The parkin gene S/N167 polymorphism in Australian Parkinson's disease patients and controls

This study determined the frequencies of a G-to-A transition (S/N167) polymorphism in exon 4 of the parkin gene in Australian Parkinson's disease patients and control subjects. The genotype of each subject was determined using the polymerase chain reaction and restriction-fragment-length-polymorphism analysis. Overall, the A allele was significantly less common in the Parkinson's disease group (1.7%) compared with the control group (3.8%, OR = 0.43, 95% CI = 0.19-1.00, P < 0.05), although the frequency in the young onset Parkinson's disease group (6.6%) was not significantly different to controls. The A allele is less common in Australian Caucasian subjects compared to Japanese Parkinson's disease patients and appears to be under-represented in older-onset Parkinson's disease. <(c)> 2001 Elsevier Science Ltd. All rights reserved.

The appearance of a second genotype of Japanese encephalitis virus in the Australasian region

In mid-January 2000, the reappearance of Japanese encephalitis (JE) virus activity in the Australasian region was first demonstrated by the isolation of JE virus from 3 sentinel pigs on Badu Island in the Torres Strait. Further evidence of JE virus activity was revealed through the isolation of JE virus from Cidex gelidus mosquitoes collected on Badu Island and the detection of specific JE virus neutralizing antibodies in 3 pigs from Saint Pauls community on Moa Island. Nucleotide sequencing and phylogenetic analyses of the premembrane and envelope genes were performed which showed that both the pig and mosquito JE virus isolates (TSOO and TS4152, respectively) clustered in genotype I, along with northern Thai, Cambodian, and Korean isolates. All previous Australasian JE virus isolates belong to genotype II, along with Malaysian and Indonesian isolates. Therefore, for the first time, the appearance and transmission of a second genotype of JE virus in the Australasian region has been demonstrated.

A novel variant genotype C of hepatitis B virus identified in isolates from Australian Aborigines: complete genome sequence and phylogenetic relatedness

There have been no reports of DNA sequences of hepatitis B virus (HBV) strains from Australian Aborigines, although the hepatitis B surface antigen (HBsAg) was discovered among them. To investigate the characteristics of DNA sequences of HBV strains from Australian Aborigines, the complete nucleotide sequences of HBV strains were determined and subjected to molecular evolutionary analysis. Serum samples positive for HBsAg were collected from five Australian Aborigines. Phylogenetic analysis of the five complete nucleotide sequences compared with DNA sequences of 54 global HBV isolates from international databases revealed that three of the five were classified into genotype D and were most closely related in terms of evolutionary distance to a strain isolated from a healthy blood donor in Papua New Guinea. Two of the five were classified into a novel variant genotype C, which has not been reported previously, and were closely related to a strain isolated from Polynesians, particularly in the X and Core genes. These two strains of variant genotype C differed from known genotype C strains by 5.9-7.4% over the complete nucleotide sequence and 4.0-5.6 % in the small-S gene, and had residues Arg(122), Thr(127) and Lys(160) characteristic of serotype ayw3, which have not been reported previously in genotype C. In conclusion, this is the first report of the characteristics of complete nucleotide sequences of HBV from Australian Aborigines. These results contribute to the investigation of the worldwide spread of HBV, the relationship between serotype and genotype and the ancient common origin of Australian Aborigines.

Association of bowel movement frequency and use of laxatives with the occurrence of symptomatic gallstone disease in a prospective study of women

OBJECTIVES: The authors prospectively examined the association between bowel movement frequency (used as a proxy for intestinal transit), laxative use, and the risk of symptomatic gallstone disease. METHODS: A total of 79,829 women, aged 36–61 yr, without a history of symptomatic gallstone disease and free of cancer, responded to a mailed questionnaire in 1982 that assessed bowel movement frequency and use of laxatives. Between 1984 and 1996, 4,443 incident cases of symptomatic gallstone disease were documented. Relative risks (RRs) of symptomatic gallstone disease and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: After controlling for age and established risk factors, the multivariate RRs were, compared to women with daily bowel movements, 0.97 (95% CI 0.86–1.08) for women with bowel movements every third day or less, and 1.00 (95% CI 0.91–1.11) for women with bowel movement more than once daily. No trend was evident. As compared to women who never used laxatives in 1982, a significant modest inverse association was seen for monthly laxative use, with a multivariate RR of 0.84 (95% CI 0.72–0.98), and weekly to daily laxative use was associated with a RR of 0.88 (95% CI 0.78–1.02). CONCLUSIONS: These findings do not support an association between infrequent bowel movements and risk of symptomatic gallstone disease in women, and indicate that simple questions directed at bowel movement frequency are unlikely to enhance our ability to predict risk of symptomatic gallstone disease. The slightly inverse association between use of laxatives and risk of symptomatic gallstone disease may be due to a mechanism that is not related to bowel movement frequency.

