bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients
Authors: Tamaki Kentaro , Sasano Hironobu , Ishida Takanori , Miyashita Minoru , Takeda Motohiro , Amari Masakazu , Tamaki Nobumitsu , Ohuchi Noriaki
Published: May 2010

The roles of core needle biopsy (CNB) have become well established as an important preoperative diagnostic method for breast lesions. We examined the concordance of histological types, nuclear grades, hormone receptors, and human epidermal growth factor receptor 2 (HER2) status between CNB and surgical specimens in 353 cases. In addition, we analyzed the correlation between the number of CNB specimens obtained and accuracy of histological factors in order to explore the optimal number of CNB specimens. Between CNB and surgical specimens, concordance rates of histological type, nuclear grade, estrogen receptor (ER), and progesterone receptor (PgR) status (cut‐off 0–<1%, 1–10%, and 10%<), and HER2 were 84.4%, 81.3%, 92.9%, and 89.3%, respectively. In 52 of 353 patients who were histopathologically diagnosed as ductal carcinoma in situ (DCIS) by CNB, final diagnosis was changed in to invasive ductal carcinoma (IDC) in surgical specimens. Statistically significant differences were detected in the discrepancy of the following factors between CNB and subsequent surgical specimens: histological types, nuclear grade, and PgR, between patients who received four or more cores and those who had received three or less cores. In addition, a similar tendency was also detected in estrogen receptor (ER) and HER2 as in the above, and the cases that received four cores reached to 100% concordance in diagnosis between CNB and surgical specimens. Therefore, the optimal numbers of CNB were considered four at least in assessing the histological type, invasion, nuclear grade, hormone receptor status, and HER2 status of individual patients in the preoperative setting. (Cancer Sci 2010)
Impacts of selective logging on population structure and dynamics of a canopy tree (Olea capensis) in Kakamega forest
Authors: Tsingalia Mugatsia
Published: May 2010

This study assessed the impacts of logging on the population structure and dynamics of Elgon teak (Olea capensis), a canopy dominant in Kakamega forest. The objective was to ascertain and determine the regeneration status of this tree species in view of its commercial value. A comparison was made between logged and unlogged sections at three sites in the forest. Pairwise comparisons of the differences in the population structure among three sites and the differences in the mean tree size revealed significant differences in all three study sites. Results also revealed a variation in stem density that was dependent on the block of forest under study. Results of the spatial contagion revealed that O. capensis had a varied clumped distribution in all the study sites. Clumping was highest in the Kisere forest. These results point to logging as the major factor that explains the differences in population structure and stem density in different parts of Kakamega forest. And while intermittent recruitment may explain clumped distribution, logging appears to explain the variation in the degree of clumping.
The activity of an insectivorous bat Neoromicia nana on tracks in logged and unlogged forest in tropical Africa
Authors: Monadjem Ara , Ellstrom Magnus , Maldonaldo Cristina , Fasel Nicolas
Published: May 2010

Logging activities and the associated creation of roads and tracks can disturb and fragment forests, which may lead to a loss of forest‐dependent species and possibly favour nonforest generalists and edge species. The effects of such disturbance are poorly known for African insectivorous bats. We studied the activity patterns of insectivorous bats in a tropical African forest at Kibale National Park, Uganda, using an Anabat bat detector. The echolocation calls of the vespertilionid bat Neoromicia nana were the most frequently detected. This species was most active in the first 5 h after sunset with activity declining rapidly after midnight until sampling finished at 01:00 h. There was no difference in activity of N. nana levels between logged or undisturbed forest; however, this species exhibited higher levels of activity along the wide tracks running through the two forests than either 30 m off these tracks or along the narrow forest trails. The wing morphology and echolocation call of N. nana may be constraining it to flying in uncluttered space on the edge of the forest, penetrating mostly along wider tracks and roads. Further research (in particular radio‐telemetry) is required to test and validate these data.
Intra‐arterial therapy with cisplatin suspension in lipiodol and 5‐fluorouracil for hepatocellular carcinoma with portal vein tumour thrombosis
Authors: Nagamatsu H. , Hiraki M. , Mizukami N. , Yoshida H. , Iwamoto H. , Sumie S. , Torimura T. , Sata M.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 543–550

Background  Portal vein tumour thrombosis is a negative prognostic factor for hepatocellular carcinoma (HCC).

Aim  To assess the efficacy of cisplatin in lipiodol emulsion combined with 5‐fluorouracil (5‐FU) for patients with HCC and portal vein tumour thrombosis.

Methods  The study subjects were 51 patients with the above‐specified criteria who received injection of cisplatin suspension in lipiodol emulsion followed by intra‐arterial infusion of 5‐FU. The primary objective was to determine tumour response to the treatment, while the secondary objectives were safety and tolerability. Independent factors for survival were also assessed.

Results  Ten patients had complete response and 34 patients had partial response (response rate, 86.3%). The median survival for all 51 patients was 33 months, while that for 10 complete response patients and 21 patients who showed disappearance of HCC following additional therapies was 39 months. The single factor that significantly influenced survival was therapeutic effect. Treatment was well tolerated and severe toxicity was infrequent, with only grade 3 toxicity (thrombocytopenia) in one patient.

