bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I and II pharmacokinetic and pharmacodynamic study of the proteasome inhibitor bortezomib in Japanese patients with relapsed or refractory multiple myeloma
Authors: Ogawa Yoshiaki , Tobinai Kensei , Ogura Michinori , Ando Kiyoshi , Tsuchiya Takahide , Kobayashi Yukio , Watanabe Takashi , Maruyama Dai , Morishima Yasuo , Kagami Yoshitoyo , Taji Hirofumi , Minami Hironobu , Itoh Kuniaki , Nakata Masanobu , Hotta Tomomitsu
Published: October 2007

The purpose of this phase I and II study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of bortezomib in Japanese patients with relapsed or refractory multiple myeloma. This was a dose‐escalation study designed to determine the recommended dose for Japanese patients (phase I) and to investigate the antitumor activity and safety (phase II) of bortezomib administered on days 1, 4, 8, and 11 every 21 days. Thirty‐four patients were enrolled. A dose‐limiting toxicity was febrile neutropenia, which occurred in one of six patients in the highest‐dose cohort in phase I and led to the selection of 1.3 mg/m2 as the recommended dose. Adverse events ≥ grade 3 were rare except for hematological toxicities, although there was one fatal case of interstitial lung disease. The overall response rate was 30% (95% confidence interval, 16–49%). Pharmacokinetic evaluation showed a biexponential decline, characterized by a rapid distribution followed by a longer elimination, after dose administration, whereas the area under the concentration–time curve increased proportionately with the dose. Bortezomib was effective in Japanese patients with relapsed or refractory multiple myeloma. A favorable tolerability profile was also seen, although the potential for pulmonary toxicity should be monitored closely. The pharmacokinetic and pharmacodynamic profiles of bortezomib in the present study warrant further investigations, including more relevant administration schedules. (Cancer Sci 2008; 99: 140–144)
Prostate cancer antigen‐1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer
Authors: Shimada Keiji , Nakamura Mitsutoshi , Ishida Eiwa , Higuchi Tomonori , Yamamoto Hiroshi , Tsujikawa Kazutake , Konishi Noboru
Published: October 2007

A novel gene, prostate cancer antigen (PCA)‐1, was recently reported to be expressed in the prostate; however, its biological roles remain unclear. Knockdown of the PCA‐1 gene by small interfering RNA transfection induced apoptosis through reducing the expression of the anti‐apoptotic molecule Bcl‐xl and cytoplasmic release of cytochrome c in the androgen‐independent prostate cancer cell line PC3. Moreover, in vitro matrigel and in vivo chorioallantoic membrane assays showed that silencing of PCA‐1 significantly downregulated discoidin receptor (DDR)‐1 expression, resulting in suppression of cancer‐cell invasion. Transfection with PCA‐1 increased the levels of both Bcl‐xl and DDR1, which made the cells more invasive through the upregulation of matrix metalloproteinase 9 in DU145. Interestingly, long‐term culture using androgen‐free medium increased the level of PCA‐1 and the related expression of Bcl‐xl and DDR‐1 in the androgen‐sensitive cancer cell line LNCaP, suggesting that PCA‐1 signaling is associated with androgen independence. Immunohistochemical analysis in a series of 169 prostate carcinomas showed that PCA‐1 and DDR1 were strongly expressed in prostate cancer cells, including preneoplastic lesions, but there was little or no expression in normal epithelium. Moreover, the expression of PCA‐1 and DDR‐1 was associated with a hormone‐independent state of prostate cancer. Taken together, we propose that PCA‐1–DDR‐1 signaling is a new important axis involved in malignant potential prostate cancer associated with hormone‐refractory status. (Cancer Sci 2008; 99: 39–45)
CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura
Authors: Li Shuguang , Wang Lin , Zhao Chunhong , Li Lizhen , Peng Jun , Hou Ming
Published: October 2007

To investigate the effect and mechanism of the CD8+ T cells in bone marrow on autologous megakaryocytopoiesis in idiopathic thrombocytopenic purpura (ITP) patients, we prepared bone marrow mononuclear cells (MNCs) from 15 chronic ITP patients and 13 controls. MNCs were cultured in vitro directly (MNC group) or after depleting CD8+ T cells (CD8+ T‐dep group) or adding purified autologous CD8+ T cells to CD8+ T‐dep MNCs (Coculture group) or adding dexamethasone to the coculture (DEX group) all in semi‐solid and liquid culture systems. The quantity and quality of megakaryocytes were measured. The megakaryocyte count was increased in the presence of autologous CD8+ T cells of patients with chronic ITP, while platelet production was reduced. In addition, lower percentages of polyploidy and apoptotic megakaryocytes, and higher levels of soluble Fas (sFas) in supernatant were observed. Dexamethasone successfully corrected this effect of CD8+ T cells on autologous megakaryocytopoiesis. These studies provide evidence that activated CD8+ T cells in bone marrow of patients with chronic ITP might suppress megakaryocyte apoptosis, leading to impaired platelet production. Megakaryocyte apoptosis would be a novel target for the management of ITP.
γ‐Tocopherol prevents airway eosinophilia and mucous cell hyperplasia in experimentally induced allergic rhinitis and asthma
Authors: Wagner J. G. , Jiang Q. , Harkema J. R. , Ames B. N. , Illek B. , Roubey R. A. , Peden D. B.
Published: October 2007

Background
Traditional therapies for asthma and allergic rhinitis (AR) such as corticosteroids and antihistamines are not without limitations and side effects. The use of complementary and alternative approaches to treat allergic airways disease, including the use of herbal and dietary supplements, is increasing but their efficacy and safety are relatively understudied. Previously, we have demonstrated that γ‐tocopherol (γT), the primary form of dietary vitamin E, is more effective than α‐tocopherol, the primary form found in supplements and tissue, in reducing systemic inflammation induced by non‐immunogenic stimuli.

