Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study

Risk factors for melanoma include environmental (particularly ultraviolet exposure) and genetic factors. In rare families, susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK4, with more common, less penetrant genes also postulated. A further, potent risk factor for melanoma is the presence of large numbers of melanocytic nevi so that genes controlling nevus phenotype could be such melanoma susceptibility genes. A large Australian study involving twins aged 12 y of predominantly U.K. ancestry showed strong evidence for genetic influence on nevus number and density. We carried out essentially the same study in the U.K. to gain insight into gene-environment interactions for nevi. One hundred and three monozygous (MZ) and 118 dizygous (DZ) twin pairs aged 10-18 y were examined in Yorkshire and Surrey, U.K. Nevus counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p = 0.009) and higher in Australia (110.4) than in the U.K. (79.2, adjusted to age 12 y, p < 0.0001), and nevus densities were higher on sun-exposed sites (92 per m(2)) than sun-protected sites (58 per m(2)) (p < 0.0001). Correlations in sex and age adjusted nevus density were higher in MZ pairs (0.94, 95% CI 0.92-0.96) than in DZ pairs (0.61, 95%CI 0.49-0.72), were notably similar to those of the Australian study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability (65% in the U.K., 68% in Australia). We conclude that emergence of nevi in adolescents is under strong genetic control, whereas environmental exposures affect the mean number of nevi.

On the heritability of inspection time and its covariance with IQ: A twin study

Using the classical twin design, this study investigates the influence of genetic factors on the large phenotypic variance in inspection time (IT), and whether the well established IT-IQ association can be explained by a common genetic factor. Three hundred ninety pairs of twins (184 monozygotic, MZ; 206 dizygotic, DZ) with a mean age of 16 years participated, and 49 pairs returned approximately 3 months, later for retesting. As in many IT studies, the pi figure stimulus was used and IT was estimated from the cumulative normal ogive. IT ranged from 39.4 to 774.1 ms (159 +/- 110.1 ms) with faster ITs (by an average of 26.9 ms) found in the retest session from which a reliability of .69 was estimated. Full-scale IQ (FIQ) was assessed by the Multidimensional Aptitude Battery (MAB) and ranged from 79 to 145 (111 +/- 13). The phenotypic association between IT and FIQ was confirmed (- .35) and bivariate results showed that a common genetic factor accounted for 36% of the variance in IT and 32% of the variance in FIQ. The maximum likelihood estimate of the genetic correlation was - .63. When performance and verbal IQ (PIQ & VIQ) were analysed with IT, a stronger phenotypic and genetic relationship was found between PIQ and IT than with VIQ. A large part of the IT variance (64%) was accounted for by a unique environmental factor. Further genetic factors were needed to explain the remaining variance in IQ with a small component of unique environmental variance present. The separability of a shared genetic factor influencing IT and IQ from the total genetic variance in IQ suggests that IT affects a specific subcomponent of intelligence rather than a generalised efficiency. (C) 2001 Elsevier Science Inc. All rights reserved.

Dipeptidyl peptidase IV is a target for covalent adduct formation with the acyl glucuronide metabolite of the anti-inflammatory drug zomepirac

The nonsteroidal anti-inflammatory drug zomepirac (ZP) is metabolised to a chemically reactive acyl glucuronide conjugate (ZAG) which can form covalent adducts with proteins. In vivo, such adducts could initiate immune or toxic responses. In rats given ZP, the major band detected in liver homogenates by immunoblotting with a polyclonal ZP antiserum was at 110 kDa. This adduct was identified as ZP-modified dipeptidyl peptidase IV (DPP IV) by immunoblotting using the polyclonal ZP antiserum and monoclonal DPP IV antibodies OX-61 and 236.3. In vitro, ZAG, but not ZP itself, covalently modified recombinant human and rat DPP IV. Both monoclonal antibodies recognized DPP IV in livers from ZP- and vehicle-dosed rats. Confirmation that the 110 kDa bands which were immunoreactive with the ZP and DPP IV antibodies represented the same molecule was obtained from a rat liver extract reciprocally immunodepleted of antigens reactive with these two antibodies. Furthermore, immunoprecipitations with OX-61 antibody followed by immunolotting with ZP antiserum, and the reciprocal experiment, showed that both these antibodies recognised the same 110 kDa molecule in extracts of ZP-dosed rat liver. The results verify that DPP IV is one of the protein targets for covalent modification during hepatic transport and biliary excretion of ZAG in rats. (C) 2001 Elsevier Science Inc. All rights reserved.

