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F Abel

Publications and source records attributed to F Abel.

At least 19 recordsLinked to original sources
PubMed2004

Investigation of the role of SDHB inactivation in sporadic phaeochromocytoma and neuroblastoma.

Germline mutations in the succinate dehydrogenase (SDH) (mitochondrial respiratory chain complex II) subunit B gene, SDHB, cause susceptibility to head and neck paraganglioma and phaeochromocytoma. Previously, we did not identify somatic SDHB mutations in sporadic phaeochromocytoma, but SDHB maps to 1p36, a region of frequent loss of heterozygosity (LOH) in neuroblastoma as well. Hence, to evaluate SDHB as a candidate neuroblastoma tumour suppressor gene (TSG) we performed mutation analysis in 46 primary neuroblastomas by direct sequencing, but did not identify germline or somatic SDHB mutations. As TSGs such as RASSF1A are frequently inactivated by promoter region hypermethylation, we designed a methylation-sensitive PCR-based assay to detect SDHB promoter region methylation. In 21% of primary neuroblastomas and 32% of phaeochromocytomas (32%) methylated (and unmethylated) alleles were detected. Although promoter region methylation was also detected in two neuroblastoma cell lines, this was not associated with silencing of SDHB expression, and treatment with a demethylating agent (5-azacytidine) did not increase SDH activity. These findings suggest that although germline SDHB mutations are an important cause of phaeochromocytoma susceptibility, somatic inactivation of SDHB does not have a major role in sporadic neural crest tumours and SDHB is not the target of 1p36 allele loss in neuroblastoma and phaeochromocytoma.

Base Sequence↗
PubMed2004

A novel 1p36.2 located gene, APITD1, with tumour-suppressive properties and a putative p53-binding domain, shows low expression in neuroblastoma tumours.

Neuroblastoma is characterised by a lack of TP53 mutations and no other tumour suppressor gene consistently inactivated has yet been identified in this childhood cancer form. Characterisation of a new gene, denoted APITD1, in the neuroblastoma tumour suppressor candidate region in chromosome 1p36.22 reveals that APITD1 contains a predicted TFIID-31 domain, representing the TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. Two different transcripts of this gene were shown to be ubiquitously expressed, one of them with an elevated expression in foetal tissues. Primary neuroblastoma tumours of all different stages showed either very weak or no measurable APITD1 expression, contrary to the level of expression observed in neuroblastoma cell lines. A reduced pattern of expression was also observed in a set of various tumour types. APITD1 was functionally tested by adding APITD1 mRNA to neuroblastoma cells, leading to the cell growth to be reduced up to 90% compared to control cells, suggesting APITD1 to have a role in a cell death pathway. Furthermore, we determined the genomic organisation of APITD1. Automated genomic DNA sequencing of the coding region of the gene as well as the promoter sequence in 44 neuroblastoma tumours did not reveal any loss-of-function mutations, indicating that mutations in APITD1 is not a common abnormality of neuroblastoma tumours. We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

Amino Acid Sequence↗
PubMed2004

Chromosome aberrations and cell inactivation induced in mammalian cells by ultrasoft X-rays: correlation with the core ionizations in DNA.

PURPOSE: To study the frequency of chromosome aberrations induced by soft X-rays. To see if the core ionization of DNA atoms is involved in this end-point as much as it appears to be in cell killing. MATERIALS AND METHODS: V79 hamster cells were irradiated by synchrotron radiation photons iso-attenuated in the cell (250, 350, 810eV). The morphological chromosome aberrations detected in the first post-irradiation cell division (dicentrics and centric rings) were studied by Giemsa staining. RESULTS: The chromosome aberrations at 350eV were, respectively, 2.6 +/- 0.8 and 2.1 +/- 0.8 times more numerous than at 250 and 810eV for the same average dose absorbed by the nucleus. These relative effectivenesses are comparable with the ones already measured for cell killing. Moreover, they roughly vary such as the relative numbers of core ionizations (including in the phosphorus L-shell) produced in DNA and its bound water (water being involved only at 810eV through the oxygen atoms). In particular, they reproduce the characteristic twofold enhancement at 350eV, above the carbon K threshold. CONCLUSIONS: Correlations suggest that the core ionization process is likely a common and essential mechanism initiating both chromosome aberration and cell killing end-points at these photon energies.