Objective
We used allergic Brown Norway rats to test the hypothesis that a dietary supplement with γT would protect from adverse nasal and pulmonary responses to airway allergen provocation.

Methods
Ovalbumin (OVA)‐sensitized Brown Norway rats were treated orally with γT before intranasal provocation with OVA. Twenty‐four hours after two challenges, histopathological changes in the nose, sinus and pulmonary airways were compared with gene expression and cytokine production in bronchoalveolar lavage fluid and plasma.

Results
We found that acute dosing for 4 days with γT was sufficient to provide broad protection from inflammatory cell recruitment and epithelial cell alterations induced by allergen challenge. Eosinophil infiltration into airspaces and tissues of the lung, nose, sinus and nasolacrimal duct was blocked in allergic rats treated with γT. Pulmonary production of soluble mediators PGE2, LTB4 and cysteinyl leukotrienes, and nasal expression of IL‐4, ‐5, ‐13 and IFN‐γ were also inhibited by γT. Mucous cell metaplasia, the increase in the number of goblet cells and amounts of intraepithelial mucus storage, was induced by allergen in both pulmonary and nasal airways and decreased by treatment with γT.

Conclusions
Acute treatment with γT inhibits important inflammatory pathways that underlie the pathogenesis of both AR and asthma. Supplementation with γT may be a novel complementary therapy for allergic airways disease.
Increasing prevalence and incidence of thyroid disease in Tayside, Scotland: the Thyroid Epidemiology Audit and Research Study (TEARS)
Authors: Leese G. P. , Flynn R. V. , Jung R. T. , MacDonald T. M. , Murphy M. J. , Morris A. D.
Published: October 2007

Objective  We aimed to describe the changing incidence of thyroid disease in a population‐based study in Tayside, Scotland (population 390 000) between 1994 and 2001.

Design  A retrospective, data‐linkage, population‐based study measuring the incidence and prevalence of thyroid disease.

Patients  All patients with newly diagnosed, treated and stable thyroid disease in Tayside were identified by electronic linkage of six datasets, including all regional biochemistry data, hospital admissions, deaths and a thyroid follow‐up register.

Results  The overall prevalence of thyroid dysfunction has increased from 2·3% to 3·8% (1994–2001). The prevalence of ever having had hyperthyroidism increased from 0·86% to 1·26% in females and 0·17% to 0·24% in males (P < 0·0001 for both). The standardized incidence of hyperthyroidism increased from 0·68 to 0·87 per 1000 females/year, representing a 6·3% annual increase (P < 0·0001). The prevalence of primary hypothyroidism increased from 3·12% to 5·14% in females and 0·51% to 0·88% in males (P < 0·0001 for both). The standardized incidence of primary hypothyroidism did not change and varied between 3·90 and 4·89 per 1000 females/year over the 8 years. Incidence of hypothyroidism in males increased from 0·65 to 1·01 per 1000 males/year (P = 0·0017). Mean age at diagnosis of primary hypothyroidism declined in females from 1994 to 2001.

Conclusions  The prevalence of primary hypothyroidism and previous hyperthyroidism has increased in Tayside, Scotland. This is partly due to an increasing incidence of disease, increased ascertainment and earlier diagnosis of disease. This will result in an increased workload for endocrinologists and general practitioners.
Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility
Authors: Zuccarello D. , Ferlin A. , Vinanzi C. , Prana E. , Garolla A. , Callewaert L. , Claessens F. , Brinkmann A. O. , Foresta C.
Published: October 2007

Context   Mutations in the androgen receptor (AR) gene can cause the androgen insensitivity syndrome (AIS). For complete and severe partial AIS, well‐characterized in vitro functional assays can be used for genotype–phenotype correlation; however, for mild forms of AIS, as associated with male infertility, experimental evidence is scarce or lacking. In particular, optimal in vitro functional tests informative about the genotype–phenotype relation have not been described.

Objective   The objective of this study was to investigate the association among genotype and phenotype for AR mutations found in infertile males by conventional functional assays and additional in‐depth studies performed with several gene reporters.

Design   To this aim, we selected four AR missense mutations associated with isolated male infertility (L547F and two novel mutations A474V and S650G) or partial AIS (Y571H). After introduction of the specific mutations in AR expression plasmid, we performed classical in vitro studies (Western immunoblotting, electrophoretic mobility shift assay, hormone‐response curves) and transactivation assays with different reporter constructs (MMTV, Sc‐ARU‐TK, TAT‐GRE‐ 2X, Slp‐ARU‐TK and PEM).