Conclusions  The present study demonstrated the efficacy of hepatic arterial infusion chemotherapy using cisplatin‐lipiodol emulsion and 5‐FU without serious adverse effects in patients with unresectable HCC and portal vein tumour thrombosis.
Treatment of ulcerative colitis with adalimumab or infliximab: long‐term follow‐up of a single‐centre cohort
Authors: Gies N. , Kroeker K. I. , Wong K. , Fedorak R. N.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 522–528

Background  Randomized, controlled trials have demonstrated that anti‐TNF agents are efficacious in inducing remission in cases of Crohn’s disease and ulcerative colitis. However, response rates for anti‐TNF agents in ‘real life’ clinical practice are less well‐defined.

Aims  To examine the response rates and long‐term outcomes of infliximab and adalimumab treatment for out‐patients with ulcerative colitis and to study the variables associated with response rates.

Methods  In a prospective study, a single‐centre out‐patient cohort was treated and followed up according to a structured protocol of clinical care. Response to treatment was assessed using a physician’s global assessment that focused on normalization of bowel frequency, absence of blood with defecation and tapering of corticosteroids to zero.

Results  Fifty‐three ulcerative colitis patients were included in the study. Responses to induction therapy were 96.4% (27/28) for infliximab and 80% (20/25) for adalimumab (P = 0.0889). Responses to maintenance therapy were similar: infliximab 77.8% (14/18) and adalimumab 70.0% (14/20) (P = 0.7190). Multivariate analyses of the induction and maintenance responses did not reveal confounding elements. No new safety signals were identified.

Conclusions  This long‐term follow‐up of a single‐centre cohort of ulcerative colitis patients demonstrates that ‘real‐life’ out‐patient treatment with infliximab and adalimumab is effective in induction and maintenance of response.
New genetic variant that might improve warfarin dose prediction in African Americans
Authors: Schelleman Hedi , Brensinger Colleen M. , Chen Jinbo , Finkelman Brian S. , Rieder Mark J. , Kimmel Stephen E.
Published: May 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Variants in the CYP2C9 (i.e. *2 and *3) and VKORC1 (i.e. 1173C/T or −1639G/A) genes have been shown to influence warfarin dose requirements. However, these factors seem to explain less of the dose variability in African Americans who have a lower prevalence of the CYP2C9*2 and *3 and VKORC1 1173T alleles.

WHAT THIS STUDY ADDS

In African Americans, the VKORC1 rs17886199 variant was statistically significantly associated with log‐transformed warfarin maintenance dose, independent of the influence of VKORC1 1173C>T and CYP2C9*2 and *3. However, replication of our finding is needed to confirm the association of rs1786199 SNP in African Americans, since Limdi et al.[3] did not examine the effect of this SNP because the prevalence of the rs1786199 A‐allele was too low.

AIMS

To raise hypotheses with regards to whether genetic variants in the VKORC1, CYP2C9, EPHX1, GGCX and ALB genes might influence warfarin dose in African Americans and Caucasians, independent of the effects of the VKORC1 1173C>T and CYP2C9*2 and *3 variants.

METHODS

From a prospective cohort study, we obtained additional DNA on 36 Caucasian and 22 African American warfarin users who reached maintenance dose and genotyped them for tagSNPs (r2 < 0.8) in VKORC1, EPHX1, GGCX and ALB genes, and one exonic CYP2C9 SNP. Linear regression models were fitted to estimate the relationship (P value) between log‐transformed maintenance dose and each SNP and the amount of the warfarin dose variability accounted for by each SNP (partial R2).

RESULTS

In African Americans, the VKORC1 rs17886199 A‐allele was associated with a lower dose (GG = 46.3 mg and GA = 25.6 mg; P= 0.002), independent of the VKORC1 1173C>T and CYP2C9*2 and *3 variants. Even after applying Bonferroni correction, the P value would still be considered statistically significant. The VKORC1 rs17886199 variant was not found in Caucasians. In Caucasians, the EPHX1 rs1051741 T‐allele was associated with a lower dose (CC = 41.3 mg and CT = 30.0 mg; P= 0.04). The latter was no longer statistically significant after applying Bonferroni correction.

CONCLUSIONS

Our pilot study suggests that the VKORC1 rs17886199 variant could influence warfarin maintenance dose among African Americans, even after accounting for the influence of the VKORC1 1173C>T variant. Future studies with a larger sample size will be needed to confirm our findings.
Influence of methotrexate exposure on outcome in patients treated with MBVP chemotherapy for primary central nervous system lymphoma
Authors: Blasco Hélène , Senecal Delphine , Le Gouge Amélie , Pinard Emmanuelle , Benz‐de Bretagne Isabelle , Colombat Philippe , Hulot Jean‐Sébastien , Chatelut Etienne , Le Guellec Chantal
Published: May 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Although treated using the same high‐dose methotrexate (HD‐MTX)‐based multiagent chemotherapy, patients with primary central nervous system lymphoma (PCNSL) have significant differences in outcome. However, little information has been published about factors influencing outcome in PCNSL. As it is known that the pharmacokinetics of MTX vary considerably between subjects leading to different exposure in patients receiving the same dose, it is important to evaluate its role in response to chemotherapy.

WHAT THIS STUDY ADDS

This study is the first to evaluate the exposure–response relationship in patients treated with MBVP chemotherapy. We found that patients who were early non‐responders to MBVP chemotherapy had poor survival, whatever the salvage regimen. Tumour response at early evaluation was not associated with MTX pharmacokinetics and increasing the dose would probably not improve results.