Animals↗
PubMed2004

Update in the pharmaceutical therapy of the irritable bowel syndrome.

The therapeutic management of the irritable bowel syndrome (IBS) is ineffective and not satisfying either patients or practitioners. Research in functions of the enteric nervous system and its interaction with the central nervous system is the basis for the development of emerging pharmaceuticals in therapy of the IBS. These pharmaceuticals include agents such as opioid agonists, psychotropic agents and particularly serotonin receptor modulators. These novel pharmaceuticals aim to provide a more comprehensive approach in the therapy of the IBS and will serve both patients and practitioners. So far, the US Food and Drug Administration has approved two agents specifically for the treatment of the IBS, both belonging to the group of serotonin receptor modulators. However, questions remain whether a single therapy is sufficient in the management of IBS because this disease is influenced by biological and psychological as well as cultural and social factors.

Gastrointestinal Agents↗
PubMed2002

Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours.

The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the 'Smallest Region of Overlap of deletions' in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT-PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics.

Alleles↗
PubMed2002

Biological effects induced by K photo-ionisation in and near constituent atoms of DNA.

In order to assess the lethal efficiency and other biological effects of inner shell ionisations of constituent atoms of DNA ('K' events), experiments were developed at the LURE synchrotron facility using ultrasoft X rays as a probe of K events. The lethal efficiency of ultrasoft X rays above the carbon K threshold was especially investigated using V79 cells and compared with their efficiency to induce double strand breaks in dry plasmid-DNA. A correlation between the K event efficiencies for these processes is shown. Beams at 340 eV were found to be twice as efficient at killing cells than were beams at 250 eV. In addition, a rough two-fold increase of the relative biological effectiveness for dicentric + ring induction has also been observed between 250 and 340 eV radiations.

Animals↗
PubMed2002

Cell inactivation and double-strand breaks: the role of core ionizations, as probed by ultrasoft X rays.

The large RBE (approximately 7) measured for the killing of Chinese hamster V79 cells by 340 eV ultrasoft X rays, which preferentially ionize the K shell of carbon atoms (Hervé du Penhoat et al., Radiat. Res. 151, 649-658, 1999), was used to investigate the location of sensitive sites for cell inactivation and the physical modes of action of radiation. The enhancement of the RBE above the carbon K-shell edge either may indicate a high intrinsic efficiency of carbon K-shell ionizations (due, for example, to a specific physical or chemical effect) or may be related to the preferential localization of these ionizations on the DNA. The second interpretation would indicate a strong local (within 3 nm) action of K-shell ionizations and consequently the importance of a direct mechanism for radiation lethality (without excluding an action in conjunction with an indirect component). To distinguish between these two hypotheses, the efficiencies of core ionizations in DNA atoms (phosphorus L-shell, carbon K-shell, and oxygen K-shell ionizations) to induce damages were investigated by measuring their capacities to produce DNA double-strand breaks (DSBs). The effect of photoionizations in isolated DNA was studied using pBS plasmids in a partially hydrated state. No enhancement of the efficiency of DSB induction by carbon K-shell ionizations compared to oxygen K-shell ionizations was found, supporting the hypothesis that it is the localization of these carbon K-shell events on DNA which gives to the 340 eV photons their high killing efficiency. In agreement with this interpretation, cell inactivation and DSB induction, which do not appear to be correlated when expressed in terms of yields per unit dose in the sample, exhibit a rather good correlation when expressed in terms of efficiencies per core event in the DNA. These results suggest that core ionizations in DNA, through core-hole relaxation in conjunction with localized effects of spatially correlated secondary and Auger electrons, may be the major critical events for cell inactivation, and that the resulting DSBs (or a constant fraction of these DSBs) may be a major class of unrepairable lesions.

