Biomedical subjects
Publications and source records attributed to S Guillou.
A yeast artificial chromosome library containing 33,000 clones with an average insert size of one megabase of human genomic DNA was extensively analysed by several different procedures for detecting overlaps and positional information. We developed an analysis strategy that resulted, after confirmatory tests, in a YAC contig map reliably covering about 75% of the human genome in 225 contigs having an average size of about ten megabases.
A continuous array of overlapping clones covering the entire human chromosome 21q was constructed from human yeast artificial chromosome libraries using sequence-tagged sites as landmarks specifically detected by polymerase chain reaction. The yeast artificial chromosome contiguous unit starts with pericentromeric and ends with subtelomeric loci of 21q. The resulting order of sequence-tagged sites is consistent with other physical and genetic mapping data. This set of overlapping clones will promote our knowledge of the structure of this chromosome and the function of its genes.
A new approach for the isolation of chromosome-specific subsets from a human genomic yeast artificial chromosome (YAC) library is described. It is based on the hybridization with an Alu polymerase chain reaction (PCR) probe. We screened a 1.5 genome equivalent YAC library of megabase insert size with Alu PCR products amplified from hybrid cell lines containing human chromosome 21, and identified a subset of 63 clones representative of this chromosome. The majority of clones were assigned to chromosome 21 by the presence of specific STSs and in situ hybridization. Twenty-nine of 36 STSs that we tested were detected in the subset, and a contig spanning 20 centimorgans in the genetic map and containing 8 STSs in 4 YACs was identified. The proposed approach can greatly speed efforts to construct physical maps of the human genome.
79 subjects (mean age 70.2 ans, 31 males, 48 females) selected as probable dementia of the Alzheimer type, at the early stage of the disease and 17 normal aged people (mean age: 72.2, 5 males, 12 females) were recorded with a 16 channel computerized-EEG (C-EEG) with topographical analysis of the observed changes and with classical visual analysis of the EEG. Quite simple C-EEG parameters as mean dominant frequency (MF) and alpha to theta ratio are able to discriminate patients from normal with a greater accuracy than visual analysis. The values of 8.6 for the MF and 1.3 for the alpha/theta ratio are proposed as cut off values between normal and DAT patients. The topographical analysis appear to be of no additional usefulness in the discrimination of the two groups.
Forty-one patients with probable dementia of the Alzheimer type (DAT) have been studied by computerized EEg (C-EEG) and single photon emission tomography (SPECT) using 123-IMP. Four groups have been distinguished according to SPECT hypoperfusion topography: frontal, temporo-parietal, fronto-parietal and fronto-temporo-parietal. C-EEG parameters were much more disturbed in the 2 latter than in the 2 former groups. Thus a normal C-EEG could indicate a dominant frontal or temporo-parietal form of DAT. Therefore some bias due to duration or rate of disease progression cannot be excluded. So far the important finding is that EEG changes are diffuse and do not reflect the topography of SPECT hypoperfusion questioning the value of EEG topographical analysis in DTA.
Twenty patients selected as probable dementia of the Alzheimer type (DAT) have been examined two times during a mean follow-up period of 14.5 months. Two groups have been distinguished at the end of this period: a cognitively impaired one and a stable one. EEG features at T1, at T2 or the difference T1-T2 does not allow an accurate and predictive discrimination between the two groups. But we cannot conclude that EEG is useless for prediction of the rate of progression of the disease in DAT because most of the cognitively stable patients are also stable for mean frequency. So mean frequency could be an interesting marker of evolutivity but this to be tested with more patients including more subjects reaching the severe stage of dementia.
Latencies, amplitudes and localization of the maximum of the peaks of late onset evoked responses have been studied in 3 groups of elderly people: normal, depressed and demented (probable dementia of Alzheimer type DAT) at the early stage of the disease. Evoked responses with an auditory oddball paradigm have been recorded with 16 electrodes in 2 situations: counting the target sounds, and motor response with measurement of the reaction time. No difference in amplitude was observed between the 3 groups. Only a significant difference for P3 latency was observed between the DAT and the depressed groups and only in the counting situation. The maximum P3 response was most often found on the anterior areas in the DAT group and in the posterior areas in the normal and depressed groups. The topographic localization of the P3 peak could therefore be of some help in the characterize of subjects with probable DAT at the early stage of the disease.
