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C Ramel

Publications and source records attributed to C Ramel.

At least 19 recordsLinked to original sources
PubMed2006

Small supernumerary marker chromosomes--progress towards a genotype-phenotype correlation.

Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they are too small to be characterized for their chromosomal origin by traditional banding techniques, but require molecular cytogenetic techniques for their identification. Apart from the correlation of about one third of the sSMC cases with a specific clinical picture, i.e. the i(18p), der(22), i(12p) (Pallister Killian syndrome) and inv dup(22) (cat-eye) syndromes, most of the remaining sSMC have not yet been correlated with clinical syndromes. Recently, we reviewed the available >1600 sSMC cases (Liehr T, sSMC homepage: http://mti-n.mti.uni-jena.de/~huwww/MOL_ZYTO/sSMC.htm). A total of 387 cases (including the 45 new cases reported here) have been molecularly cytogenetically characterized with regard to their chromosomal origin, the presence of euchromatin, heterochromatin and satellite material. Based on analysis of these cases we present the first draft of a basic genotype-phenotype correlation for sSMC for all human chromosomes apart from the chromosomes Y, 10, 11 and 13.

Adolescent↗
PubMed2001

Analysis of sporadic neuroendocrine tumours of the enteropancreatic system by comparative genomic hybridisation.

BACKGROUND: Chromosomal instability is observed in a wide spectrum of human cancer syndromes. However, to date, little is known of the characteristic genetic changes in sporadic neuroendocrine tumours of the gastroenteropancreatic system. AIMS AND METHOD: We have studied copy number aberrations (CNAs) in 26 sporadic neuroendocrine tumours of the enteropancreatic system (12 foregut and 14 midgut tumours) by comparative genomic hybridisation (CGH), allowing simultaneous evaluation of the entire tumour genome. RESULTS: Nearly all tumours (25/26; that is, 96%) showed chromosomal imbalances, including full chromosomal aneuploidies, losses and gains of chromosome arms, interstitial deletions, and amplifications. Whereas gains of chromosomes 4, 5, and 19 were found in both foregut and midgut tumours, gains of chromosomes 20q (58%), 19 (50%), as well as 17p (50%), and partial losses of chromosomes 1p (42%), 2q (42%), 3p, 4q, and 6q (25% each) were frequently observed only in foregut tumours. In contrast, midgut tumours displayed less CNAs. Gains were detected for chromosomes 17q and 19p (57%). Most frequent losses affected chromosomes 18 (43%) and 9p (21%). CONCLUSIONS: The results of our CGH analyses revealed new distinct candidate regions in the human genome associated with sporadic neuroendocrine tumours. Some of the genetic alterations were shared by foregut and midgut tumours while others discriminated between the two groups. Thus our results allude to the involvement of identical as well as discriminative genetic loci in tumorigenesis and progression of neuroendocrine neoplasms of the foregut and midgut. Based on these findings potential new candidate genes will be discussed.

Adolescent↗
PubMed1999

Environmental radioactivity, population exposure and related health risks in the east Baltic region.

The paper considers radioactive contamination of the east Baltic region, population exposures, and the risk of damage to human health. Principal sources include global fallout, the Chernobyl accident, and marine transport of radionuclides. A mean annual exposure of 2-3 mSv comes from environmental radioactivity. Main contributors are primarily radon and its decay products. The Chernobyl accident brought an additional dose of about 0.5 mSv in southern Finland and 1.4 mSv in the most contaminated districts of the Leningrad region, Russia. Both external and internal exposure via contaminated food contributed. Currently, significant long-term radiological consequences of the Chernobyl accident include persistent radioactive contamination of natural terrestrial (forest) and freshwater (oligotrophic lakes) ecosystems and food products. Radiation health risks are lung cancer among the general population from indoor exposure to radon, acute radiation syndrome from occupational exposure, thyroid cancer among children in heavily contaminated non-Baltic areas, and mutations among offspring of exposed parents.

Air Pollutants, Radioactive↗
PubMed1997

Mini- and microsatellites.