The microsomal epoxide hydrolase Tyr113His polymorphism: Association with risk of ovarian cancer

Functional significance has been demonstrated in vitro for the exon 3 T-->C Tyr113His amino acid substitution polymorphism of the microsomal epoxide hydrolase (EPHX) gene. The higher activity or fast TT genotype was previously reported to be associated with an increased risk of ovarian cancer, and this association may reflect enhanced activation of endogenous or exogenous substrates to more reactive and mutagenic derivatives. Components of cigarette smoke are examples of exogenous substrates subject to such bioactivation, and smoking exposure may thus modify the risk associated with the EPHX polymorphism. We examined 545 cases of epithelial ovarian cancer and 287 unaffected controls for this EPHXT-C genetic variant to investigate whether, in the Australian population, the TT genotype was associated with (i) specific ovarian tumor characteristics; (ii) risk of ovarian cancer, overall or for specific subgroups; and (iii) risk of ovarian cancer in smokers specifically. Genotyping was carried out using the Perkin-Elmer ABI Prism 7700 Sequence Detection System for fluorogenic polymerase chain reaction allelic discrimination. Stratification of the ovarian cancer cases according to tumor behavior (low malignant potential or invasive), grade, stage, and p53 immunohistochemical status failed to show any heterogeneity with respect to the genotype defined by the EPHX polymorphism. There was a suggestion of heterogeneity with respect to histologic subtype (P= 0.03), largely due to a decreased frequency of the TT genotype in endometrioid tumors. EPHX genotype distribution did not differ significantly between unaffected controls and ovarian cancer cases (overall, low malignant potential, or invasive) either overall or after stratification by smoking status. However, the TT genotype was associated with a decreased risk of invasive ovarian cancer of the endometrioid subtype specifically (age-adjusted odds ratio = 0.38, 95% confidence interval=0.17-0.87). The results suggest that the proposed EPHX-mediated bioactivation of components of cigarette smoke to mutagenic forms is unlikely to be involved in the etiology of ovarian cancer in general but that a greater rate of EPHX-mediated detoxification may decrease the risk of endometrioid ovarian cancer. (C) 2001 Wiley-Liss, Inc.

Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype

The phase II glutathione S-transferases (GSTs) GSTT1, GSTM1 and GSTP1 catalyse glutathione-mediated reduction of exogenous and endogenous electrophiles. These GSTs have broad and overlapping substrate specificities and it has been hypothesized that allelic variants associated with less effective detoxification of potential carcinogens may confer an increased susceptibility to cancer. To assess the role of GST gene variants in ovarian cancer development, we screened 285 epithelial ovarian cancer cases and 299 unaffected controls for the GSTT1 deletion (null) variant, the GSTM1 deletion (null) variant and the GSTP1 codon 104 A-->G Ile-->Val amino acid substitution variant, The frequencies of the GSTT1, GSTM1 and GSTP1 polymorphic variants did not vary with tumour behaviour (low malignant potential or invasive) or p53 immunohistochemical status. There was a suggestion that ovarian cancers of the endometrioid or clear cell histological subtype had a higher frequency of the GSTT1 and GSTM1 deletion genotype than other histological subgroups. The GSTT1, GSTM1 and GSTP1 genotype distributions did not differ significantly between unaffected controls and ovarian cancer cases (overall or invasive cancers only). However, the GSTM1 null genotype was associated with increased risk of endometrioid/clear cell invasive cancer [age-adjusted OR (95% CI) = 2.04 (1.01-4.09), P = 0.05], suggesting that deletion of GSTM1 may increase the risk of ovarian cancer of these histological subtypes specifically. This marginally significant finding will require verification by independent studies.

