bluuebunny/crossref_metadata_2025 huggingface dataset:
A Genomic Scan for Selection Reveals Candidates for Genes Involved in the Evolution of Cultivated Sunflower (Helianthus annuus)
Authors: Chapman Mark A. , Pashley Catherine H. , Wenzler Jessica , Hvala John , Tang Shunxue , Knapp Steven J. , Burke John M.
Published: November 2008

Genomic scans for selection are a useful tool for identifying genes underlying phenotypic transitions. In this article, we describe the results of a genome scan designed to identify candidates for genes targeted by selection during the evolution of cultivated sunflower. This work involved screening 492 loci derived from ESTs on a large panel of wild, primitive (i.e., landrace), and improved sunflower (Helianthus annuus) lines. This sampling strategy allowed us to identify candidates for selectively important genes and investigate the likely timing of selection. Thirty-six genes showed evidence of selection during either domestication or improvement based on multiple criteria, and a sequence-based test of selection on a subset of these loci confirmed this result. In view of what is known about the structure of linkage disequilibrium across the sunflower genome, these genes are themselves likely to have been targeted by selection, rather than being merely linked to the actual targets. While the selection candidates showed a broad range of putative functions, they were enriched for genes involved in amino acid synthesis and protein catabolism. Given that a similar pattern has been detected in maize (Zea mays), this finding suggests that selection on amino acid composition may be a general feature of the evolution of crop plants. In terms of genomic locations, the selection candidates were significantly clustered near quantitative trait loci (QTL) that contribute to phenotypic differences between wild and cultivated sunflower, and specific instances of QTL colocalization provide some clues as to the roles that these genes may have played during sunflower evolution.
Arabidopsis bZIP60 Is a Proteolysis-Activated Transcription Factor Involved in the Endoplasmic Reticulum Stress Response
Authors: Iwata Yuji , Fedoroff Nina V. , Koizumi Nozomu
Published: November 2008

Proteins synthesized in the endoplasmic reticulum (ER) of eukaryotic cells must be folded correctly before translocation out of the ER. Disruption of protein folding results in the induction of genes for ER-resident chaperones, for example, BiP. This phenomenon is known as the ER stress response. We report here that bZIP60, an Arabidopsis thaliana basic leucine zipper (bZIP) transcription factor with a transmembrane domain, is involved in the ER stress response. When compared with wild-type Arabidopsis plants, homozygous bzip60 mutant plants show a markedly weaker induction of many ER stress-responsive genes. The bZIP60 protein resides in the ER membrane under unstressed condition and is cleaved in response to ER stress caused by either tunicamycin or DTT. The N-terminal fragment containing the bZIP domain is then translocated into the nucleus. Cleavage of bZIP60 is independent of the function of Arabidopsis homologs of mammalian S1P and S2P proteases, which mediate the proteolytic cleavage of the mammalian transcription factor ATF6. In Arabidopsis, expression of the bZIP60 gene and cleavage of the bZIP60 protein are observed in anthers in the absence of stress treatment, suggesting that the ER stress response functions in the normal development of active secretory cells.
Genome characterization ofPyrenophora tritici‐repentisisolates reveals high plasticity and independent chromosomal location ofToxAandToxB
Authors: ABOUKHADDOUR R. , CLOUTIER S. , BALLANCE G. M. , LAMARI L.
Published: November 2008