Animals↗
PubMed2001

Fine mapping of a tumour suppressor candidate gene region in 1p36.2-3, commonly deleted in neuroblastomas and germ cell tumours.

BACKGROUND: A common genetic feature of neuroblastomas, which is also an important prognostic factor, is deletion of chromosome region 1p. The deletion of 1p often involves a deletion of varying size, with a consensus region within the most distal bands 1p36.2-3. The neuroblastoma SRO (shortest region of overlap of (deletions) presented earlier by our group was defined distally by the cluster of loci D1S80/ D1Z2/CDC2L1 and proximally by loci D1S244, i.e., approximately 25 cM. The 1p deletions are, however, not restricted to neuroblastoma tumours. In fact, a large spectrum of tumour types display deletions to varying degrees of 1p. PROCEDURE: We have exploited the possibility of using deletions of other tumour types, preferentially that of germ cell tumours, and combining the deletions with that of the neuroblastoma SRO. Also in germ cell tumours, distal 1p-deletions have been shown to have prognostic significance. RESULTS: We found in our germ cell tumours a SRO ranging from D1S508 to D1S200. Interestingly, this region only partially overlapped (approximately 5 cm) with our neuroblastoma SRO in region D1S508 to D1S244. We have thus focused on analysing this smaller region in the search for genes involved in the genesis of different cancers. We have performed radiation hybrid mapping of a large number of markers, STSs, ESTs, and others known to reside in 1p. We have also initiated the development of a BAC contig of the region. FISH, and fibre-FISH mapping of BACs were also performed. CONCLUSIONS: The data presented here constitute an ongoing work with the aim of identifying and cloning gene(s) important for development of germ cell tumours, neuroblastomas, and possibly other tumours.

Chromosome Mapping↗
PubMed2001

Effectiveness of endoscopic and open surgical management in benign ureteral strictures.

OBJECTIVE: To assess the effectiveness of different treatment modalities for benign ureteric strictures. SETTING: Department of Urology, Al-Emiri Hospital, Kuwait. PATIENTS AND METHODS: Twenty four cases (19 unilateral and 5 bilateral) of ureteral strictures were reviewed. Retrograde endoscopic dilatation was tried, initially for all of the strictures. Technical failure was observed in 8/29 (27.5%) strictures. Three of them were negotiated through antegrade endoscopic dilatation, while in 5 of the strictures open surgical repair was required. Both the balloon and fascial dilator were used for endoscopic dilatation; ureteroneocystostomy with or without Boari's bladder flap were the procedures employed for open repair. RESULTS: Of the 29 strictures the majority were secondary to Bilharzial cystitis (66.6%). Twenty-four (82.7%) strictures underwent endoscopic manipulation and 5 (17.2%) had open repair. Among the 24 strictures that had endoscopic dilatation, 21 (87.5%) were managed in retrograde fashion while in 3 (12.5%) technical failures were due to the inability to canulate the strictured ureter with a guide wire in retrograde fashion. All these patients were treated successfully by antegrade stenting. Among 24 strictures that were initially managed with dilatation and stenting, recurrence was found in 9 (37.5%) patients. The group had open repair, no recurrence was found during the follow up. There was no serious intraoperative or postoperative complications of both the procedures. Patients were followed up with intravenous urography. CONCLUSION: Endoscopic dilatation is an effective treatment modality for partial benign ureteric strictures. However, open ureteroneocystostomy with or without Boari's flap or Psoas hitch should be reserved for complete or recurrent ureteric strictures. Bilharzial strictures are amenable to endoscopic dilation but recurrence rate is high and re-implantation is frequently required.

Adolescent↗
PubMed2000

Fine mapping of the human preprocortistatin gene (CORT) to neuroblastoma consensus deletion region 1p36.3-->p36.2, but absence of mutations in primary tumors.