Early diagnosis of lymphedema using multiple frequency bioimpedance

Multiple frequency bioelectrical impedance analysis (MFBIA) has previously been shown to provide accurate relative measures of lymphedema in the upper limb of patients (1). This paper reports the results of a three year prospective study to evaluate the efficacy of MFBIA to predict the early onset of lymphedema in patients following treatment for breast cancer. Bioelectrical impedance measurements and circumferential measurements of each upper limb were recorded in healthy control subjects (n=60) to determine the normal range of the ratio (dominant/non-dominant) of extracellular and total limb volumes respectively. Patients undergoing surgery for the treatment of breast cancer were recruited as the study group; MFBIA and circumferential measurements were recorded pre-surgery, one month post-surgery and then at two month intervals for 24 months. One hundred and two patients were recruited into the study. Twenty patients developed lymphedema in the 24 months follow up period of this study. In each of these 20 cases MFBIA predicted the onset of the condition up to 10 months before the condition could be clinically diagnosed. Estimates of the sensitivity and specificity were both approximately 100%. At the time of detection by MFBIA, only one of the patients returned a positive test result from the total limb volumes determined from the circumferential measures. These results confirmed the suitability of the MFBIA technique as a reliable diagnostic procedure for the early detection of lymphedema.

Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma

MC1R gene variants have previously been associated with red hair and fair skin color, moreover skin ultraviolet sensitivity and a strong association with melanoma has been demonstrated for three variant alleles that are active in influencing pigmentation: Arg151Cys, Arg160Trp, and Asp294His. This study has confirmed these pigmentary associations with MC1R genotype in a collection of 220 individuals drawn from the Nambour community in Queensland, Australia, 111 of whom were at high risk and 109 at low risk of basal cell squamous cell carcinoma. Comparative allele frequencies for nine MC1R variants that have been reported in the Caucasian population were determined for these two groups, and an association between prevalence of basal cell carcinoma, squamous cell carcinoma, solar keratosis and the same three active MC1R variant alleles was demonstrated [odds ratio=3.15 95% CI (1.7, 5.82)]. Three other commonly occurring variant alleles: Val60Leu, Val92Met, and Arg163Gln were identified as having a minimal impact on pigmentation phenotype as well as basal cell carcinoma and squamous cell carcinoma risk. A significant heterozygote effect was demonstrated where individuals carrying a single MC1R variant allele were more likely to have fair and sun sensitive skin as well as carriage of a solar lesion when compared with those individuals with a consensus MC1R genotype. After adjusting for the effects of pigmentation on the association between MC1R variant alleles and basal cell carcinoma and squamous cell carcinoma risk, the association persisted, confirming that presence of at least one variant allele remains informative in terms of predicting risk for developing a solar-induced skin lesion beyond that information gained through observation of pigmentation phenotype.

Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APE muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested. (C) 2001 Published by Elsevier Science B.V.

Relationships between non-occupational cadmium exposure and expression of nine cytochrome P450 forms in human liver and kidney cortex samples

This study was undertaken to assess associations between age, gender, cigarette smoke and non-workplace cadmium exposure, and liver pathology and inter-individual variation in cytochrome P450 (CYP) expression in human tissues. Autopsy specimens of twenty-eight Queensland residents whose ages ranged from 3 to 89 years were analyzed for the presence of nine CYP protein isoforms by immunoblotting. All subjects were Caucasians and their liver cadmium contents ranged from 0.11 to 3.95 kg/g wet weight, while their kidney cadmium contents were in the range of 2 to 63 mug/g wet weight. CYP1A2, CYP2A6, CYP2D6, CYP3A4, and CYP3A5 were detected in liver but not in kidney, and CYP1A1 and CYP1B1 were not found in liver or kidney. Lowered liver CYP2C8/19 protein contents were found to be associated with liver pathology. Importantly, we show elevated levels of CYP2C9 protein to be associated with cadmium accumulation in liver. No mechanism that explains this association is apparent, but there are two possibilities that require further study. One is that variation in CYP2C9 protein levels may be, in part, attributed to an individual's non-workplace exposure to cadmium, or an individual's CYP2C9 genotype may be a risk factor for cadmium accumulation. A positive correlation was found between liver CYP3A4 protein and subject age. Levels of liver CYPIA2 protein, but not other CYP forms, were increased in people more exposed to cigarette smoke, but there was no association between CYPIA2 protein and cadmium. CYP2A6 protein was found in all liver samples and CYP2A6 gene typing indicated the absence of CYP2A6 null allele (CYP2A6(D)) in this sample group, confirming very low prevalence of homozygous CYP2A6(D) in Caucasians. CYP2A6 gene types W/W, WIC, and CIC were not associated with variations in liver microsomal CYP2A6 protein. CYP2D6 protein was absent in all twenty-five kidney samples tested but was detectable in liver samples of all but two subjects, indicating the prevalence of the CYP2D6 null allele (CYP2D6(D)) in this sample group to be about 7%, typical of Caucasian populations. (C) 2001 Elsevier Science Inc. All rights reserved.