Prediction of many new exons and introns in Plasmodium falciparum chromosome 2

The current prediction or genes in the Plasmodium falciparum genome database relies upon a limited number of specially developed computer algorithms. We have re-annotated the sequence of chromosome 2 of P. falciparum by a computer-assisted manual analysis. which is described here. Of 161 newly predicted introns, we have experimentally confirmed 98. We regard 110 introns from the previously published analyses as probable, we delete 3, change 26 and add 135. We recognise 214 genes in chromosome 2. We have predicted introns in 121 genes. The increased complexity or gene structure on chromosome 2 is likely to be mirrored by the entire genome. (C) 2001 Elsevier Science B.V. All rights reserved.

Seedling responses of three Australian tree species to toxic concentrations of zinc in solution culture

A frequently desired outcome when rehabilitating Zn toxic sites in Australia is to establish a self-sustaining native ecosystem. Hence, it is important to understand the tolerance of Australian native plants to high concentrations of Zn. Very little is known about the responses of Australian native plants, and trees in particular, to toxic concentrations of Zn. Acacia holosericea, Eucalyptus camaldulensis and Melaleuca leucadendra plants were grown in dilute solution culture for 10 weeks. The seedlings (42 days old) were exposed to six Zn treatments viz., 0.5, 5, 10, 25, 50 and 100 muM. The order of tolerance to toxic concentrations of Zn was E. camaldulensis > A. holosericea > M. leucadendra, the critical external concentrations being approximately 20, 12 and 1.5 muM, respectively. Tissue Zn concentrations increased as solution Zn increased for all species. Root tissue concentrations were higher than shoot tissue concentrations at all solution Zn concentrations. The critical tissue Zn concentrations were approximately 85 and 110 mug g(-1) DM for M. leucadendra, 115 and 155 mug g(-1) DM for A. holosericea and 415 and 370 mug g(-1) DM for E. camaldulensis for the youngest fully expanded leaf and total shoots, respectively. The results from this paper provide the first comprehensive combination of growth responses, critical external concentrations, critical tissue concentrations and plant toxicity symptoms for three important Australian genera, viz., Eucalyptus, Acacia and Melaleuca, for use in the rehabilitation of potentially Zn toxic sites.

Reversal of cardiovascular remodelling with candesart

Cardiovascular remodelling, defined as ventricular and vascular hypertrophy together with fibrosis, characterises hypertension following inhibition of the production of the endogenous vasodilator, nitric oxide (NO). This study has determined whether the cardiovascular remodelling following chronic NO synthase inhibition can e reversed by administration of the selective angiotensin II AT(1)-receptor antagonist, candesartan. Male Wistar rats were treated with L-nitroarginine methyl ester (L-NAME, 400 mg/l in drinking water) for eight weeks and with candesartan cilexetil (2 mg/kg/day by oral gavage) for the last four weeks. L-NAME-treated rats became hypertensive with systolic blood pressure increasing from 110 +/- 4 mmHg (control) to 170 +/- 10 mmHg. Rats developed left ventricular hypertrophy (control 1.70 +/- 0.06; L-NAME 2.10 +/- 0.04 mg/kg body wt) with markedly increased deposition of perivascular and interstitial collagen. Candesartan returned blood pressure, left ventricular weights and collagen deposition to control values. Echo cardiographic assessment showed concentric hypertrophy with an increased fractional shortening; this was reversed by candesartan treatment. Heart failure was not evident. In the isolated Langendorff heart, diastolic stiffness increased in L-NAME-treated rats while the rate of increase in pressure (+dP/dt) increased after eight weeks only; candesartan reduced collagen deposition and normalised +dP/dt. In isolated left ventricular papillary muscles, the potency (negative log EC50) of noradrenaline as a positive inotropic compound was unchanged, (control 6.56 +/- 0.14); maximal increase in force before ectopic beats was reduced from 5.0 +/- 0.4 mN to 2.0 +/- 0.2 mN. Noradrenaline potency as a vasoconstrictor in thoracic aortic rings was unchanged, but maximal contraction was markedly reduced from 25.2 +/- 2.0 mN to 3.0 +/- 0.3 mN; this was partially reversed by candesartan treatment. Thus, chronic inhibition of NO production with L-NAME induces hypertension, hypertrophy and fibrosis with increased toxicity and significant decreases in vascular responses to noradrenaline. These changes were at least partially reversible by treatment with candesartan, implying a significant role of AT(1)-receptors in L-NAME-induced cardiovascular changes.