The processed product of the human gene preprocortistatin, the peptide cortistatin-17 (hCST-17), bears a strong structural resemblance to the peptide somatostatin (SST), which has an identical receptor binding domain. CST has affinity to all known SST receptor (SSTR) subtypes. Expression of both SST and its receptors has been shown in previous studies to have biological and clinical significance in neuroblastomas, with a putative role in tumor differentiation and apoptosis in vivo. In this work we have employed radiation hybrid mapping and BAC physical mapping to map the human preprocortistatin gene (CORT) to chromosome region 1p36.3-->p36.2, close to the genetic marker D1S244. D1S244 defines the centromeric border of the smallest region of overlap of deletion in our primary neuroblastoma material. We have also defined the genomic sequence of the gene by BAC sequencing and found that preprocortistatin consists of two exons divided by a 1-kb intron. Two polymorphic sites, neither of which causes amino acid exchange, have been detected in the coding region of the gene. Expression studies showed that preprocortistatin is expressed in neuroblastomas of all different stages, as well as in ganglioneuromas. Through genomic sequencing we made mutation analyses of exonic sequences in 49 primary neuroblastomas of all different stages, but no mutations could be detected.

Base Sequence↗
PubMed2000

Patched 2, located in 1p32-34, is not mutated in high stage neuroblastoma tumors.

Neuroblastoma is a childhood malignancy originating from cells of the sympathetic nervous system, exhibiting a marked diversity in outcome, with spontaneous regression at one end of the spectrum and severe disease and death at the other end. Features associated with frequent recurrence, a poor prognosis, and high tumor stage are loss of heterozygosity in the distal region of chromosome 1p and amplification of the N-myc gene. Patched 2 is a novel homologue to the tumor suppressor gene Patched 1, and has been mapped to 1p32-34, a part of chromosome 1 frequently deleted in high stage neuroblastoma tumors. RT-PCR analysis of 9 neuroblastoma cell lines showed expression of both Patched 1 and 2. We analyzed 14, mainly high stage, neuroblastoma tumors for mutations in the Patched 2 gene with denaturing HPLC using the Wave DNA fragment analysis system. In four tumor samples variations were detected within the coding sequence, and two of them gave rise to amino-acid substitutions. These variations were, however, also detected in normal DNA from the respective patients. We conclude that Patched 2 is expressed, but not frequently mutated, in high stage neuroblastomas and is therefore not likely to be involved in the genesis of this tumor.

Chromatography, High Pressure Liquid↗
PubMed2000

[Fetal home telemonitoring: the Nancy experience from 1992-1997. analysis of 12649 recordings].

We report the French experience with high risk pregnancies and fetal heart rate monitoring at home. Data were recorded for 376 patients who underwent obstetrical home monitoring from 1992 to 1997 (12,649 recordings). In comparison with data in the literature, our findings show this method is technically reliable. Telemonitoring of high risk pregnancies is as about as safe as traditional hospitalization. Perinatal mortality was not higher in high risk pregnancies followed with home monitoring. We this method, we achieved a lower number of hospitalization days and stays.

Adult↗
PubMed2000

Teaching through clinical cases: a good method to study bioethics. Experience at the Lleida Faculty of Medicine.

This paper summarises our experience in the teaching of bioethics during the final course in medicine at the Universitat de Lleida. Teaching has been based on the discussion of real clinical cases, the ethical implications of which have been extracted and presented by the professor, and analysed under his supervision. We present here the objectives, the programme and the course and evaluation methodology used, as well as the results of an inquiry carried out among the 55 students attending the course. The acceptance level was 92% and the attendance 95%. We believe the methodology used to be successful, since it makes possible the introduction of theoretical aspects of bioethics in order to solve actual cases, as well as encourage wide discussion. At the same time it emphasises that the students discover the values involved.

