Microscopic R2* mapping of reduced brain iron in the Belgrade rat.

R2* mapping has recently been used to detect iron overload in patients with movement disorders. We demonstrate here that this technique can also be used to detect reduced brain iron, as in the case of a missense mutation in the iron-transporting protein divalent metal transporter 1. Surprisingly, we found that the same brain regions are affected (ie, the globus pallidus, substantia nigra, and cerebellar dentate nucleus); this suggests a much more extensive role for these structures in regulating overall brain iron homeostasis.

Surrogates for finding unstable periodic orbits in noisy data sets.

Recently, searches for unstable periodic orbits in biological and medical applications have become of interest. The motivations for this research range, in order of ascending complexity, from efforts to understand the dynamics of simple sensory neurons, through speculations regarding neural coding, to the hopeful development of new diagnostic and/or control techniques for cardiac and epileptic pathologies. Biological and medical data are, however, noisy and nonstationary.

Does pneumatic dilatation affect the outcome of laparoscopic cardiomyotomy?

Background: Controversy surrounds the choice of laparoscopic cardiomyotomy as the primary treatment for achalasia or a second-line treatment following the failure of nonsurgical treatment. Laparoscopic cardiomyotomy can be more difficult technically following pneumatic dilatations. The aim of this study was to compare the outcome obtained with primary laparoscopic cardiomyotomy to that achieved when the procedure is performed following failed pneumatic dilatation.

Iron uptake and Nramp2/DMT1/DCT1 in human bronchial epithelial cells.

The capacity of natural resistance-associated macrophage protein-2 [Nramp2; also called divalent metal transporter-1 (DMT1) and divalent cation transporter-1 (DCT1)] to transport iron and its ubiquitous expression make it a likely candidate for transferrin-independent uptake of iron in peripheral tissues. We tested the hypothesis that non-transferrin-bound iron uptake by airway epithelial cells is associated with Nramp2/DMT1/DCT1 and that exposure to iron can increase Nramp2/DMT1/DCT1 mRNA and protein expression and transport of this metal. Exposure of BEAS-2B cells to ferric ammonium citrate (FAC) resulted in a decrease in Fe(3+) concentration in the supernatant that was dependent on time and initial iron concentration.

Effect of the iron chelator desferrioxamine on manganese-induced toxicity of rat pheochromocytoma (PC12) cells.

Alterations in iron levels are likely to influence the biological actions of Mn in PC12 cells, because both metals are transported via the divalent metal transporter 1 (DMT1; also Nramp2 or DCT1). Studies were performed to determine the effect of the iron chelator desferrioxamine (DfO) on Mn-induced PC12 cell death and neuronal differentiation. Cell death almost doubled when PC12 cells were exposed for 24 hr to both DfO (10 microM) and Mn (0.

Surrogate analysis of coherent multichannel data.

We present a method for generating surrogate data for multichannel time series. By preserving both the power spectra and the cross spectrum of the original data, we can determine if a given statistical test (such as the synchronization index) is being biased by the presence of coherence due to linear superposition of the separate measurements. Current methods based on phase randomization techniques are unsuitable for this particular task.

Surveillance and prevention of hepatitis C in Australian prisons.

Hepatitis C (HCV) prevalence rates in prisons are even higher than HIV prevalence rates. Studies undertaken in the early and mid 1990s in Canadian prisons revealed rates of between 28 and 40 percent, and rates continue to rise. In one federal prison, 33 percent of study participants tested positive in 1998, compared to 27.

Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat.

Iron accumulation in the brain occurs in a number of neurodegenerative diseases. Two new iron transport proteins have been identified that may help elucidate the mechanism of abnormal iron accumulation. The Divalent Metal Transporter 1 (DMT1), is responsible for iron uptake from the gut and transport from endosomes.

Surrogate for nonlinear time series analysis.

We present a surrogate for use in nonlinear time series analysis. This surrogate algorithm has significant advantages over the most commonly used surrogates, in that it provides a more robust statistical test by producing an entire population of surrogates that are consistent with the null hypothesis. We will show that for the currently used surrogate algorithms, although individual surrogate files are consistent with the null hypothesis the population of surrogates generated is not.

Pilot randomized controlled study of dexamphetamine substitution for amphetamine dependence.

Aims: To test the feasibility of conducting a definitive randomized controlled trial of dexamphetamine substitution for amphetamine dependent people and provide preliminary data.

Design: An open, two-group pre-post randomized controlled trial.

Participants: Forty-one long-term, dependent amphetamine users seeking treatment.

Extracting dynamical structure from unstable periodic orbits.

The topological recurrence algorithm provides a fast and robust method for detecting the presence of unstable periodic orbits (UPO's) in short, noisy experimental data files. We present here a technique for improving this method by using a matrix fitting algorithm to extract dynamical information about the system from these UPO's. This method greatly increases the sensitivity of the algorithm, and also provides a method for identifying false positive results.