Diagnostic accuracy of paediatric echocardiograms interpreted by individuals other than paediatric cardiologists

Objective: To assess the diagnostic error rate among echocardiograms undertaken by individuals other than paediatric cardiologists in our referral area. Methodology: External group: The charts and echocardiographic results of all patients who had undergone outside echocardiograms between January 1996 and December 1999 were reviewed (110). Age at echocardiography, diagnostic complexity, presence of any diagnostic errors and the severity of any diagnostic errors were identified. Internal group: To assess our own error rate, the initial echocardiographic diagnoses of 100 patients undergoing cardiac catheterisation or corrective surgery were compared with the post-catheterisation or postoperative diagnoses. Age and diagnostic complexity were also assessed in the control group. Results: Diagnostic errors occurred in 47/110 patients (44%) of the externally studied group (of which 24% were either major or life threatening) as opposed to 3/100 of the internally studied group, despite the internally studied group being of increased diagnostic complexity. Errors were more common and of increased severity in infants less than 1 month of age but extended throughout all age groups. Major and life threatening errors increased with increasing diagnostic complexity. In the externally studied group, 8/47 errors were patients inappropriately designated as normal. Four of these patients required cardiac surgery or interventional cardiac catheterisation. Conclusions: This study suggests an unacceptably high error rate in paediatric echocardiographic diagnoses by non-paediatric cardiologists throughout all age groups. Such errors are more likely in younger infants and with increasing diagnostic complexity.

Identity and genetic diversity of the sorghum ergot pathogen in Australia

Sorghum ergot was first discovered in Australia in 1996. It affects seed production and grain usage in stock feed due to concerns of animal toxicity. Three species of Claviceps are known to cause ergot of sorghum with different epidemiological, animal toxicity, and management implications. Claviceps africana was identified as the causal agent but morphological differences between isolates raised the possibility of more than one species being involved. The major aim of this study was to identify the Claviceps species causing sorghum ergot and to determine the genetic diversity among isolates of the ergot pathogen from Australia and overseas. Symptom development, sequencing of the ITS1 region, and radiolabelled DNA amplification fingerprints (RAF) were used to confirm that ergot of sorghum in Australia is caused by C. africana. The morphology of sphacelia, microconidia, macroconidia, and secondary conidia of all 36 Australian isolates studied matched the description for C. africana and the DNA sequence of the ITS1 region of 2 selected Australian isolates was identical to that of C. africana. Based on RAF analysis of 110 Australian and overseas isolates of Claviceps spp., C. africana isolates could be clearly distinguished (

Veterinary parasitology teaching in eastern Australia

There are tendencies in universities globally to change undergraduate teaching in veterinary parasitology. To be able to give considered advice to universities, faculties, governmental bodies and professional societies about a discipline and to establish how particular changes may impact on the quality of a course, is the requirement to record and review its current status. The present paper contributes toward this objective by providing a snap-shot of the veterinary parasitology courses at the Universities of Melbourne, Sydney and Queensland in eastern Australia. It includes a description of the veterinary science curriculum in each institution, and provides an outline of its veterinary parasitology course, including objectives, topics covered, course delivery, student examination procedures and course evaluation. Student contact time in veterinary parasitology during the curriculum is currently higher in Melbourne (183 h) compared with Sydney and Queensland (106-110 h). In the teaching of parasitology, Melbourne adopts a taxonomic approach (in the pre-clinical period) followed by a combined disciplinary and problem-based approach in the clinical semesters, whereas both Sydney and Queensland focus more on presenting parasites on a host species-basis followed by a problem-based approach. (C) 2002 Elsevier Science B.V. All rights reserved.

