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Biomedical subjects

P Bigler

Publications and source records attributed to P Bigler.

11 recordsLinked to original sources
PubMed2001

HMSC: simultaneously detected heteronuclear shift correlation through multiple and single bonds.

A new 2D pulse sequence HMSC (heteronuclear multiple-bond and single-bond coupling connectivities) for the simultaneous detection of long-range and one-bond heteronuclear connectivities is proposed which allows the two types of responses to be separated and the corresponding (n)J(CH) and (1)J(CH) connectivity maps to be calculated. (n)J(CH) coherences are selectively labeled in the course of the pulse sequence, the correspondingly acquired data are separately stored, and a simple add/subtract procedure is applied to disentangle and edit (n)J(CH) and (1)J(CH) responses prior to final data processing. Unlike standard methods, which are designed to measure one single type of heteronuclear spin-spin interactions and to efficiently suppress the other, both (n)J(CH) and (1)J(CH) are measured simultaneously in a single experiment with the HMSC pulse sequence. Compared to the common strategy with two standard experiments applied one after the other, e.g., HMBC and HMQC, valuable measuring time may be saved with this single experiment approach. The efficiency of the new pulse sequence and the quality of the corresponding spectra are demonstrated using strychnine. Features such as sensitivity, lineshapes, and the suppression of (1)J(CH) residual peaks in the final (n)J(CH) subspectra are investigated and compared with the corresponding results obtained with standard methods. The attractive and unique single experiment approach, its high efficiency, and its easy experimental setup together with straightforward data processing make HMSC a valuable experimental alternative for the today's more time-consuming "two-step" practice and makes it suitable for standard routine applications.

Journal Article↗
PubMed2000

Analysis of nitro musk compounds and their amino metabolites in liquid sewage sludges using NMR and mass spectrometry.

A method using HRGC ion trap MS/MS for measuring simultaneously amino metabolites and the parent compounds, the nitro musks, an important group of organic fragrance components found in sewage sludges, was developed. The monoamino metabolites were synthesized and characterized by 1H/13C NMR and mass spectroscopy. Among the nitro musks, musk ketone was the major compound, found at an average concentration of 5 microg/kg of dry mass (dm) whereas musk xylene was detected in only one sample (30 microg/kg dm). Three amino metabolites were identified, namely, 1-tert-butyl-3,5-dimethyl-4-amino-2,6-dinitrobenzene, 1,1,3,3,5-pentamethyl-4-nitro-6-aminoindane, and 4-acetyl-1-tert-butyl-3,5-dimethyl-2-nitro-6-aminobenzene, the corresponding reduction products of the nitro musks xylene, moskene, and ketone. These metabolites were present in partly higher concentrations in the sludges than the corresponding nitro musk compounds. Musk xylene and musk moskene were mainly found as their monoamino metabolites, underlining the importance of anaerobic reduction processes in the sewage treatment plant.

Amino Acids↗
PubMed1999

Gene ste20 controls amiloride sensitivity and fertility in Schizosaccharomyces pombe.

It has been shown previously that amiloride, a widely used diuretic drug, inhibits growth in Schizosaccharomyces pombe. Here we show that the drug also alleviates repression by various nutrients of mating and sporulation in fission yeast. We selected spontaneous mutants that are amiloride-resistant and unable to mate and sporulate. One of them defines the gene ste20. This gene has been cloned and sequenced. It codes for a putative protein of 1309 amino acids. Its sequence does not provide any clues to its function. In contrast to the wild-type, mutants defective in this gene can grow in a medium containing 40 microm amiloride, do not arrest in G(1), and do not induce ste11 expression upon nitrogen starvation and thus are sterile. In addition the ste20 mutants are methylamine-sensitive, exhibit enhanced medium acidification and are defective in the utilization of gycerol as a carbon source.

Amiloride↗
PubMed1999

Efficacies of albendazole sulfoxide and albendazole sulfone against In vitro-cultivated Echinococcus multilocularis metacestodes.

The metacestode stage of Echinococcus multilocularis is the causative agent of alveolar echinococcosis (AE), a parasitic disease affecting the liver, with occasional metastasis into other organs. Benzimidazole carbamate derivatives such as mebendazole and albendazole are currently used for chemotherapeutic treatment of AE. Albendazole is poorly resorbed and is metabolically converted to its main metabolite albendazole sulfoxide, which is believed to be the active component, and further to albendazole sulfone. Chemotherapy with albendazole has been shown to have a parasitostatic rather than a parasitocidal effect; it is not effective in all cases, and the recurrence rate is rather high once chemotherapy is stopped. Thus, development of new means of chemotherapy of AE is needed. This could include modifications of benzimidazoles and elucidiation of the respective biological pathways. In this study we performed in vitro drug treatment of E. multilocularis metacestodes with albendazole sulfoxide and albendazole sulfone. High-performance liquid chromatography analysis of vesicle fluids showed that the drugs were taken up rapidly by the parasite. Transmission electron microscopic investigation of parasite tissues and nuclear magnetic resonance spectroscopy of vesicle fluids demonstrated that albendazole sulfoxide and albendazole sulfone had similar effects with respect to parasite ultrastructure and changes in metabolites in vesicle fluids. This study shows that the in vitro cultivation model presented here provides an ideal first-round test system for screening of antiparasite drugs.

Albendazole↗
PubMed1998

DEPTQ: distorsionless enhancement by polarization transfer including the detection of quaternary nuclei.

