Prenatal ultrasound diagnosis of a 48,XXYY syndrome.

The 48,XXYY syndrome is a rare uncommon gonosome aneuploidy and its incidence is estimated to be 1:18,000-1:40,000. The phenotype associated with this syndrome, classically described as Klinefelter variant, is extremely variable but developmental abnormalities are always present. Ultrasound signs during pregnancy are inconsistent, and only three prenatal cases have been described in the literature. Here, we report a case of 48,XXYY syndrome identified in prenatal period because of the presence of polyhydramnios and bilateral clubfeet on second trimester ultrasound. This observation shows the importance of chromosomal prenatal diagnosis in cases with bilateral clubfeet on morphologic ultrasound. This diagnosis is essential for further characterization of the prenatal phenotype and to improving genetic counselling.

The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and SMAC/Diablo.

ARTS (Sept4_i2) is a pro-apoptotic tumor suppressor protein that functions as an antagonist of X-linked IAP (XIAP) to promote apoptosis. It is generally thought that mitochondrial outer membrane permeabilization (MOMP) occurs before activation of caspases and is required for it. Here, we show that ARTS initiates caspase activation upstream of MOMP. In living cells, ARTS is localized to the mitochondrial outer membrane. In response to apoptotic signals, ARTS translocates rapidly to the cytosol in a caspase-independent manner, where it binds XIAP and promotes caspase activation. This translocation precedes the release of cytochrome C and SMAC/Diablo, and ARTS function is required for the normal timing of MOMP. We also show that ARTS-induced caspase activation leads to cleavage of the pro-apoptotic Bcl-2 family protein Bid, known to promote MOMP. We propose that translocation of ARTS initiates a first wave of caspase activation that can promote MOMP. This leads to the subsequent release of additional mitochondrial factors, including cytochrome C and SMAC/Diablo, which then amplifies the caspase cascade and causes apoptosis.

Prenatal diagnosis of a rare de novo centromeric chromosome 6 variant.

Cytogenetic heteromorphisms are described as heritable variations at specific chromosomal regions without phenotypic effect. Polymorphisms of the size of heterochromatic centromeric regions of chromosomes 1, 9 and 16 have been well documented in humans but only four previous reports described centromeric polymorphism of chromosome 6. We present a prenatal diagnosis of a rare de novo centromeric chromosome 6 variant. Cytogenetic and molecular techniques were used to characterize this variant and confirm the de novo nature of this event. This case illustrates the importance of reporting unusual variant chromosomes for genetic counseling and for determination of the frequency of variant chromosomes in the general population.

Encoding, rehearsal, and recall in signers and speakers: shared network but differential engagement.

Short-term memory (STM), or the ability to hold verbal information in mind for a few seconds, is known to rely on the integrity of a frontoparietal network of areas. Here, we used functional magnetic resonance imaging to ask whether a similar network is engaged when verbal information is conveyed through a visuospatial language, American Sign Language, rather than speech. Deaf native signers and hearing native English speakers performed a verbal recall task, where they had to first encode a list of letters in memory, maintain it for a few seconds, and finally recall it in the order presented. The frontoparietal network described to mediate STM in speakers was also observed in signers, with its recruitment appearing independent of the modality of the language. This finding supports the view that signed and spoken STM rely on similar mechanisms. However, deaf signers and hearing speakers differentially engaged key structures of the frontoparietal network as the stages of STM unfold. In particular, deaf signers relied to a greater extent than hearing speakers on passive memory storage areas during encoding and maintenance, but on executive process areas during recall. This work opens new avenues for understanding similarities and differences in STM performance in signers and speakers.

Molecular-genetic biodiversity in a natural population of the yeast Saccharomyces cerevisiae from "Evolution Canyon": microsatellite polymorphism, ploidy and controversial sexual status.

The yeast S. cerevisiae is a central model organism in eukaryotic cell studies and a major component in many food and biotechnological industrial processes. However, the wide knowledge regarding genetics and molecular biology of S. cerevisiae is based on an extremely narrow range of strains. Studies of natural populations of S. cerevisiae, not associated with human activities or industrial fermentation environments, are very few. We isolated a panel of S. cerevisiae strains from a natural microsite, "Evolution Canyon" at Mount Carmel, Israel, and studied their genomic biodiversity. Analysis of 19 microsatellite loci revealed high allelic diversity and variation in ploidy level across the panel, from diploids to tetraploids, confirmed by flow cytometry. No significant differences were found in the level of microsatellite variation between strains derived from the major localities or microniches, whereas strains of different ploidy showed low similarity in allele content. Maximum genetic diversity was observed among diploids and minimum among triploids. Phylogenetic analysis revealed clonal, rather than sexual, structure of the triploid and tetraploid subpopulations. Viability tests in tetrad analysis also suggest that clonal reproduction may predominate in the polyploid subpopulations.

[Von Hippel-Lindau syndrome with spinal, cerebellar, and retinal hemangioblastoma in identical twins]. / Von-Hippel-Lindau-Syndrom mit spinalen, zerebellären und retinalen Hämangioblastomen bei eineiigen Zwillingen.

