Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21-22

An Australian family with autosomal dominant presenile nonspecific dementia was recently described. The disease results in behavioral changes, usually disinhibition, followed by the onset of dementia accompanied occasionally by parkinsonism. Twenty-eight affected individuals were identified with an age of onset of 39 to 66 years (mean, 53 +/- 8.9 years). We mapped the disease locus to an approximately 26-cM region of chromosome 17q21-22 with a maximum two-point LOD score of 2.87. Affected individuals share a common haplotype between markers D17S783 and D17S808. This region of chromosome 17 contains the loci for several neurodegenerative diseases that lack distinctive pathological features, suggesting that these dementias, collectively referred to as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), are caused by mutations in the same gene. The entire coding region of five genes, mapped to the FTDP-17 candidate region, were also sequenced. This analysis included the microtubule-associated protein tau that is the major component of the paired helical filaments observed in Alzheimer's disease. No pathogenic mutations were identified in either the tau gene or in any of the other genes analyzed.     

Myosin VIIa, the product of the Usher 1B syndrome gene, is concentrated in the connecting cilia of photoreceptor cells

Usher syndrome is the most common form of combined deafness and blindness. The gene that is defective in Usher syndrome 1B (USH1B) encodes for an unconventional myosin, myosin VIIa. To understand the cellular function of myosin VIIa and why defects in it lead to USH1B, it is essential to determine the precise cellular and subcellular localization of the protein. We investigated the distribution of myosin VIIa in human and rodent photoreceptor cells and retinal pigment epithelium (RPE), primarily by immunoelectron microscopy, using antibodies generated against two different domains of the protein. In both human and rodent retinae, myosin VIIa was detected in the apical processes of the RPE and in the cilium of rod and cone photoreceptor cells. Immunogold label was most concentrated in the connecting cilium. Here, myosin VIIa appeared to be distributed outside the ring of doublet microtubules near the ciliary plasma membrane. These observations indicate that a major role of myosin VIIa in the retina is in the photoreceptor cilium, perhaps in such a function as trafficking newly synthesized phototransductive membrane or maintaining the diffusion barrier between the inner and outer segments. Our results support the notion that defective ciliary function is the underlying cellular abnormality that leads to cellular degeneration in Usher syndrome.     

In vitro activities of co-amoxiclav at concentrations achieved in human serum against the resistant subpopulation of heteroresistant Staphylococcus aureus: a controlled study with vancomycin

The effects of concentrations that simulated those in human serum after a single intravenous dose of amoxicillin (2 g), amoxicillin-clavulanic acid (2,000 and 200 mg, respectively), or vancomycin (500 mg), on the viability and beta-lactamase activity of two isogenic (beta-lactamase and non-beta-lactamase producer) heteroresistant Staphylococcus aureus strains were studied in an in vitro pharmacodynamic model. A reduction of > or = 97% of the initial inoculum was obtained with vancomycin and amoxicillin-clavulanic acid against both strains, with respect to the total bacterial population and the oxacillin-resistant subpopulation. The same pattern was observed with amoxicillin and the beta-lactamase-negative strain. beta-Lactamase activity in the beta-lactamase-positive strain changed over time parallel to viability, decreasing with amoxicillin-clavulanic acid or vancomycin and increasing in the amoxicillin and control groups. Clavulanic acid concentrations achievable in serum that changed over time allowed amoxicillin to act against the beta-lactamase-producing methicillin-resistant S. aureus to a similar extent as vancomycin.     

Characterisation of a new human and murine member of the DnaJ family of proteins

We report the characterisation of a human gene, designated MCG18 (multiple endocrine neoplasia type 1 candidate gene 18), that encodes a new member of the DnaJ family of proteins. Database searches indicate that MCG18 also has the locus name HSPF2. MCG18 lies 250bp centromeric of the VRF/VEGFB gene on chromosome 11q13. The MCG18 cDNA is predicted to encode a 241 amino acid product that has partial homology to Escherichia coli dnaJ in that it contains the J domain. However, MCG18 has greatest similarity to a functionally undefined protein from Caenorhabditis elegans, both of which are predicted to have a membrane-spanning region adjacent to their J domains. The cDNA encoding the murine homolog (Mcg18) was also cloned and sequenced, and the encoded protein shares 81% similarity to MCG18. The coding region of MCG18 is interrupted by 4 introns and the mRNA is expressed as a 1.4kb message in all tissues examined, including those derived from the breast, ovary, bladder, lung and keratinocytes.     

