Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Emotional cue exposure for alcohol abuse: Development of a new treatment procedure to train moderation drinking in the context of dysphoria

Negative mood states are credited to exacerbate excessive drinking among problem drinkers. We developed an emotional cue exposure treatment procedure and applied it to three problem drinkers who have a history of drinking excessively under stressful emotional states. All three preferred a controlled drinking goal and received an average of seven sessions of treatment. Treatment comprised of providing alcohol (priming doses), followed by negative mood induction and response prevention of further drinking. Reductions were observed in the quantity and frequency of drinking, the Beck Depression Inventory, the Severity of Alcohol Dependence Questionnaire (Form C) and the Impaired Control Questionnaire scores. Increments were observed in self-efficacy to face different difficult situations. These gains were maintained at the 6-month follow-up. Providing alcohol to problem drinkers in treatment, followed by negative mood induction and response prevention, is clinically feasible and may benefit clients who drink under a variety of stressful mood states. Copyright (C) 2001 John Wiley & Sons, Ltd.

Inorganic nitrogen requirements during shoot organogenesis in tobacco leaf discs

The role of nitrate, ammonium, and culture medium pH on shoot organogenesis in Nicotiana tabacum zz100 leaf discs was examined. The nitrogen composition of a basal liquid shoot induction medium (SIM) containing 39.4 mM NO3- and 20.6 mM NH4+ was altered whilst maintaining the overall ionic balance with Na+ and Cl- ions. Omission of total nitrogen and nitrate, but not ammonium, from SIM prevented the initiation and formation of shoots. When nitrate was used as the sole source of nitrogen, a high frequency of explants initiated and produced leafy shoots. However, the numbers of shoots produced were significantly fewer than the control SIM. Buffering nitrate-only media with the organic acid 2[N-morpholinol]thanesulphonic acid (MES) could not compensate for the omission of ammonium. Ammonium used as the sole source of nitrogen appeared to have a negative effect on explant growth and morphogenesis, with a significant lowering of media pH. Buffering ammonium-only media with MES stabilized pH and allowed a low frequency of explants to initiate shoot meristems. However, no further differentiation into leafy shoots was observed. The amount of available nitrogen appears to be less important than the ratio between nitrate and ammonium. Shoot formation was achieved with a wide range of ratios, but media containing 40 mM nitrate and 20 mM ammonium (70:30) produced the greatest number of shoots per explant. Results from this study indicate a synergistic effect between ammonium and nitrate on shoot organogenesis independent of culture medium pH.

Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions., recovery of simulated genetic and environmental correlations becomes possible, Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

Sun exposure and interaction with family history in risk of melanoma, Queensland, Australia

Sun exposure is the main environmental risk factor for melanoma, but the timing of exposure during life that confers increased risk is controversial. Here we provide the first report of the association between lifetime and age-specific cumulative ultraviolet exposure and cutaneous melanoma in Queensland, Australia, an area of high solar radiation, and examine the association separately for families at high, intermediate and low familial melanoma risk. Subjects were a population-based sample of melanoma cases diagnosed and registered in Queensland between 1982 and 1990 and their relatives. The analysis included 1,263 cases and relatives with confirmed cutaneous melanoma and 3,111 first-degree relatives without melanoma as controls. Data an lifetime residence and sun exposure, family history and other melanoma risk factors were collected by a mailed questionnaire. Using conditional multiple logistic regression with stratification by family, cumulative sun exposure in childhood and in adulthood after age 20 was significantly associated with melanoma, with estimated relative risks of 1.15 per 5,000 minimal erythemal doses (MEDs) from age 5 to 12 years, and 1.52 per 5 MEDs/day from age 20. There was no association with sun exposure in families at high familial melanoma risk. History of nonmelanoma skin cancer (relative risk [RR] = 1.26) and multiple sunburns (RR = 1.31) were significant risk factors. These findings indicate that sun exposure in childhood and in adulthood are important determinants of melanoma but not in those rare families with high melanoma susceptibility, in which genetic factors are likely to be more important. (C) 2002 Wiley-Liss, Inc.