Wolbachia-mediated sperm modification is dependent on the host genotype in Drosophila

Estimates of Wolbachia density in the eggs, testes and whole flies of drosophilid hosts have been unable to predict the lack of cytoplasmic incompatibility (CI) expression in so-called mod(-) variants. Consequently, the working hypothesis has been that CI expression, although related to Wolbachia density, is also governed by unknown factors that are influenced by both host and bacterial genomes. Here, we compare the behaviour of the mod(-) over-replicating Wolbachia popcorn strain in its native Drosophila melanogaster host to the same strain transinfected into a novel host, namely Drosophila simulans. We report that (i) the popcorn strain is a close relative of other D. melanogaster infections, (ii) the mod(-) status of popcorn in D. melanogaster appears to result from its inability to colonize sperm bundles, (iii) popcorn is present in the bundles in D. simulans and induces strong CI expression, which demonstrates that the bacterial strain does not lack the genetic machinery for inducing CI and that there is host-species-specific control over Wolbachia tissue tropism, and (iv) infection of sperm bundles by the mod(-) D. simulans wCof strain indicates that there are several independent routes by which a strain can be a CI non-expressor.

Genotype-by-management interactions for grain yield and grain protein concentration of wheat

The magnitude of genotype-by-management (G x M) interactions for grain yield and grain protein concentration was examined in a multi-environment trial (MET) involving a diverse set of 272 advanced breeding lines from the Queensland wheat breeding program. The MET was structured as a series of management-regimes imposed at 3 sites for 2 years. The management-regimes were generated at each site-year as separate trials in which planting time, N fertiliser application rate, cropping history, and irrigation were manipulated. irrigation was used to simulate different rainfall regimes. From the combined analysis of variance, the G x M interaction variance components were found to be the largest source of G x E interaction variation for both grain yield (0.117 +/- 0.005 t(2) ha(-2); 49% of total G x E 0.238 +/- 0.028 t(2) ha(-2)) and grain protein concentration (0.445 +/- 0.020%(2); 82% of total G x E 0.546 +/- 0.057%(2)), and in both cases this source of variation was larger than the genotypic variance component (grain yield 0.068 +/- 0.014 t(2) ha(-2) and grain protein 0.203 +/- 0.026%(2)). The genotypic correlation between the traits varied considerably with management-regime, ranging from -0.98 to -0.31, with an estimate of 0.0 for one trial. Pattern analysis identified advanced breeding lines with improved grain yield and grain protein concentration relative to the cultivars Hartog, Sunco and Meteor. It is likely that a large component of the previously documented G x E interactions for grain yield of wheat in the northern grains region are in part a result of G x M interactions. The implications of the strong influence of G x M interactions for the conduct of wheat breeding METs in the northern region are discussed. (C) 2001 Elsevier Science B.V. All rights reserved.

Preprocessing and time-frequency analysis of newborn EEG seizures

Neurological disease or dysfunction in newborn infants is often first manifested by seizures. Prolonged seizures can result in impaired neurodevelopment or even death. In adults, the clinical signs of seizures are well defined and easily recognized. In newborns, however, the clinical signs are subtle and may be absent or easily missed without constant close observation. This article describes the use of adaptive signal processing techniques for removing artifacts from newborn electroencephalogram (EEG) signals. Three adaptive algorithms have been designed in the context of EEG signals. This preprocessing is necessary before attempting a fine time-frequency analysis of EEG rhythmical activities, such as electrical seizures, corrupted by high amplitude signals. After an overview of newborn EEG signals, the authors describe the data acquisition set-up. They then introduce the basic physiological concepts related to normal and abnormal newborn EEGs and discuss the three adaptive algorithms for artifact removal. They also present time-frequency representations (TFRs) of seizure signals and discuss the estimation and modeling of the instantaneous frequency related to the main ridge of the TFR.