AIMS

Although the standard treatment for primary central nervous system lymphoma (PCNSL) consists of three cycles of MBVP (methotrexate, BCNU, VP16, methylprednisolone) and radiotherapy, early failure of treatment may require modification of the treatment. However, our understanding of the outcome in such patients and of the factors involved in early failure of treatment is poor. In addition to known prognostic factors, we evaluated the influence of methotrexate (MTX) exposure on the response to MBVP chemotherapy in patients treated for PCNSL after the first two cycles.

METHODS

We retrospectively analyzed all patients with PCNSL treated with the MBVP regimen over the previous 10 years. Clinical, personal data and known prognostic factors were studied. The parameters of MTX exposure were estimated using a population pharmacokinetic approach with NONMEM. Objective response (OR), overall survival (OS) and failure‐free survival (FFS) were evaluated in all patients.

RESULTS

Thirty‐seven patients were studied. We observed lower FFS and OS (0.49 years) in patients who were not able to receive the planned treatment (group 1, n= 12) than in those who received three cycles (8.04 years) (group 2, n= 25). Known prognostic factors were comparable in both groups, but mean dose of MTX and mean AUC tended to be lower in patients who failed prematurely or showed no response after two cycles.

CONCLUSIONS

We found that patients who were early non‐responders to MBVP chemotherapy had poor survival, without major influence of MTX exposure. It is thus probably unlikely that increasing the dose of MTX would improve outcome.
What do asthmatics have to fear from food and additive allergy?
Authors: Gillman A. , Douglass Jo A.
Published: May 2010

International studies report marked increases in the prevalence of food allergy, along with increases in hospital admissions and emergency presentations for severe allergic reactions due to foods. The prevalence of self‐reported food allergy is common, but generally exceeds that which can be verified from challenge studies, although nut allergies appear to be an important exception to this rule. Studies examining food allergy deaths suggest that those who die of food allergy usually have co‐existent asthma. Adolescents and young adults are at most risk, and adrenaline auto‐injectors are sub‐optimally used. Food chemical sensitivity is very commonly reported but not usually verified by challenge testing. However, the exception to this is sulphite sensitivity, which can elicit reproducible reactions in some. The increasing prevalence of severe food allergies and awareness of its risk in those with asthma demands an especially rigorous approach to the diagnosis and management of co‐existent food allergy and asthma, especially in young people who appear to be at most risk from death from severe food allergy.

Cite this as: A. Gillman and Jo A. Douglass, Clinical & Experimental Allergy, 2010 (40) 1295–1302.
Organic matter in size‐density fractions after 16–50 years of grass ley, cereal cropping and organic amendments
Authors: Magid J. , De Nowina K. R. , Lindedam J. , Andrén O.
Published: May 2010

Size‐density fractionation, which was originally developed to examine short‐term decomposition of added material in sandy soil, was highly sensitive to medium‐ to long‐term changes in loam and clay soils. Materials from different size classes (>1 mm, 0.1–1 mm, 0.05–0.1 mm and <0.05 mm) were separated by density into light (ρ < 1.0 g cm−3), medium (1.0 < ρ < 1.85 g cm−3) and heavy (ρ > 1.85 g cm−3) fractions. In 16–18‐year cropping experiments the 0.1–1‐mm heavy fraction contained 17–19% of total carbon in ley soils compared with 7% in continuously cropped soils. Greater N‐mineralization rates after sieving of ley cropped soils could not be related to differences in C:N ratios of fractions, but this was assumed to be related to exposure of aggregate‐binding agents. In a 50‐year trial 40% of total soil carbon was contained in the 0.1–1‐mm heavy fraction in soil treated with sewage sludge compared with 7–9% in the fallow and ‘zero N’ treatments. Thus, the soils studied expressed an aggregate hierarchy dependent on organic carbon dynamics. The relative abundance of carbon in heavy organo‐mineral fractions >0.1 mm was inversely related to the relative abundance of C in black‐brown medium density material <0.1 mm, defined as uncomplexed particulate organic matter that was presumably released during ultrasonic disruption deterioration of finer (<0.1 mm) aggregated organo‐mineral particles. The size density fractionation allowed identification of materials of contrasting visual appearance, chemical qualities and, by inference, biological turnover times. However, they were found to be predominantly composite fractions and may be too complex to be represented by unique model pools.
Delayed smolt migration of stocked Atlantic salmon parr
Authors: SKILBREI O. T. , WENNEVIK V. , DAHLE G. , BARLAUP B. , WIERS T.
Published: May 2010

Abstract The timing of the smolt run in the Dale River in western Norway was monitored from 2002 to 2007 after annual stocking in late autumn 2000 to 2005 with 5000–10800, 11–16 g, Atlantic salmon,Salmo salarL., parr. The releases yielded an annual smolt production of 1000–2000 individuals, mainly 1+ smolts. Almost 5700 stocked smolts were trapped during smolt migration and 60% of these were genotyped for family identification. The date for 50% descent varied by 14 days from year to year. For the most part, however, the 2+ stocked smolts and the majority of the wild smolts left the river in May, while the 1+ stocked smolts migrated 23–26 days later in June. It was concluded that the strategy of stocking large parr in late autumn may conflict with the natural timing of smolt migration the following spring.
Global analysis of functional relationships between histone point mutations and the effects of histone deacetylase inhibitors
Authors: Sato Lui , Noguchi Shuhei , Hayashi Yohei , Sakamoto Makoto , Horikoshi Masami
Published: May 2010

