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G M Muschik

Publications and source records attributed to G M Muschik.

At least 37 records · Page 2Linked to original sources

Laser-induced fluorescence detection of 9-fluorenylmethyl chloroformate derivatized amino acids in capillary electrophoresis.

Laser-induced fluorescence (LIF) was applied to the detection of 9-fluorenylmethyl chloroformate (FMOC-Cl) derivatized amino acids separated by capillary electrophoresis. Fluorescence excitation was provided by a pulsed, KrF laser operating at 248 nm. A limit of detection of 5 x 10(-10) M was obtained for FMOC-alanine (S/N = 2). Separation of FMOC-derivatized proline, hydroxyproline, and sarcosine was achieved with a 20 mM borate buffer (pH 9.2), and the separation of FMOC-derivatized amino acid standard mixture was obtained using a 20 mM borate buffer (pH 9.2) containing 25 mM sodium dodecyl sulfate.

Amino Acids↗

Taxol: quantitative internuclear proton-proton distances in CDCl3 solution from nOe data: 2D nmr ROESY buildup rates at 500 MHz.

Quantitative nmr internuclear proton-proton distance measurements obtained by observation of the initial buildup rates of nOe's in 2D ROESY spectra of taxol [1] in CDCl3 are reported. A comparison to the X-ray crystal structure of taxotere [2] is made, and the results are discussed in terms of previous studies of structure-activity relationships.

Antineoplastic Agents, Phytogenic↗

Optimization of resolution in capillary zone electrophoresis: combined effect of applied voltage and buffer concentration.

Expressions are formulated for the prediction of solute migration time and resolution as a function applied voltage and buffer concentration in capillary zone electrophoresis. The resolution equation assumes that solute diffusion is the only operative zone-broadening mechanism. A resolution surface in applied voltage and buffer concentration space is presented featuring isochrones that are used to predict the behavior of resolution under constant analysis time. In the resolution-voltage planes the resolution increases continuously with increasing voltage. At the high-voltage border, the resolution decreases continuously with increasing concentration, however, at the low-voltage border the resolution passes through a shallow maximum as the buffer concentration is increased. At constant analysis time, resolution is optimized by simultaneously increasing the voltage and the buffer concentration. In comparison, this theoretical approach, which predicts resolution from solute migration times only, gives values that are consistently about 40-50% higher than experimentally determined resolution.

Acetates↗

Lung cancer and the debrisoquine metabolic phenotype.

In a case-control study, we tested the hypothesis that the genetically determined ability to metabolize debrisoquine is related to risk of lung cancer. Overall, individuals who were extensive metabolizers of debrisoquine were at significantly greater risk of lung cancer than those who were poor or intermediate metabolizers (odds ratio = 6.1; 95% confidence interval = 2.2-17.1). In this study, case patients had lung cancer, and control subjects had either chronic obstructive pulmonary disease or cancers other than lung cancer. Results were adjusted for age, race, asbestos exposure, and smoking. Both black and white individuals who were extensive metabolizers of debrisoquine were at significantly increased risk after similar adjustment (for blacks, odds ratio = 4.5, 95% confidence interval = 1.1-18.1; for whites, odds ratio = 10.2, 95% confidence interval = 2.0-51.4). Significantly increased risk of lung cancer was also present for individuals who were extensive metabolizers when subjects with chronic obstructive pulmonary disease or other cancers were considered separately. These data confirm that the ability to metabolize debrisoquine is a major determinant of susceptibility to lung cancer. Evaluation of the marker in other case-control settings, further exploration of racial differences, and the prospective evaluation of this marker in subgroups at high risk of lung cancer are areas worthy of further study.

Adenocarcinoma↗

Effect of alcohol chain length, concentration and polarity on separations in high-performance liquid chromatography using bonded cyclodextrin columns.