Results and conclusions   Our results showed that standard functional tests provide sufficient information only for severe AR mutations, whereas for AR mutations found in mild AIS patients with male infertility, only an extensive analysis with different in vitro systems, and in particular with PEM promoter, can give information on the functionality of the AR and therefore on the pathogenicity of the mutations and on genotype–phenotype correlation.
Relation between plasma fibroblast growth factor‐23, serum fetuin‐A levels and coronary artery calcification evaluated by multislice computed tomography in patients with normal kidney function
Authors: Roos Marcel , Lutz Jens , Salmhofer Hermann , Luppa Peter , Knauß Amelie , Braun Siegmund , Martinof Stefan , Schömig Albert , Heemann Uwe , Kastrati Adnan , Hausleiter Jörg
Published: October 2007

Objective  To examine the correlation of plasma fibroblast growth factor (FGF)‐23 and serum fetuin A levels with the coronary artery calcification score (CACS) in patients with normal kidney function.

Background  Vascular calcification is an active process that may be aggravated by hyperphosphataemia and hypercalcaemia. FGF‐23 and human fetuin‐A have been associated with calcifying arteriosclerosis in renal failure. Plasma FGF‐23 was identified as an independent factor negatively associated with peripheral vascular calcification. Fetuin‐A acts as a systemic inhibitor of ectopic calcification in dialysis patients and can be correlated to the survival of these patients. Very few data exists on the role of FGF‐23 and fetuin‐A in coronary calcification of patients without impaired kidney function.

Materials and methods  Sixty‐four patients, 21 females and 43 males, were subjected to 64‐slice coronary computed tomography (CT) to evaluate coronary artery calcification (CAC). Plasma intact FGF‐23 was determined by ELISA. Serum fetuin‐A concentration were evaluated nephelometrically.

Results  Mean plasma FGF‐23 level was 20·4 ± 9·1 pg/ml and serum fetuin‐A was 0·46 ± 0·09 g/l. There was no correlation between FGF‐23 (P = 0·777) and fetuin‐A (P = 0·767) levels and the CACS. No correlation was found between the presence of noncalcified plaques and coronary artery stenosis (CAS) ≥  50%, and FGF‐23 (P = 0·313 and P = 0·775) and fetuin‐A levels (P = 0·601 and P = 0·659).

Conclusion  Plasma intact FGF‐23 and serum fetuin‐A concentration do not correlate with the CACS, the grade of stenosis or presence of noncalcified plaques of the coronary arteries in patients with normal kidney function.
Water repellency of organic growing media related to hysteretic water retention properties
Authors: Naasz R. , Michel J.‐C. , Charpentier S.
Published: October 2007

With respect to soils, most growing media can exhibit hysteresis during drying/wetting cycles, which greatly affects their hydraulic properties. In the case of organic substrates, hydrophobicity during desiccation could be considered as one of the main factors leading to hysteretic behaviour. The purpose of this study was to estimate the influence of changes in wettability on the water retention properties, θ(ψ), of peat and pine bark during a drying/wetting cycle. Major differences in the hydraulic behaviour of the two organic materials studied were observed. For peat, hysteresis was found in the water retention curve (21%) and also in the contact angle/water potential relationship, (α(ψ), 20%), whereas in pine bark, this phenomenon was less pronounced in the water retention curve (10%) and even more limited in the α(ψ) curve (> 5%). Water retention hysteresis was successfully modelled using a modified van Genuchten‐Durner approach (VGα model), which took into account the local hydrophobicity of each poral domain of the porous media, regardless of the extent of hysteresis. Incorporating the parameters of the VGα water retention model into a α(ψ) equation to characterize overall or average changes in the hydrophobicity of the material during desiccation resulted in values very similar to those of the contact angles calculated with the capillary rise method. These results indicate that water retention properties of these organic substrates are strongly influenced by hydrophobicity.
Sorption and desorption of non‐ionic herbicides onto particulate organic matter from surface soils under different land uses
Authors: Benoit P. , Madrigal I. , Preston C. M. , Chenu C. , Barriuso E.
Published: October 2007

In vegetative filter strips used to intercept pesticides present in run‐off, particulate organic matter derived from the vegetation plays an important function in pesticide sorption processes, because it accumulates at the soil surface and quickly responds to changes in land use. Two herbicides with contrasted properties: isoproturon, moderately hydrophobic (log Kow= 2.5), diflufenican, strongly hydrophobic (log Kow= 4.9), and isopropylaniline, a metabolite of isoproturon, were used to characterize the sorption and desorption properties of POM originating from soils under three different land uses: a cropped plot under conventional wheat/maize rotation, an adjacent 10‐year‐old grassed strip and a nearby 80‐year‐old oak/chestnut forest. Chemical structural composition information obtained from solid‐state 13C CPMAS NMR and estimation of hydrophobicity from contact angle measurements were used to explain the different sorption capacities of POM according to their size and origins. Sorption of isoproturon and diflufenican increased with hydrophobicity of POM, which was greater in the forest soil. Aromaticity of POM was positively correlated to sorption coefficients (Koc). Desorption of the more hydrophobic compounds, diflufenican and isopropylaniline was weak for all POM fractions, regardless of their origin and size. On the other hand, desorption of isoproturon depended on land use and POM characteristics. The sorption capacities of POM were not only controlled by their chemical composition, but also by their size, due to a greater number of sorptive sites related to a greater surface area with decreasing particle‐size.
Distribution and controls on gross N mineralization‐immobilization‐turnover in soil subjected to zero tillage
Authors: Luxhøi J. , Fillery I. R. P. , Murphy D. V. , Bruun S. , Jensen L. S. , Recous S.
Published: October 2007