Comprehensive analyses of the histone‐GLibrary in previous studies showed that most mutants of modification sites in the histone core regions show phenotypes, whereas those with modifications in the histone N‐terminal unstructured tail regions (N‐tails) do not. One possible reason is that modifications in N‐tails are linked to each other to form a scale‐free network termed histone ‘modification web’. In the network, the compensatory pathways are created to acquire the robustness against the any defects. Because of this robustness, it is difficult to determine the significance of the individual histone modifications in N‐tails in vivo. To overcome this problem, we used a strategy using drugs coordinately to inhibit modification enzymes and observed the mutant phenotypes when the compensatory pathways are largely interrupted. We analyzed histone‐GLibrary using inhibitors of histone deacetylases (HDACs) and identified novel phenotypic mutants. We also examined the phenotypic changes through the combined use of an HDAC inhibitor and an inhibitor of DNA‐mediated reactions. Mutation of modifiable sites H3‐K4 and H4‐K16 in histone N‐tails, which are presumed to be the ‘hubs’ of the network, resulted in identifiable phenotypes. The data obtained provide valuable information for speculation on novel relationships between histone modification in N‐tails and biological function and for predicting unknown modification sites in core histones.
Effects of elevated ozone concentration on methane emission from a rice paddy in Yangtze River Delta, China
Authors: ZHENG FEIXIANG , WANG XIAOKE , LU FEI , HOU PEIQIANG , ZHANG WEIWEI , DUAN XIAONAN , ZHOU XIAOPING , AI YONGPING , ZHENG HUA , OUYANG ZHIYUN , FENG ZONGWEI
Published: May 2010

Few investigations have been made on the impact of elevated ozone (O3) concentration on methane (CH4) emission from rice paddies. Using open‐top chambers in situ with different O3 treatments, CH4 emissions were measured in a rice paddy in Yangtze River Delta, China in 2007 and 2008. There were four treatments applied: charcoal‐filtered air (CF), nonfiltered air (NF), and charcoal‐filtered air with different O3 additions (O3‐1 and O3‐2). The mean O3 concentrations during the O3 fumigation were 19.7, 22.6, 69.6 and 118.6 ppb in 2007 and 7.0, 17.4, 82.2 and 138.3 ppb in 2008 for treatments CF, NF, O3‐1 and O3‐2, respectively. The rice yields, as compared with CF, were reduced by 32.8% and 37.1%, 58.3% and 52.1% in treatments O3‐1 and O3‐2 in 2007 and 2008, respectively. The diurnal patterns of CH4 emission varied temporally with treatments and there was inconsistence in diurnal variations in CH4 emissions from the paddy field. The daily mean CH4 emissions were significantly lower in treatments O3‐1 and O3‐2 than those in treatments CF and NF. Compared with CF treatment, CH4 emissions from the paddy field were decreased to 46.5% and 38.3%, 50.6% and 46.8% under treatments O3‐1 and O3‐2 in the whole growing seasons of 2007 and 2008, respectively. The seasonal mean CH4 emissions were negatively related with AOT40 (accumulative O3 concentration above 40 ppb; P < 0.01 in both years), but positively related to the relative rice yield (reference to CF; P < 0.01 in 2007 and P < 0.001 in 2008), aboveground biomass (P < 0.01 in both years) and underground biomass (P < 0.01 in 2007 and P < 0.05 in 2008). The decreased CH4 emission from the rice paddy due to an increased O3 exposure might partially mitigate the global warming potential induced by soil carbon loss under elevated O3 concentrations.
Feedback of carbon and nitrogen cycles enhances carbon sequestration in the terrestrial biosphere
Authors: ESSER GERD , KATTGE JENS , SAKALLI ABDULLA
Published: May 2010

The efforts to explain the ‘missing sink’ for anthropogenic carbon dioxide (CO2) have included in recent years the role of nitrogen as an important constraint for biospheric carbon fluxes. We used the Nitrogen Carbon Interaction Model (NCIM) to investigate patterns of carbon and nitrogen storage in different compartments of the terrestrial biosphere as a consequence of a rising atmospheric CO2 concentration, in combination with varying levels of nitrogen availability. This model has separate but closely coupled carbon and nitrogen cycles with a focus on soil processes and soil–plant interactions, including an active compartment of soil microorganisms decomposing litter residues and competing with plants for available nitrogen. Biological nitrogen fixation is represented as a function of vegetation nitrogen demand. The model was validated against several global datasets of soil and vegetation carbon and nitrogen pools. Five model experiments were carried out for the modeling periods 1860–2002 and 2002–2100. In these experiments we varied the nitrogen availability using different combinations of biological nitrogen fixation, denitrification, leaching of soluble nitrogen compounds with constant or rising atmospheric CO2 concentrations. Oversupply with nitrogen, in an experiment with nitrogen fixation, but no nitrogen losses, together with constant atmospheric CO2, led to some carbon sequestration in organismic pools, which was nearly compensated by losses of C from soil organic carbon pools. Rising atmospheric CO2 always led to carbon sequestration in the biosphere. Considering an open nitrogen cycle including dynamic nitrogen fixation, and nitrogen losses from denitrification and leaching, the carbon sequestration in the biosphere is of a magnitude comparable to current observation based estimates of the ‘missing sink.’ A fertilization feedback between the carbon and nitrogen cycles occurred in this experiment, which was much stronger than the sum of separate influences of high nitrogen supply and rising atmospheric CO2. The demand‐driven biological nitrogen fixation was mainly responsible for this result. For the modeling period 2002–2100, NCIM predicts continued carbon sequestration in the low range of previously published estimates, combined with a plausible rate of CO2‐driven biological nitrogen fixation and substantial redistribution of nitrogen from soil to plant pools.
The impact of temperature variability on wheat yields
Authors: ASSENG SENTHOLD , FOSTER IAN , TURNER NEIL C.
Published: May 2010