The effect of alcohol chain length, concentration and polarity on separation in high-performance liquid chromatography using beta-cyclodextrin-bonded silica is discussed. The results show that retention times cannot be predicted merely from the polarity of the binary mobile phase. Although organic modifiers with the same physico-chemical properties and from the same solvent group were used, the retention times obtained using binary mobile phases having the same polarity, were different. It was also observed that normal-chain carbon alcohols gave retention times shorter than those obtained with a branched-chain alcohol (n-propanol vs. isopropanol), and the longer the alcohol chain the shorter the retention times. A plot of ln k' vs. alcohol volume fraction for benzene, toluene, ethylbenzene, propylbenzene, butylbenzene, 1-phenylhexane and 1-phenyloctane gave a linear relationship in methanol, ethanol and propanol (except for 1-phenylhexane). A non-linear relationship was obtained for all the solutes in isopropanol, tert.-butanol and 1-butanol, in the alcohol volume fraction studied.

1-Propanol↗

The simultaneous use of solute vapor pressure and geometry in multidimensional capillary gas chromatographic separations of polychlorinated biphenyls.

The separation of coeluting congeners of Aroclor 1242, 1254, and 1260 on a DB-1 (low polarity) capillary gas chromatographic (GC) column is achieved when cuts of those peaks are transferred onto a smectic liquid crystalline column, which is commercially available. This procedure requires the use of a gas chromatograph equipped with two independent ovens for optimizing the temperature conditions of each column. Excellent base line separations are achieved on multicuts, up to six, of the same injection. This unique multidimensional/multimodal capillary GC system, in which the two separation modes of vapor pressure and molecule geometry are employed, is a powerful analytical technique for the separation of complex organic mixtures.

Chromatography, Gas↗

An NMR blood test for cancer: a critical assessment.

An evaluation of the reproducibility and accuracy of the NMR human blood test for cancer described by Fossel, E. T., Carr, J. M. and McDonagh, J., (New England Journal of Medicine 315, 1369-1376) in 1986 has been conducted jointly at the National Cancer Institute-Frederick Cancer Research Facility, Frederick, MD (NCI-FCRF) and the National Research Council, Ottawa, Canada (NRC). The influences on the test of the following were studied: (a) subject fasting; (b) sample collection, storage and handling; (c) use of plasma or serum; (d) variations of test results from the same individual with time; (e) NMR observation parameters including field strength and temperature; and (f) variations in obtaining the Fossel Index (FI) (a number defined by Fossel and co-workers as the average of the widths at half height of the regions in the NMR spectrum of human plasma at 1.3 and 0.88 ppm) by different people from the same plotted spectrum. This test was found to be reproducible but not accurate for screening a general asymptomatic population. The accuracy is defined in terms of the sensitivity, specificity, and predictive values of the test. The accuracy of the test results from our laboratories is compared with the accuracies from other laboratories including Fossel's. The correlation of the Fossel Index with total triglyceride content in the serum has been confirmed by analysing blood components using the following technologies: KBr density gradient centrifugation, high resolution agarose gel electrophoresis, high performance gel permeation chromatography, and chemical analysis.

Blood Chemical Analysis↗

Large-scale recovery and purification of L-asparaginase from Erwinia carotovora.

A large-scale process was developed to purify gram quantities of a therapeutic enzyme, L-asparaginase, from submerged cultures of Erwinia carotovora. Cells were harvested from 150 L of fermentation broth and washed. A cellular acetone powder was prepared and extracted with pH 9.5 borate buffer. After continuous centrifugation and filtration to remove cell debris, the acetone powder extract was adjusted to pH 7.7 and adsorbed onto a 16-L CM-Sepharose Fast Flow column, with a precolumn packed with Cell Debris Remover. The enzyme was desorbed from the catin-exchange column at pH 9.0 and further purified with an affinity column of L-asparagine Sepharose CL-4B. After dialysis-concentration to remove buffer salt, the enzyme was depyrogenated, formulated, sterile filled, and lyophilized as a single-dose final product. The final-product evaluation included analysis of the content of protein, sodium chloride, glycine, sodium, glucose hydrate, phosphate, and endotoxin, as well as reconstitution, potency, pH, specific activity, uniformity of fill, and sterility. The product was further subjected to visual examination, sodium dodecyl sulfate polyacrylamide gel electrophoresis, native gel electrophoresis, isoelectric focusing, amino acid analysis, N-terminal sequencing, peptide mapping, and immunological comparison.