While the faithful transmission of genetic information requires a fidelity and stability of DNA that is involved in translation into proteins, it has become evident that a large part of noncoding DNA is organized in repeated sequences, which often exhibit a pronounced instability and dynamics. This applies both to longer repeated sequences, minisatellites (about 10-100 base pairs), and microsatellites (mostly 2-4 base pairs). Although these satellite DNAs are abundantly distributed in all kinds of organisms, no clear function has been discerned for them. However, extension of trinucleotide microsatellite sequences has been associated with several severe human disorders, such as Fragile X syndrome and Huntington's disease. Rare alleles of a minisatellite sequence have been reported to be associated with the ras oncogene leading to an increased risk for several human cancers. A dynamic behavior of repeated DNA sequences also applies to telomeres, constituting the ends of the chromosomes. Repeated DNA sequences protect the chromosome ends from losing coding sequences at cell divisions. The telomeres are maintained by the enzyme telomerase. Somatic cells, however, lose telomerase function and gradually die. Cancer cells have activated telomerase and therefore they acquire immortality.

DNA Fingerprinting↗
PubMed1996

Somatic recombination, gene amplification and cancer.

The principle objective of this research programme, to analyse chemical induction of somatic recombination and related endpoints, i.e., mobilization of transposing elements and gene amplification, has been approached by means of several assay systems. These have included Drosophila, Saccharomyces and mammalian cell cultures. 6.1. Screening assays for mitotic recombination. A large number of chemicals have been investigated in the three Drosophila assay systems employed--the multiple wing hair/flare wing spot system developed by Graf et al., 1984, the white-ivory system developed by Green et al., 1986 and the white/white+ eye spot assay developed by Vogel (Vogel and Nivard, 1993). Particularly the screening of 181 chemicals, covering a wide array of chemical classes, by the last mentioned assay has shown that measurement of somatic recombination in Drosophila constitutes a sensitive and efficient short-term test which shows a remarkably good correlation with the agent score of 83 short-term tests analysed by ICPEMC (Mendelsohn et al., 1992; Table 2) as well as the assay performance in international collaborative programmes measuring carcinogen/non-carcinogens (de Serres and Ashby, 1981; Ashby et al., 1985, 1988). Also the wing spot assay has gained wide international recognition as a similarly sensitive test. These two assay systems in Drosophila measure both intrachromosomal events and interchromosomal recombination. The white-ivory system on the other hand is based on the loss of a tandem duplication in the white locus, the mechanism of which is less known, but probably involves intrachromosomal recombination. The difference in the mechanism between this assay and the former two was indicated by the lack of response to methotrexate in the white-ivory assay, while this compound was strongly recombinogenic in both the wing spot and white/white+ assays. The use of different strains of Drosophila with the white/white+ assay demonstrated the importance of the background genotype for the outcome of the test. Up to a 60-fold variation was found between the different genotypes in the response to procarcinogens, evidently dependent on differences in the metabolic activation of procarcinogens. In 1989 Schiestl presented results on intrachromosomal recombination in the strain RS112 of Saccharomyces, which indicated a capability to detect a range of chemical carcinogens, which gave negative results in Ames Salmonella assay. Such a test system, which could identify a larger range of potential carcinogens than conventional short-term tests evidently would be of great value and it therefore seemed of importance to follow up the observations by Schiestl. However, studies within this programme on the same strain of Saccharomyces, as well as the strains D7 (measuring intragenic recombination, intergenic recombination, and point mutation) and JD1 (measuring intragenic recombination at two loci) could not support the observations and interpretation by Schiestl (1989). The Drosophila white-ivory system, which presumably responds primarily by intrachromosomal recombination, did not give positive results with these Salmonella-negative agents either. One system to measure mitotic recombination in mammalian cell cultures was developed in the present programme. It was based on heterozygous mutations in both alleles of the adenosine deaminase gene (ADA). The system selects for proficient recombinants generated by the deficient cells. So far only pilot experiments, indicating that this experimental system operates as planned, have been performed. 6.2 Mechanisms of mitotic recombination The induction of mosaic spots in the wing spot and the white/white+ assays is predominantly dependent on interchromosomal recombination. This is evident from the fact that heterozygous inversions reduce the frequency of spots. A relationship between the length of inversions and the reduction of spots was demonstrated in the white/white+ assay--the long inversion ln(l)sc4L

Animals↗
PubMed1996

Common subtypes of idiopathic generalized epilepsies: lack of linkage to D20S19 close to candidate loci (EBN1, EEGV1) on chromosome 20.