With current annual production at over 600 million tonnes, wheat is the third largest crop in the world behind corn and rice, and an essential source of carbohydrates for millions of people. While wheat is grown over a wide range of environments, it is common in the major wheat‐producing countries for grain filling to occur when soil moisture is declining and temperature is increasing. Average global temperatures have increased over the last decades and are predicted to continue rising, along with a greater frequency of extremely hot days. Such events have already been reported for major wheat growing regions in the world. However, the direct impact of past temperature variability and changes in averages and extremes on wheat production has not been quantified. Attributing changes in observed yields over recent decades to a single factor such as temperature is not possible due to the confounding effects of other factors. By using simulation modelling, we were able to separate the impact of temperature from other factors and show that the effect of temperature on wheat production has been underestimated. Surprisingly, observed variations in average growing‐season temperatures of ±2 °C in the main wheat growing regions of Australia can cause reductions in grain production of up to 50%. Most of this can be attributed to increased leaf senescence as a result of temperatures >34 °C. Temperature conditions during grain filling in the major wheat growing regions of the world are similar to the Australian conditions during grain filling. With average temperatures and the frequency of heat events projected to increase world‐wide with global warming, yield reductions due to higher temperatures during the important grain‐filling stage alone could substantially undermine future global food security. Adaptation strategies need to be considered now to prevent substantial yield losses in wheat from increasing future heat stress.
A climatic basis for microrefugia: the influence of terrain on climate
Authors: DOBROWSKI SOLOMON Z.
Published: May 2010

There is compelling evidence from glacial and interglacial periods of the Quaternary of the utilization of microrefugia. Microrefugia are sites that support locally favorable climates amidst unfavorable regional climates, which allow populations of species to persist outside of their main distributions. Knowledge of the location of microrefugia has important implications for climate change research as it will influence our understanding of the spatial distribution of species through time, their patterns of genetic diversity, and potential dispersal rates in response to climate shifts. Indeed, the implications of microrefugia are profound and yet we know surprisingly little about their climatic basis; what climatic processes can support their subsistence, where they may occur, their climatic traits, and the relevance of these locations for climate change research. Here I examine the climatic basis for microrefugia and assert that the interaction between regional advective influences and local terrain influences will define the distribution and nature of microrefugia. I review the climatic processes that can support their subsistence and from this climatic basis: (1) infer traits of the spatial distribution of microrefugia and how this may change through time; (2) review assertions about their landscape position and what it can tell us about regional climates; and (3) demonstrate an approach to forecasting where microrefugia may occur in the future. This synthesis highlights the importance of landscape physiography in shaping the adaptive response of biota to climate change.
IR spectral imaging of secreted mucus: a promising new tool for the histopathological recognition of human colonic adenocarcinomas
Authors: Travo Adrian , Piot Olivier , Wolthuis Rolf , Gobinet Cyril , Manfait Michel , Bara Jacques , Forgue‐Lafitte Marie‐Elisabeth , Jeannesson Pierre
Published: May 2010

Travo A, Piot O, Wolthuis R, Gobinet C, Manfait M, Bara J, Forgue‐Lafitte M‐E & Jeannesson P  (2010) Histopathology 56, 921–931

IR spectral imaging of secreted mucus: a promising new tool for the histopathological recognition of human colonic adenocarcinomas

Aims:  During colonic carcinogenesis, mucin‐type glycoproteins are known to undergo quantitative and qualitative alterations. The aim of this study was to determine the value of infrared (IR) spectral histology for the histopathological recognition of colonic adenocarcinomas based on mucin‐associated IR spectral markers.

Methods and results:  Paraffin‐embedded tissue sections of normal human colon and adenocarcinomas were analysed directly by IR‐microspectroscopy (IR‐MSP), without prior chemical dewaxing. IR‐MSP imaging combined with multivariate analysis permitted the construction of IR colour‐coded images of the tissue sections providing spatially resolved biochemical information. This allowed localization of mucin‐rich areas and provided label‐free spectral‐based staining of secreted mucus related to the biochemical heterogeneity of its mucin content. IR images of secreted mucus display the same spectral clusters in both normal and adenocarcinomatous colonic tissues, but with significant differences in surface percentages. Such differences allow a distinction between these two tissue types. Spectral variations associated with changes of mucin secondary structure were the most accurate mucus spectral marker for discriminating between normal colon and adenocarcinomas in the sample set.