The fungusPyrenophora tritici‐repentis(Died.) causes tan spot, an important leaf disease of wheat worldwide. Isolates of this pathogen have been collected and characterized into eight races on the basis of their ability to produce three different host‐selective toxins. The karyotype of 47 isolates was determined by pulsed field gel electrophoresis. The collection originated from different parts of the world and included genotypes from all races. A single isolate was characterized for each of races 3, 4 and 6, whereas fourteen, five, nine, five and eleven isolates were karyotyped for races 1, 2, 5, 7 and 8, respectively. The survey showed that the chromosome number ofP. tritici‐repentiswas highly variable, with some isolates having as few as eight chromosomes, but others having 11 or more. Similarly, the genome size ranged from 25.5 to 48.0 Mb, and individual chromosome sizes ranged from 1.3 to more than 5.7 Mb. Considerable variation was observed in karyotype patterns among theP. tritici‐repentisisolates tested. A total of 29 different karyotypes was identified among the 47 isolates. These chromosome level variations were as variable for isolates within a race as for isolates across races. Southern blot analysis of the 47 isolates withToxAandToxBprobes revealed that the toxin genes were always located on different chromosomes. Furthermore, with six chromosome‐specific single‐copy probes, theToxA‐carrying chromosome was shown to be homologous among the Ptr ToxA‐producing isolates, with a related chromosome in the non‐ToxA‐producing isolates, suggesting that the chromosome on whichToxAgenerally resides is of an essential nature. Interestingly, a molecular rearrangement involving a translocation ofToxAto a different chromosome was identified in one isolate.
Metabolic and histological features of non‐alcoholic fatty liver disease patients with different serum alanine aminotransferase levels
Authors: WONG V. W.‐S. , WONG G. L.‐H. , TSANG S. W.‐C. , HUI A. Y. , CHAN A .W.‐H. , CHOI P. C.‐L. , CHIM A. M.‐L. , CHU S. , CHAN F. K.‐L. , SUNG J. J.‐Y. , CHAN H. L.‐Y.
Published: November 2008

Background  Non‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear.

Aim  To evaluate the metabolic and histological features of NAFLD patients with different ALT levels.

Methods  A total of 173 consecutive patients with biopsy‐proven NAFLD were studied. Patients with persistently normal ALT and those with abnormal ALT were compared.

Results  Patients with persistently normal ALT had lower steatosis grade than patients with abnormal ALT, but they had similar degree of lobular inflammation, ballooning and fibrosis. Among 19 patients with ALT below 0.5 times the upper limit of normal (ULN) at the time of liver biopsies, 8 (42%) and 3 (16%) had steatohepatitis and significant fibrosis respectively. The within‐patient coefficient of variance was similarly high in patients with simple steatosis and steatohepatitis (33.5). Age and glucose, but not ALT, were independent factors associated with significant fibrosis.

Discussion  Metabolic factors, but not ALT, are associated with histological severity. Patients with ALT < 0.5 × ULN may still have non‐alcoholic steatohepatitis (NASH) and significant fibrosis. Evaluation of NAFLD patients should be based on metabolic risk factors, but not ALT level.
High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program
Authors: Mikhael Joseph R. , Belch Andrew R. , Prince H. Miles , Lucio Maria Nambo , Maiolino Angelo , Corso Alessandro , Petrucci Maria Teresa , Musto Pellegrino , Komarnicki Mieczyslaw , Stewart A. Keith
Published: November 2008

Phase 2 trials have demonstrated that bortezomib ± dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open‐label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1·3 mg/m2 on days 1, 4, 8, and 11 of a maximum of eight 3‐week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after ≥2 cycles or for stable disease after ≥4 cycles. Responses were assessed based on M‐protein changes. Overall response rate was 67%, including 11% complete (100% M‐protein reduction), 22% very good partial (75–99% reduction), 18% partial (50–74% reduction), and 16% minimal response (25–49% reduction). Dexamethasone was added in 208 patients (33%), of whom 70 (34%) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39%), neutropenia (16%), anaemia (12%), diarrhoea (7%), and peripheral neuropathy (6%). Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.
Thrombotic thrombocytopenic purpura precipitated by acute pancreatitis: a report of seven cases from a regional UK TTP registry
Authors: McDonald V. , Laffan M. , Benjamin S. , Bevan D. , Machin S. , Scully M. A.
Published: November 2008

Thrombotic thrombocytopenic purpura (TTP) may be idiopathic or secondary. We report seven TTP cases precipitated by pancreatitis. The patients were admitted with acute pancreatitis and at that time had no clinical or laboratory features of TTP. The median time to develop TTP after pancreatitis was 3 d. The patients had moderately reduced ADAMTS13 activity (mean activity 49%; normal range 66–126%) with no evidence of anti‐ADAMTS13 inhibitory autoantibodies. The median number of plasma exchanges to remission was 10 (range 7–14) and no additional treatment with immunosuppression was required to maintain remission. There have been no relapses to date.
Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study
Authors: Bomben Riccardo , Dal Bo Michele , Capello Daniela , Forconi Francesco , Maffei Rossana , Laurenti Luca , Rossi Davide , Del Principe Maria Ilaria , Zucchetto Antonella , Bertoni Francesco , Rossi Francesca Maria , Bulian Pietro , Cattarossi Ilaria , Ilariucci Fiorella , Sozzi Elisa , Spina Valeria , Zucca Emanuele , Degan Massimo , Lauria Francesco , Del Poeta Giovanni , Efremov Dimitar G. , Marasca Roberto , Gaidano Gianluca , Gattei Valter
Published: November 2008

