Search PubMed⌕ Search

Biomedical subjects

C Nogues

Publications and source records attributed to C Nogues.

At least 19 recordsLinked to original sources
PubMed2006

Sequence dependence of charge transport properties of DNA.

The electrical conduction through three short oligomers (26 base pairs, 8 nm long) with differing numbers of GC base pairs was measured. One strand is poly(A)-poly(T), which is entirely devoid of GC base pairs. Of the two additional strands, one contains 8 and the other 14 GC base pairs. The oligomers were adsorbed on a gold substrate on one side and to a gold nanoparticle on the other side. Conducting atomic force microscope was used for obtaining the current versus voltage curves. We found that in all cases the DNA behaves as a wide band-gap semiconductor, with width depending on the number of GC base pairs. As this number increases, the band-gap narrows. For applied voltages exceeding the band-gap, the current density rises dramatically. The rise becomes sharper with increasing number of GC base pairs, reaching more than 1 nA/nm2 for the oligomer containing 14 GC pairs.

Base Composition↗
PubMed2006

The contribution of germline rearrangements to the spectrum of BRCA2 mutations.

BACKGROUND: Few germline BRCA2 rearrangements have been described compared with the large number of germline rearrangements reported in the BRCA1 gene. However, some BRCA2 rearrangements have been reported in families that included at least one case of male breast cancer. OBJECTIVE: To estimate the contribution of large genomic rearrangements to the spectrum of BRCA2 defects. METHODS: Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2 gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions/duplications in many genes including BRCA1 and BRCA2. RESULTS: We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of < or = 50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36 index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the BRCA2 mutation spectrum. CONCLUSION: The molecular diagnosis of breast cancer predisposition should include screening for BRCA2 rearrangements, at least in families with a high probability of BRCA2 defects.

Exons↗
PubMed2001

[Li-Fraumeni syndrome: update, new data and guidelines for clinical management].

The Li-Fraumeni syndrome (LFS) is an inherited form of cancer, affecting children and young adults, and characterized by a wide spectrum of tumors, including soft-tissue and bone sarcomas, brain tumours, adenocortical tumours and premenopausal breast cancers. In most of the families, LFS results from germline mutations of the tumor suppressor TP53 gene encoding a transcriptional factor able to regulate cell cycle and apoptosis when DNA damage occurs. Recently, germline mutations of hCHK2 encoding a kinase, regulating cell cycle via Cdc25C and TP53, were identified in affected families. The LFS working group recommendations are the following: (i) positive testing (screening for a germline TP53 mutation in a patient with a tumor) can be offered both to children and adults in the context of genetic counseling associated to psychological support, to confirm the diagnosis of LFS on a molecular basis. This will allow to offer to the patient a regular clinical review in order to avoid a delay to the diagnosis of another tumor; (ii) the 3 indications for positive testing are: a proband with a tumor belonging to the narrow LFS spectrum and developed before age 36 and, at least, first- or second-degree relative with a LFS spectrum tumor, before age 46, or a patient with multiple primary tumors, 2 of which belonging to the narrow LFS spectrum, the first being developed before 36 or a child with an adenocortical tumour; (iii) presymptomatic testing must be restricted to adults; (iv) the young age of onset of the LFS tumors the prognosis of some tumors, the impossibility to ensure an efficient early detection and the risk for mutation carriers to develop multiple primary tumors justify that prenatal diagnosis might be considered in affected families.

Adult↗
PubMed1998

Factors affecting the efficiency of introducing precise genetic changes in ES cells by homologous recombination: tag-and-exchange versus the Cre-loxp system.

The introduction of genetic modifications in specific genes by homologous recombination provides a powerful tool for elucidation of structure-function relationships of proteins of biological interest. Presently, there are several alternative methods of homologous recombination that permit the introduction of small genetic modifications in specific loci. Two of the most widely used methods are the tag-and-exchange, based on the use of positive-negative selection markers, and the Cre-loxP system, based on the use of a site-specific recombinase. The efficiency of detection of targeting events at different loci using the two systems was compared. Additionally, we analysed how the distance between two gene markers placed within the region of homology of a targeting vector affects the rate at which both markers are introduced into the locus during the homologous recombination event. Our results indicate that the method based on the use of positive-negative selection markers was less efficient than the Cre-loxP based system, irrespective of locus or type of positive-negative selection. It was also determined that as the distance between the selectable marker and the genetic modification being introduced increases, there is a progressive reduction in the efficiency of detecting events with the desired genetic modification.

Animals↗
PubMed1998

Analysis of alterations adjacent to invasive vulvar carcinoma and their relationship with the associated carcinoma: a study of 67 cases.

