chemistry Techniques, Analytical↗
PubMed2002

Development of a research strategy for integrated technology-based toxicological and chemical evaluation of complex mixtures of drinking water disinfection byproducts.

Chemical disinfection of water is a major public health triumph of the 20th century. Dramatic decreases in both morbidity and mortality of waterborne diseases are a direct result of water disinfection. With these important public health benefits comes low-level, chronic exposure to a very large number of disinfection byproducts (DBPs), chemicals formed through reaction of the chemical disinfectant with naturally occurring inorganic and organic material in the source water. This article provides an overview of joint research planning by scientists residing within the various organizations of the U.S. Environmental Protection Agency Office of Research and Development. The purpose is to address concerns related to potential health effects from exposure to DBPs that cannot be addressed directly from toxicological studies of individual DBPs or simple DBP mixtures. Two factors motivate the need for such an investigation of complex mixtures of DBPs: a) a significant amount of the material that makes up the total organic halide and total organic carbon portions of the DBPs has not been identified; and b) epidemiologic data, although not conclusive, are suggestive of potential developmental, reproductive, or carcinogenic health effects in humans exposed to DBPs. The plan is being developed and the experiments necessary to determine the feasibility of its implementation are being conducted by scientists from the National Health and Environmental Effects Research Laboratory, the National Risk Management Research Laboratory, the National Exposure Research Laboratory, and the National Center for Environmental Assessment.

Chemistry Techniques, Analytical↗
PubMed2002

On-Line HPLC-UV-mass spectrometry and tandem mass spectrometry for the rapid delineation and characterization of differences in complex mixtures: a case study using toxic oil variants.

An integrated differential approach to the characterization of complex mixtures is presented which includes the targeting of liquid chromatography (LC) peaks for identification using characteristic UV adsorption of the LC peak, subsequent molecular weight and formula determination using accurate mass LC mass spectrometry (MS), and structure characterization using accurate mass LC-tandem mass spectrometry. The use of differential UV adsorption aids in narrowing the scope of the study to only specific peaks of interest. Accurate mass measurement of the molecular ion species provides molecular weight information as well as atomic composition information. The tandem MS (MS/MS) spectra provide fragmentation information which allows for structural characterization of each component. Accurate mass assignment of each of the fragment ions in the MS/MS spectrum provides atomic composition for each of the fragment ions and thus further aids in the structural characterization. These experiments are facilitated through the use of on-line LC-MS and LC-MS/MS with in-line UV detection. A synthetic toxic oil (STO) related to Toxic Oil Syndrome is studied with a focus on possible contaminants resulting from the interaction of aniline, used as a denaturant, with the normal components of the oil. A differential analysis between the STO and a control oil is performed. LC peaks were targeted using UV absorbance to indicate the possible presence of the aniline moiety. Further differential analysis was performed through the determination of the MS signals associated with each component separated on the LC. Finally, the MS/MS data was also used to determine if the fragmentation of the targeted components indicated the presence of aniline. The MS/MS and accurate mass data were used to assign the structures for the targeted components.

Chromatography, High Pressure Liquid↗
PubMed2000

Optimization of the high-performance liquid chromatographic separation of a complex mixture containing urinary steroids, boldenone and bolasterone: application to urine samples.

An HPLC separation of a complex mixture containing 13 urinary anabolics and corticoids, and boldenone and bolasterone (synthetic anabolics) has been carried out. The applied optimization method involved the use of binary, ternary and quaternary mobile phases containing acetonitrile, methanol or tetrahydrofuran as organic modifiers. The effect of different reversed-phase packings and temperature on the separation was studied. The optimum separation was achieved by using a water-acetonitrile (60:40, v/v) mobile phase in reversed-phase HPLC at 30 degrees C, allowing the separation of all the analytes in about 24 min. Calibration graphs were obtained using bolasterone or methyltestosterone as internal standards. Detection limits were in the range 0.012-0.107 microg ml(-1). The optimized separation was applied to the analysis, after liquid-liquid extraction, of human urine samples spiked with steroids.