A fraction of chronic lymphocytic leukaemia (CLL) cases carry highly homologous B‐cell receptors (BCR), i.e. characterized by non‐random combinations of immunoglobulin heavy‐chain variable (IGHV) genes and heavy‐chain complementarity determining region‐3 (HCDR3), often associated with a restricted selection of IGVK/L light chains. Such ‘stereotyped’ BCR occur more frequently in CLL with unmutated (UM) than mutated (M) IGHV genes. We analysed 1426 IG rearrangements (from 1398 CLL cases) by a clustering driven by HCDR3 similarities. Molecular findings were correlated to time‐to‐treatment (TTT) and presence of known prognosticators. Sixty‐nine clusters (319 IG‐rearrangements, 22·4%) with stereotyped BCR were identified. Among 30 confirmed clusters (≥3 IG‐rearrangements/cluster), we found 14 novel clusters, of which 11 had M IG rearrangements (M clusters) and predominantly (8/11) used IGHV3 subgroup genes. Recurrent cluster‐biased amino acid changes were found throughout IGHV sequences of these ‘M clusters’. Regarding clinical outcome: (i) UM CLL from the IGHV1‐2/1‐3/1‐18/1‐46/7‐4‐1/IGKV1‐39 cluster had poorer prognosis than UM/M cases, or UM cases using the same IGHV genes but not in clusters; (ii) M CLL from the IGHV3‐21/IGLV3‐21 cluster had TTT similar to UM CLL, and shorter than M CLL expressing IGHV3‐21 but not in cluster. Altogether, our analysis identified additional molecular and clinical features for CLL expressing stereotyped BCR.
Ca2+‐CaM activation of AMP deaminase contributes to adenine nucleotide dysregulation and phosphatidylserine externalization in human sickle erythrocytes
Authors: Sabina Richard L. , Wandersee Nancy J. , Hillery Cheryl A.
Published: November 2008

Ca2+‐calmodulin (Ca2+‐CaM) activates erythrocyte adenosine monophosphate deaminase (AMPD) in conditions of disturbed calcium homeostasis, prompting us to investigate adenine nucleotide metabolic dysregulation in sickle cell disease (SCD). However, higher ATP concentrations in reticulocytes, compared to erythrocytes, confound a comparative evaluation of SCD and normal RBCs. Therefore, a combination of centrifugation and antiCD71‐labelled magnetic bead selection was used to prepare reticulocyte‐poor fractions (reticulocytes <4% of total RBCs) of SCD RBCs. ATP and total adenine nucleotide concentrations were 12% lower in sickle erythrocytes compared to normal erythrocytes and inosine monophosphate (IMP) concentrations were threefold elevated (allP < 0·05). Furthermore, preincubation with a diffusible CaM antagonist slowed IMP accumulation in sickle erythrocytes during an experimental period of energy imbalance, thus showing that Ca2+‐CaM activates AMPD in SCD. Finally, adenine treatment (100 μmol/l) ofex vivoSCD RBCs significantly expanded ATP levels (16% higher) and reduced phosphatidylserine (PS)‐exposure, specifically those cells with the highest levels of PS externalization (46% fewer events) (bothP‐values <0·05 compared to untreated samples). We conclude that Ca2+‐CaM activation of AMPD contributes to increased turnover of the adenine nucleotide pool in sickle erythrocytes and that this metabolic dysregulation promotes PS exposure that may contribute to the pathogenesis of SCD.
In vitro anti‐leukaemia activity of sphingosine kinase inhibitor
Authors: Ricci Clara , Onida Francesco , Servida Federica , Radaelli Franca , Saporiti Giorgia , Todoerti Katia , Deliliers Giorgio Lambertenghi , Ghidoni Riccardo
Published: November 2008