A pulse sequence DEPTQ yielding the signals and multiplicity information for all carbon types including the signals of quaternary carbons and encompassing all the known advantages of the basic DEPT experiment is proposed. Its behavior has been studied theoretically and experimentally and has been compared critically with alternative methods dedicated for the same purpose. Its marked insensitivity to experimental parameters and its potential for complete and efficient spectral editing makes DEPTQ the ideal experimental platform for a semi- or fully automated analysis of 1D 13C spectra.

Magnetic Resonance Spectroscopy↗
PubMed1993

A proton magnetic resonance study of two synthetic agonist-antagonist pairs of bradykinin analogues.

The conformation of two agonist-antagonist pairs of bradykinin (Arg1-Pro2-Pro2-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) analogues were studied in CD3OH/H2O solution by 1H-nmr techniques. The first agonist peptide studied, D-Arg0-Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6-Pro7- Thi8-Arg9, differs from the bradykinin sequence by the addition of D-Arg0, the replacement of the Phe moieties in positions 5 and 8 by Thi (Thi = beta-(2-thienyl)-L-alanine), and Hyp3 (Hyp = L-4-hydroxy-L-proline) in position 3. In the corresponding antagonist sequence, Pro7 is replaced by D-Phe7. The second agonist-antagonist pair studied does not contain the D-Arg0 residue, which is present only to slow down the rate of metabolism. Based on complete resonance assignments from two-dimensional total correlation spectroscopy and rotating frame nuclear Overhauser effect spectroscopy spectra at 500 MHz, the peptides were analyzed in terms of intraresidue, sequential, and medium-range nuclear Overhauser effects, amide proton temperature coefficients, and vicinal coupling constants. Both agonist peptides show clear evidence for the existence of a type I beta-turn comprising the C-terminal residues Ser6-Pro7-Thi8-Arg9 in fast conformational equilibrium with extended structures throughout. Although the conformational space is dominated by extended structures, the presence of the beta-turn is spectroscopically clearly discernible. The two antagonist peptides, on the other hand, do not show evidence of turn formation but rather the presence of an extended conformation with some irregularities in the N-terminal region of the peptide. While the existence of a turn at the C-terminal end of bradykinin and its analogues with agonist activity has been predicted by empirical calculations and measurements in very apolar solvents, this study, for the first time, provides evidence based on physical data in a polar solvent environment that the turn is present, that it is type I and that it is essential for agonist activity. In the particular solvent used in these studies, the Pro7 to D-Phe7 substitution precluded the formation of the turn for the C-terminal residues of the antagonist.

Amino Acid Sequence↗
PubMed1993

A rare complication of the use of a finger cot to protect the cuff of a tracheal tube during nasotracheal intubation.

Some anesthetists in Switzerland and elsewhere use a finger cot to protect the cuff of the endotracheal tube during nasotracheal intubation. In the presented report the finger cut was lost during the procedure and the patient presented 3 months later with a lateral neck mass. The finger cot was found within that mass at exploration. Apart from the other potential risks of this manoeuvre, this severe complication should incite caution against the practice described above.

Aged↗
PubMed1990

Brain development: 1H magnetic resonance spectroscopy of rat brain extracts compared with chromatographic methods.

We compared in vitro 1H magnetic resonance spectroscopy (MRS) measurements of rat brain extracts (rats: 2-56 days old) with chromatographic measurements and in a further step also with results of in vitro MRS. The following substances can be reliably measured in brain extracts by in vitro MRS: N-acetylaspartate (NAA), total creatine (Cr), phosphorylethanoloamine (PE), taurine (Tau), glutamate (Glu), glutamine (Gln), gamma-aminobutyrate (GABA) and alanine (Ala). Two different methods of MRS data evaluation compared with chromatographic data on Cr and NAA are shown. During development of the rat from day 2-56 brain concentrations of PE, Tau and Ala decrease, those of NAA, Cr, Glu and Gln increase, while GABA does not change. The developmental patterns of these substances are the same, whether measured by in vitro MRS or by chromatographic methods. Quantification of NAA, Cr, Tau, GABA and PE leads to the same results with both methods, while Glu, Gln and Ala concentrations determined by in vitro MRS are apparently lower than those measured chemically. The NAA/Cr ratios of 7 to 35-day-old rats were determined by in vivo 1H MRS. These results correlate with chromatographic and in vitro data. Using appropriate methods in the in vivo and in vitro MR-technique, the obtained data compare well with the chromatographic results.

Aging↗
PubMed1988

Correlation between 31P NMR phosphomonoester and biochemically determined phosphorylethanolamine and phosphatidylethanolamine during development of the rat brain.

Phosphomonoesters were measured in the developing rat brain by in vivo and in vitro 31P nuclear magnetic resonance (NMR) spectroscopy and by classical biochemical methods. In vitro NMR showed that the main component of the phosphomonoester peak is phosphorylethanolamine. Phosphomonoesters measured by in vivo NMR decreased during development at the same rate as the biochemically estimated phosphorylethanolamine. Phosphorylethanolamine, a precursor of the membrane lipid phosphatidylethanolamine, decreased during development parallel to an increase of the lipid phosphatidylethanolamine, which was measured biochemically. These studies show that 31P NMR can be used to monitor brain development in vivo.

Aging↗
PubMedDate not supplied

Identification of mephenytoin metabolites in the dog.

In two dogs p-hydroxymephenytoin, m-hydroxymephenytoin, 5-ethyl-5-phenylhydantoin (nirvanol), and 5-ethyl-5-(p-hydroxyphenyl)hydantoin (p-hydroxynirvanol) were identified by use of synthetic metabolites as standards for comparison.

Animals↗