The aim of this investigation was to provide quantitative measures of gross nitrogen (N) mineralization‐immobilization‐turnover (MIT) in soil, and of the parameters controlling MIT. This is needed to predict adequately mineral N availability in agricultural land. Respiration, MIT, soil microbial biomass (SMB)‐C, soil organic matter (SOM)‐C and dissolved organic matter (DOM)‐C were determined in soil collected over three depths at three stages in a continuous crop rotation. MIT was strongly correlated to the size and activity of SMB‐C and the size of SOM‐C but was only marginally affected by the stage in the crop rotation. The strength of the correlation of mineralization, immobilization and respiration with SOM‐C increased when analysed by curvilinear regression compared with linear regression because SOM bioavailability varied with depth. It is argued that the limiting step in the decomposition was the breakdown of SOM into DOM. The major pathway for degradation of organic‐N in this soil system appeared to be the MIT route, while only a small amount of N was likely to be assimilated in the organic form (direct route). Our findings suggest that modellers of C and N turnover in zero tillage cropping systems need to incorporate a curvilinear relationship between SOM pool size and MIT into their computer model(s).
Restoration of wet features for breeding waders on lowland grassland
Authors: Eglington Sarah M. , Gill Jennifer A. , Bolton Mark , Smart Mark A. , Sutherland William J. , Watkinson Andrew R.
Published: October 2007

Over the last century, the loss of around half of the world's wetlands, principally through drainage and conversion to agriculture, has been one of the main drivers of declines in breeding waders. Across Europe, nature reserves have been effective conservation islands for breeding waders, but management of the wider countryside is needed for more wide‐scale population recovery. This is likely to require the restoration of wet features, but in a manner which is compatible with farming operations.

Here we explore the extent to which three types of wet feature influence the distribution of breeding lapwings Vanellus vanellus and their chicks on grassland. Footdrains are shallow channels used historically for drainage, but which can also be created and managed for water retention and cause little disruption to farming activities. Footdrain floods are areas where water overtops footdrains. Isolated pools are unmanaged areas of surface water resulting from rainfall or high water tables.

We selected 70 fields on nine sites which spanned the range of wet feature type and cover in early April. By May, only around 10% of the water within isolated pools remained, whereas 30–40% water was maintained in footdrains into June.

Fields with high footdrain flood densities attracted significantly higher densities of nesting lapwing and nests were more likely to be within 50 m of footdrain floods. Later in the season, footdrains were the primary remaining water source, and chick field use increased significantly with footdrain density. Chicks were also more likely to forage nearer footdrain floods in areas of wet mud created by receding water levels.

Synthesis and applications. Areas of shallow, small‐scale flooding are of critical importance for breeding waders. Management tools such as footdrains, coupled with appropriate hydrological management, provide a means of retaining water throughout the breeding season. Installation of these features is relatively simple, but maintaining sufficient water levels within the system is critical, especially in the face of increasingly unpredictable water supplies associated with climate change. Such management tools offer a solution that may be both effective at improving breeding wader populations and practicable for commercial grazing marsh management.
Using subsets of species in biodiversity surveys
Authors: Vellend Mark , Lilley Patrick L. , Starzomski Brian M.
Published: October 2007

In many biodiversity surveys, a small proportion of species require a disproportionate amount of a researcher's time and effort to detect or identify. If we are interested in predicting species diversity or composition, what are the consequences for statistical power of ignoring difficult species – that is, of surveying only a subset of the full suite of species?

We analysed 10 data sets on a variety of taxa, at different spatial scales, to assess correlations for species richness and species composition between a full data set and subsets of data with different numbers of species deleted at random, or according to the time investment required for inclusion. Power analyses characterized the trade‐off between the number of sites surveyed and the completeness of the survey in each site.

For species richness, the majority of information regarding among‐site patterns was retained even with large numbers of species removed. With only half the full species pool, the lower 95th percentile of correlations between the full vs. randomly generated reduced data sets was >0·75 in all 10 cases. With 10% of the full species pool removed, correlations were 0·95.

Subsets of species were not as good at capturing among‐site patterns of species composition (ordination scores and pairwise site dissimilarities). With half the full species pool, lower 95th percentile correlations between the full and randomly generated reduced data sets were as low as 0·1. Nonetheless, in most cases the lower 95th percentile correlation with half the number of species was >0·7, and removing 10% of species gave correlations >0·8 across all data sets.

For the three data sets in which species were also removed according to the time investment for inclusion, correlations fell within the range of variability observed for random species removals.

Synthesis and applications. In biological surveys, ignoring a relatively small proportion of species (e.g. <10%), and often a much larger proportion, results in very little loss of information on patterns of biodiversity. As such, statistical power in many biodiversity studies may be maximized by eliminating difficult species from a survey in order to increase the number of sites surveyed.
Participation in the 2005 general election by adults with intellectual disabilities
Authors: Keeley H. , Redley M. , Holland A. J. , Clare I. C. H.
Published: October 2007

Background  International and UK legislation confirms and supports the right of adults with intellectual disabilities (ID) to vote. It is widely accepted, although not previously empirically confirmed, that citizens with ID are under‐represented at the polls.