Conclusions:  IR‐MSP imaging provides a new type of histology, independent of visual morphology, presenting tremendous possibilities for discovery and clinical monitoring of cancer markers.
Breast cancer precursors revisited: molecular features and progression pathways
Authors: Lopez‐Garcia Maria A , Geyer Felipe C , Lacroix‐Triki Magali , Marchió Caterina , Reis‐Filho Jorge S
Published: May 2010

Lopez‐Garcia M A, Geyer F C, Lacroix‐Triki M, Marchió C & Reis‐Filho J S (2010) Histopathology 57, 171–192 Breast cancer precursors revisited: molecular features and progression pathways

Increasingly more coherent data on the molecular characteristics of benign breast lesions and breast cancer precursors have led to the delineation of new multistep pathways of breast cancer progression through genotypic–phenotypic correlations. It has become apparent that oestrogen receptor (ER)‐positive and ‐negative breast lesions are fundamentally distinct diseases. Within the ER‐positive group, histological grade is strongly associated with the number and complexity of genetic abnormalities in breast cancer cells. Genomic analyses of high‐grade ER‐positive breast cancers have revealed that a substantial proportion of these tumours harbour the characteristic genetic aberrations found in low‐grade ER‐positive disease, suggesting that at least a subgroup of high‐grade ER‐positive breast cancers may originate from low‐grade lesions. The ER‐negative group is more complex and heterogeneous, comprising distinct molecular entities, including basal‐like, HER2 and molecular apocrine lesions. Importantly, the type and pattern of genetic aberrations found in ER‐negative cancers differ from those of ER‐positive disease. Here, we review the available molecular data on breast cancer risk indicator and precursor lesions, the putative mechanisms of progression from in situ to invasive disease, and propose a revised model of breast cancer evolution based on the molecular characteristics of distinct subtypes of in situ and invasive breast cancers.
Pleuropulmonary pathology of vascular Ehlers–Danlos syndrome: spontaneous laceration, haematoma and fibrous nodules
Authors: Kawabata Yoshinori , Watanabe Akira , Yamaguchi Shozaburo , Aoshima Masahiro , Shiraki Akira , Hatamochi Atushi , Kawamura Tetsuji , Uchiyama Takashi , Watanabe Atushi , Fukuda Yuh
Published: May 2010

Kawabata Y, Watanabe A, Yamaguchi S, Aoshima M, Shiraki A, Hatamochi A, Kawamura T, Uchiyama T, Watanabe A & Fukuda Y (2010) Histopathology 56, 944–950 Pleuropulmonary pathology of vascular Ehlers–Danlos syndrome: spontaneous laceration, haematoma and fibrous nodules

Aims:  The aim was to clarify the pleuropulmonary pathological findings of vascular Ehlers–Danlos syndrome (vEDS).

Methods and results:  Nine patients with confirmed vEDS by means of cell culture and/or molecular biological studies who had undergone surgical lung biopsy (SLB), lobectomy or autopsy were studied. Six patients were male and three were female with a mean age of 23.2 years. Histological features were as follows: (i) the main pulmonary lesions related to fragility and spontaneous laceration, these being haematomas in seven, acute haemorrhage in nine, fibrous nodule in eight, with ossification or bone marrow formation in six; vascular disruption in five; intraluminal haemosiderosis in nine; interstitial haemosiderosis in seven, with iron deposition in the alveolar wall and/or vessel wall in five and foreign body reaction in two; emphysematous changes in eight; and bleb formation in two; (ii) secondary iatrogenic pleuropulmonary injuries during SLB or lobectomy comprised pleural laceration in seven of 10 and lung laceration in eight of 10 specimens.

Conclusions:  Spontaneous laceration of lung tissue is an essential feature and is followed by haematoma and possible fibrous nodule formation.
Enhancement of anti‐Aspergillus T helper type 1 response by interferon‐β‐conditioned dendritic cells
Authors: Gafa Valérie , Remoli Maria E. , Giacomini Elena , Severa Martina , Grillot Renée , Coccia Eliana M.
Published: May 2010

Although data show the importance of type I interferons (IFNs) in the regulation of the innate and adaptive immunity elicited in response to viral, bacterial and parasitic infections, the functional activities of these cytokines during fungal infections are poorly understood. We examined here the impact of IFN‐β on the response of human monocyte‐derived dendritic cells (DCs) infected in vitro with Aspergillus fumigatus. Having found that A. fumigatus‐infected DCs do not express IFN‐β, we evaluated the effect of the exogenous addition of IFN‐β on the maturation of human DCs induced by the infection with A. fumigatus conidia. Although the phagocytosis of the fungus was not affected by IFN‐β treatment, the expression of CD86 and CD83 induced upon A. fumigatus challenge was enhanced in IFN‐β‐conditioned DCs, which also showed an increased expression of IL‐27 and IL‐12p70, members of IL‐12 family. Through these modifications, IFN‐β improved the capacity of DCs to promote an anti‐Aspergillus T helper type 1 response, as evaluated by mixed leucocyte reaction, which plays a crucial role in the control of invasive aspergillosis. Our results identified a novel effect of IFN‐β on anti‐Aspergillus immune responses which, in turn, might open new perspectives on the use of IFN‐β in immunotherapy for fungal infections aimed at enhancing the immunological functions of DCs.
The role of endothelial interleukin‐8/NADPH oxidase 1 axis in sepsis
Authors: Miyoshi Takashi , Yamashita Kouhei , Arai Toshiyuki , Yamamoto Kokichi , Mizugishi Kiyomi , Uchiyama Takashi
Published: May 2010

