Expression analysis of delta-catenin and prostate-specific membrane antigen: Their potential as diagnostic markers for prostate cancer

The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour sample and I BPH sample. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and I 1 BPH samples. Two genes, delta-catenin (delta-catenin; CTNND2) and prostate-specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for S-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer. (C) 2002 Wiley-Liss. Inc.

Sponge halogenated natural products found at parts-per-million levels in marine mammals

Several unknown, abundant brominated compounds (BCs) were recently detected in the blubber of dolphins and other marine mammals from Queensland (northeast Australia). The BC were interpreted as potential natural products due to the lack of anthropogenic sources for these compounds. This study investigated whether some of the BCs accumulated by diverse marine mammal species are identical with natural BCs previously isolated from sponges (Dysidea sp.) living in the same habitat. Isolates from sponges and mollusks (Asteronotus cespitosus) were compared with the signals detected in the mammals' tissue. Mass spectra and gas chromatography retention times on four different capillary columns of the isolates from sponges and mammals were identical in all respects. This proves that the chemical name of the compound previously labeled BC-2 is 4,6-dibromo-2-(2'-dibromo)phenoxyanisole and that the chemical name of BC-11 is 3,5-dibromo-2-(3',5'-dibromo-2'-methoxy)phenoxyanisole. Using a quantitative reference solution of BC-2, we established that the concentrations of the brominated metabolies found in the marine mammals are frequently >1 mg/kg. The highest concentration (3.8 mg/kg), found in a sample of pygmy sperm whale (Kogia breviceps), indicates that BC-2 is a bioaccumulative, natural organohalogen compound. This is supported by the concentrations of the BCs in our samples being equal to the highest concentrations of anthropogenic BCs in any environmental sample. The quantitative determination of BC-2 in blubber of marine mammals from Africa and the Antarctic suggests that BC-2 is wide-spread. These results are direct proof that marine biota can produce persistent organic chemicals that accumulate to substantial concentrations in higher trophic organisms.

The effects of haemogregarine-like parasites on brown tree snakes (Boiga irregularis) and slatey-grey snakes (Stegonotus cucullatus) in Queensland, Australia

We described the effects of haemogregarine-like parasites on the blood chemistry and health of brown tree snakes (Boiga irregularis) and slatey-grey snakes (Stegonotus cucullatus) to evaluate the potential for these parasites to be used as a form of biological wildlife control for introduced brown tree snakes on Guam. We quantified the level of parasitic infection and found no significant correlation between parasitic infection and blood chemistry (P-values ranged from 0.94 to 0.13) or snake condition (P = 0.65 and 0.40 in brown tree snakes and slatey-grey snakes, respectively). These findings indicate that haemogregarines may not be a good candidate to control brown tree snakes. However, parasitic infection in our specimens was low ( < 10%) and higher infection rates may yield significant effect on the health of these snakes. Further research should be conducted on the effects of haemogregarines to host species, the life histories of these parasites, and the potential negative effects to other fauna before blood parasites are employed as a viable biological control technique. (C) 2002 Published by Elsevier Science Ltd.

Experimental investigation of contaminant transport in coastal groundwater

Contaminant transport in coastal aquifers is of increasing interest since, with the development of coastal areas, contaminants from surface sources may enter coastal aquifers and pollute the groundwater flow. Coastal groundwater flow is complicated because of the presence of a freshwater-saltwater diffusion zone and the tidal variation of sea level at the seaward end. This paper investigates experimentally the behaviour of contaminant plumes with different densities in an unconfined coastal aquifer. Experiments were performed in a flow tank filled with glass beads as the porous medium. Results show that the dense contaminant has a more diffusive front than the less dense one in the seaward direction towards the coastline. The plume becomes more diffusive when it travels closer to the saltwater interface. On the contrary, the less dense contaminant presents a relatively sharp outline. It tends to migrate in the upper portion of the aquifer and exits in a concentrated manner over a small discharge area at the coastline, not further seaward under the sea. Non-dimensional parameters show that instabilities occur in our experiments for a density difference of 1.2% or larger between the contaminant and the ambient water. The experimental results provide guidance for field monitoring and numerical modelling. (C) 2002 Elsevier Science Ltd. All rights reserved.