A retrospective analysis of histological lesions adjacent to 67 invasive vulvar squamous cell carcinomas (SCC) was undertaken to analyse their nature, as well as their relationship to SCC. Patient age, clinical presentation and histological type of carcinoma, ISSVD classification of its adjacent lesions, disease-free and overall survival were reviewed. Severe undifferentiated vulvar intra-epithelial neoplasia (VIN3) was found in 19.4% of cases and vulvar lichen sclerosus (VLS) in 76.1% of cases. All VLS, except 2 cases, were associated with squamous cell hyperplasia (SCH), and a concomitant differentiated VIN was found in 76.6% of cases. Undifferentiated VIN3 was never associated with VLS. VLS was significantly associated with a keratinizing, well-differentiated SCC (98% of cases), while undifferentiated VIN3, was linked preferentially to 2 other types of SCC: in 77% of cases, a moderately-differentiated SCC with the same histological features as the so-called basaloid carcinoma and, in 23% of cases, a well-differentiated SCC with a variable extent of koilocytic atypia, similar to the so-called warty carcinoma. Carcinoma of the fourchette was more often associated with undifferentiated VIN3. Disease-free and overall survival were significantly better for carcinoma associated with undifferentiated VIN3 (p < 0.01 and p < 0.05, respectively). These findings suggest invasive vulvar SCC occurs on 2 distinct types of vulvar lesions: differentiated VIN and/or SCH associated with VLS and undifferentiated VIN3. Furthermore, the histological type of the carcinoma seems to differ according to adjacent lesions.

Adult↗
PubMed1997

Isolation, characterization and chromosomal localization of the porcine ciliary neurotrophic factor (CNTF) gene.

In the mouse, ciliary neurotrophic factor (CNTF) maintains embryonic stem cells in an undifferentiated state; yet, the heterologous protein has no similar effects on porcine embryonic stem (ES) cells. Consequently, we cloned and sequenced the porcine CNTF gene and assigned it to chromosome 2. The CNTF gene was found to contain two exons, which encoded a deduced polypeptide of 200 amino acids in length with 83%, 82%, 82% and 81% amino acid similarity when compared to known sequences in the rabbit, rat, human and mouse, respectively. Eight non-conservative amino acid changes were identified in the porcine protein when compared with other species. Comparison of the 5' region of the porcine CNTF and other mammalian cytokines indicated the presence of several conserved transcription-factor binding motifs, suggesting their importance for controlling the specific expression of these proteins. In addition, CNTF was localized to porcine chromosomes by fluorescence in situ hybridization (FISH). Chromosome arm length ratios were calculated for 40 early metaphase chromosomes and 32 (80%) indicated that the pig CNTF gene is located on chromosome 2p1.6. This was confirmed by aligning R-banded FISH-labelled chromosomes to the standard porcine ideogram.

Animals↗
PubMed1995

[Genetics and cancer: application to the breast].

Various gene systems are involved in events occurring during transformation of a normal cell into a cancer cell. By order of intervention, genes responsible for an increased individual susceptibility to cancer can be distinguished from actual cancer genes, followed by genes involved at other levels of carcinogenesis. 15 to 20% of patients with breast cancer have a first-degree relative affected by the same cancer, although an inherited predisposition to cancer is only established in 4 to 10% of cases. The genetic heterogeneity of familial forms of breast cancer make it difficult to identify susceptibility genes. At the present time, 3 regions of the genome have been implicated in the predisposition to breast cancer in women: the BRCA1 gene, the BRCA2 gene and the TP53 gene. All predisposition genes are able to transmit susceptibility due to a mutation or inherited microdeletion.

Breast Neoplasms↗
PubMed1994

Changes in rat atrial ANF granules induced by hindlimb suspension.

It is well known that the heart releases a factor called ANF (atrial natriuretic factor) or ANP (atrial natriuretic peptide) capable of inducing rapid diuretic and natriuretic actions. This factor is stored in secretory granules mainly located in myocytes in both atria. The main secretory stimulus is the distention of the atrial cavity resulting, for example, from enhanced venous return. However, the cellular events which occur after the stimulation remain to be clarified. The aim of this investigation was to study the intra-cellular events preceding the ANF release, using the rat hindlimb suspension as model of stimulation. In this model, Wistar rats were placed in a 30 degrees anti-orthostatic position and a blood shift towards the heart was obtained. Different durations (1/4 h, 1/2 h, 3/4 h, 1 h, 2 h and 6 h) were studied. The ANF plasma level was investigated by Radio Immuno Assay and granule immunoreactivity was measured by counting gold particles on micrographs. The ANF plasma level was significantly increased (+60%) after 1 h of suspension. The response was transient and then decreased to basal values. Morphological criteria established at the beginning of this study, and measured throughout the experiment, were found transiently modified after suspension. The surface of the perinuclear area was transitory enlarged by 36% 30 min after suspension. Moreover, in the same time immunoreactivity of the secretory granules was enhanced without changes in granule size. These results suggest an increase in the ANF synthesis and storage in the granules during the stimulation. However, the cellular regulatory mechanism of the ANF synthesis which could explain the transitory aspect of these events, requires further investigation.