Acute hepatitis C virus infection in an Australian prison inmate: tattooing as a possible transmission route.

Clinically apparent hepatitis C virus (HCV) infection developed in a prison inmate after two tattooing episodes within the recognised incubation period for HCV infection. Seroconversion and HCV viraemia with subsequent resolution of hepatitis and loss of plasma viraemia were documented. Introducing licensed tattooists, and thereby improving infection control practices, may reduce the risk of hepatitis C virus infection in prisons.

The evolution of loss of heterozygosity on chromosome 17 during the progression to barrett's adenocarcinoma involves a unique combination of target sites in individual specimens.

We have previously identified thirteen common minimally deleted regions (MRs) on chromosome 17 in twelve Barrett's esophageal adenocarcinoma (BOA) specimens using 41 precisely mapped microsatellite markers (Dunn et al., Oncogene, 17: 987-993, 1999). The aim of the present study has been to identify the earliest sites of loss on this chromosome that arise and persist during the progression to BOA.

Detecting the onset of bifurcations and their precursors from noisy data.

We study the problem of the detection of noise-induced precursors of periodic motion instabilities in stochastic dynamical systems. In particular, we concentrate on the period-doubling bifurcation. We have developed a statistical method to detect the onset of bifurcations and their precursors based on the previously established topological recurrence technique.

Differential localization of divalent metal transporter 1 with and without iron response element in rat PC12 and sympathetic neuronal cells.

Two isoforms of divalent metal transporter 1 (DMT1) (Nramp2 and DCT1) are encoded by two mRNA species, one of which contains an iron response element (IRE) motif in the 3'-noncoding region. The subcellular distribution of the two isoforms of DMT1 is distinct, and the -IRE species accumulates in the nucleus of neuronal or neuronal-like cells. Reverse transcription-PCR and Western blot analysis of PC12 cells reveals that these cells express both forms of DMT1.

Separate pathways for cellular uptake of ferric and ferrous iron.

Separate pathways for transport of nontransferrin ferric and ferrous iron into tissue cultured cells were demonstrated. Neither the ferric nor ferrous pathway was shared with either zinc or copper. Manganese shared the ferrous pathway but had no effect on cellular uptake of ferric iron.

Functional comparison of the NAD binding cleft of ADP-ribosylating toxins.

Although a common core structure forms the active site of ADP-ribosylating (ADPRT) toxins, the limited-sequence homology within this region suggests that different mechanisms are being used by toxins to perform their shared function. To explain differences in their mechanisms of NAD binding and hydrolysis, the functional interrelationship of residues predicted to perform similar functions in the beta3-strand of the NAD binding cleft of different ADPRT toxins was compared. Replacing Tyr54 in the A-subunit of diphtheria toxin (DTA) with a serine, its functional homologue in cholera toxin (CT), resulted in the loss of catalytic function but not NAD binding.

Histological and molecular mapping of adenocarcinoma of the oesophagus and gastroesophageal junction: loss of heterozygosity occurs in histologically normal epithelium in the oesophagus and stomach.

Seventy malignant, premalignant and histologically normal biopsies from 7 oesophagogastrectomy specimens of adenocarcinomas of the lower oesophagus and gastroesophageal junction were analysed for loss of heterozygosity (LOH) at 9 known or putative gene loci. LOH was detected in 20 of 27 (74%) malignant biopsies, 4 of 7 (57%) biopsies of dysplasia, 2 of 12 (25%) biopsies of histologically normal oesophagus adjacent to adenocarcinoma, and in 2 of 14 (14%) biopsies of histologically normal stomach adjacent to adenocarcinoma. LOH at the VHL, APC, CDKN2 and DCC tumour suppressor and MSH3 mismatch repair gene loci can be detected in histologically normal tissue and in adjacent adenocarcinoma, and are potential markers of early neoplastic progression.

Hepatitis C virus antibody prevalence among injecting drug users at selected needle and syringe programs in Australia, 1995-1997. Collaboration of Australian NSPs.

Objectives: To describe point prevalence of HCV antibody and relevant risk behaviour among people who inject drugs and who attended selected needle and syringe programs throughout Australia in 1995, 1996 and 1997.

Design And Setting: Repeated cross-sectional surveys of one week's duration were carried out in 21, 20 and 23 needle and syringe program sites throughout Australia in 1995, 1996 and 1997, respectively.

Participants: All clients attending participating sites during the designated survey week were asked to complete a self-administered questionnaire and provide a finger-prick blood sample for HCV antibody testing.

In vitro characterization of five humanized OKT3 effector function variant antibodies.

Orthoclone OKT 3 (mOKT3) is a highly effective agent for the reversal of steroid-resistant renal allograft rejection. However, its wider use has been limited by the development of a human anti-mouse antibody response (HAMA) and by the "cytokine release syndrome" (CRS). CRS has been associated with T cell/monocyte activation and, secondarily, with activation of the complement cascade.