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Biomedical subjects

B Renault

Publications and source records attributed to B Renault.

At least 19 recordsLinked to original sources

Gene amplification and proliferative kinetics in relation to prognosis of patients with gastric carcinoma.

BACKGROUND: The differences in survival of gastric carcinoma patients who have identical clinical or pathologic stages prompted the authors to investigate the prognostic significance of biologic features that are known to affect the clinical aggressiveness of other tumor types. METHODS: One hundred twenty-four tumor samples from patients who had received radical or palliative surgery were analyzed for c-myc, c-K-ras, hst, and c-erb B-2 gene amplification by means of the Southern blot technique. Of these tumors, 70 were also examined for cell kinetics by means of the thymidine labeling index (TLI). RESULTS: The analysis of associations between gene amplification and the anatomicopathologic variables (TNM classification, site of tumor, and histology) showed that amplification represents a late event in the natural history of gastric carcinoma. Gene amplification showed a slight, statistically insignificant, negative impact on overall survival (OS) (P = 0.09). Amplification of c-erb B-2 correlated in a statistically significant way with reduced OS (P = 0.03). Cox multiple regression analysis revealed that neither c-erb B-2 amplification nor TLI had prognostic significance in relation to OS. CONCLUSIONS: These data indicate that amplification of the examined oncogenes did not reveal a new independent prognostic factor for patients with gastric carcinoma. However, the authors' results did show a strong correlation between gene amplification and tumor progression, which warrants further study involving larger series of patients. At the same time, the TLI results underlined the need to identify the most suitable biologic material for use in the estimation of proliferative indexes in gastric carcinoma.

Adult

Functional anatomy of human auditory attention studied with PET.

Positron emission tomography was used to investigate the functional anatomy of selective auditory attention in 17 right-handed male volunteers who submitted to different tasks: silent rest (REST) listening to frequent low- or rare high-pitched tones (LIS) delivered randomly to the right or the left ear, selective auditory attention where subjects had to attend to deviants in one ear, right (ATTR) or left (ATTL). Six subjects had the series REST, LIS, ATTR twice, eight subjects the series REST, LIS, ATTL, and the last three subjects the sereis REST, ATTR, ATTL. Event-related potentials were simultaneously recorded with PET and showed significant task and electrode site effects on the N100 amplitude. When compared to REST, LIS elicited bilateral temporal activations of the Heschl's gyri and the planum temporale, with a significant rightward asymmetry, and of the posterior part of the superior temporal gyrus. Significant right precentral and anterior cingulate gyri normalized regional cerebral blood flow increases were observed in the frontal lobe. Both the ATTR and the ATTL conditions, compared to LIS, activated the supplementary motor area, bilateral precentral, and left postcentral cortices without any temporal cortex activation. In addition, the ATTL condition resulted in a right prefrontal cortex activation. Pooling the 14 subjects revealed an asymmetry in the superior temporal gyrus favoring the cortex contralateral to the attended ear. Two major networks seem thus to be involved during selective auditory attention: (1) a local temporal network, on which selective attention produces a modulation of the functional lateralization, and (2) a frontal network that could mediate the temporal cortex modulation by attention.

Adult

Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome.

Holt-Oram syndrome is characterized by upper limb malformations and cardiac septation defects. Here, we demonstrate that mutations in the human TBX5 gene underlie this disorder. TBX5 was cloned from the disease locus on human chromosome 12q24.1 and identified as a member of the T-box transcription factor family. A nonsense mutation in TBX5 causes Holt-Oram syndrome in affected members of one family; a TBX5 missense mutation was identified in affected members of another. We conclude that TBX5 is critical for limb and heart development and suggest that haploinsufficiency of TBX5 causes Holt-Oram syndrome.

Abnormalities, Multiple

Physical mapping of the human neurotensin gene (NTS) between markers D12S1444 and D12S81 on chromosome 12q21.