A group of 10 subjects, normal volunteers (6 men, 4 women), mean age 27.2 years, right-handers, has been selected for a double-blind study of caffeine effects (400 mg per os) versus placebo. One week delay separated the two EEG sessions quantified by spectral analysis. During each session (16 EEG channels, common reference), each subject was recorded four times: 2.5 min, in eyes-closed condition, under diffuse attention, followed by 2.5 min, during a visuo-spatial task ("eyes open" condition: presentation of a picture). These two EEG recordings were obtained before the oral administration and repeated 1 hr after the administration of caffeine or placebo. Individual and group results presented globally: 1) an increase in mean frequencies of alpha activity in "eyes closed" condition, and of delta activity in "eyes open" condition; 2) a decrease of alpha activity amplitudes (both RMS and % values) in both conditions; 3) a decrease of total RMS amplitudes in "eyes closed" condition; 4) an increase of relative % amplitudes for beta 2% fast activity in the "eyes open condition". These results characterize the psycho-stimulant effects of caffeine, especially over the left temporal area which was confirming an initial statistical hypothesis of specific cerebral local activation. The non-parametric permutation tests of Fisher, were not always reaching statistical significance for the same EEG channel quantified by one of the 17 analyzed spectral parameters, except on the left temporal area. During the visuo-spatial task, the decrease in alpha amplitudes (RMS and %) was also statistically significant, but over larger areas: over left and right temporal, central and parietal regions. In both conditions, eyes closed and eyes open, the alpha RMS amplitude was also decreased over the right anterior frontal area.
A night of sleep has been recorded under the conditions of a sleep laboratory. The subject was a woman of 55 years, well-trained in dream recall. The subject was awakened three times at the end of sleep cycles. EEG was monitored for 7 h with a 16-channel polygraph (REEGA 16, Alvar) connected to two systems of EEG cartography: minicomputers (HP Fourier Analyser 5451 C and HP 1000) and a microinformatic system (Cartovar, Alvar). A second 8-channel polygraph (Mini-huit, Alvar) was used in parallel for polygraphy (EOG, EMG, respiration, actogram, EKG). Based on immediate visual inspection of EEG and polygraphic tracings, 500 EEG recordings of selected epochs (of 6, 30 or 60 s length) have been quantified, submitted on-line to spectral analysis (on Cartovar) and stored on floppy disks for further printing of EEG maps. The 16 EEG channels were placed over the scalp according to the 10/20 system and following Giannitrapani's placement. We have chosen a common average electrode. For each of the 500 EEG epochs, four EEG maps were edited (raw EEG between 0 and 30 Hz, 0 and 7 Hz, 8 and 12 Hz, 13 and 30 Hz). Each of these 2,000 maps has been checked visually in comparison with the polygraphic recordings for visual rejection of artifacts or transitory states. The remaining EEG epochs and EEG maps, scored by 2 independent trained sleep scorers, were classified into stages I, II, III-IV, and REM, apart from control runs of active wakefulness with eyes open (EO) and quiet wakefulness with eyes closed (EC), which were undertaken on mini- and microsystems of EEG analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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Twenty young volunteers (10 men, 10 women), righthanded, students, have been recorded in EEG cartography in different situations. We have compared the quantified EEGs when the subjects were resting, eyes closed and later, eyes opened, looking at a cartoon. The EEGs were quantified by spectral Fourier analysis and submitted to data reduction. Ten spectral parameters were computed, yielding 51 variables allowing computations and drawings of 90 EEG maps. Mean parameters, mean variables, averaged EEG maps have been computed for the entire group, between sub-groups, between hemispheres. Non-parametric permutation Fisher tests have been applied for statistical comparisons and statistical validations of the EEG maps computed between subjects. The activation of EEG tracings produced by the opening of the eyes were caracterized topographically by: mean alpha frequencies increased over temporal and rolandic areas; mean alpha amplitudes in microV divided by a factor 3 for occipital areas but unchanged in topography; mean relative amplitudes divided by a factor 2 but with a topography being more parietal than occipital for the alpha rhythm; a resonance coefficient greater over the left parietal than the right (alpha more regular), whereas it was greater over the right occipital than the left during the resting condition. Statistically for the whole group, the left hemisphere, recorded after the right, is more 'activated' in the eyes closed situation. During visual attention, the left hemisphere is less activated than the right.
An electric potential measurement tells us only about the difference between two electrode locations. When prior experiments or present measurements prove that an electrode's location is inactive (especially in 'mono-polar' or scalp-to-reference technique), then EEG records and EEG maps can be interpreted regionally near each electrode location. Topographical mapping requires spatial interpolation which is one factor involved in spatial resolution. The interpolation algorithm has been studied by changing the power exponent n of the interelectrode distance d. When n is close to zero, interpolated values are all equal to the average of the four electric potential measurement Vs bounding the quadrilateral in which the interpolated points of the EEG map are located. When n is very high (n = 20 or higher), the values are essentially equal to the V which is at the minimum distance d. For n = 1, the map seems unlikely to represent the true scalp field. The choice between n = 2 and n = 3 is difficult, but n = 3 EEG mapping looks better (more plausible) and is our regular choice. The choice of recording/reporting method has also been studied. If the quantitative EEG map is linearly calculated from observations, the interpretation of record activity resulting from charge separation near the non-reference electrode attached to a particular channel is only possible when inactivity can be assured. This is completely different when the quantity mapped is not linearly calculated from observations (like power values or rms amplitudes in microvolts).(ABSTRACT TRUNCATED AT 250 WORDS)