Constitutive expression of a phenylalanine ammonia-lyase gene from Stylosanthes humilis in transgenic tobacco leads to enhanced disease resistance but impaired plant growth

Transgenic tobacco plants expressing a phenylalanine ammonia-lyase cDNA (ShPAL), isolated from Stylosanthes humilis, under the control of the 35S promoter of the cauliflower mosaic virus were produced to test the effect of high level PAL expression on disease resistance. The transgenic plants showed up to eightfold PAL activity and were slowed in growth and flowering relative to non-transgenic controls which have segregated out the transgene. The expression of the ShPAL transgene and elevated PAL levels were correlated and stably inherited. In T-1 and T-2 tobacco plants with increased PAL activity, lesion expansion was significantly reduced by up to 55% on stems inoculated with the Oomycete pathogen Phytophthora parasitica pv. nicotianae, Lesion area was significantly reduced by up to 50% on leaves inoculated with the fungal pathogen Cercospora nicotianae. This study provides further evidence that PAL has a role in plant defence. (C) 2002 Elsevier Science Ltd. All rights reserved.

HPLC measurement of harderoporphyrin in the harderian glands of rodents as a biomarker for sub-lethal or chronic arsenic exposure

An improved HPLC method has been established for the measurement of harderoporphyrin (HP) in the harderian gland of rats and mice. Groups of female Wistar rats were given a single oral dose of sodium arsenite at 0, 0.5 or 5.0 mg As(III)/kg body weight, or a slurry of arsenic-contaminated soil at equivalent dose rates and the animals were sacrificed 96 h after dosing. A group of C57BL/6J female mice were chronically exposed to drinking water containing 500 mug As(V)/I of sodium arsenate ad libitum for over 2 years. Porphyrins were measured in the harderian glands of rats and mice. Our results suggest that HP and the alteration of the porphyrin profile in the harderian glands of rodents is a highly sensitive biomarker for both single sub-lethal and chronic arsenic exposure. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Improving attitude-behavior correspondence through exposure to normative support from a salient ingroup

Two experiments were conducted to test predictions derived from social identity/self-categorization theory concerning the role of group norms in attitude-behavior consistency. In Experiment 1, 160 students who could be classified as having a more or less certain target attitude were exposed to attitude congruent versus incongruent normative support from a relevant reference group (own university) under conditions of low versus high group salience. Experiment 2 was very similar in design and methodology (N=180), but a different correlate of attitude accessibility was used (an experimental manipulation of repeated expression), the target attitude was changed, and the reference group was gender. Across the 2 experiments there was consistent support for the hypothesis that participants would behave more in accordance with their attitudes when they received normative support for, rather than opposition to, their original attitude from a relevant reference group (i.e., their ingroup, not an outgroup). There was slightly weaker support for the second hypothesis that this effect would be stronger under high-than low-salience conditions. The third hypothesis (see Fazio, 1986), that attitude certainty and repeated expression of the attitude would strengthen attitude-behavior consistency, was well supported, as was the expectation that accessibility effects would be independent of reference group norm effects on attitude-behavior consistency.

McCabe v Goliath: The case against British American tobacco Australia Services Ltd

Significance of the decision in McCabe v British American Tobacco Australia Services Ltd - ramifications for the possibilities for success of future litigation of this nature in Australia and overseas - ethical and public policy issues regarding the duties of lawyers to the courts and to their clients - whilst a lawyer's implication in the destruction of documents to prevent a fair trial ultimately involves stricter duties, it exposes a need for vigilance against the possibilities for corporations to act outside the public interest, if not the justice system.