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). A trait locus (EBN1) for a rare subtype of IGEs, the benign neonatal familial convulsions, and a susceptibility gene (EEGV1) for the common human low-voltage electroencephalogram have been mapped close together with D20S19 to the chromosomal region 20q13.2. Both loci are potential candidates for the susceptibility to IGE spectra with age-related onset beyond the neonatal period. The present study tested the hypothesis that a putative susceptibility locus linked to D20S19 predisposes to spectra of IGEs with age-related onset from childhood to adolescence. Linkage analyses were conducted in 60 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy or childhood absence epilepsy. Our results provide evidence against linkage of a putative susceptibility gene for four hierarchically broadened IGE spectra with D20S19 assuming tentative single-locus genetic models. The extent of an "exclusion region" (lod scores below-2) varied from 0.5 cM up to 22 cM on either side of D20S19 depending on the trait assumed. These results are contrary to the expectation that a susceptibility gene in vicinity to D20S19 confers a common major gene effect to the expression of IGE spectra with age-related onset from childhood to adolescence.

Chromosome Mapping↗
PubMed1995

Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies.

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). The pivotal function of glutamate receptors (GluRs) in excitatory neurotransmission implicates their involvement in epileptogenesis and genetic susceptibility to IGEs. A trinucleotide repeat polymorphism detected in the 3' untranslated region of the kainate-selective GluR6 receptor gene (GRIK2) on chromosome 6 makes it possible to perform linkage and association studies with this high-ranking candidate gene. The present study tested the hypothesis that allelic variants of GRIK2 contribute to the genetic susceptibility to the common IGEs. Linkage and association analyses were conducted in 63 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, or childhood absence epilepsy. Our linkage and association results suggest that allelic variants of GRIK2 are not involved in the expression of the common familial IGEs, and radiation hybrid mapping assigns GRIK2 to the chromosomal region 6q16.3-q21. This localization excludes GRIK2 as a candidate for the putative IGE susceptibility locus "EJM1" on the short arm of chromosome 6.

Chromosome Mapping↗
PubMed1994

Modulating influence of inorganic arsenic on the recombinogenic and mutagenic action of ionizing radiation and alkylating agents in Drosophila melanogaster.

In bacterial systems and in mammalian in vitro cell cultures, inorganic arsenic has been found to potentiate the mutagenic action of UV as well as of a number of mutagenic agents, probably by interfering with the later steps of DNA-repair. The Drosophila wing spot test (SMART) was used to study the modulating action of inorganic arsenic on the recombinogenic and mutagenic effects of the alkylating agents ethylnitrosourea (ENU), methylmethane sulphonate (MMS), and ethylene oxide (EO) as well as of gamma-rays. It was found, that arsenic in this in vivo test system exerted an inhibitory effect on mitotic recombination induced by alkylating agents and gamma-irradiation. These results are in contrast to the synergistic effect of inorganic arsenic on point mutations and deletions as reported for human lymphocytes and primary fibroblasts. The reason for the discrepancy between the mammalian systems and Drosophila with respect to the modulating action of arsenic is discussed.

Alkylating Agents↗
PubMed1992

Detection of DNA alterations in human bladder tumors by DNA fingerprint analyses.