Hepatic covalent adduct formation with zomepirac in the CD26-deficient mouse

Background and Aims: Zomepirac (ZP), a non-steroidal anti-inflammatory drug (NSAID), has been reported to cause immune-mediated liver injury. In vivo, ZP is metabolized to a chemically reactive acyl glucuronide conjugate (ZAG) which can undergo covalent adduct formation with proteins. Such acyl glucuronide-derived drug-protein adducts may be important in the development of immune and toxic responses caused by NSAID. We have shown using immunoabsorptions that the 110 kDa CD26 (dipeptidyl peptidase IV) is one of the hepatic target proteins for covalent modification by ZAG. In the present study, a CD26-deficient mouse strain was used to examine protein targets for covalent modification by ZP/metabolites in the liver. Methods and Results: The CD26-deficient phenotype was confirmed by immunohistochemistry, flow cytometry analysis, RT-PCR, enzyme assay and immunoblotting. Moreover, by using monoclonal antibody immunoblots, CD26 was not detected in the livers of ZP-treated CD26-deficient mice. Immunoblots using a polyclonal antiserum to ZP on liver from ZP-treated mice showed three major sizes of protein bands, in the 70, 110 and 140 kDa regions. Most, but not all, of the anti-ZP immunoreactivity in the 110 kDa region was absent from ZP-treated CD26-deficient mice. Conclusion: These data definitively showed that CD26 was a component of ZP-modified proteins in vivo. In addition, the data suggested that at least one other protein of approximately 110 kDa was modified by covalent adduct formation with ZAG. (C) 2002 Blackwell Science Asia Pty Ltd.

Avian paramyxoviruses and influenza viruses isolated from mallard ducks (Anas platyrhynchos) in New Zealand

A comprehensive study using virological and serological approaches was carried out to determine the status of live healthy mallard ducks (Anas platyrhynchos) in New Zealand for infections with avian paramyxoviruses (APMV) and influenza viruses (AIV). Thirty-three viruses isolated from 321 tracheal and cloacal swabs were characterized as: 6 AIV (two H5N2 and four H4N6), 10 APMV-1 and 17 APMV-4. Of 335 sera samples tested for AIV antibodies, 109 (32.5%) sera were positive by nucleoprotein-blocking ELISA (NP-B-ELISA). Serum samples (315) were examined for antibody to APMV-1, -2, -3, -4, -6, -7, -8, -9 by the haemagglutination inhibition test. The largest number of reactions, with titres up to greater than or equal to 1/64, was to APMV-1 (93.1%), followed by APMV-6 (85.1%), APMV-8 (56%), APMV-4 (51.7%), APMV-7 (47%), APMV-9 (15.9%), APMV-2 (13.3%) and APMV-3 (6.0%). All of the H5N2 isolates of AIV and the APMV-1 isolates from this and earlier New Zealand studies had low pathogenicity indices assessed by the Intravenous Pathogenicity Index (IVPI) with the result 0.00 and Intracerebral Pathogenicity Index (ICPI) with results 0.00-0.16. Partial genomic and antigenic analyses were also consistent with the isolates being non-pathogenic. Phylogenetic analysis of the 10 APMV-1 isolates showed 9 to be most similar to the reference APMV-1 strain D26/76 originally isolated in Japan and also to the Que/66 strain, which was isolated in Australia. The other isolate was very similar to a virus (MC 110/77) obtained from a shelduck in France.

Airborne Pinus pollen in the atmosphere of Brisbane, Australia and relationships with meteorological parameters

Relationships between weather parameters andairborne pollen loads of Pinus inBrisbane, Australia have been investigated overthe five-year period, June 1994–May 1999.Pinus pollen accounts for 4.5% of the annualairborne pollen load in Brisbane where thePinus season is confined to the winter months,July–early September. During the samplingperiod loads of 11–>100 grains m3 wererecorded on 24 days and 1–10 grains m3 on204 days. The onset and peak dates wereconsistent across each season, whereas the enddates varied. The onset of the Pinuspollen season coincided with the coolestaverage monthly temperatures (< 22°C),lowest rainfall (< 7mm), and four weeks afterdaily minimum temperatures fell to 5–9°Cin late autumn. Correlations obtained betweendaily airborne Pinus pollen counts andtemperature/rainfall parameters show thatdensities of airborne Pinus pollen arenegatively correlated with maximum temperature(p < 0.0001), minimum temperature (p < 0.0001)and rainfall (p < 0.05) during the mainpollination period. The mean duration of eachpollen season was 52 days; longer seasons wereshown to be directly related to lower averageseasonal maximum temperatures (r2 = 0.85,p = 0.025). These results signify that maximumand minimum temperatures are the majorparameters that influence the onset andduration of the Pinus pollen season inthe environs of Brisbane. Respiratory allergyis an important health issue in Brisbane,Australia, but it remains unknown whether ornot airborne Pinus pollen is acontributing factor.