Dielectric and morphological investigations of phase separation and cure in rubber-modified epoxy resins: Comparison between teta- and DDM-based systems

Real-time and equilibrium dielectric measurements, covering the frequency range 10^?1–10⁵ Hz, are reported on a series of rubber-modified epoxy resins, based on reaction of the diglycidyl ether of bisphenol A (DGEBA) with either triethylenetetramine (TETA) or diaminodiphenylmethylene (DDM). The rubber modifier used was a carboxyl-terminated butadiene acrylonitrile (CTBN) reactive oligomer and the phase-separated structure, the results of which was examined using both dielectric and electron microscopic techniques. The mixture was initially homogeneous, but after a short period of time, it underwent phase separation and this process was marked by the appearance of a dielectric peak associated with ion-charge migration within the occluded rubbery phase. Analysis of the peak provided information on the morphology of the system and these data were compared with information obtained from scanning electron microscopy. A phase-separated morphology was observed consisting of spherical rubber particles dispersed in an epoxy matrix. For high concentrations of rubber ≥ 10 wt %, precipitation of epoxy domains within the rubbery phase was observed. Detailed dielectric studies of the peak associated with phase separation revealed that in the case of the TETA system the peak continued to shift after vitrification, whereas in the case of DDM, it was invariant with time. The point at which the peak appears was used to determine the time at which phase separation occurred. Differences observed in the lower temperature dielectric spectra were associated with variations in the form of the phase structure and possibly reflect different degrees of densification of the matrix. Good agreement was observed between the predictions of the Maxwell—Wagner—Sillers (MWS) theory and experimental observation for these systems. © 1993 John Wiley & Sons, Inc.     

Potassium and sodium intake and excretion in calcium stone forming patients

We reviewed the results of 15 patients (16 feet) in whom a hallux valgus procedure had failed. Salvage was by proximal crescentic first metatarsal osteotomy with distal soft-tissue reconstruction. Results based on a clinical scale considering the level of pain, activity limitations, support requirement, footwear limitations, and alignment were good in 11, fair in two, and poor in three. Patients were satisfied with the results in 10 feet, satisfied with reservations in four feet, and dissatisfied in two feet. Complications were: transfer metatarsalgia in three, hallux varus in one, and osteotomy nonunion in one. One of the patients required reoperation to bone graft a proximal osteotomy. Metatarsal osteotomy was helpful in the salvage treatment of recurrent, symptomatic hallux valgus when the first metatarsophalangeal joint was functional and painless.     

Locomotor activation and dopamine release produced by nicotine and isoarecolone in rats

1. Isoarecolone was approximately 250 times less potent than nicotine as an inhibitor of [3H]-nicotine binding to rat brain membranes. Isoarecolone failed to inhibit the binding of the nicotinic ligand [125I]-alpha-bungarotoxin or of the muscarinic ligand [3H]-QNB. 2. Nicotine (0.01-30 microM) evoked the release of [3H]-dopamine from striatal and frontal cortex synaptosomes, with EC50 values of approximately 0.5 microM in each case. This release was largely mecamylamine-sensitive. 3. Isoarecolone (1-200 microM) evoked predominantly mecamylamine-sensitive dopamine release from both striatal and cortical synaptosomes, with a potency at least 20 times less than that of nicotine. The maximum effect of isoarecolone was less than that of nicotine, particularly in the frontal cortex preparation. 4. In control rats treated chronically with saline, neither nicotine nor isoarecolone had clear effects on locomotor activity at the doses tested. Chronic treatment with nicotine clearly sensitized rats to the locomotor activating effect of isoarecolone was seen at a dose about 40 times larger than that of nicotine. 5. The low potency and efficacy of isoarecolone in facilitating sensitized locomotor activity resembled its lower potency and efficacy, compared with nicotine, in evoking dopamine release in vitro. The agonist profile of the nicotinic receptor population mediating dopamine release may determine the pharmacological characteristics of consequent locomotor behaviour.     

Sacral hydatidosis: value of MRI in the diagnosis

We present a case of primary hydatid disease of the sacrum. The diagnosis was made on MR imaging obtained to evaluate the spine for recurrent disc disease. The patient had previously undergone laminectomy elsewhere for L4-5 radiculopathy. Ultrasound-guided aspiration and visualisation of scolices confirmed the diagnosis. No other site of involvement was found.