DNA fingerprint analyses were used to examine the constitutional and tumor DNA from 22 bladder tumor patients. DNA alterations, such as loss of bands, new bands, and intensity shifts were observed in 10 of the 22 patients. The most frequent DNA alteration, occurring in 80% of the patients, was a complete loss of one or several bands. Fingerprint abnormalities were present both in low-malignant superficial tumors and in high-malignant invasive tumors, but were also lacking in the latter group. Apparently no relationship exists between fingerprint abnormalities and gross chromosomal aberrations or the proportion of S-phase cells as measured by flow cytometry or development of recurrent tumors during a limited observation period. Thus, whether fingerprint aberrations express genetic alterations directly involved in the malignancy potential of bladder carcinoma remains an open question.

Adult↗
PubMed1992

Modulation of genotoxicity in Drosophila.

The extensive knowledge of the genetics of Drosophila melanogaster and the long experimental experience with this organism have made it of unique usefulness in mutation research and genetic toxicology. The development of somatic mutation and recombination tests (SMART) has provided sensitive, rapid and cheap assays for investigations of mutagenic and recombinogenic properties of chemicals. The present paper deals with the SMART wing spot assay, developed by Graf et al. (1984). The use of two genetic markers, multiple wing hair (mwh) and flare (flr) in the third chromosome, makes it possible to discern localized recombinogenic effects on the two intervals--the major, euchromatic, part of the chromosome, and the mostly heterochromatic centromere region. The distribution of induced mitotic recombination varied between test chemicals. Ethylene oxide caused a specific increase of twin spots, indicating a localized induction of somatic recombination in the centromere region. The wing spot assay has turned out to be suitable for combined treatment with chemicals in order to study antimutagenic and other modulating effects by mutagenic and recombinogenic chemicals. Examples of the use of this assay for such a purpose are presented in this paper. The inhibitor of poly ADP-ribosylation, 3-aminobenzamide (3AB), caused a pronounced increase of wing spots, induced by alkylating agents. The data indicate that this interaction between alkylating agents and 3AB is solely due to an effect on somatic recombination but not on point mutations. The inhibitor of topoisomerases, novobiocin, which presumably acts on the chromatin configuration, had different modulating effects on spots induced by methyl methanesulfonate (MMS) and ethylnitrosourea (ENU). Novobiocin essentially acted as an antirecombinogenic agent in cotreatment experiments with MMS and as antimutagenic agent with ENU. Attempts to interfere with mutagenic and recombinogenic effects of the radical-generating agents bleomycin, menadione and paraquat, by agents acting on the defence mechanisms against oxygen radicals, were essentially unsuccessful.

Animals↗
PubMed1992

Evolutionary aspects of human cancer.

Evolutionary aspects of human cancer can be dealt with at two levels--on the one hand long-term evolution involving hereditary effects between generations; and on the other hand evolutionary processes operating within the organisms between tissues, cells and cell constituents, which also comprise genetic alterations, selection and adaptation. These two levels of evolution can be designated as phylogenetic and ontogenetic evolution, respectively. Concerning phylogenetic evolution there must have been a strong selection against neoplastic diseases occurring at reproductive age and a variety of protective mechanisms against carcinogenic agents have been developed. Cancer is therefore primarily a disease of old age, which does not constitute a significant risk in natural populations for the simple reason that the life length is too short. The development of an individual comprises selection forces between cells and tissues, which are particularly striking for the multistage development of tumours. The accumulation of several genetic alterations in the same cells, as illustrated by the analysis of colorectal tumours, must require a pronounced clonal expansion between each event. Such selective growth effect has recently been demonstrated for the tumour suppressor gene p53 in brain tumours. Cancer often implies a break down of between balanced systems antagonistic forces, such as oncogenes and suppressors of oncogenes. Examples of this are provided by the genetic regulation of metastasis, involving metalloproteinase as well as the inhibitor of metalloproteinase. The immortalization of cells by transformation points to the fact that programmed cell death and the balance between suicide genes and suppressors of such suicide genes is affected.

Apoptosis↗
PubMed1991

On the mechanism of the hepatocarcinogenicity of peroxisome proliferators.