Attitude of Health Personnel↗
PubMed1999

Gain of chromosome arm 17q is associated with unfavourable prognosis in neuroblastoma, but does not involve mutations in the somatostatin receptor 2(SSTR2) gene at 17q24.

Deletion of chromosome arm 1p and amplification of the MYCN oncogene are well-recognized genetic alterations in neuroblastoma cells. Recently, another alteration has been reported; gain of the distal part of chromosome arm 17q. In this study 48 neuroblastoma tumours were successfully analysed for 17q status in relation to known genetic alterations. Chromosome 17 status was detected by fluorescence in situ hybridization (FISH). Thirty-one of the 48 neuroblastomas (65%) showed 17q gain, and this was significantly associated with poor prognosis. As previously reported, 17q gain was significantly associated with metastatic stage 4 neuroblastoma and more frequently detected than both deletion of chromosome arm 1p and MYCN amplification in tumours of all stages. 17q gain also showed a strong correlation to survival probability (P = 0.0009). However, the most significant correlation between 17q gain and survival probability was observed in children with low-stage tumours (stage 1, 2, 3 and 4S), with a survival probability of 100% at 5 years from diagnosis for children with tumours showing no 17q gain compared to 52.5% for those showing 17q gain (P = 0.0021). This suggests that 17q gain as a prognostic factor plays a more crucial role in low-stage tumours. Expression of the somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, has in previous studies been shown to be positively related to survival in neuroblastoma. A point mutation in the SSTR2 gene has earlier been reported in a human small-cell lung cancer. In this study, mutation screening of the SSTR2 gene in 43 neuroblastoma tumours was carried out with polymerase chain reaction-based single-stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing, and none of the tumours showed any aberrations in the SSTR2 gene. These data suggest that mutations in the SSTR2 gene are uncommon in neuroblastoma tumours and do not correlate with either the 17q gain often seen or the reason some tumours do not express SSTR2 receptors. Overall, this study indicates that gain of chromosome arm 17q is the most frequently occurring genetic alteration, and that it is associated with established prognostic factors.

Chromosome Aberrations↗
PubMed1999

Lethal effect of carbon K-shell photoionizations in Chinese hamster V79 cell nuclei: experimental method and theoretical analysis.

To test a possible specific effect of carbon K-shell ionizations in DNA, survival curves for Chinese hamster V79 cells were measured for X irradiations at energies below and above the carbon K-shell ionization threshold. Specific values of the X-ray energies (250 and 340 eV) were chosen to ensure isoattenuation of the two kinds of radiation within the cell. An enhancement of lethality by a factor of about 2 was found for X rays at 340 eV compared to below the threshold at 250 eV. This may be attributed to the production of highly efficient carbon K-shell ionizations located on DNA. A model of X-ray lethality (Goodhead et al., Radiat. Prot. Dosim. 52, 217-223, 1994) was extended to allow for a possible lethal effect from clusters of reactive species induced by K-shell photoionizations (K-shell clusters). Within this model, the increase in lethality above the carbon K-shell threshold may be explained by a value of 2% for the lethal efficiency of K-shell clusters overlapping the DNA. An extrapolation to the lethal effect of more complex ion-induced K-shell ionizations indicates that K-shell ionization may be a major process in the biological effectiveness of heavy ions.

Animals↗
PubMed1998

Loss of human hippocampal adenosine A1 receptors in dementia: evidence for lack of specificity.

The density of hippocampal adenosine A1 receptors was measured in autopsy samples of six patients with dementia with either Alzheimer (three) or sclerosis type pathology (three) in hippocampus and six control patients. Kinetic parameters (Bmax and KD) were determined by means of quantitative autoradiography using [3H]8-cyclopentyl-1 ,3-dipropylxanthine as a radioligand. A significant 50% reduction of CA1 adenosine A1 receptors was observed in patients with dementia independent of the specific pathology. These results suggest that loss of hippocampal adenosine A1 receptors in dementia is not specific for Alzheimer type pathology.

Aged↗