We report about a case of a 22-year-old women who was admitted because of sudden and painless proximal paraparesis, sensory loss at distal L 1, and bladder dysfunction. In MRI, cystic lesions in the spinal cord were identified at C 1,C 6,T 1,T 6,and T 11 as well as in the cerebellum.A tentative diagnosis of spinal hemangioblastomas was confirmed by spinal angiography and postoperative histology of the symptomatic tumor at T11.Furthermore, retinal hemangioblastomas were detected by fluorescence angiography and treated with laser surgery. Based on the clinical findings,we assumed the diagnosis of von Hippel-Lindau syndrome (vHL).Postoperatively, the paraparesis and sensory deficit improved, but the bladder dysfunction persisted. The patient's identical twin was screened for hemangioblastomas, too, and spinal, retinal, and one cerebellar tumor with a nearly identical location pattern were found. There was no evidence for pancreatic, adrenal, or renal involvement in both twins. The twins were investigated for inactivating mechanisms of the vHL germline mutations using single-strand conformational polymorphism (SSCP) and Southern blotting, but none of the known germline mutations were identified. Because the family history is devoid of vHL disease, spontaneous mutation might be causal for the syndrome in our patients.

Encephalitis related to primary varicella-zoster virus infection in immunocompetent children.

INTRODUCTION: Encephalitis is a rare complication of primary varicella-zoster virus (VZV) infection in immunocompetent children. METHODS: The clinical and laboratory findings of two girls with VZV-related encephalitis are reported. RESULTS: Both children presented with focal epileptic seizures, corresponding to cortical/subcortical as well as white matter lesions. The first showed a typical vesicular skin rash. She was easily diagnosed and made a rapid recovery during acyclovir and steroid treatment. In the second girl, a preceding measles-mumps-rubella virus vaccination and the absence of skin vesicles were misleading with respect to the diagnosis, which was finally proven by IgG seroconversion and intrathecal synthesis of IgG antibodies to VZV. She developed left parieto-occipital tissue necrosis and recovered only transiently during initial acyclovir/steroid treatment. Eight weeks after onset, progressive white matter demyelination and the occurrence of erythema nodosum in the lower limbs necessitated a second 4-month course of oral steroids. The VZV PCR from cerebrospinal fluid was negative in both children. CONCLUSIONS: Primary VZV infection may cause severe encephalitis that may occur without skin vesicles and lead to a chronic course with systemic vasculitis. The coincidence of vaccination and neurologic diseases offers no proof per se of a causal relationship.

Metabolic and electrophysiological validation of functional MRI.

OBJECTIVES: Although functional MRI is widely used for preoperative planning and intraoperative neuronavigation, its accuracy to depict the site of neuronal activity is not exactly known. Experience with methods that may validate fMRI data and the results obtained when coregistering fMRI with different preoperative and intraoperative mapping modalities including metabolically based (18)F-fluorodeoxyglucose PET, electrophysiologcally based transcranial magnetic stimulation (TMS), and direct electrical cortical stimulation (DECS) are described. METHODS: Fifty patients were included. PET was performed in 30, TMS in 10, and DECS in 41 patients. After coregistration using a frameless stereotactic system, results were grouped into overlapping (<1 cm distance), neighbouring (<2 cm), or contradictory (>2 cm). RESULTS: Comparing fMRI with PET, 18 overlapping, seven neighbouring, and one contradictory result were obtained. In four patients no comparison was possible (because of motion artefacts, low signal to noise ratio, and unusual high tumour metabolism in PET). The comparison of TMS and fMRI showed seven overlapping and three neighbouring results. In three patients no DECS results could be obtained. Of the remaining 38 patients, fMRI hand motor tasks were compared with DECS results of the upper limb muscles in 36 patients, and fMRI foot motor tasks were compared with DECS results of the lower limb on 13 occasions. Of those 49 studies, overlapping results were obtained in 31 patients, and neighbouring in 14. On four occasions fMRI did not show functional information (because of motion artefacts and low signal to noise). CONCLUSIONS: All validation techniques have intrinsic limitations that restrict their spatial resolution. However, of 50 investigated patients, there was only one in whom results contradictory to fMRI were obtained. Although it is not thought that fMRI can replace the intraoperatively updated functional information (DECS), it is concluded that fMRI is an important adjunct in the preoperative assessment of patients with tumours in the vicinity of the central region.

Asymmetries of visual attention after circumscribed subcortical vascular lesions.