Neurotensin (NTS) is an endogenous tridecapeptide of the central nervous system and the gastrointestinal tract of different mammalian species including human. The human gene encoding neurotensin has previously been assigned to chromosome 12 but no regional localization was available. We now confirm this assignment and place the NTS gene on the physical and cytogenetic maps. The NTS gene is located on a yeast artificial chromosome contig that contains several polymorphic markers and is close to a polymorphic marker located at 95.8 cM on the Généthon linkage map. NTS is immediately proximal to four polymorphic markers, including D12S81 (AFM102xg9) and D12S88 (AFM158yb4). Using fluorescence in situ hybridization, we map the gene cytogenetically to band 12q21.

Animals

Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations.

To identify genes potentially relevant in atopic asthma, we analyzed markers in chromosome 12q15-q24.1 for linkage to asthma and total serum IgE concentration. Sib-pair analyses of 10 markers in 345 full- and 219 half-sib pairs from 29 multiplex Afro-Caribbean families provided evidence for linkage to this region for both asthma and total serum IgE. Certain alleles at these loci showed significant evidence of transmission disequilibrium with both asthma and high IgE. Using 6 of these markers and 11 additional markers, evidence for linkage of total IgE to 12q was also found in 12 Caucasian Amish kindreds (24 nuclear families) by both sib-pair and transmission disequilibrium analyses. These findings suggest that the 12q15-q24.1 region may contain a gene(s) controlling asthma and the associated "high total IgE" trait.

Adolescent

Physical mapping of a commonly deleted region, the site of a candidate tumor suppressor gene, at 12q22 in human male germ cell tumors.

A candidate tumor suppressor gene (TSG) site at 12q22 characterized by a high frequency of loss of heterozygosity (LOH) and a homozygous deletion has previously been reported in human male germ cell tumors (GCTs). In a detailed deletion mapping analysis of 67 normal-tumor DNAs utilizing 20 polymorphic markers mapped to 12q22-q24, we identified the limits of the minimal region of deletion at 12q22 between D12S377 (proximal) and D12S296 (distal). We have constructed a YAC contig map of a 3-cM region of this band between the proximal marker D12S101 and the distal marker D12S346, which contained the minimal region of deletion in GCTs. The map is composed of 53 overlapping YACs and 3 cosmids onto which 25 polymorphic and nonpolymorphic sequence-tagged sites (STSs) were placed in a unique order. The size of the minimal region of deletion was approximately 2 Mb from overlapping, nonchimeric YACs that spanned the region. We also developed a radiation hybrid (RH) map of the region between D12S101 and D12S346 containing 17 loci. The consensus order developed by RH mapping is in good agreement with the YAC STS-content map order. The RH map estimated the distance between D12S101 and D12S346 to be 246 cR8000 and the minimal region of deletion to be 141 cR8000. In addition, four genes that were previously mapped to 12q22 have been excluded as candidate genes. The leads gained from the deletion mapping and physical maps should expedite the isolation and characterization of the TSG at 12q22.

Chromosomes, Human, Pair 12

Heterogeneity of information-processing alterations according to dimensions of depression: an event-related potentials study.

To identify alterations in elementary cognitive operations according to dimensions of depression, two stages of information processing, namely the response choice and the motor preparation stages, were explored using an event-related potential paradigm in two subgroups of depressed patients (retarded and blunted affect versus anxious-agitated and impulsive) compared to controls. Two results are common to all depressed patients: a slow encoding of stimuli (P1 wave) and a prolonged processing of stimulus-response compatibility (after P3b). This is compensated by a global velocity increase in stimulus evaluation or decision making (P3b) in anxious-agitated patients or, on the contrary, cumulated with its velocity decrease in retarded-blunted-affect patients. Such results could provide an explanation for the massive retardation observed in blunted-affect patients, contrary to anxious-agitated patients, whose normal reaction times may come from a very high energetical involvement at the P3b level. Results as a whole suggest that impairments in blunted-affect patients concern effort mechanisms, whereas those in anxious-agitated patients concern perceptual processes.

Adult

Depression as a dynamical disease.