Compelling evidence indicates the role of sphingosine kinase 1 (SPHK1) deregulation in the processes of carcinogenesis and acquisition of drug resistance, providing the rationale for an effective anti‐cancer therapy. However, no highly selective inhibitors of SPHK1 are available for in vitro and in vivo studies, except for the newly discovered ‘SK inhibitor’ (SKI). The present study showed that, in a panel of myeloid leukaemia cell lines, basal level of SPHK1 correlated with the degree of kinase inhibition by SKI. Exposure to SKI caused variable anti‐proliferative, cytotoxic effects in all cell lines. In particular, SKI induced an early, significant inhibition of SPHK1 activity, impaired cell cycle progression and triggered apoptosis in K562 cells. Moreover, SKI acted synergistically with imatinib mesylate (IM) to inhibit cell growth and survival. Finally, the inhibitor affected the clonogenic potential and viability of primary cells from chronic myeloid leukaemia (CML) patients, including one harbouring the IM‐insensitive Abl kinase domain mutation T315I. Due to the fact that the phenomenon of resistance to IM remains a major issue in the treatment of patients with CML, the identification of alternative targets and new drugs may be of clinical relevance.
Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells
Authors: Loizzo M. R. , Tundis R. , Menichini F. , Saab A. M. , Statti G. A. , Menichini F.
Published: November 2008

Abstract.  Objectives: The purpose of this study was to evaluate cytotoxic activity of Platycladus orientalis, Prangos asperula and Cupressus sempervirens ssp. pyramidalis essential oils and to identify active components involved in inhibition of population growth of human cancer cell lines. Materials and methods: Essential oils were obtained by hydrodistillation and were analysed by gas chromatography and gas chromatography coupled to mass spectrometry. Antiproliferative activity was tested on amelanotic melanoma C32 cells and on renal cell adenocarcinoma cells, using the sulphorhodamine B assay. Results: Cupressus sempervirens ssp. pyramidalis leaf oil exerted the highest cytotoxic activity with an IC50 value of 104.90 µg/mL against C32, followed by activity of P. orientalis and P. asperula on the renal adenocarcinoma cell line (IC50 of 121.93 and 139.17 µg/mL, respectively). P. orientalis essential oil was also active against amelanotic melanoma with an IC50 of 330.04 µg/mL. Three identified terpenes, linalool, β‐caryophyllene and α‐cedrol, were found to be active on both cell lines tested. Conclusions: Our findings provide novel insights into the field of cytotoxic properties of essential oils. This study provided evidence on how cytotoxic activity of the oils is not always related to their major constituents, except for lower activity found in both cell lines for α‐cedrol. Interestingly, β‐caryophyllene and linalool exhibited comparable IC50 values to the commercial drug vinblastine on the ACHN cell line. This opens a new field of investigation to discover mechanisms responsible for the observed activity.
Evolutionary game theory elucidates the role of glycolysis in glioma progression and invasion
Authors: Basanta D. , Simon M. , Hatzikirou H. , Deutsch A.
Published: November 2008

Abstract.  Objectives: Tumour progression has been described as a sequence of traits or phenotypes that cells have to acquire if the neoplasm is to become an invasive and malignant cancer. Although genetic mutations that lead to these phenotypes are random, the process by which some of these mutations become successful and cells spread is influenced by tumour microenvironment and the presence of other cell phenotypes. It is thus likely that some phenotypes that are essential in tumour progression will emerge in the tumour population only with prior presence of other different phenotypes. Materials and methods: In this study, we use evolutionary game theory to analyse the interactions between three different tumour cell phenotypes defined by autonomous growth, anaerobic glycolysis, and cancer cell invasion. The model allows us to understand certain specific aspects of glioma progression such as the emergence of diffuse tumour cell invasion in low‐grade tumours. Results: We have found that the invasive phenotype is more likely to evolve after appearance of the glycolytic phenotype which would explain the ubiquitous presence of invasive growth in malignant tumours. Conclusions: The result suggests that therapies, which increase the fitness cost of switching to anaerobic glycolysis, might decrease probability of the emergence of more invasive phenotypes.
In vivo characterization of transplanted human embryonic stem cell‐derived pancreatic endocrine islet cells
Authors: Eshpeter A. , Jiang J. , Au M. , Rajotte R. V. , Lu K. , Lebkowski J. S. , Majumdar A. S. , Korbutt G. S.
Published: November 2008