Audit of maternal and fetal outcomes in women treated for glucose intolerance during pregnancy

Objective To determine whether one should aim for glycaemia that is statistically 'normal' or for levels of glycaemia low enough to prevent macrosomia (if such a threshold exists) when glucose intolerance is detected during pregnancy Design An audit of pregnancy outcomes in women with impaired glucose tolerance in pregnancy as compared to a local age-matched reference group with normal glucose tolerance. Results Our study suggests that for most patients, more intensive therapy would not have been justified. Maternal smoking appeared to convey some 'advantages' in terms of neonatal outcomes, with reduction in large-for-gestational-age (LGA) infants and jaundice in babies of impaired glucose tolerance (IGT) mothers. Conclusions These observations demonstrate the importance of considering risk factors other than GTT results in analysing pregnancy outcomes, while emphasising that 'normalisation' of fetal size should not be our only therapeutic endpoint. Our detailed outcome review allows us to reassure patients with GDM that with current treatment protocols, they should have every expectation of a positive pregnancy outcome.

Ex vivo profiling of CD8(+)-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers

Human cytomegalovirus (HCMV) can establish both nonproductive (latent) and productive (lytic) infections. Many of the proteins expressed during these phases of infection could be expected to be targets of the immune response; however, much of our understanding of the CD8(+)-T-cell response to HCMV is mainly based on the pp65 antigen. Very little is known about T-cell control over other antigens expressed during the different stages of virus infection; this imbalance in our understanding undermines the importance of these antigens in several aspects of HCMV disease pathogenesis. In the present study, an efficient and rapid strategy based on predictive bioinformatics and ex vivo functional T-cell assays was adopted to profile CD8(+)-T-cell responses to a large panel of HCMV antigens expressed during different phases of replication. These studies revealed that CD8(+)-T-cell responses to HCMV often contained multiple antigen-specific reactivities, which were not just constrained to the previously identified pp65 or IE-1 antigens. Unexpectedly, a number of viral proteins including structural, early/late antigens and HCMV-encoded immunomodulators (pp28, pp50, gH, gB, US2, US3, US6, and UL18) were also identified as potential targets for HCMV-specific CD8(+)-T-cell immunity. Based on this extensive analysis, numerous novel HCMV peptide epitopes and their HLA-restricting determinants recognized by these T cells have been defined. These observations contrast with previous findings that viral interference with the antigen-processing pathway during lytic infection would render immediate-early and early/late proteins less immunogenic. This work strongly suggests that successful HCMV-specific immune control in healthy virus carriers is dependent on a strong T-cell response towards a broad repertoire of antigens.

Heritability of adult body height: A comparative study of twin cohorts in eight countries

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.

Influence of ageing, heat shock treatment and in vivo total antioxidant status on gene-expression profile and protein synthesis in human peripheral lymphocytes

Ageing results in a progressive, intrinsic and generalised imbalance of the control of regulatory systems. A key manifestation of this complex biological process includes the attenuation of the universal stress response. Here we provide the first global assessment of the ageing process as it affects the heat shock response, utilising human peripheral lymphocytes and cDNA microarray analysis. The genomic approach employed in our preliminary study was supplemented with a proteomic approach. In addition, the current study correlates the in vivo total antioxidant status with the age-related differential gene expression as well as the translational kinetics of heat shock proteins (hsps). Most of the genes encoding stress response proteins on the 4224 element microarray used in this study were significantly elevated after heat shock treatment of lymphocytes obtained from both young and old individuals albeit to a greater extent in the young. Cell signaling and signal transduction genes as well as some oxidoreductases showed varied response. Results from translational kinetics of induction of major hsps, from 0 to 24 It recovery period were broadly consistent with the differential expression of HSC 70 and HSP 40 genes. Total antioxidant levels in plasma from old individuals were found to be significantly lower by comparison with young, in agreement with the widely acknowledged role of oxidant homeostasis in the ageing process. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Phylogeny of the lice (Insecta, Phthiraptera) inferred from small subunit rRNA