Sepsis is a generalized inflammatory disease, caused by the hyperinflammatory response of the host, rather than by invading organisms. Endothelial cells play a crucial role in the pathogenesis of sepsis. In this study, we investigated the effects of interleukin‐8 (IL‐8), a known neutrophil chemoattractant, on lipopolysaccharide (LPS) ‐induced reactive oxygen species (ROS) production by endothelial cells, and its significance in the pathogenesis of LPS‐mediated sepsis. The results revealed that IL‐8 directly induced ROS production in human umbilical vein endothelial cells (HUVECs), and also mediated LPS‐induced ROS production by HUVECs. Stimulation of HUVECs by LPS strongly enhanced tissue factor expression, a hallmark of severe sepsis, which was suppressed by IL‐8 knockdown. We further discovered that NADPH oxidase (Nox) 1 expression in LPS‐stimulated HUVECs was markedly repressed by IL‐8 knockdown, and Nox1 knockdown reduced tissue factor expression, suggesting that the LPS/IL‐8 signalling in endothelial cells was predominantly mediated by Nox1. In conclusion, LPS stimulation of endothelial cells causes activation of the IL‐8–Nox1 axis, enhances the production of ROS, and ultimately contributes to the progression of severe sepsis.
T regulatory cells control T‐cell proliferation partly by the release of soluble CD25 in patients with B‐cell malignancies
Authors: Lindqvist Camilla A. , Christiansson Lisa H. , Simonsson Bengt , Enblad Gunilla , Olsson‐Strömberg Ulla , Loskog Angelica S. I.
Published: May 2010

Interleukin‐2 (IL‐2) is one of the most studied cytokines driving T‐cell proliferation, activation and survival. It binds to the IL‐2 receptor consisting of three chains, the α (CD25), β and common γ (γc). The binding of the CD25 chain to IL‐2 is necessary to expose high‐affinity binding sites for the β and γc chains, which, in turn, are responsible for downstream signalling. A high level of soluble CD25 (sCD25) has been associated with a poor prognosis in patients with non‐Hodgkin’s lymphoma. The function and source of origin of this soluble receptor is not well investigated. In the present study we hypothesized that T regulatory (Treg) cells may release CD25 to act as a decoy receptor for IL‐2, thereby depriving T‐effector cells of IL‐2. Peripheral blood from patients with B‐cell malignancies (n = 26) and healthy controls (n = 27) was investigated for the presence and function of FoxP3+ Treg cells and sCD25 by multi‐colour flow cytometry and enzyme‐linked immunosorbent assay. Further, the proliferative capacity of T cells was evaluated with or without the presence of recombinant sCD25. The results demonstrate that Treg cells from patients had lower CD25 expression intensity and that they released CD25 in vitro. Further, high levels of Treg cells correlated with sCD25 plasma concentration. Recombinant sCD25 could suppress T‐cell proliferation in vitro. In conclusion, the release of sCD25 by Treg cells may be a mechanism to deprive IL‐2 and thereby inhibit anti‐tumour T‐cell responses.
Characterization of cuticular chitin‐binding proteins of Leptinotarsa decemlineata (Say) and post‐ecdysial transcript levels at different developmental stages
Authors: Zhang J. , Pelletier Y.
Published: May 2010

Seven cuticle chitin‐binding proteins (Ld‐CP1v1 to 7) were deduced from antenna cDNAs of adult Colorado potato beetles, Leptinotarsa decemlineata (Say), based on their consensus sequences. The mature proteins consisted of 87–188 residues. Ld‐CP1v1 formed a distinct orthologous protein cluster (OP1) along with four proteins from other insect species in a neighbor‐joining phylogenetic tree. These proteins also contained a proline glutamine‐rich (PQ‐rich) region and a highly conserved C‐terminal motif (Phr). Their consensus region lacked the defined aromatic triad. Ld‐CP2 to 6 clustered with those bearing RR‐1 consensus and Ld‐CP7 with RR‐2 consensus. Ld‐CP1v1 to 4 were expressed at the post‐ecdysial period in all the developmental stages whereas Ld‐CP5 to 7 were expressed mainly in adults.
Analysis of expressed sequence tags for Frankliniella occidentalis, the western flower thrips
Authors: Rotenberg D. , Whitfield A. E.
Published: May 2010

Thrips are members of the insect order Thysanoptera and Frankliniella occidentalis (the western flower thrips) is the most economically important pest within this order. F. occidentalis is both a direct pest of crops and an efficient vector of plant viruses, including Tomato spotted wilt virus (TSWV). Despite the world‐wide importance of thrips in agriculture, there is little knowledge of the F. occidentalis genome or gene functions at this time. A normalized cDNA library was constructed from first instar thrips and 13 839 expressed sequence tags (ESTs) were obtained. Our EST data assembled into 894 contigs and 11 806 singletons (12 700 nonredundant sequences). We found that 31% of these sequences had significant similarity (E≤ 10−10) to protein sequences in the National Center for Biotechnology Information nonredundant (nr) protein database, and 25% were functionally annotated using Blast 2GO. We identified 74 sequences with putative homology to proteins associated with insect innate immunity. Sixteen sequences had significant similarity to proteins associated with small RNA‐mediated gene silencing pathways (RNA interference; RNAi), including the antiviral pathway (short interfering RNA‐mediated pathway). Our EST collection provides new sequence resources for characterizing gene functions in F. occidentalis and other thrips species with regards to vital biological processes, studying the mechanism of interactions with the viruses harboured and transmitted by the vector, and identifying new insect gene‐centred targets for plant disease and insect control.
Response of green alder (Alnus viridis subsp. fruticosa) patch dynamics and plant community composition to fire and regional temperature in north‐western Canada
Authors: Lantz Trevor C. , Gergel Sarah E. , Henry Greg H. R.
Published: May 2010

Aim  Feedbacks between climate warming and fire have the potential to alter Arctic and sub‐Arctic vegetation. In this paper we assess the effects and interactions of temperature and wildfire on plant communities across the transition between the Arctic and sub‐Arctic.

