Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes.

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts' maps could uncover functionally and clinically related genes.

Feature extraction and signal processing for nylon DNA microarrays.

BACKGROUND: High-density DNA microarrays require automatic feature extraction methodologies and softwares. These can be a potential source of non-reproducibility of gene expression measurements. Variation in feature location or in signal integration methodology may be a significant contribution to the observed variance in gene expression levels. RESULTS: We explore sources of variability in feature extraction from DNA microarrays on Nylon membrane with radioactive detection. We introduce a mathematical model of the signal emission and derive methods for correcting biases such as overshining, saturation or variation in probe amount. We also provide a quality metric which can be used qualitatively to flag weak or untrusted signals or quantitatively to modulate the weight of each experiment or gene in higher level analyses (clustering or discriminant analysis). CONCLUSIONS: Our novel feature extraction methodology, based on a mathematical model of the radioactive emission, reduces variability due to saturation, neighbourhood effects and variable probe amount. Furthermore, we provide a fully automatic feature extraction software, BZScan, which implements the algorithms described in this paper.

[Memory disorders following rupture of anterior communicating artery aneurysm. 22 cases]. / Troubles mnésiques après rupture d'anévrysme de l'artère communicante antérieure. 22 cas.

Twenty-two patients who underwent surgery for ruptured aneurysm of the anterior communicating artery were investigated by a battery of neuropsychological tests, including memory evaluation tests. According to the results obtained at these tests the patients were divided into three groups: 1) 7 patients had no memory disorders; 2) 10 patients presented with memory disorders affecting memory; their complaints concerned behavior, and the memory deficit was discovered at neuropsychological examination; 3) 5 patients presented with an obvious amnesic syndrome, and the tests confirmed a severe learning deficit and a severe forgetting while recognition remained normal in 4 patients. Age, residual lesions at CT and electrophysiological signs of focalization correlated well with the residual neuropsychological disorders. Leaving aside quantitative aspects, the memory deficits observed in the second and third groups seemed to be qualitatively different and might correspond to different anatomical and functional sequelae.

[Treatment of Parkinson tremor by chronic stimulation of the ventral intermediate nucleus of the thalamus]. / Traitement du tremblement parkinsonien par stimulation chronique du noyau ventral intermédaire du thalamus.

Stereotactic ventral intermediate nucleus (Vim) thalamotomy may improve drug resistant severe parkinsonian tremor. However, tremor may recur and bilateral thalamotomy is known to induce unacceptable side effects in a proportion of patients. A high frequency (130 Hz) chronic Vim stimulation was performed in 4 parkinsonian patients, 2 of them having previously undergone a thalamotomy on the other side. Tremor was suppressed in all patients at the price of slight paresthesias. This improvement has been lasting from 2 to 14 months. Beneficial and adverse effects were suppressed at once each time the stimulation was stopped. These preliminary results are encouraging but a longer delay and more patients are obviously needed.

[Catheterization of the inferior petrosal sinus. Its role in the diagnosis of Cushing's syndrome. Experience with 23 explorations]. / Le cathétérisme des sinus pétreux inférieurs. Sa place dans le diagnostic du syndrome de Cushing. Expérience de 23 explorations.

Selective catheterization of the inferior petrosal sinus has been performed in 23 patients: 11 Cushing's disease, 5 lung carcinoid tumors whose diagnosis has been confirmed by surgery and 7 ACTH-dependent hypercortisolism whose final diagnosis has not yet been proved. The pituitary origin of hormone secretion is accepted if the central-to-peripheral ratio (C/PR) is equal or greater than 2 on basal values and/or during CRF test. On basal values, all subjects but one with confirmed pituitary lesions exhibited a C/PR > or = 2; the carcinoid tumors never exceeded the value of 1.3. After CRF injection, all the pituitary tumors showed an increase in C/PR; one patient with a lung carcinoid tumor (CRF-negative) showed a pituitary ACTH secretion (C/PR = 3.7). The localization of pituitary adenoma by the lateralization of hormone secretion is disappointing, except, perhaps, for very small extremely lateral adenomas. No accident occurred in our series, nor in the literature. This investigation seems the most reliable approach to prove the pituitary origin of hormonal hypersecretion. We recommend it to be performed in ACTH-dependent Cushing's syndrome when the secretory pattern is not typical and/or pituitary imaging is normal.

[Our experience with surgery of neuromas of the 8th nerve]. / Notre expérience de la chirurgie des neurinomes du VIII.