The last dicynodont: An Australian Cretaceous relict

Some long-forgotten fossil evidence reveals that a dicynodont (mammal-like reptile of the infraorder Dicynodontia) inhabited Australia as recently as the Early Cretaceous, ca. 110 Myr after the supposed extinction of dicynodonts in the Late Triassic. This remarkably late occurrence more than doubles the known duration of dicynodont history (from ca. 63 Myr to ca. 170 Myr) and betrays the profound impact of geographical isolation on Australian terrestrial faunas through the Mesozoic. Australia's late-surviving dicynodont may be envisaged as a counterpart of the ceratopians (homed dinosaurs) in Cretaceous tetrapod faunas of Asia and North America.

Use of an accelerated chest pain assessment protocol in patients at intermediate risk of adverse cardiac events

Objective: To determine the feasibility, safety and effectiveness of a structured clinical pathway for stratification and management of patients presenting with chest pain and classified as having intermediate risk of adverse cardiac outcomes in the subsequent six months. Design: Prospective clinical audit. Participants and setting: 630 consecutive patients who presented to the emergency department of a metropolitan tertiary care hospital between January 2000 and June 2001 with chest pain and intermediate-risk features. Intervention: Use of the Accelerated Chest Pain Assessment Protocol (ACPAP), as advocated by the Management of unstable angina guidelines - 2000 from the National Heart Foundation and the Cardiac Society of Australia and New Zealand. Main outcome measure: Adverse cardiac events during six-month follow-up. Results: 409 patients (65%) were reclassified as low risk and discharged at a mean of 14 hours after assessment in the chest pain unit. None had missed myocardial infarctions, while three (1%) had cardiac events at six months (all elective revascularisation procedures, with no readmissions with acute coronary syndromes). Another 110 patients (17%) were reclassified as high risk, and 21 (19%) of these had cardiac events (mainly revascularisations) by six months. Patients who were unable to exercise or had non-diagnostic exercise stress test results (equivocal risk) had an intermediate cardiac event rate (8%). Conclusions: This study validates use of ACPAP. The protocol eliminated missed myocardial infarction; allowed early, safe discharge of low-risk patients; and led to early identification and management of high-risk patients.

Aging per se does not influence glucose homeostasis - In vivo and in vitro evidence

OBJECTIVE - To assess the effect of age on glucose metabolism by examining 1) glucose metabolism in young and middle-aged subjects when total or regional adiposity is taken into account and 2) in vitro glucose transport in adipose tissue explants from young and middle-aged women paired for total and abdominal adiposity. RESEARCH DESIGN AND METHODS - Study 1: body composition, subcutaneous abdominal and visceral adipose tissue areas, and fasting and oral glucose-stimulated glucose and insulin were measured in 84 young and 81 middle-aged men and in 110 young and 91 middle-aged women. Study 2: glucose uptake in subcutaneous abdominal and visceral adipose tissue explants were measured in eight young and eight middle-aged women. RESULTS - Study 1: young and middle-aged men showed similar subcutaneous abdominal tissue area, whereas fat mass and visceral adipose tissue were greater in middle-aged than in young men (P < 0.01). Fat mass and subcutaneous and visceral adipose tissue areas were greater in middle-aged as compared with young women (P < 0.01). Fasting plasma glucose and the glucose response to an oral glucose tolerance test were significantly higher in middle-aged than in young men and women (P < 0.001). Statistical control for visceral adipose tissue area eliminated the difference seen in glucose response in men and women. Study 2: glucose transport in subcutaneous and omental adipose tissue did not differ between young and middle-aged women. CONCLUSIONS - 1) Visceral obesity, more than age per se, correlates with glucose intolerance in middle-aged subjects; 2) aging does not influence in vitro adipose tissue glucose uptake.