Method  To document the extent of their under‐representation at the polls, the names and addresses of adults using services for people with ID in one county in the UK, were compared with the marked electoral register following the 2005 general election. Adults using services for people with ID were identified either as un‐registered, as registered to vote but not having voted, or as having voted.

Results  Adults with ID living in the county at the time of 2005 general election were substantially under‐represented at the polls. Compared with the general population, proportionally fewer of them were registered to vote, and proportionally fewer of them voted. Compared with adults living in private homes, those in supported accommodation were more likely to be registered to vote, but less likely to use their vote. The most significant predictor of participation was living in a household with at least one other active voter.

Conclusions  The importance of the close proximity of an active voter is likely to be different for adults in supported accommodation compared with those living in private households. Further research is required to understand what features of these two very different types of residences are affecting voting opportunities.
Spleen mass as a measure of immune strength in mammals
Authors: CORBIN E. , VICENTE J. , MARTIN‐HERNANDO M. P. , ACEVEDO P. , PÉREZ‐RODRÍGUEZ L. , GORTAZAR C.
Published: October 2007

In studies of birds and their pathogens, spleen size has frequently been used to make inferences about immune system strength. However, the use of spleen size in mammals is more complicated because, in addition to having an immune function, the mammalian spleen is also a reservoir for red blood cells.

To assess the reliability of mammalian spleen mass as an indicator of immune activity, we quantified the white and red pulp mass by histology of spleens from shot red deer Cervus elaphus. We then analysed the relationships among spleen mass, the amounts of white and red pulp, and the deer's body condition relative to faecal counts of the nematode parasite Elaphostrongylus cervi.

White and red pulp mass were positively correlated so that an increase in spleen mass was a positive function of both components of the spleen. In male deer, which had significantly lower body condition and higher parasite loads than females, parasite counts were negatively correlated with spleen mass, white pulp mass, and red pulp mass.

Our findings suggest that (i) spleen mass in shot red deer is a reliable measure of white and red pulp content; and (ii) when looking at the red deer life history, which is greatly influenced by sex of the deer, splenic mass and white pulp mass could be used as reflections of immune system strength.

Future studies of mammalian spleens can contribute to the understanding of evolved strategies of immune response investment in mammals. However, determination of the white and red pulp spleen components using various sampling methods must be made prior to their application.
A phylogeographic analysis of populations of the wood turtle (Glyptemys insculpta) throughout its range
Authors: AMATO MARINA L. , BROOKS RONALD J. , FU JINZHONG
Published: October 2007

We investigated the phylogeography of wood turtles, Glyptemys insculpta, in North America using 750 bp of the mitochondrial control region from 117 individuals sampled at 29 localities across the species’ range. A total of 21 haplotypes were identified and little genetic variation was found. The highest pairwise difference was 2%. From nested clade analysis (NCA), one main postglacial dispersal route was inferred along the east coast, with subsequent westward dispersal. NCA further revealed some patterns of restricted gene flow/dispersal. We propose that wood turtles experienced a combined effect of bottleneck during the Pleistocene as well as of selective sweep, which produced the low level of variation observed. Following the Pleistocene, wood turtles would have undergone a rapid northward expansion from a common southern refugium as glaciers retreated. These findings shed light on where to direct conservation priorities, on conservation strategies needed, and on the potential effects of interpopulation transfers for this vulnerable species.
Comparative study of the physiological roles of three peroxidases (NADH peroxidase, Alkyl hydroperoxide reductase and Thiol peroxidase) in oxidative stress response, survival inside macrophages and virulence of Enterococcus faecalis
Authors: La Carbona Stephanie , Sauvageot Nicolas , Giard Jean‐Christophe , Benachour Abdellah , Posteraro Brunella , Auffray Yanick , Sanguinetti Maurizio , Hartke Axel
Published: October 2007

The opportunistic pathogen Enterococcus faecalis is well equipped with peroxidatic activities. It harbours three loci encoding a NADH peroxidase, an alkyl hydroperoxide reductase and a protein (EF2932) belonging to the AhpC/TSA family. We present results demonstrating that ef2932 does encode a thiol peroxidase (Tpx) and show that it is part of the regulon of the hydrogen peroxide regulator HypR. Characterization of unmarked deletion mutants showed that all three peroxidases are important for the defence against externally provided H2O2. Exposure to internal generated H2O2 by aerobic growth on glycerol, lactose, galactose or ribose showed that Npr was absolutely required for aerobic growth on glycerol and optimal growth on the other substrates. Growth on glycerol was also dependent on Ahp. Addition of catalase restored growth of the mutants, and therefore, extracellular H2O2 concentrations have been determined. This showed that the time point of growth arrest of the Δnpr mutant correlated with the highest H2O2 concentration measured. Analysis of the survival of the different strains inside peritoneal macrophages revealed that Tpx was the most important antioxidant activity for protecting the cells against the hostile phagocyte environment. Finally, the Δtpx and the triple mutant showed attenuated virulence in a mouse peritonitis model.
The contribution of cerebral vascular semicarbazide‐sensitive amine oxidase to cerebral amyloid angiopathy in Alzheimer's disease
Authors: Jiang Z. J. , Richardson J. S. , Yu P. H.
Published: October 2007