The absence of a genotoxic action in the rat of several peroxisome proliferators (PP) has been confirmed by measuring gross degradation, unscheduled DNA-synthesis (UDS), as well as by measurement of single strand breaks using alkali unwinding in absence and presence of inhibitors of DNA-repair. Similar results were obtained even after drastically lowering the glutathione content of liver. Further, after oral administration of ciprofibrate, no potentiating effect was found in vivo on the generation of micronuclei in hepatocytes by ionizing radiation. The metabolically inert PP, perfluorooctanoic acid, was found to act as a promoter of liver tumors in the rat induced by diethylnitrosamine in an initiation-selection-promotion protocol. The results are discussed in light of available information concerning the mechanism of action of PPs.

Animals↗
PubMed1991

Pollution, carcinogenesis and cancer prevention.

Epidemiological and other data indicate that most cancer is due to environmental factors in the broader sense of the term and, therefore, presumably preventable to a great extent. Consequently, the identification of carcinogens in the environment is of fundamental importance in cancer prevention. Oncogene research has given new insight into the cellular signal pathways, as well as genetic alterations leading to neoplastic growth. This information provides a foundation for improvement of the current testing strategy for carcinogenic chemicals released into the environment. The testing protocols must take into consideration the carcinogenic agents that act through both genotoxic and non-genotoxic mechanisms. Also, it should be pointed out that human exposure often involves complex mixtures of chemicals, and the possibility of interactions between initiating and promoting carcinogens. Current test procedures rarely deal with such chemical interactions. Analyses of environmental factors responsible for the induction of cancer in humans indicate that naturally-occurring, rather than man-made, chemicals constitute a prevalent cancer risk. It must, however, be stressed that this conclusion applies to Western industrialized countries. In eastern European and developing countries, environmental pollutants, synthetic pesticides and other man-made chemicals very likely pose a larger cancer risk for the general population.

Animals↗
PubMed1990

Unusual prophase structures and multiple nucleoli in male meiosis of Drosophila species of the virilis group.

With silver nitrate (Ag-NOR) staining, unusual fibrillar structures, apparently coupled to the nucleolus, were found is several species of the D. virilis group. In D. littoralis, beaded strings appear in connection with these structures, whereas the late prophase is characterized by the appearance of multiple nucleoli in the nucleoplasm. In D. virilis, the nucleus has a prominent pointed protrusion in the region of the nucleolus and often a fibril protrudes from this point. Small nucleoli are 'budding' from the nucleolus during prophase. The multiple nucleoli at late prophase are smaller and fewer. A 'nucleolar body' with black spots appears at prometaphase and persists through metaphase and anaphase. In D. lummei, the nucleolus becomes surrounded by fibrils, which are released into the nucleoplasm and on which multiple nucleoli are synthesized. These phenomena are similar to the events described in oocyte meiosis of many animals, where rDNA amplification, coupled to the synthesis of multiple nucleoli in late prophase, has been established.

Animals↗
PubMed1990

A comparative study of male meiosis in Drosophila melanogaster and D. virilis.

Male meiosis in D. melanogaster cytologically follows the usual pattern, whereas in D. melanogaster and in D. virilis oocytes the chromosomes clump into a karyosphere at early meiotic prophase and remain so up to metaphase I. Male meiosis in D. virilis spermatocytes has an intermediate character: a part of the chromatin clumps together in a karyosphere at early prophase, whereas the other part of the chromatin remains diffuse all through prophase. At the end of prophase, the diffuse chromatin becomes integrated into the karyosphere before metaphase I. During the meiotic divisions the chromosomes have the same clumped aspect as those in Drosophila oocytes and thus differ strikingly from the dividing chromosomes in D. melanogaster spermatocytes. In D. virilis spermatocytes the nucleolus exhibits changes during the meiotic prophase that may be related to synthetical activities. The DNA specific staining with the fluorochrome DAPI reveals the existence of extrachromosomal DNA in the later prophase. Other striking differences in meiotic events between the two Drosophila species concern the centrioles and spermiogenesis.

Animals↗