Abstract.  Objectives: Islet‐like clusters (ILCs), differentiated from human embryonic stem cells (hESCs), were characterized both before and after transplantation under the kidney capsule of streptozotocin‐induced diabetic immuno‐incompetent mice. Materials and methods: Multiple independent ILC preparations (n = 8) were characterized by immunohistochemistry, flow cytometry and cell insulin content, with six preparations transplanted into diabetic mice (n = 42), compared to controls, which were transplanted with either a human fibroblast cell line or undifferentiated hESCs (n = 28). Results: Prior to transplantation, ILCs were immunoreactive for the islet hormones insulin, C‐peptide and glucagon, and for the ductal epithelial marker cytokeratin‐19. ILCs also had cellular insulin contents similar to or higher than human foetal islets. Expression of islet and pancreas‐specific cell markers was maintained for 70 days post‐transplantation. The mean survival of recipients was increased by transplanted ILCs as compared to transplanted human fibroblast cells (P < 0.0001), or undifferentiated hESCs (P < 0.042). Graft function was confirmed by secretion of human C‐peptide in response to an oral bolus of glucose. Conclusions: hESC‐derived ILC grafts continued to contain cells that were positive for islet endocrine hormones and were shown to be functional by their ability to secrete human C‐peptide. Further enrichment and maturation of ILCs could lead to generation of a sufficient source of insulin‐producing cells for transplantation into patients with type 1 diabetes.
The roles of Wnt antagonists Dkk1 and sFRP4 during adipogenesis of human adipose tissue‐derived mesenchymal stem cells
Authors: Park J.‐R. , Jung J.‐W. , Lee Y.‐S. , Kang K.‐S
Published: November 2008

Abstract.  Objectives: The canonical Wnt signalling pathway performs an important function in the control of adipogenesis. However, the mechanisms and mediators underlying these interactions have yet to be defined in detail. Thus, this study was performed in order to elucidate the roles of the Wnt family during adipogenic differentiation of human adipose tissue‐derived mesenchymal stem cells (hAMSCs). Materials and methods: We assessed several members of the Frizzled (FZD) family, the receptors of Wnts, inhibitors including the secreted frizzled‐related protein (sFRP) family and Dickkopfs (Dkks), and the downstream factor, β‐catenin. Expressional levels of adipogenic markers regulated by the small interfering RNA of Dkk1 (siDkk1) and sFRP4 (sisFRP4) were assessed using real‐time quantitative PCR and Western blot analysis. Results: The mRNA level of Dkk1 was expressed abundantly in the early stages of adipogenesis and decreased rapidly during the late stages of adipogenesis. However, sFRP4 mRNA was up‐regulated gradually during adipogenic differentiation in hAMSCs. Expression of FZD1, FZD7 and β‐catenin were reduced during adipogenic differentiation. Transfection of hAMSCs with siDkk1 or sisFRP4 partially inhibited differentiation of hAMSCs into adipocytes and restored levels of β‐catenin. Conclusions: We determined that Dkk1 was up‐regulated transiently in the early stages of adipogenesis, and that sFRP4 levels increased gradually during adipogeneis via inhibition of Wnt signalling. Collectively, these results show that Dkk1 and sFRP4 perform an important function in adipogenesis in hAMSCs.
Retracted: Role of α7‐nicotinic acetylcholine receptor in human non‐small cell lung cancer proliferation
Authors: Paleari L. , Catassi A. , Ciarlo M. , Cavalieri Z. , Bruzzo C. , Servent D. , Cesario A. , Chessa L. , Cilli M. , Piccardi F. , Granone P. , Russo P.
Published: November 2008