Semicarbazide‐sensitive amine oxidase (SSAO) catalyses the oxidative deamination of a variety of endogenous substrates, such as methylamine and aminoacetone, to produce highly reactive aldehydes, which are capable of inducing protein cross‐linkage, beta amyloid (Aβ) aggregation and advanced glycation end‐product formation. In the brain, SSAO is exclusively located on the blood vessels. Deposits of Aβ, the hallmark of Alzheimer's disease (AD), are closely associated with cerebral blood vessels, that is, cerebral amyloid angiopathy (CAA). In the present study, we examined whether SSAO‐mediated deamination contributes to CAA in AD. We employed immunohistochemistry to examine the colocalization of SSAO and Aβ in post mortem brains of AD patients. To assess the role of SSAO‐mediated deamination in the deposition of Aβ on blood vessel walls, we developed an in vitro blood vessel model using sections of human umbilical cord. We found a strong expression of SSAO colocalized with Aβ deposits on the blood vessels in AD brains. We also demonstrated that SSAO‐mediated deamination increases the deposition of Aβ onto blood vessel walls. Our results support the hypothesis that cerebral vascular SSAO‐catalysed deamination contributes to CAA in AD brains.
Histological features and expression of enzymes implicated in melatonin synthesis in pineal parenchymal tumours and in cultured tumoural pineal cells
Authors: Fevre‐Montange M. , Champier J. , Szathmari A. , Brisson C. , Reboul A. , Mottolese C. , Fauchon F. , Claustrat B. , Jouvet A.
Published: October 2007

Pineal parenchymal tumours (PPT) are rare neoplasms and there have been few in vitro studies. Their capacity for synthesizing and secreting melatonin has been only partially examined. We investigated the presence of messenger RNA (mRNA) encoding tryptophan hydroxylase (TPH), arylalkylamine N‐acetyltransferase (AANAT), hydroxyindol‐O‐methyltransferase (HIOMT), three enzymes involved in melatonin synthesis, and c‐myc, a tumoural marker, in 10 PPT, one papillary tumour of the pineal region (PTPR), cell cultures derived from four PPTs and from three other tumours of the pineal region, and in normal pineal gland. Moreover, protein expression of TPH was investigated in three PPT and PTPR. Quantitative real‐time reverse transcriptase‐polymerase chain reaction and immunohistochemistry were used and the melatonin production by tumoural cells in vitro was analysed by radioimmunoassay. We showed that all the tumoural tissues and cells contained c‐myc mRNA. mRNAs encoding TPH, AANAT and HIOMT were detected in all PPT, suggesting that tumour cells can synthesize melatonin. Only PPT expressed TPH protein. Cultured cells lost expression of transcripts throughout passages even if ultrastructural study revealed the presence of characteristic organelles in these tumoural cells. Nevertheless, the basal secretion of melatonin observed in one PPT culture is in favour of a maintained melatonin production and secretion by tumoural pinealocytes, but melatonin production was not stimulated by a beta noradrenergic agonist. Moreover, PTPR never expressed mRNA encoding TPH, AANAT and HIOMT. Our results may contribute to a better understanding of the biology of PTT and PTPR and may help to the diagnosis of these rare tumours.
Local DNA features affect RNA‐directed transcriptional gene silencing and DNA methylation
Authors: Fischer Ute , Kuhlmann Markus , Pecinka Ales , Schmidt Renate , Mette Michael F.
Published: October 2007

Transcription of a nopaline synthase promoter (pNOS) inverted repeat provides an RNA signal that can trigger transcriptional gene silencing and methylation of pNOS promoters in trans. The degree of silencing is influenced by the local DNA features close to the target promoter integration sites. Among 26 transgenic Arabidopsis thaliana lines harbouring single copies of a T‐DNA including a pNOS‐NPTII reporter gene at different chromosomal loci, NPTII RNA levels showed limited variation. When challenged by the silencer transgene providing the pNOS RNA signal, reduction of the NPTII RNA levels in the F1 generation varied by more than 100‐fold, ranging from no reduction to reduction to <1% of the non‐silenced level. Silencing was generally correlated with proportional DNA methylation in the pNOS region, except for one target transgene showing substantial DNA methylation without adequate silencing. Silencing was progressive through generations. Differences in the degree of silencing among the target transgenes were transmitted at least to the F3 generation, and seemed to be influenced by transgene‐flanking sequences. Apparently, close‐by repeats promoted, whereas close‐by functional genes diminished, the response to the silencing signal.
HLA‐G polymorphism in a Polish population and reproductive failure
Authors: Sipak‐Szmigiel O. , Cybulski C. , Lubiński J. , Ronin‐Walknowska E.
Published: October 2007

To investigate whether human leukocyte antigen (HLA)‐G gene polymorphism is associated with reproductive failure in a Polish population, we sequenced exons 2–4 of the HLA‐G gene in 58 couples with three recurrent spontaneous abortions (RSAs) in the first trimester of pregnancy and 58 fertile control couples. We identified 12 different HLA‐G alleles. Neither allele was found to be associated with an increased risk of RSA in the population. HLA‐G allele sharing was similar in couples with RSA and in control fertile couples. All cases and controls were also genotyped for the −725C>G polymorphisms in the promoter region and the 14‐bp insertion deletion in the 3′ untranslated region of the HLA‐G gene. The frequencies of both variants in RSA women and control fertile women were similar. These results suggest that HLA‐G gene polymorphism does not influence the risk of RSA in the Polish population, but further studies are needed in this regard.
Description of two new HLA‐C alleles in a Black South African population
Authors: Minevich G. , Kuhn L. , Polistena C. , Nuara J. , Winchester R.
Published: October 2007