Adrenal Cortex Hormones↗
PubMed1988

[Toxicologic evaluation of individual chemical compounds and complex mixtures using a motile cell test object].

The possibility of quantitative prognosis of chemical compounds and complex mixtures toxicity by means of a biotechnical system with suspension of bull spermatozoa sensor was investigated. The concentration of some chemical compounds, inhibiting by half spermatozoa motility has been experimentally determined. A correlation between the values determined and acute toxicity of the compounds tested has been established. The possible use of the biotechnical system for the screening of medical polymer materials has been demonstrated.

Animals↗
PubMed2004

A homodecoupled diffusion experiment for the analysis of complex mixtures by NMR.

Diffusion ordered spectroscopy (DOSY) relies on differences in translation diffusion as a means to separate components in a solution mixture. However, the analysis of spectra of mixtures can be problematic because spectral overlap. It is the aim of this article to propose a pulse sequence and processing method that leads to a complete 2D homodecoupled-DOSY experiment. This experiment offers several advantages that could extend the range of applications to more complex mixtures by achieving important improvements in both signal dispersion and sensitivity.

Benzazepines↗
PubMed2004

Toxicity characterization of complex mixtures using biological and chemical analysis in preparation for assessment of mixture similarity.

In the United States, several proposed approaches for using bioassays for the risk assessment of complex hazardous mixtures require that selected mixtures be "sufficiently similar" to each other. The goal of this research was to evaluate the utility of a protocol using in vitro bioassays and chemical analysis as a basis for assessing mixture similarity. Two wood preserving wastes (WPWs) containing polycyclic aromatic hydrocarbons and pentachlorophenol were extracted and fractionated to generate potentially similar mixtures. Chemical analysis was conducted using gas chromatography/mass spectrometry. Genotoxicity was evaluated using the Salmonella/microsome and Escherichia coli prophage induction assays. The crude extract of one WPW was also tested in the chick embryotoxicity screening test (CHEST) assay. The CHEST assay provided the most sensitive measurement of toxicity. Overall, the biological potency of the samples was not well correlated with predicted potency based on chemical analysis. Although several mixtures appeared similar based on chemical analysis, the magnitude of the response in bioassays was often dissimilar. Fractionation was required to detect the genotoxicity of mixture components in vitro. The results confirm the need for an integrated protocol, combining chemical analysis, fractionation, and biological testing to characterize the risk associated with complex mixtures.

Biological Assay↗
PubMed1985

Influence of cell proliferation on initiating activity of pure polychlorinated biphenyls and complex mixtures in resistant hepatocyte in vivo assays for carcinogenicity.

The abilities of various pure polychlorinated biphenyls (PCB) and complex mixtures to generate resistant gamma-glutamyltransferase (GGT)-positive hepatocellular nodules was evaluated in F344 rats in which hepatocytes were proliferating. The PCB examined were 2,2',4,4',5,5'-hexachlorobiphenyl (CAS: 35065-27-1), 2,2',4,4'-tetrachlorobiphenyl, 2,2',5,5'-tetrachlorobiphenyl, Aroclor 1254 (CAS: 11097-69-1), and a prepared mixture of pure PCB isomers and congeners similar to those found in human breast milk. The PCB were administered either to male and female suckling rats (weekly for 3 wk) during liver growth or to adult male rats (150-160 g body wt) previously subjected to two-thirds partial hepatectomy (PH). Rats were subsequently given a selection regimen consisting of 3 daily doses (20 mg/kg) of 2-acetylamino-fluorene (2-FAA; CAS: 53-96-3) followed by either PH or necrotizing carbon tetrachloride (CAS: 56-23-5) in adult rats that previously underwent PH. None of the PCB exposures generated GGT-positive nodules after selection, whereas known initiators such as diethylnitrosamine (CAS: 55-18-5), 3-methylcholanthrene (CAS: 56-49-5), benzo[a]pyrene (CAS: 50-32-8), and 2-FAA were active initiators of nodules in suckling or hepatectomized rats. These findings indicate that short-term exposures to these PCB during liver cell proliferation do not show initiating action in an in vivo assay that detects both hepatic and nonhepatic initiating carcinogens.

Animals↗