There has been much argument about the phylogenetic relationships of the four suborders of lice (Insecta: Phthiraptera). Lyal's study of the morphology of lice indicated that chewing/biting lice (Mallophaga) are paraphyletic with respect to sucking lice (Anoplura). To test this hypothesis we inferred the phylogeny of 33 species of lice from small subunit (SSU) rRNA sequences (18S rRNA). Liposcelis sp. from the Liposcelididae (Psocoptera) was used for outgroup reference. Phylogenetic relationships among the four suborders of lice inferred from these sequences were the same as those inferred from morphology. The Amblycera is apparently the sister-group to all other lice whereas the Rhynchophthirina is apparently sister to the Anoplura; these two suborders are sister to the Ischnocera, i.e. (Amblycera (Ischnocera (Anoplura, Rhynchophthirina))). Thus, the Mallophaga (Amblycera, Ischnocera, Rhynchophthirina) is apparently paraphyletic with respect to the Anoplura. Our analyses also provide evidence that: (i) each of the three suborders of lice that are well represented in our study (the Amblycera, Ischnocera, and Anoplura) are monophyletic; (ii) the Boopiidae is monophyletic; (iii) the genera Heterodoxus and Latumcephalum (Boopiidae) are more closely related to one another than either is to the genus Boopia (also Boopiidae); (iv) the Ricinidae and Laemobothridae may be sister-taxa; (v) the Philopteridae may be paraphyletic with respect to the Trichodectidae; (vi) the genera Pediculus and Pthirus are more closely related to each other than either is to the genus Pedicinus ; and (vii) in contrast to published data for mitochondrial genes, the rates of nucleotide substitution in the SSU rRNA of lice are not higher than those of other insects, nor do substitution rates in the suborders differ substantially from one another.

Voluntary disclosure of forward-looking earnings forecasts in Australia

This study examines the voluntary disclosure of future earnings information in annual reports for Australian listed companies. We find that most Australian companies in our sample do not provide quantitative earnings, forecasts in their annual reports, although more than half of the sample do disclose forward-looking information relating to earnings, without specifically disclosing point estimates for the future. These companies mostly supply qualitative information with a positive bias, while the remainder of the sample discloses no forward-looking information relating to earnings. Our findings also suggest that larger companies with less volatile earnings tend to provide more future earnings information than smaller companies with relatively volatile earnings.

Suppressor of cytokine signalling gene expression is elevated in breast carcinoma

Cytokines are important for breast cell function, both as trophic hormones and as mediators of host defense mechanisms against breast cancer. Recently, inducible feedback suppressors of cytokine signalling (SOCS/JAB/SSI) have been identified, which decrease cell sensitivity to cytokines. We examined the expression of SOCS genes in 17 breast carcinomas and 10 breast cancer lines, in comparison with normal tissue and breast lines. We report elevated expression of SOCS-1-3 and CIS immunoreactive proteins within in situ ductal carcinomas and infiltrating ductal carcinomas relative to normal breast tissue. Significantly increased expression of SOCS-1-3 and CIS transcripts was also shown by quantitative in situ hybridisation within both tumour tissue and reactive stroma. CIS transcript expression was elevated in all 10 cancer lines, but not in control lines. However, there was no consistent elevation of other SOCS transcripts. CIS protein was shown by immunoblot to be present in all cancer lines at increased levels, mainly as the 47 kDa ubiquitinylated form. A potential proliferative role for CIS overexpression is supported by reports that CIS activates ERK kinases, and by strong induction in transient reporter assays with an ERK-responsive promoter. The in vivo elevation of SOCS gene expression may be part of the host/tumour response or a response to autocrine/paracrine GH and prolactin. However, increased CIS expression in breast cancer lines appears to be a specific lesion, and could simultaneously shut down STAT 5 signalling by trophic hormones, confer resistance to host cytokines and increase proliferation through ERK kinases.

Evaluating plant breeding strategies by simulating gene action and dryland environment effects

Functional genomics is the systematic study of genome-wide effects of gene expression on organism growth and development with the ultimate aim of understanding how networks of genes influence traits. Here, we use a dynamic biophysical cropping systems model (APSIM-Sorg) to generate a state space of genotype performance based on 15 genes controlling four adaptive traits and then search this spice using a quantitative genetics model of a plant breeding program (QU-GENE) to simulate recurrent selection. Complex epistatic and gene X environment effects were generated for yield even though gene action at the trait level had been defined as simple additive effects. Given alternative breeding strategies that restricted either the cultivar maturity type or the drought environment type, the positive (+) alleles for 15 genes associated with the four adaptive traits were accumulated at different rates over cycles of selection. While early maturing genotypes were favored in the Severe-Terminal drought environment type, late genotypes were favored in the Mild-Terminal and Midseason drought environment types. In the Severe-Terminal environment, there was an interaction of the stay-green (SG) trait with other traits: Selection for + alleles of the SG genes was delayed until + alleles for genes associated with the transpiration efficiency and osmotic adjustment traits had been fixed. Given limitations in our current understanding of trait interaction and genetic control, the results are not conclusive. However, they demonstrate how the per se complexity of gene X gene X environment interactions will challenge the application of genomics and marker-assisted selection in crop improvement for dryland adaptation.