Objectives: Lung cancer is the most common cause of cancer death in the world. Cigarette smoking represents the major risk factor. Nicotine, an active component of cigarettes, can induce cell proliferation, angiogenesis and apoptosis resistance. All these events are mediated through the nicotinic acetylcholine receptor (nAChR) expressed on lung cancer cells. We speculate that new insights into the pathophysiological roles of nAChR may lead to new therapeutic avenues to reduce non‐small cell lung cancer (NSCLC) tumour growth.Materials and methods: Human samples of NSCLC, cell lines and mouse models were utilized in Western blotting, reverse transcriptase polymerase chain reaction and apoptosis studies.Results: Human NSCLC tissues expressed α7‐nAChR. This expression was higher in smoking patients with squamous carcinomas than those with adenocarcinomas and in male smoking patients than in females. All the data support the hypothesis that major expression of α7‐nAChR is related to major activation of the Rb–Raf‐1/phospho‐ERK/phospho‐p90RSK pathway. α7‐nAChR antagonists,viamitochondria associated apoptosis, inhibited proliferation of human NSCLC primary and established cells. Nicotine stimulates tumour growth in a murine model, A549 cells orthotopically grafted. The effects of nicotine were associated with increases in phospho‐ERK in tumours. Proliferation effects of nicotine could be blocked by inhibition of α7‐nAChR by the high affinity ligand α‐cobratoxin.Conclusion: These results showed that α7‐nAChR plays an important role in NSCLC cell growth and tumour progression as well as in cell death.
Exploring the role of polymorphisms in ficolin genes in respiratory tract infections in children
Authors: Ruskamp J M , Hoekstra M O , Postma D S , Kerkhof M , Bottema R W , Koppelman G H , Rovers M M , Wijga A H , De Jongste J C , Brunekreef B , Sanders E A M
Published: November 2008

Ficolins are pattern-recognition molecules that appear to be relevant for innate immune defence against infections. The ficolin genes in Caucasians are polymorphic and genetic variations may have functional consequences, both in relation to function and concentration. Low levels of Ficolin-2 have been suggested to associate with recurrent respiratory tract infections (RTI), whereas data on Ficolin-3 are still very limited. We investigated the association between variation in genes encoding Ficolin-2 (FCN2) and Ficolin-3 (FCN3) and frequency of RTI during the first 4 years of life. The study population consisted of 900 children from a large, population-based birth cohort of Dutch children, followed prospectively from birth to 4 years of age. The number of RTI was assessed by annual parental questionnaires. Nine single nucleotide polymorphisms in FCN2 and two in FCN3, all based on functionality or haplotype-tagging characteristics, were determined and haplotypes constructed. We found that single nucleotide polymorphisms in FCN2 and FCN3 were not associated with increased risk of RTI during the first 4 years of life. No difference existed between haplotype-frequencies of FCN2 and FCN3 in children grouped according to the reported number of RTI. In conclusion, at a population level, genetic variation in ficolin genes FCN2 and FCN3 do not seem to contribute to the risk of RTI in Caucasian children.
European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1
Authors: Jordan J. , Arbyn M. , Martin‐Hirsch P. , Schenck U. , Baldauf J‐J. , Da Silva D. , Anttila A. , Nieminen P. , Prendiville W.
Published: November 2008

The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18:213–9). A woman with a high‐grade cytological lesion, a repeated low‐grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow‐up for each woman seen. Reflex testing for high‐risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow‐up of low‐grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high‐grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC‐H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow‐up of special cases such as women who are pregnant, postmenopausal or immunocompromised.
Elastin degradation within the abdominal aortic aneurysm wall – relationship between intramural pH and adjacent thrombus formation
Authors: Wiernicki I. , Cnotliwy M. , Baranowska‐Bosiacka I. , Urasinska E. , Kwas A. , Bober J. , Gutowski P.
Published: November 2008

Background  The natural history of abdominal aortic aneurysm (AAA) is wall remodelling potentially leading to a final rupture. The pathogenesis of AAA appears to be multifactorial. The aim of this pilot prospective study was to assess the relationship between the thickness of the thrombus within the abdominal aortic aneurysm, intramural pH and local elastin degradation.

Materials and methods  The AAA size, intraluminal thrombus (ILT) morphology and location were evaluated in 206 consecutive patients. Thirty patients with large AAA (aortic diameter ≥ 50 mm) and adjacent ILT with the thinnest part ≤ 10 mm and thickest ≥ 25 mm, measured in the region of the maximum diameter of AAA, were included for further study. During AAA surgery intramural pH measurements were performed and specimens taken from both thin thrombus‐covered and thick thrombus‐covered wall for computerized morphometric analysis.

Results  Mean intramural pH value was 7·21 ± 0·18 for the wall covered by thick ILT and 7·64 ± 0·10 for the thin one (P < 0·001). Computerized morphometric analysis demonstrated that elastin fibres in the thin thrombus‐covered wall were decreased in size (for width – P < 0·0001, for length –P < 0·13), irregularly orientated (P < 0·000001) and the amount of fibres was reduced when compared to the wall covered by thick ILT (P < 0·0004).