Two new HLA‐C alleles, Cw*0333 and Cw*0217, were identified in a Black South African population. HLA‐Cw*0333 differs from Cw*030201 by an A→G substitution at nucleotide 323, yielding an unusual missense substitution of Cys for the conserved Tyr‐84 at the antigen cleft terminus. Molecular modeling suggests that this alters the predicted interactions of this critical residue with the opposite α2‐helix, the peptide COOH terminus and possibly KIR2DL2. The second allele, Cw*0217, differs from Cw*0205 by an A→T substitution at nucleotide 368, resulting in a Tyr→Phe substitution at residue 99 of the HLA‐C β‐pleated sheet that likely influences peptide side‐chain binding. Both Cw*0333 and Cw*0217 appear to have arisen by missense mutations, respectively, from the HLA‐B*5801‐Cw*0302 and B*080101‐Cw*0205 haplotypes.
Oral exfoliative cytology as a rapid diagnostic tool for paracoccidioidomycosis
Authors: Talhari Carolina , Braga de Souza João Vicente , Parreira Vilmar José , Reinel Dieter , Talhari Sinésio
Published: October 2007

Paracoccidioidomycosis is a common deep mycosis in South America. It is caused by the dimorphic fungus Paracoccidioides brasiliensis. We report a case of a 47‐year‐old Brazilian man with oral lesions due to paracoccidioidomycosis, which was diagnosed by exfoliative cytology without any special staining. We highlight this diagnostic tool as a simple, low‐cost, painless, non‐invasive and fast method for the diagnosis of paracoccidioidomycosis.
Detection of Aspergillus fumigatus‐specific DNA, (1–3)‐β‐d‐glucan and galactomannan in serum and bronchoalveolar lavage specimens of experimentally infected rats
Authors: Khan Z. U. , Ahmad S. , Theyyathel A. M.
Published: October 2007

The aim of this study was to detect Aspergillus fumigatus‐specific DNA by nested PCR (nPCR) in serum and bronchoalveolar lavage (BAL) specimens of experimentally infected rats and compare the results with (1–3)‐β‐d‐glucan (BDG) and galactomannan (GM) detection. Sixty Wistar rats, immunosuppressed with an intraperitoneal injection of cyclophosphamide (70 mg kg−1) were infected with 1 × 106A. fumigatus conidia. The rats were killed on days 1, 3, 5, 7 and 9 postinfection in groups of six each and their BAL, blood and lungs were cultured. The A. fumigatus‐specific DNA, BDG and GM in serum and BAL were detected by nPCR, Fungitell kit and Aspergillus Platelia kit respectively. Base line values were obtained by using sera from six healthy rats. Except the lungs, blood and BAL specimens of all the infected rats were negative for A. fumigatus culture. The BDG, GM and nPCR positivity in serum specimens was 80%, 77% and 63% respectively. The sensitivity of GM and nPCR tests in BAL specimens was 77% and 70% respectively. The data suggest that BDG and GM appear early in the course of infection, and have similar kinetics (r = 0.483, P = 0.007). Hence, their combined detection could be useful in the early diagnosis of invasive aspergillosis.
Peritonitis due to Aspergillus terreus in a patient undergoing continuous ambulatory peritoneal dialysis
Authors: Verghese Susan , Palani Ravichandran , Thirunavakarasu Natarajan , Chellamma Thabitha , Pathipata Padmaja
Published: October 2007

Aspergillus peritonitis is a rare, potentially fatal complication of continuous ambulatory peritoneal dialysis (CAPD). We report a case of CAPD peritonitis caused by Aspergillus terreus in a 55‐year‐old female patient.
Australia's place in the global restoration challenge: Interview with Richard Hobbs
Authors: Hobbs Richard , McDonald Tein
Published: October 2007

Summary  This interview with Professor Richard Hobbs, a prominent Australian researcher, professor and journal editor, traces his involvement in ecology and the relatively new disciplines of landscape ecology and restoration ecology. Born and educated as a plant ecologist in Scotland, Richard undertook postdoctoral research in the USA before taking up a series of research positions in Australia that steered him towards landscape ecology and restoration ecology. Having maintained an interest and involvement in international organizations, Richard provides comment in this interview on the progress of ecological restoration practice in Australasia compared to North America and comments on the need for ensuring research in these disciplines is strongly linked to management, is as broadly relevant as possible, and, is carried out at appropriate scales.
Depletion of regenerative bud resources during cyclic drought: What are the implications for fire management?
Authors: Croft Peter , Hunter John T. , Reid Nick
Published: October 2007

