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G Cornelius

Publications and source records attributed to G Cornelius.

10 recordsLinked to original sources

A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry.

A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s (CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2C19, CYP2A6, and CYP2C8) was developed. This method uses an in vitro cocktail of specific substrates (midazolam, bufuralol, diclofenac, ethoxyresorufin, S-mephenytoin, coumarin, and paclitaxel) and fast gradient liquid chromatography tandem mass spectrometry. The assay incubation time is 20 min, which is in the linear range for all of the substrates, and the analysis time is 4 min/sample. Substrate specificity was confirmed by incubating Escherichia coli-expressed enzymes with the cocktail. Potent specific inhibitors of the seven enzymes (ketoconazole, quinidine, sulfaphenazole, tranylcypromine, quercetin, furafylline, and 8-methoxypsoralen) were evaluated in cocktail and individual substrate incubations. Five of these inhibitors were further studied to determine more precise IC(50) values for inhibition of the seven enzymes. The IC(50) values obtained in both cocktail and individual incubations were in good agreement with published values. This cocktail method offers an efficient, robust way to determine the cytochrome P450 inhibition profile of large numbers of compounds. The enhanced throughput of this method greatly facilitates its use to assess CYP inhibition as a drug candidate selection criterion.

Chromatography, Liquid↗

Stress causes induction of MAP kinase-specific phosphatase and rapid repression of MAP kinase activity in Drosophila.

Heat shock and chemical stress induce activation of heat shock (stress) genes and synthesis of heat shock proteins. It is not yet fully understood which molecular mechanism leads to activation. Probably denatured proteins play an important role in activating the transcription factor (HSF), but on the other hand there are many hints that a phosphorylation event is involved, too. During a search for a possible signal transduction system in Drosophila Schneider 2 cells we analysed the response of the mitogen-activated protein (MAP) kinase after stress and its regulation by phosphatases. We show here that stress activates a MAP kinase-specific phosphatase in Drosophila and inhibits MAP kinase activity.

8-Bromo Cyclic Adenosine Monophosphate↗

The play behavior of hearing-impaired kindergarten children.

This exploratory study examined the cognitive and social play behaviors of hearing-impaired kindergarten children with regard to classroom instructional mode and communication strategies. Two classes were observed--one using sign communication and the other using an oral-based method of communication. Functional, constructive, dramatic, and social play behaviors were observed and documented. Statistically significant differences were found between the two groups of children with regard to social and dramatic play as well as with regard to levels of aggression. For example, children in the sign-based class demonstrated higher levels of social play behavior and lower levels of aggression than the children in the oral-based class. Guidelines and strategies to help children initiate and sustain play are suggested.

Child↗

Inositol trisphosphate induces calcium release from Neurospora crassa vacuoles.

Inositol 1,4,5-trisphosphate is known to release calcium ions from intracellular stores thought to be parts of endoplasmic reticulum in animal cells. In Neurospora crassa, however, inositol 1,4,5-trisphosphate acts on vacuoles stimulating a calcium efflux with a Km of 5.28 microM. The calcium release is inhibited effectively by dantrolene. These results were obtained by applying two independent methods, measuring calcium binding to fura-2 and loading vacuoles with 45Ca.

Benzofurans↗

Possible link between circadian rhythm and heat shock response in Neurospora crassa.

3-h pulses of elevated temperatures (30 degrees C, 35 degrees C, 40 degrees C) phase shift the circadian conidiation rhythm of Neurospora crassa. The phase and amplitude of the phase response curves (PRC) were measured in wild type (frq+) and frequency mutants (frq 1, frq 7). The dose dependence of the phase shifts was compared to the dose dependence of total protein synthesis inhibition and heat shock protein induction in the three strains. All processes showed an almost linear dependence on temperature. These experiments and other available data suggest that a temperature increase may act on the circadian rhythm by a process belonging to the heat shock response.

Circadian Rhythm↗

[Real-time sonography in the diagnosis of neck cysts].

The diagnostic possibility of high resolution real time sonography has been investigated in 31 patients with cysts in the neck. The method is of special value preoperatively by demonstrating neighbouring structures, such as the parotid and thyroid glands and the major vessels in the neck; it contributes to differential diagnosis and surgical planning. Lateral cysts, because of their contents, may be highly echogenic and may be difficult to distinguish from lymphomas. The differential diagnosis of various cysts in the neck is discussed. An important aspect of sonography of the neck is the experience of the operator and his detailed knowledge of the local anatomy.

Cysts↗