Amino Acid Sequence↗

Separation of polychlorinated biphenyls (Aroclor 1254) by high-performance liquid chromatography.

The separation of Aroclor 1254 on various reversed-phase columns was investigated. The results show that the cyano- and phenyl-bonded columns performed poorly, but C18 bonded columns gave better results. It was also found that the absorption wavelength at which the effluent is monitored has great effect on the detection of these isomers. The optimum conditions for the separation and detection are: C18, 5 micron; reversed-phase column, 20 cm X 4.6 mm I.D.; acetonitrile-water (60-40); flow-rate 1.5 ml/min; detection at 210 nm or 205 nm.

Aroclors↗

Distribution of the liver carcinogen methapyrilene in Fischer rats and its interaction with macromolecules.

The anti-histaminic drug methapyrilene hydrochloride, which induces liver tumors in ras, was labeled with tritium by exchange and administered at a does of 21 mg containing 700 microCi to each of 15 male Fischer rats. At 1 h, 6 h, 14 h, 24 h, and 44 h after treatment three rats were killed and their livers, pancreas, kidneys, and lungs were removed. The pooled organs were homogenized and DNA, RNA, and soluble protein were isolated from each. The extent of interaction of radioactive methapyrilene with liver nucleic acids was exceedingly small and did not differ significantly from the binding to nucleic acids in kidney, lung, or pancreas, which are not target organs of this carcinogen in rats. Binding of radioactivity to soluble proteins of the liver was considerable and substantially greater than in the other organs. If the mechanism of carcinogenic action of methapyrilene involves covalent interaction with DNA this must be at a very low and highly specific level.

Aminopyridines↗

The identification of bile acid methyl esters by gas chromatography methane chemical ionization mass spectrometry.

Methane chemical ionization mass spectrometric data and gas chromatography retention parameters are reported for 31 bile acid methyl esters. The group includes both saturated and unsaturated compounds with up to three keto or hydroxyl groups. Major ions include the quasimolecular ions and fragments resulting from the loss of neutral species such as methanol, water and methane. The combination of gas-liquid chromatography retention and mass spectral data is sufficient for an unequivocal distinction among all the bile acids studied. Application of this data to the identification of bile acid metabolites is cited.

Bile Acids and Salts↗

The metabolic fate of cholesterol-5 alpha, 6 alpha-expoxide in vivo.

[14C] Cholesterol-5 alpha, 6 alpha-expoxide, administered to mice by either gastric intubation or skin painting, was rapidly and primarily excreted in the feces. Residual amonts of the epoxide and its metabolites were found in a wide variety of organs, and persisted for at least 72 hr. At some sites (principally the liver, the small intestinal contents and the combined stomach/duodenum and their contents), the labeled compound existed in a water-soluble form which could not be extracted with chloroform/methanol. Treatment of the small intestinal contents with a preparation of beta-glucuronidase/sulfatase produced a marked increase in the amount of organic-solvent-extractable cholesterol-alpha-epoxide and other polar metabolites. Unchanged epoxide was found mainly in the feces and the skin at the site of application. On the basis of these results, stool specimens, and not blood samples, should be analyzed to detect the presence of this compound and/or its metabolites in vivo.

Administration, Topical↗

The metabolism of lithocholic acid-3alpha-sulfate by human intestinal microflora.

Lithocholic acid-3alpha-sulfate is metabolized by human intestinal microflora to nonpolar metabolites which have been partially purified by Sephadex LH-20 chromatography. These metabolites were characterized by thin layer and gas liquid chromatography as well as combined gas liquid chromatography-mass spectrometry. The chromatographic properties of one of the metabolites are consistent with those described for a delta2- or delta3-cholenate. The formation of cholenates by the microflora may represent a retoxification of the sulfate ester of lithocholic acid.

Cholenes↗