Porphyrin profiles in blood and urine as a biomarker for exposure to various arsenic species

A sensitive method using HPLC with fluorescence detection has been established for the measurement of porphyrins in biological materials. The assay recoveries were 88.0 +/- 1.8% for protoporphyrin IX in the blood, and ranged from 98.3 +/- 2.7% to 111.1 +/- 7.4% for various porphyrins in the urine. This method was employed to investigate the altered porphyrin profiles in rats after a single dose of various arsenicals including soluble sodium arsenate and sodium arsenite, and the relatively insoluble calcium arsenite, calcium arsenate and arsenic-contaminated soils at dose rates of 5 mg/kg or 0.5 mg/kg body weight. Porphyrin concentrations increased within 24-48hr after the arsenic treatment in blood and urine. Protoporphyrin IX is the predominant porphyrin in the blood. In rats administered 5 mg As(III)/kg body weight, protoporphyrin IX concentration elevated to 123% of them control values in rats, 24 hr after the treatment. Higher increases were recorded in the urinary protoporphyrin IX (253% at 24 hr; 397% on day 2), uroporphyrin (121% at 24 hr; 208% on day 2) and coproporphyrin 111 (391% at 24 hr; 304% on day 2), while there was no significant increase (109% on day 3) observed in the urinary coproporphyrin I excretion. In rats administered 5 mg As(V)/kg, urinary excretion of protoporphyrin IX, uroporphyrin, coproporphyrin Ill and coproporphyrin I elevated to the maximum levels by 48 hr with the corresponding percentage values compared to the control being 177%, 158%, 224% and 143%, respectively. In rats dosed with 5 mg As(III)/kg, the increases (expressed as % of the control values) of protoporphyrin IX in the blood were in the order: sodium arsenite (144%) > sodium arsenate (125%) greater than or equal to calcium arsenite (123%) > calcium arsenate. In contrast, there was no significant increase of protoporphyrin K when the six arsenic-contaminated cattlei dip soils and nine copper chrome arsenate (CCA-contaminated) soils were administered to the rats. Probable explanations are discussed.

Neonatal ethanol exposure reduces AMPA but not NMDA receptor levels in the rat neocortex

Fetal alcohol syndrome (FAS) is the leading cause of mental retardation in western society. We investigated possible changes in glutamate receptor levels in neonatal animals following ethanol exposure using radioligand binding and western blot analysis. We used a vapor chamber to administer ethanol to neonatal Wistar rats 3 h a day from postnatal day (PND) 4-9. A separation control group was separated from their mothers for the same time and duration as the vapor treatment, while a normal control group was left to develop normally. Daily ethanol administrations resulted in decreased brain weight and body weight, as well as microencephaly (decreased brain:body weight ratio). Neither the affinity nor maximum binding of [H-3]MK-801 (dizoclipine maleate) in the cortex of PND10 rats differed between treatment groups. Western blot analysis also failed to reveal any changes in NMDAR1, NMDAR2A, or NMDAR2B receptor levels. In contrast, the AMPA receptor subunit GluR1 was greatly reduced in vapor-treated pups compared with control pups, as revealed by western blot analysis. A similar reduction was found in westerns with an antibody recognizing the GluR2 and 4 subunits. These results indicate that ethanol reduces AMPA rather than NMDA receptors in the developing neocortex, possibly by blocking NMDA receptors during development. (C) 2002 Elsevier Science B.V. All rights reserved.

Behaviour of caregivers to protect their infants from exposure to the sun in Queensland, Australia.

Exposure to the sun by infants has been demonstrated to increase the risk of the development of melanoma and other skin cancers later in life. A cohort of 508 women who delivered healthy Caucasian babies were followed up at 1 year to determine their knowledge, attitudes and practices regarding sun protection towards themselves and their child. In addition, the 1-year-old infants were assessed by a trained nurse for the number of nevi they had on their skin. Results indicate caregivers reported a high level of sun-protection practices towards their child, with 93% of the caregivers reporting usually or always placing the child in the shade when going outside. Further, 81% of the caregivers reported usually or always placing a hat on the child, while 64% reported usually or always applying sunscreen to the child's exposed skin. Interestingly, only 61% of the caregivers reported that they stayed in the shade to reduce sun exposure and only 42% wore a hat when out in the sun. Mother's own personal sun-protection methods predicted the method of sun protection that she would most likely use for the child. While children appear to be reasonably protected from the sun, they are influenced by their mother's own behaviors.

Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P