The importance of quality in the consolidation of textile in Minho

The textile industry has a long tradition in Portugal and it is one of the most important sectors, despite the current economic crisis. It has always assumed a prominent role in terms of employment and a relevant position within the Portuguese economy. The lack of quality and the lower prices that other countries offer causes the loss of clients. Quality is a main tool to survive nowadays in the textile sector. To undertake our analysis, we made use of an existing database where 55 firms belonged to the textile industry, namely to the manufacturing sector. A new survey was created based on the original survey and was sent to 5 firms. Besides the survey, we also sent a few questions to the firms in order to retract more information about the actually situation in our country, concerning the textile industry. Several tables, graphs and pie charts were made to help shed light on our findings. This research was conducted in order to determine the importance of quality in the consolidation of textile firms in the north of Portugal. Most firms in our sample feel that quality improvement, business benefits, mobilizing employees’ knowledge and business image were important and that competition is very intense and is mainly by price and not by differentiation of product or service. The quality program has contributed to improve their competitive position and the improvement of their overall performance. The majority of the firms in our sample undertake TQM measures for quality purposes to meet customer expectations and prevent errors. Of all firms surveyed, the quality is certainly very important for its survival.

Mortality problems in Brazil and in Germany: past-present-future. Learning from each other?

This article was written by a Swiss-German historical demographer after having visited different Brazilian Universities in 1984 as a guest-professor. It aims at promoting a real dialog between developed and developing countries, commencing the discussion with the question: Can we learn from each other? An affirmative answer is given, but not in the superficial manner in which the discussion partners simply want to give each other some "good advice" or in which the one declares his country's own development to be the solely valid standard. Three points are emphasized: 1. Using infant mortality in S. Paulo from 1908 to 1983 as an example, it is shown that Brazil has at its disposal excellent, highly varied research literature that is unjustifiably unknown to us (in Europe) for the most part. Brazil by no means needs our tutoring lessons as regards the causal relationships; rather, we could learn two things from Brazil about this. For one, it becomes clear that our almost exclusively medical-biological view is inappropriate for passing a judgment on the present-day problems in Brazil and that any conclusions so derived are thus only transferable to a limited extent. For another, we need to reinterpret the history of infant mortality in our own countries up to the past few decades in a much more encompassing "Brazilian" sense. 2. A fruitful dialog can only take place if both partners frankly present their problems. For this reason, the article refers with much emprasis to our present problems in dealing with death and dying - problems arising near the end of the demographic and epidemiologic transitions: the superanuation of the population, chronic-incurable illnesses as the main causes of death, the manifold dependencies of more and more elderly and really old people at the end of a long life. Brazil seems to be catching up to us in this and will be confronted with these problems sooner or later. A far-sighted discussion already at this time seems thus to be useful. 3. The article, however, does not want to conclude with the rather depressing state of affairs of problems alternatingly superseding each other. Despite the caution which definitely has a place when prognoses are being made on the basis of extrapolations from historical findings, the foreseeable development especially of the epidemiologic transition in the direction of a rectangular survival curve does nevertheless provide good reason for being rather optimistic towards the future: first in regards to the development in our own countries, but then - assuming that the present similar tendencies of development are stuck to - also in regard to Brazil.

The risk-return trade-off in Europe: A temporal and cross-sectional analysis

This paper analyzes the risk-return trade-off in European equities considering both temporal and cross-sectional dimensions. In our analysis, we introduce not only the market portfolio but also 15 industry portfolios comprising the entire market. Several bivariate GARCH models are estimated to obtain the covariance matrix between excess market returns and the industrial portfolios and the existence of a risk-return trade-off is analyzed through a cross-sectional approach using the information in all portfolios. It is obtained evidence for a positive and significant risk-return trade-off in the European market. This conclusion is robust for different GARCH specifications and is even more evident after controlling for the main financial crisis during the sample period.