Location  Mackenzie Delta region, Northwest Territories, Canada.

Methods  We sampled air temperatures, green alder (Alnus viridis ssp. fruticosa) cover, growth, reproduction and age distributions, and overall plant community composition on burned and unburned sites across a latitudinal gradient.

Results  Mean summer temperature across the study area decreased by 3 °C per degree of increasing latitude (6 °C across the study area). In the northern part of the study area, where seed viability was low, alder was less dominant than at southern sites where seed viability was high. The age structure of alder populations across the temperature gradient was highly variable, except in the northern part of the forest–tundra transition, where populations were dominated by young individuals. Alder growth and reproduction were significantly greater on burned sites (38–51 years following fire) than on unburned sites. North to south across the temperature gradient, vegetation changed from a community dominated by dwarf shrubs and fruticose lichens to one characterized by black spruce (Picea mariana), alder and willows (Salix spp.). Regardless of the position along the temperature gradient, burned sites were dominated by tall shrubs.

Main conclusions  Temperature limitation of alder abundance and repro‐duction, combined with evidence of recent recruitment on unburned sites, indicates that alder is likely to respond to increased temperature. Elevated alder growth and reproduction on burned sites shows that wildfire also has an important influence on alder population dynamics. The magnitude of alder’s response to fire, combined with observations that burns at the southern margin of the low Arctic are shrub dominated, suggest that increases in the frequency of wildfire have the potential to alter northern vegetation on decadal scales. By creating new seedbeds, fire provides opportunities for colonization that may facilitate the northward movement of tall shrubs. Feedbacks between the global climate system and low Arctic vegetation make understanding the long‐term impact of increasing fire frequency critical to predicting the response of northern ecosystems to global change.
Evidence for climatic niche and biome shifts between native and novel ranges in plant species introduced to Australia
Authors: Gallagher Rachael V. , Beaumont Linda J. , Hughes Lesley , Leishman Michelle R.
Published: May 2010

1. The potential invasive success of exotic plant species is thought to be associated with similarity in climate and biome between the original and novel range. We tested this assumption by quantifying the match between the realized climatic niches and biomes occupied in the exotic and native range of 26 plant species introduced to Australia. We then explored correlations between the propensity to shift climatic niche with residence time, invasion status, geographic range size, and species traits.

2. Occurrence data from the native and exotic range of 26 species introduced to Australia were obtained, and the overlap between native and exotic climate niches was calculated using between‐class analysis. Shifts into novel biomes were assessed using a Geographic Information System (GIS). Correlations between introduction, distribution and species traits and the degree of climate matching were examined using nonparametric statistical tests.

3. Exotic species frequently occurred in climatic conditions outside those occupied in their native range (20 of 26 species). Nineteen species inhabited biomes in Australia not occupied in the native range and in some instances this shift represented the establishment of populations in novel biomes not present in the native range. No single‐species trait, introduction or distributional characteristic was significantly associated with the degree of climatic niche shift.

4. Synthesis. Exotic species are able to occupy climate niches in the new range that differ substantially from those of the native range, and generally do not show biome conservatism between their native and introduced ranges. This implies that novel climatic conditions are not a major obstacle for exotic species establishing populations outside their native range. These results have important implications for the use and interpretation of ecological niche models used to predict the distribution of species in novel climates in time or space. The results also highlight the importance of alternate mechanisms, such as enemy release, phenotypic plasticity or rapid evolution, in the establishment of naturalized and invasive populations.
Effects of a leisure programme on quality of life and stress of individuals with ASD
Authors: García‐Villamisar D. A. , Dattilo J.
Published: May 2010

Background  Even though there is research demonstrating a positive relationship between leisure participation and the two constructs of quality of life and stress reduction, current conceptualisation of leisure as a contributor to quality of life is limited. In addition, in spite of improvements in accurate diagnosis of autism spectrum disorder (ASD) at increasingly earlier ages and proliferation of interventions, research associated with leisure and quality of life for people with ASD is lacking.

Methods  Therefore, a study using a repeated measures design was used to measure effects of a 1‐year group leisure programme intended to facilitate interaction with media, engagement in exercise, playing games and doing crafts, attending events, and participating in other recreation activities on quality of life and stress of 37 participants (22 male, 15 female), ages 17–39 (M = 31.49) years at the beginning of the programme) diagnosed with an ASD and a group of 34 adults with ASD as control group (waiting list) (19 male, 15 female), ages 24–38 (M = 30 at programme initiation) years.

Results  There was a significant decrease in overall scores of stress levels for participants over the course of the study and there was a significant increase in the four factors of quality of life that were measured (satisfaction, independence, competence and social interaction) as well as the total score for quality of life from baseline to the end of the intervention 12 months later. In contrast, the control group demonstrated no significant improvements related to stress or quality of life. Implications of these findings to leisure services and the quality of life of individuals with ASD are discussed.

Conclusion  Findings support the contention that participation in recreation activities positively influenced the stress and quality of life of adults with ASD.