Before 1982 the suboccipital approach was reserved for neurinomas larger than 2 cm diameter, whereas since that date the translabyrinthine approach has been employed in all cases where no attempt was made to preserve hearing. Of the 85 patients operated upon between 1978 and 1985, 5 were through a supra-petrous approach, 35 a retro-sigmoid approach, 44 a translabyrinthine approach and one by a transotic approach. Translabyrinthine approaches allowed the best postoperative course and conservation of normal facial motility in 22 patients of 33 with stages II and III lesions. An attempt was made to preserve hearing in 9 patients, with one reasonable result by the supra-petrous approach and 2 satisfactory results including one perfect operated upon using a rectosigmoid approach.

[Technical considerations on lumbar disk surgery. Results of a survey of 49 centers]. / Considérations techniques sur la chirurgie discale lombaire. Résultats d'une enquête portant sur 49 centres.

The lumbar discectomy, how do you see it? That could be the title of this inquiry which 49 neurosurgeons answered. At first we discuss the timing of the operation (as a rule sooner than the conventional indication of the third month) the use of operative microscope which is still uncommon (11 surgeons out of 49) and the operative policy. The more specific technical features regarding the different stages of the operation are then analysed. Opinions of neurosurgeons differ on many points particularly on the ligament and bone removal which exposes the disco-radicular conflict: whereas one third of the neurosurgeons refuse to open the lumbar facet joint, one third always open it widely and the remaining third take a mid-way position. On the whole, this inquiry points cut both a great diversity in technical details, but also a stagnation because this operation hardy improved and only slightly benefited from the technical progress.

[Hyperproduction of CSF in choroid plexus papillomas in children]. / L'hyper-production de LCR dans les papillomes du plexus choroïde de l'enfant

Two cases of papilloma of the choroid plexus in children, one in the fourth ventricle and the other in the central part of the left lateral ventricle, are reported. Hyperproduction of CSF could be suspected in the first case by the productive character of pre-operative external ventricular drainage and demonstrated in the second by measurement of pre and post-operative flow rates through a ventriculo-peritoneal bypass which had been installed previously. The origin of this over-production of CSF is discussed, in the pathogenesis of hydrocephalus, in comparison with other factors such as subarachnoid haemorrhage, hyperproteinorachia impairing the resorption of CSF.

[Delineation of brain tumors by stereo-impedo-encephalography (SIEG) (author's transl)]. / Délimitation des tumeurs cérébrales par stéréo-impedo-encéphalographie (SIEG).

Authors describe the SEEG technique which is routinely used during stereotactic investigations of brain tumors. By the way of the Talairach's stereoencephalographic electrodes, the brain tissue impedance is measured along the probe trajectory with a four electrode impedancemeter (0.25 mA; 5 KHz). The impedance profile provides a good pattern of the brain structures which are crossed; in pathological areas, the impedance significantly decreases as well in gliomas as in edema; cysts and CSF spaces also decrease the recorded impedance. As a contrary, metastases and meningiomas increase the impedance. SEEG appears to be a sharp method for stereotactic delineation of the brain tumors; a larger series as well as the real-imaginary decomposition of the impedance are needed for a best selectivity of the method.

[Surgery of acoustic neurinoma. Apropos of a personal series. Development of techniques and results]. / La chirurgie du neurinome de l'acoustique. A propos d'une série personnelle. Evolution des techniques et résultats.

Between 1973 and 1987, 125 acoustic neurinomas were operated on in oto-neuro-surgery. The sub-occipital approach route was used for Stages III and IV up to 1982 (30 cases). Subsequently, surgery for all the neurinomas used the translabyrinthine approach route (82 cases), except for those cases where an attempt was made to preserve hearing by a supra-petrosal route (6 cases) or a retrosigmoid route (6 cases). The translabyrinthine approach route provided the simplest sequellae and the best preservation of the function of the facial nerve: grades I and II in 68% of cases (in 80% of cases by excluding Stage IV). Preservation of hearing was perfect in 2 cases, and partial in 2 cases, out of 12 attempts. The use of a facial nerve monitor proved highly satisfactory.

Genome-wide re-sequencing of multidrug-resistant Mycobacterium leprae Airaku-3.

Genotyping and molecular characterization of drug resistance mechanisms in Mycobacterium leprae enables disease transmission and drug resistance trends to be monitored. In the present study, we performed genome-wide analysis of Airaku-3, a multidrug-resistant strain with an unknown mechanism of resistance to rifampicin. We identified 12 unique non-synonymous single-nucleotide polymorphisms (SNPs) including two in the transporter-encoding ctpC and ctpI genes. In addition, two SNPs were found that improve the resolution of SNP-based genotyping, particularly for Venezuelan and South East Asian strains of M. leprae.