Summary  Resprouting is a common regenerative strategy in plant taxa that occurs in fire and drought‐prone environments. When plants are forced to use bud resources in quick succession as a result of repeated disturbances, recovery vigour may be diminished. The loss of bud resources through the combined effect of successive fire and drought is likely to be more damaging for plant survival and persistence than one or other disturbance on its own. In this study, we examine the resprouting response of seven trees and two shrubs after fire and drought in woodland communities in the New England and Bioregion of New South Wales. We also investigate whether there is a cumulative impact on plant vitality as a result of the combined disturbances of fire followed by drought. Preliminary results suggest that resprouting after drought occurs from buds located on the same morphological parts of tree and shrub species as after fire, although the response reflects the intensity of impact. Mortality in nine species affected by drought was similar to that in plants affected by both fire and drought. Since a drought between successive fires has the potential to deplete bud resources and debilitate plants, drought should be taken into account when determining fire regimes, and a severe drought between two fires should be considered in a similar way to an unplanned burn. Failure to do so may lead to reduced vigour and excessive mortality in resprouting species after planned fire.
Faunal response to revegetation in agricultural areas of Australia: A review
Authors: Munro Nicola T. , Lindenmayer David B. , Fischer Joern
Published: October 2007

Summary  We reviewed the literature on fauna in revegetation in Australian agricultural areas. Of 27 studies, 22 examined birds, with few studies focusing on other faunal groups (four to six studies for each remaining group) and nine examined multiple groups. Existing evidence suggests that revegetation provides habitat for many species of bird and some arboreal marsupials. Species richness of birds was greater in revegetated areas that were large, wide, structurally complex, old and near remnant vegetation. Bats, small terrestrial mammals, reptiles and amphibians did not appear to benefit significantly from revegetation in the short term. Evidence to date suggests that revegetation is not a good replacement of remnant vegetation for many species. Key information gaps exist in the faunal response to (i) revegetation as it ages; (ii) different structural complexities of revegetation; (iii) revegetation that is composed of indigenous vs. non‐indigenous plant species; and (iv) revegetation that is in riparian vs. non‐riparian locations. In addition, little is known on the value of revegetation for declining or threatened fauna, or of the composition of fauna in revegetation. There is a need to better understand the balance between quantity of revegetation in the landscape, and the quality or complexity of revegetation at the patch scale. Based on current evidence, we recommend revegetation be conducted in patches that are large, wide and structurally complex to maximize the benefits to fauna.
Recovery of Tawa‐dominated forest fragments in the Rotorua Basin, New Zealand, after cessation of livestock grazing
Authors: Dodd Mike B. , Power Ian L.
Published: October 2007

Summary  Tawa (Beilschmiedia tawa)‐dominated forest fragments on farms within the Rotorua Basin were surveyed to quantify the likely recovery processes following exclusion of domestic livestock grazing, using a space‐for‐time substitution approach. Vegetation structure, plant diversity and soil fertility were measured at 24 sites within 15 forest fragments on six farms, covering a range in time since exclusion from grazing of 1–53 years. The forest fragments were compared with a large area of ungrazed forest in the nearby Lake Okataina Scenic Reserve. As time since exclusion from grazing increased, indigenous plant species diversity increased (up to 30–35 years); ground fern and epiphyte abundance increased (up to 30–35 years); tree seedling and sapling numbers, and litter cover also increased (up to 10–15 years); and overall tree numbers increased, while average tree diameter at breast height and overall tree basal area did not differ significantly. The soil fertility status was highly variable, obscuring clear patterns, although Olsen P status decreased with time since grazing exclusion. Once grazing of forest fragments ceases, significant changes in their diversity, structure and soil characteristics can be expected, which indicate recovery of these plant communities towards the conditions observed in ungrazed forest.
ANZ JOURNAL OF SURGERY: A MOST HEARTY COLLABORATION
Authors: Burke Peter F.
Published: October 2007

At the very first meeting of the Council of the newly formed College of Surgeons of Australasia, held in Dunedin in February 1927, the decision was made to publish a surgical journal. The journal was to serve as a record of the various activities of the College; pride of place being given to articles on the science and art of surgery, and, as the first editor, Mervyn Archdall, reported to the Council in February 1929, the journal was to publish ‘political or propagandist contributions’, with regard to postgraduate training and hospital practice. W. N. Robertson of Brisbane, one of the College Founders, was a director of the Australasian Medical Publishing Company, publisher of the Medical Journal of Australia, and was able to offer to undertake production of such a journal, conditional on guaranteed financial provision. Mervyn Archdall, Editor of the Medical Journal of Australia, was permitted by the directors of the Australasian Medical Publishing Company to undertake editorship of the proposed College journal in his leisure time. July 1928 saw the first issue of The Journal of the College of Surgeons of Australasia which includes New Zealand, with Hugh Devine as Chairman of an Editorial Committee and Mervyn Archdall as Editor. This article traces the development of the College Journal until this point in time, a period of some 79 years.
FIRST PARATHYROID SURGEON: SIR JOHN BLAND‐SUTTON AND THE PARATHYROIDS
Authors: Delbridge Leigh W. , Palazzo Fausto F.
Published: October 2007

Felix Mandl from Vienna has long been acclaimed as having carried out the first parathyroidectomy for primary hyperparathyroidism in 1925. He was not, however, the first surgeon to have seen the parathyroid glands, either at surgery or in the pathology laboratory. There is evidence that the first intentional removal of a parathyroid tumour was probably carried out at the Middlesex Hospital, London, UK, by Sir John Bland‐Sutton at least a decade earlier. Indeed, Sir John Bland‐Sutton appeared to have been very much aware of the parathyroid gland and the pathology associated with it for many years, even before this first parathyroid operation. He described a post‐mortem specimen of a parathyroid tumour in 1886; he surgically removed a parathyroid cyst in 1909; and then carried out an intentional parathyroidectomy for a parathyroid tumour some time before 1917.