Delineation of an estimated 6.7 MB candidate interval for an anophthalmia gene at 3q26.33-q28 and description of the syndrome associated with visible chromosome deletions of this region

Anophthalmia or microphthalmia occur in approximately one in 10 children who have severe visual impairment. These eye malformations are often of unknown aetiology, but can be inherited in autosomal dominant, recessive or X-linked forms, and can also occur in association with specific chromosome abnormalities. Four children are described in the medical literature with microphthalmia or anophthalmia in association with chromosome rearrangements involving distal 3q, suggesting the presence of a micro/anophthalmia gene in this region. We have identified two further patients with micro/anophthalmia and chromosome rearrangements involving 3q26-->3q27 and identified a 6.7 MB common deleted region. Patient 1 had multiple abnormalities including bilateral anophthalmia, abnormalities of the first and second cranial nerves and partial absence of the corpus callosum. His karyotype was 46,XY,del(3)(q26.33q28). Patient 2 had right anophthalmia and left extreme microphthalmia. Her karyotype was 46,XX,del(3)(q26.33q28)t(3;7)(q28;q21.1). Both patients had intrauterine growth retardation (IUGR) and strikingly similar dysmorphic facies consisting of bossed forehead, downward-slanting palpebral fissures, grooved bridge of the nose, prominent low-set ears, small down-turned mouth and small mandible. We identified BAC clones mapping to distal 3q from the ENSEMBL and NCBI Entrez databases. These BAC clones were used as fluorescence in situ hybridisation (FISH) probes to identify the minimum deleted region common to both patients. This interval, between clones RPC11-134F2 and RPC11-132N15, was estimated to be 6.7 MB. We conclude that there is an anophthalmia locus within this interval. Candidate genes mapping to this region include Chordin and DVL3, a homologue of the Drosophila Dishevelled gene.     

Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1

Lipoproteins or lipopeptides (LP) are bacterial cell wall components detected by the innate immune system. For LP, it has been shown that TLR2 is the essential receptor in cellular activation. However, molecular mechanisms of LP recognition are not yet clear. We used a FLAG-labeled derivative of the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (Pam(3)CSK(4)) to study the roles of CD14, TLR2 and TLR1 in binding and signaling of LP and their molecular interactions in human cells. The activity of Pam(3)CSK(4)-FLAG was TLR2 dependent, whereas the binding was enabled by CD14, as evaluated by flow cytometry and confocal microscopy. Using FRET and FRAP imaging techniques to study molecular associations, we could show that after Pam(3)CSK(4)-FLAG binding, CD14 and Pam(3)CSK(4)-FLAG associate with TLR2 and TLR1, and TLR2 is targeted to a low-mobility complex. Thus, LP binding to CD14 is the first step in the LP recognition, inducing physical proximity of CD14 and LP with TLR2/TLR1 and formation of the TLR2 signaling complex.     

Occupational stress in migraine is weekend headache a myth or reality?

To determine whether or not the frequency of migraine attacks increased at weekends in employed patients and if so, whether or not this was related to the type of migraine, 35 female patients prospectively recorded the presence or absence of migraine attacks daily over a six-week period. They were also asked to estimate the frequency with which emotional factors predisposed to their migraine attacks and to provide details of their occupation. A diagnosis of common (migraine without aura) or classical migraine (migraine with aura) was made according to both the criteria of the Ad Hoc Committee on the Classification of Headache and those of the International Headache Society. Eleven percent and 6% of patients, respectively, felt that emotional factors "usually" or "always" predisposed to migraine attacks. There was no significant increase in the frequency of migraine attacks at weekends in either the total group or in the employed patients. Similarly, the type of migraine made no difference to the results. There was therefore no evidence for a delayed onset of migraine at weekends related to the weekday stress of employment.     

Control of the Biofouling Mollusc,Dreissena polymorpha (Bivalvia: Dreissenidae), with sodium hypochlorite and with polyquaternary ammonia and benzothiazole compounds

Small adult zebra mussels (Dreissena polymorpha), 2–8 mm valve length, collected from Lake St. Clair were exposed to a range of concentrations of three biocides in static, acute toxicity tests in the laboratory. Laboratory conditions (22°C; pH 7.8; water hardness 100 mg/L) were representative of midsummer conditions in the nearshore of Lakes Erie and St. Clair. Mussels actively colonized styrene test substrates which were transferred to three replicate, 1-L test vessels. Sodium hypochlorite was an effective biocide at concentrations exceeding 1.00 mg/L and resulted in complete mortality of mussels by 157 and 264 h at concentrations of 5.00 and 2.50 mg/L, respectively. Poly [oxyethylene (dimethylimino) ethylene (dimethylimino) ethylene dichloride] at 1,2,4 and 8 mg/l and (2-(thiocyanomethylthio) benzothiazole) at 0.5,1,2 and 4 mg/L resulted in 100% mortality at all concentrations in times ranging from 144 to 250 h and 110 to 192 h, respectively. Biocide concentration significantly affected the mean time of death for all three of the compounds tested. Mussel valve length had a significant positive effect on time of death in (2-(thiocyanomethylthio) benzothiazole) but only explained a maximum 18% of the variance. Resistance of these actively colonizing mussels to biocides was greater than that found by other laboratory studies, perhaps because of lowered handling stress in our experimental manipulations.     