Animals↗
PubMed1993

The effects of a 5-month physical training on iliac bone morphology in monkeys.

The present study was designed to provide data on the effects on bone of 5 months of daily exercise in nonhuman primates. The subjects were five male rhesus monkeys with mature skeletons with a body mass of 8-10 kg. The exercise schedule selected to provide endurance training was a daily continuous 1-h climbing task. An iliac crest bone biopsy was performed prior to and at the end of the physical training. The histomorphometric bone study was based upon bone mass and bone cell activity measurements made on nondecalcified bone slides, using trichromic and fluorescent labelling techniques. Results showed a decrease in bone formation, resulting in reduced bone mass at the end of the 5 months. This effect is suggested to be related to the unphysiological climbing regimen imposed on these animals which are naturally used to short periods of rapid exercise. From these investigations it was concluded that even if it is well tolerated, long-term physical endurance training can induce bone loss in primates. Further investigations are needed to determine with accuracy the relationships between bone physiology and physical exercise, and particularly with regard to its type, intensity and duration.

Animals↗
PubMed1993

Results of a randomized clinical trial comparing two radiation schedules in the palliative treatment of brain metastases.

In 216 patients with brain metastases two schedules of brain irradiation were compared in a randomized trial: one course of 18 Gy/3 fractions/3 days versus the same fractionation followed by a second course of radiotherapy with a one-month time interval. The second course was identical to the first one or delivered 25 Gy/10 fractions/14 days. No difference in overall survival, nor in the neurologic response or in the incidence of complications was demonstrated. Two clinical factors appeared to be prognostic of the overall survival: the presence of multiple brain metastases and the presence of extracerebral metastases.

Brain Neoplasms↗
PubMed1990

Five months of daily standardized exercise for sedentary monkeys.

A system to physically exercise rhesus monkeys is described, based on their natural capacity to climb. It is composed of an enclosure where a motor-driven rope is continually going down. The two stage training to this task is easily performed. The total work of each run, evaluated with the weight of the animal and the distance climbed, may be very stable. It was used to provide five sedentary monkeys with daily physical training for five months.

Animals↗
PubMed1988

A new technique for iliac crest biopsy in rhesus monkeys for use in weightlessness experiments: some results of ground studies.

The similarity of major physiological functions between man and monkey make non-human primates a suitable model, especially for experiments in weightlessness. Bone tissue of rhesus monkeys can easily be analysed by histological techniques in order to appreciate the effects of hypogravity upon the skeletal system. A technique for iliac crest biopsy has been developed in a laboratory. It is to be used on rhesus monkeys used in various experimental situations, and especially after exposure to the space environment.

Animals↗
PubMed1987

Histiocytes X and X body reactivity with concanavalin A, peanut agglutinin and BSPT.

The ultrastructural and histochemical exploration of histiocytes X done by the means of Concanavalin A (Con A), peanut agglutinin (PNA) and BSPT demonstrate that the plasma membrane of histiocytes X shared some properties with all the other cells and is also specialized. The rod part of the X body has the same properties as the plasma membrane while its vesicular part differs and is closer to the inner membrane system of the cell. In consequence it is suggested that the rod part of the X body is a specialized pathway or shuttle for receptor linked glycoprotein exchanges in highly specialized cells.

Benzothiazoles↗
PubMed1985

Anatomo-pathological findings in a case of combined deficiency of sulphite oxidase and xanthine oxidase with a defect of molybdenum cofactor.

A case of combined deficiency of sulphite-oxidase and xanthine-oxidase with a defect of the molybdenum cofactor, which is vital to the activity of sulphite-, xanthine- and aldehyde-oxidase, is reported here. Seven cases of combined deficiencies have been described with regard to both clinical and laboratory findings. The clinical, laboratory and anatomo-pathological features and, in particular, the central nervous system lesions of the present case correspond exactly to those in the case described Rosenblum in which an isolated deficiency in sulphite-oxidase was present. As the cerebral alterations in the present case are comparable to those described in Rosenblum's case, they probably result from the defect in sulphite-oxidase activity.

Amino Acid Metabolism, Inborn Errors↗
PubMed1985

Failure of histiocytosis X cells to express i blood group antigen.

Expression of HLADR, I, i blood group antigen and T6 antigen were studied in Histiocytosis X cells and pulmonary alveolar macrophages using double labelling immunofluorescence technique or immuno-peroxidase procedure. Alveolar macrophages express simultaneously HLADR and i blood group antigen. Histiocytosis X cells, characterized by HLADR and T6 antigens, and by their ultra-structural marker do not express i antigen. These results confirm the hypothesis that histiocytosis X cells constitute a specialized sub-population of the mononuclear phagocyte system.

Blood Group Antigens↗