OBJECTIVE: To investigate the role of the basal ganglia and the thalamus for basic processes of visuospatial attention METHODS: Fifteen patients with acute circumscribed vascular lesions (10 with haemorrhage and five with infarction) were included in the study. The lesions were confined exclusively to subcortical structures, such as the basal ganglia, internal capsule, and thalamus, which was confirmed by initial CT on the day of referral and MRI taken 14-28 days after clinical onset. These patients were examined with two computerised attentional tasks (one detection and one search task) measuring spatial visual attention. RESULTS: There was a clear attentional asymmetry in patients with right hemispheric lesions (RHLs) in the visual search task. Seven out of eight patients with RHLs tended to be slower and/or missed significantly more target stimuli in the left sided part of a stimulus array consisting of 25 small squares than in right sided parts, although none of these patients showed signs of visual hemineglect in the visual detection task presenting visual information simultaneously to the right and left visual hemispace. All but one of these patients showed lesions in the posterior limb of the internal capsule and the putamen. On the other hand, patients with left hemispheric lesions were not impaired in the search task with only one patient showing more contralesional omissions of target stimuli than could be expected from the behaviour of normal controls. CONCLUSIONS: The results are in line with previous results showing a dominant role of right hemispheric neuronal structures for spatial attention. Furthermore, the data suggest that even with right hemispheric subcortical lesions without cortical involvement deficits in spatial orienting of attention to the left hemispace can be seen. These asymmetries of visual attention in the absence of neglect symptoms are supposed to be caused (1) by a disruption of the motor corticostriato-pallidothalamo-cortical neuronal circuit or (2) by a (partial) disconnection of relevant parts within the posterior attention network-namely, parietal and thalamic structures.

Optical resolution of 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline by supercritical fluid extraction.

6-Fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ) enantiomers were separated by supercritical fluid extraction using carbon dioxide. Diastereoisomeric salts were formed from the racemic base with less than one equivalent of O,O'-di-(4-toluoyl)-(2R,3R)-tartaric acid (DPTTA). Further purification was achieved by partial salt formation of the enantiomeric mixture with an achiral acid (HCl) followed by the supercritical fluid extraction of the free enantiomers.

Functional MRI for presurgical planning: problems, artefacts, and solution strategies.

OBJECTIVES: Presurgical mapping of motor function is a widely used clinical application of functional (f) MRI, employing the blood oxygenation level dependent contrast. The aim of this study was to report on 3 years experience of 194 fMRI studies on the representation of motor function in 103 patients and to describe the problems and artefacts that were typically present. METHODS: An evaluation was carried out to determine whether the patients' age, type or location of the tumourous lesion, severity of the paresis, or the tasks used during the investigation have an effect on artefacts of fMRI studies and how these artefacts are best overcome. RESULTS: Functional MRI identified the motor regions in 85% of all investigated paradigms. In 11% of the investigated patients no information at all on functional localisation was obtained. A draining vein within the central sulcus was present in all patients that showed activation within the parenchyma of the precentral gyrus but also in three patients in whom no parenchymal activation was present. Head movement artefacts were the most frequent cause for fMRI failure, followed by low signal to noise ratio. Motion artefacts were correlated with the degree of paresis and with the functional task. Tasks involving more proximal muscles led to significantly more motion artefacts when compared with tasks that primarily involved distal muscles. Mean MR signal change during task performance was 2.5%. CONCLUSIONS: Most of the artefacts of functional MRI can be reliably detected and at least in part be reduced or eliminated with the help of mathematical algorithms, appropriate pulse sequences and tasks, and-probably most important-by evaluating the fMRI raw data-that is, the MR signal time courses.

Navigated transcranial magnetic stimulation for presurgical planning--correlation with functional MRI.

PURPOSE: This paper describes the potential of navigated transcranial magnetic stimulation to map the motor cortex in patients with mass lesions near the primary motor cortex by comparing the results of this technique to those of functional MRI. MATERIAL AND METHODS: Ten patients with mass lesions near the central sulcus were studied preoperatively using a figure-of-eight transcranial magnetic stimulator attached to a neuronavigation system to allow for direct visualization of the stimulated brain region. Subsequently, in all patients a blood oxygenation level dependent 2D multislice multishot T2*-weighted gradient echo EPI sequence on a 1.5 T Philips Gyroscan during motor activation was performed. Results of both methods were coregistered and compared. RESULTS: The distances between the peak parenchymal fMRI activation and the cortical area where TMS elicited the maximum MEPs ranged between 0 and 1.2 cm (mean 0.6 cm, SD 0.4 cm). CONCLUSION: We conclude that navigated TMS is a reliable alternative for localizing the motor-related areas in the human brain preoperatively and therefore may be a useful adjunct or, in selected patients, even a helpful alternative to functional MRI.

The representation of the plegic hand in the motor cortex: a combined fMRI and TMS study.

TMS mapping and fMRI were used to investigate changes in the motor cortex representation of the hand in a patient with complete loss of right hand function following traumatic avulsion of the cervical roots C7 and C8. Both TMS and fMRI demonstrated an expansion of the motor representation of the forearm into the hand area contralateral to the injured side. fMRI of the hand area, however, revealed that this area could still be activated when the patient was instructed to imagine finger tapping with his plegic hand. These results indicate that the plegic hand is still represented in the motor cortex, despite the fact that the same cortical area is also now active during movements involving forearm muscles.