Linear Accelerator Configurations for Radiosurgery

The dramatic proliferation of radiosurgery in the 1980s and 1990s has resulted in the development of a plethora of hardware systems and an exponential increase in clinical use. This article summarizes the initial, now mostly historical, developments and emphasizes that most linear accelerator radiosurgery systems are based on three early prototypical systems from Buenos Aires, Heidelberg, and Montréal. These systems have more recently been tailored to permit fractionated radiosurgery, blurring the distinction between radiosurgery and radiotherapy. The commonly used fractionated systems are described. Clinical outcome data for arteriovenous are described. Clinical outcome data for arteriovenous malformations, acoustic neuroma, and meningioma, are mostly preliminary but substantial data are available for the radiosurgical management of metastases. With the recent emphasis on cost containment, cost-effectiveness issues have become significant and at least for metastases some preliminary data suggest a potential "cost benefit" with radiosurgery. The recent publication of data from a prospective randomized trial has established the superiority of boost therapy for malignant glioma and in this article, we present preliminary evidence supporting the use of radiosurgery. Finally, some of the new and exciting developments such as the robot-mounted linear accelerator, the use of shaped fields, and tomotherapy are described.     

A proposal for a standard electronic anthropomorphic phantom for radiotherapy.

To create a database of human male and female computed tomography (CT) slices, the National Library of Medicine organized the "Visible Human Project." Since the male and female data sets provided are approximately 269 MB and 915 MB, respectively, both the size and complexity have been reduced. While making the slices accessible to those with limited computing resources, the production of these reduced data sets also presents a unique opportunity to establish a standard human CT slice library for research in radiation therapy. A brief history of the original data sets is included, as well as details of the reduction process, applications to radiotherapy, and information on accessing these reduced image files.     

Cytoskeletal integration in a highly ordered sensory epithelium in the organ of Corti: reponse to loss of cell partners in the Bronx waltzer mouse

This report is concerned with control of cell shaping, positioning, and cytoskeletal integration in a highly ordered cochlear neuroepithelium. It is largely based on investigations of events that occur during abnormal morphogenesis of the organ of Corti in the Bronx waltzer (bv/bv) mutant mouse. The organ's sensory hair cells and adjacent supporting cells ordinarily construct a spatially elaborate and supracellularly integrated cytoskeletal framework. Large microtubule bundles are connected to cytoskeletal components in neighbouring cells by actin-containing meshworks that link them to substantial arrays of adherens junctions. In bv/bv mice, degeneration and loss of most inner hair cells and outer pillar cells occurs during organ development. These cells flank each side of a row of inner pillar cells that respond by upregulating assembly of their actin-containing meshworks. This only occurs in surface regions where they no longer contact cell types involved in construction of the cytoskeletal framework. The meshworks are larger and exhibit a more extensive sub-surface deployment than is normally the case. Hence, assembly of intercellular cytoskeletal connecting components can proceed without contact with appropriate cell neighbours but termination of assembly is apparently subject to a negative feedback control triggered by successful completion of intercellular connection with the correct cell neighbours. In addition, inner pillar cells compensate for loss of cell neighbours by interdigitating and overlapping each other more extensively than is usually the case to increase opportunities for generating adherens junctions. Certain adherens junctions in the organs of +/+ and bv/bv mice exhibit features that distinguish them from all previously described cell junctions. The dense plaques on their cytoplasmic faces are composed of aligned ridges. We suggest that they are called ribbed adherens junctions. Perturbations of cell shaping and positioning indicate that loss of inner hair cells is the primary consequence of the bv mutation. Most of the other abnormalities can be understood in terms of a secondary sequence of morphogenetic aberrations (precipitated by loss of inner hair cells). These aberrations provide new information about the ways in which supporting cells help to control hair cell positioning.     

SIDS: parental awareness and infant care practices in contrasting socioeconomic areas in Cardiff

Parental awareness of risk factors for sudden infant death syndrome (SIDS) and infant care practices were compared in an area of relative deprivation and one of relative affluence in Cardiff. Awareness was high in both areas. More infants slept on the side in the deprived area (p < 0.02). One in three babies was exposed to cigarette smoking, significantly more in the deprived area (p < 0.001). Health professionals should discourage side sleeping and smoking, especially in areas of deprivation.     

Chromosomal Mosaicism in Cleavage-Stage Human Embryos and the Accuracy of Single-Cell Genetic Analysis

Purpose: Our purpose was to assess the effect of chromosomal mosaicism in cleavage-stage human embryos on the accuracy of single-cell analysis for preimplantation genetic diagnosis. Methods: Multicolor fluorescence in situ hybridization with X, Y, and 7 or X, Y, 7, and 18 chromosome-specific probes was used to detect aneuploidy in cleavage-stage human embryos. Results: Most nuclei were diploid for the chromosomes tested but there was extensive mosaicism including monosomic, double-monosomic, nullisomic, chaotic, and haploid nuclei. Conclusions: Identification of sex by analysis of a single cleavage-stage nucleus is accurate but 7% of females are not identified. One or both parental chromosomes 7 were absent in at least 6.5% of the nuclei. With autosomal recessive conditions such as cystic fibrosis, carriers would be misdiagnosed as normal or affected. With autosomal dominant conditions, failure to analyze the affected parents allele (1.6–2.5%) would cause a serious misdiagnosis and analysis of at least two nuclei is necessary to reduce errors.