Mathematical models are helpful in the understanding of diseases through the use of dynamical indicators. A previous study has shown that brain activity can be characterized by a decrease of dynamical complexity in depressive subjects. The present paper confirms and extends these conclusions through the use of recent methodological advances: first episode and recurrent patients strongly differ in their dynamical response to therapeutic interventions. These results emphasize the need for clinical follow-ups to avoid recurrence and the necessity of specific therapeutic intervention in the case of recurrent patients.

Adult

Microsatellite instability and mutations of p53 and TGF-beta RII genes in gastric cancer.

To investigate the molecular mechanism of gastric carcinogenesis, we analyzed genetic instability and p53 gene mutations in 40 primary gastric carcinomas. Tumor samples were from untreated patients with no family history suggestive of genetic predisposition to cancer. We screened six microsatellite loci by the polymerase chain reaction (PCR) method, and exons 5-8 of the p53 gene by the PCR-based denaturing gradient gel electrophoresis and sequencing techniques. Microsatellite instability was detected in 32.5% (13/40), and gene mutations in 40% (16/40), of the tumors analyzed. No statistically significant associations were found between genetic alterations and clinico-pathological variables (with the exception of diffusion of lymph node metastases, which was inversely associated with the presence of microsatellite alterations; P < 0.01). Interestingly, a negative association was found between genetic instability and p53 gene mutations: 11 out of 13 tumors showing instability proved to carry a nonmutated p53 gene versus 2/13 carrying a mutated gene (P = 0.03). These observations suggest that genetic instability and p53 gene mutations play a crucial role in the gastric carcinogenic process, but likely act through distinct pathways during cancer development. However, genetic instability is not in and of itself neoplastic. Therefore, we investigated whether insertion/deletion mutations of the polyadenine tract within the transforming growth factor-beta type II receptor gene (TGF-beta RII) were frequently present in gastric tumors with an RER+ (replication error) phenotype. We found RII mutations in 8/40 (20%) samples: mutations were present in 7/13 (54%) RER+ tumors versus 1/27 (4%) RER- cases (P < 0.001).

DNA Mutational Analysis

Brain events related to normal and moderately scrambled faces.

The neural basis of normal and scrambled face processing was investigated by recording evoked potentials from 21 electrodes at standard EEG sites, with respect to a nose reference. Temporal negativities were found that result from two overlapping phenomena: they arise from the polarity reversal on temporal electrodes of the vertex P2, a positive wave peaking about 170-200 ms after the onset of a face stimulus, and also from an overlapping 'processing negativity' of long duration associated with the processing difficulty of the scrambled face stimulus. The comparisons of scalp potential and current density mappings support the proposal that some neuronal networks are active both for faces and scrambled faces and are compatible with the involvement of the superior temporal sulcus, the inferotemporal cortex and the parahippocampal and fusiform gyri, whereas the processing negativity would only involve the deepest generators of this network. Furthermore, the encoding of both faces and scrambled faces seems to take place predominantly in the right hemisphere.

Adult

[Bowel complications in gynecologic laparoscopic surgery and their immediate repair without laparotomy. Four cases].

Laparoscopic surgical procedures are increasing throughout the world, and with this increase in its utilization, a renewed interest in its possible complications. We presented four case reports of bowels injuries and their repair by laparoscopy. We reviewed the literature and discuss common complications with suggestions to avoid such injuries and for management. We conclude that small and large bowel enterostomies can be repaired safely via the laparoscope with minimum morbidity in patients with a prepared bowel. More serious complications occur if visceral trauma is not handled immediately. There is no place for adopting a "wait and see" approach.

Adult

N400-like potentials elicited by faces and knowledge inhibition.

