PubMed Health⌕ Search

Biomedical subjects

F Locher

Publications and source records attributed to F Locher.

11 recordsLinked to original sources

Evaluation of a new procedure for the flow cytometric analysis of in vitro, chemically induced micronuclei in V79 cells.

Measurement of the frequency of micronuclei induced in cells by ionizing radiation or by chemical treatment is widely used to analyze cytogenetic damage. The microscopic scoring of micronuclei is a tedious and time-consuming procedure. Therefore, attempts have been made to automate micronuclei scoring by means of image analysis or flow cytometry. A new procedure for the flow cytometric analysis of chemically induced micronuclei in V79 Chinese hamster cells has been established in our laboratory. Debris was separated from micronuclei by means of a new gating procedure using area and width fluorescence of the stained suspension of micronuclei and nuclei. In order to test the sensitivity and specificity of this improved method of flow cytometric analysis, five well-known mutagenic compounds were tested. With the new technique, the frequency of micronuclei measured and analyzed corresponded well with results obtained by conventional microscopy. In addition, a large series of negative compounds, and weak, middle, and strong micronuclei inducers, were tested in order to establish criteria for discrimination between genotoxic and nongenotoxic compounds by flow cytometry. This new procedure for flow cytometric detection of micronuclei represents a quick, reliable, and relatively simple method for in vitro micronucleus testing.

Animals↗

Comparative evaluation of the in vitro micronucleus test and the in vitro chromosome aberration test: industrial experience.

Because of its rapidness, simplicity and potential for automation, the measurement of micronucleated cells in vivo is not only equivalent to the analysis of chromosome aberrations, but often even preferred within routine genotoxicity testing. In order to evaluate the correlation between the in vitro micronucleus assay (MNT) and the in vitro chromosome aberration test (CA), we collected data from four pharmaceutical companies obtained either in Chinese hamster cell lines (CHO-K5, CHO-K1, V79) or in human peripheral blood lymphocytes. Among the 57 compounds included in this comparison, 45 compounds gave rise to concordant results in both assays (26 compounds negative in both assays; 19 compounds positive in both assays). The high percentage of concordance, i.e. about 79% is very promising and can be even increased to about 88% by omitting the 3 aneugenic compounds and 2 compounds inducing endoreduplicated chromosomes which were found positive only in the in vitro MNT. The results are remarkable in particular considering that most of the compounds evaluated are 'standard' pharmaceutical compounds and thus are at most weak inducers of chromosome damage. Our comparison strongly supports that the in vitro micronucleus test is a suitable alternative to the in vitro chromosome aberration assay. Moreover, the MNT has the potential of not only detecting clastogens but additionally aneuploidy inducing chemicals.

Animals↗

Evaluation of the in vivo genotoxic potential of three carcinogenic aromatic amines using the Big Blue transgenic mouse mutation assay.

Three genotoxic mouse carcinogens, 4-chloro-o-phenylenediamine (4-C-o-PDA), 2-nitro-p-phenylenediamine (2-N-p-PDA), and 2,4-diaminotoluene (2,4-DAT), were tested in the Big Blue transgenic mouse mutation assay. Each experiment consisted of a vehicle control group with ten Big Blue C57BL/6 mice, five of either sex, and an equally sized group treated with a high dose of the test chemical. In addition, four animals were treated with the vehicle and six animals with the test compound for the measurement of bromodeoxyuridine (BrdU) incorporation to determine cellular proliferation. Prior to the mutagenicity experiments, the maximally tolerated dose of each compound was determined using nontransgenic C57BL/6 mice. Based on these results the doses used in the main study were 200 mg/kg/day for 4-C-o-PDA, 150 mg/kg/ day for 2-N-p-PDA, and 80 mg/kg/day for 2,4-DAT. Animals were treated for 10 days over a 2 week period and were killed 10 days after the ast treatment. In an additional experiment with 2,4-DAT, animals were killed 28 days after treatment. Since all three chemicals are liver carcinogens in the mouse, the DNA of the liver was analyzed using the standard procedures for the Big Blue assay. Hepatocyte proliferation was assessed by immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and, in some studies, by measuring BrdU incorporation. 4-C-o-PDA and 2-N-p-PDA did not induce an increase in PCNA expression when measured 10 days after the last treatment. There was no increase in BrdU incorporation immediately after treatment with 4-C-o-PDA or with 2,4-DAT. However, 10 days after the last treatment with 2,4-DAT, a strong mitogenic effect was found with both techniques, i.e., in the PCNA and BrdU assays. 4-C-o-PDA, a liver carcinogen in both genders of mice, induced a small, statistically significant increase of the mutant frequencies in females. No increase was found in males. 2-N-p-PDA, which has been reported to induce liver tumors only in females, was found positive in males and was clearly negative in females. 2,4-DAT, a liver carcinogen in female mice, was positive in females and negative in males when the animals were killed 10 days after the last treatment. After an expression time of 28 days, 2,4-DAT induced a statistically significant increase in both sexes. The effect in females was marginally stronger than after 10 days' expression time and almost identical to the effect observed in males under these test conditions. In conclusion, the experiments showed that the Big Blue assay detects the genotoxicity of the three carcinogenic monocyclic aromatic amines tested. However, it seems that the sex specificity of the carcinogenic effects of these compounds is not reflected by the mutagenicity data in Big Blue mice.