Within the theoretical framework of reference, the brain errs in processing complex stimuli, such as faces. Thus, these stimuli not only activate accurate representations but also inaccurate representations corresponding to known persons who resemble the face stimulus, and hence knowledge about these known persons. Since more errors are made in processing unfamiliar than familiar stimuli, these inaccurate activations are assumed to be more frequent, and/or more intense, with unknown than with known faces. Moreover, top-down mechanisms favor representations of stimuli that are congruent with the context, and representations of known persons, even if inaccurate, receive an additional amount of activation in contexts wherein known faces are expected. Inaccurate representations have to be inhibited to achieve accurate recognition. Thus, more inhibition would be required for unknown than for known faces, and in contexts wherein known faces are expected. The aim of the present work is to study the hypothesis that the N400 component of the event-related potentials (ERPs) reflects the inhibition of knowledge, and to see whether this hypothesis accounts for the N400-like potential elicited by faces. To achieve that goal, ERPs to known and unknown faces were recorded while the richness in known faces of each experimental block, and thus the expectancy for known faces, was manipulated. Consistent with the hypothesis, the amplitudes of the N400-like components were greater in conditions where more inhibition was required, i.e. for unknown rather than for known faces, and in the context of the block rich in known faces. This context effect was larger for unknown than for faces, and in the context of the block rich in known faces. This context effect was larger for unknown than for known faces.

Adult

Localization of the human achaete-scute homolog gene (ASCL1) distal to phenylalanine hydroxylase (PAH) and proximal to tumor rejection antigen (TRA1) on chromosome 12q22-q23.

ASCL1, the human achaete-scute homolog, is a helix-loop-helix transcription factor that was previously assigned to chromosome 12 using a rodent-human somatic hybrid panel. We now placed this gene on a yeast artificial chromosome contig encompassing position 119 cM of the Généthon genetic map between the two genes phenylalanine hydroxylase (PAH) and tumor rejection antigen 1 (TRA1). We also localized ASCL1 in the 12q22-q23 cytogenetic interval by using fluorescence in situ hybridization.

Antigens, Neoplasm

A second-generation YAC contig map of human chromosome 12.

Human chromosome 12 constitutes approximately 4.5% of the human genome and has an estimated size of 135 million base pairs (Mb). We have started to construct a high-resolution physical map of chromosome 12 as overlapping yeast artificial chromosomes (YACs), using as a foundation the first-generation physical map of this chromosome covers nearly 102 Mb of DNA and includes 426 highly polymorphic, monomorphic and gene-based markers. We also mapped 119 of the YACs, most of which are part of the physical map, by cytogenetic methods. Thus the map integrates genetic, physical and cytogenetic data and provides information about the organization of this chromosome and will help in the localization and cloning of disease-related genes. The strategy used here to generate the chromosome-12 map could be applied for the rapid construction of physical and expression maps for other human chromosomes.

Base Sequence

A comparative study of ERP correlates of psychometric and Piagetian intelligence measures in normal and hyperactive children.

Verbal and performance scores of the Wechsler Intelligence Scale for Children-Revised (WISC-R 1981) and of a Piagetian battery, the Cognitive Development Scale for Children (EDC 1984), were obtained on 30 normal control and 19 hyperactive 6-8-year-old children. Amplitudes and latencies of a fronto-central P250 and of the parieto-occipital N250, P350 and P500 were measured concurrently in 4 categorization tasks derived from tests of the WISC-R and EDC batteries. Spearman correlations were computed between the intelligence and the ERP factor scores. Results showed that age-related and age-corrected Wechsler's scores were correlated with similar ERP changes (reduced amplitude, decreased latency). With regard to the amplitude changes, each type of intelligence was associated with a specific ERP pattern. The verbal scores were correlated with the P350 and the P500 amplitudes, and the performance scores with the frontal P250 and occipital N250 amplitudes. By contrast, Piagetian development and intelligence scores yielded ERP correlates in the opposite direction: P500 amplitude was negatively correlated with raw EDC scores, but positively with scaled EDC scores. In addition, Piagetian intelligence was not related to the general peak latency decrease with age. In hyperactive children, additional negative correlations were found between P250 amplitude and the subjects' verbal test scores. Correlations with some performance tests that were negative in normal controls, were positive in hyperactive children. In addition, latency-based correlations found in normal controls were lacking in hyperactive children. These findings provide strong evidence that intelligence comprises different components related to different subsets of cognitive processes, as indexed by different ERP waves. They also suggest that the development and intelligence do not always rely on the same changes, and that intelligence forms may not be referred to the same use of the same processes in hyperactive and normal children.

Attention Deficit Disorder with Hyperactivity