Animals↗

Rapid detection and characterization of foot-and-mouth disease virus by restriction enzyme and nucleotide sequence analysis of PCR products.

Reverse transcription coupled with PCR was used for the detection of foot-and-mouth disease virus serotypes A, C, and O in organ extracts from experimentally infected cattle. Primers were selected from conserved sequences flanking the genome region coding for the major antigenic site of the capsid located in the C-terminal part of viral protein 1 (VP1). Because this region of the capsid is highly variable its coding sequence is considered to be the most appropriate for the characterization of virus isolates and, therefore, for the determination of the epidemiological relationships between viruses of the same serotype. For differentiation between serotypes and for detailed characterization of individual virus isolates restriction enzyme cleavage and nucleotide sequence analysis of the respective PCR products were carried out. In order to minimize the time required for sample preparation from clinical material, viral RNA was released from particles by heating the sample for 5 min at 90 degrees C. Finally, an air thermocycler was used, which allows performance of a PCR of 30 cycles in approximately 20 min. The results show that reverse transcription PCR followed by restriction enzyme analysis and/or nucleotide sequence analysis of the PCR products is useful for the rapid detection and differentiation of foot-and-mouth disease virus.

Animals↗

[Pacemakers].

Explore the source record for details and available documents.

Aftercare↗

Survey of European pharmaceutical journals in circulation in 1993.

Journals represent a very important source of information to pharmacists. This survey aimed to list current European pharmaceutical journals with their main characteristics. First, we provide a working definition of "European pharmaceutical journal". Then, the methodology and our sources which included books, databases, and questionnaires are reported. The following section details the results of the survey: journal creation for the period 1930 to 1993, geographic distribution, characteristics of the different types of journals (scientific, professional, scientific and professional/educational journals), inclusion in international bibliographic indexes. Finally, the list of the European pharmaceutical journals with their main characteristics and the list of the independent European pharmaceutical journals are reported in Appendix.

Europe↗

[CD-ROM and pharmacy: a new means of accessing information. I. Characteristics and analysis of CD-ROMs of interest to pharmacy].

CD-ROMs represent a new data medium which is not used enough by health professionals. This survey aimed to list current CD-ROMs useful in pharmacy field with their main characteristics. Thus, databases and directories from health information providers were consulted. A database was then made in order to exploit data collected as well as possible. The following section detailed the results of the survey: 205 CD-ROMs were selected, 95% are bibliographic or full-text data, 94% use English language, 84% present international information, 82% allow us previous years information retrieval, 65% are updated at least every three months, 97% work on PC computers, 74% are provided by american companies.

CD-ROM↗

[French language pharmaceutical publications in 1995. I. Assessment and analysis of French language pharmaceutical periodicals].

Periodicals constitute a vital source of information and an invaluable continuing education medium to pharmacists. The aim of the present study was to compile the list of the 83 pharmacy-related periodicals published in French as at 1995 with a view to establishing their main characteristics. The first part focuses on the definition of the concept of "French language pharmaceutical periodicals" selected for the survey needed a) to be in circulation in 1995 and published at least two times a year, b) published by pharmacists or non-pharmacists but must carry articles intended to help, inform, or retrain pharmacists irrespective of their specialties (community, hospital, biological or industrial pharmacy) as well as their closest collaborators (assistants, technicians, etc.) and c) published in French. The second section presents the methodology of the survey, which consisted essentially in consulting publisher and library catalogs and direct interviews with embassies and Pharmacy Associations in French-speaking countries. Questionnaires were also sent out to editors of periodicals and the information gathered was analysed by computer. The following section reproduces the results of the the survey: These were classified into three categories: scientific, professional, and continuing education periodicals. The last section concentrates on their readership (national, international), frequency, modalities of publication, date of creation, indexing in bibliographic databases.

Language↗