Conclusion  A strong relationship between intramural pH and elastin net destruction suggests that the local alkaline status within the thin thrombus‐covered part of the aneurysm wall is contributing to the elastinolytic process.
Comorbidity predicts survival in myelodysplastic syndromes or secondary acute myeloid leukaemia after allogeneic stem cell transplantation
Authors: Boehm A. , Sperr W. R. , Leitner G. , Worel N. , Oehler L. , Jaeger E. , Mitterbauer M. , Haas O. A. , Valent P. , Kalhs P. , Rabitsch W.
Published: November 2008

Background Recent data suggest that, among other factors, comorbidity may be an important prognostic variable in patients with myelodysplastic syndromes (MDS) who are eligible for haematopoietic stem cell transplantation (SCT).

Patients and methods We examined the overall survival (OS) and underlying risk factors in 45 adult patients with MDS (n = 38), chronic myelomonocytic leukaemia (n = 1), or secondary acute myeloid leukaemia (AML) arising from MDS (n = 6), who underwent allogeneic SCT at our Institution.

Results With a median follow‐up of 37 months, OS for all patients was 23%, post‐transplant relapse occurred in 11 patients, and 10 patients died from treatment‐related complications. The overall outcome and survival was independent of cytogenetic abnormalities and International Prognostic Scoring System (IPSS). However, we identified comorbidity as defined by the haematopoietic cell transplantation specific comorbidity index (HCT‐CI), as a significant adverse prognostic variable in our MDS patients.

Conclusions Based on these data and similar published data we recommend selecting patients with MDS or secondary AML for SCT according to the presence of comorbidities.
Clinical correlates of blood serotonin levels in patients with mastocytosis
Authors: Kushnir‐Sukhov N. M. , Brittain E. , Scott L. , Metcalfe D. D.
Published: November 2008

Background  Mastocytosis is a clonal disorder associated with an increased mast cell burden. We have recently demonstrated the ability of human mast cells to express and be activated through multiple serotonin receptors; to synthesize and release serotonin; and that mastocytosis patients may have abnormal serotonin levels. As serotonin has been implicated in the genesis of clinical symptoms found in association with some chronic diseases, we have now determined the whole blood serotonin levels in 29 patients diagnosed with mastocytosis, and correlated these levels with multiple clinical and laboratory parameters.

Materials and methods  Patients with mastocytosis were categorized according to disease variant. Blood serotonin values were determined and correlated with values reported for normal subjects; and clinical and laboratory features of the disease.

Results  Total blood serotonin levels followed a bimodal distribution in line with our earlier report,unlike the normal distribution reported for normal individuals. Serotonin levels did not correlate with platelet numbers, liver function tests or serum tryptase levels. Patients with lower serotonin values had greater rates of fatigue (P = 0·0001), migraine headaches (P = 0·0028), psychiatric symptoms (P = 0·0001), diarrhoea (P = 0·0407), flushing (0·0085), and abdominal and bone pain (P = 0·0001).

Conclusions  Our study suggests that low blood serotonin levels help define a sub‐group of patients with mastocytosis that are more likely to present with neurological and gastrointestinal complaints, and suggests that the use of pharmacologic agents that alter blood serotonin levels could be explored in selected patients.
Variability of IgE reactivity profiles among European mite allergic patients
Authors: Weghofer M. , Thomas W. R. , Kronqvist M. , Mari A. , Purohit A. , Pauli G. , Horak F. , Grönlund H. , Van Hage M. , Valenta R. , Vrtala S.
Published: November 2008

Background  House dust mites (HDM) Dermatophagoides pteronyssinus are a frequent indoor allergen source. Our aim was to determine the frequencies of IgE reactivity to purified HDM allergen molecules in mite allergic patients from different parts of Europe in order to establish an allergen panel for diagnosis of HDM allergy.

Materials and methods  Populations of D. pteronyssinus‐allergic patients from Austria (n = 56), France (n = 55), Italy (n = 67) and Sweden (n = 65) and storage mite allergic patients from Sweden (n = 31) were analysed for IgE reactivity to eight purified natural (n) and recombinant (r) D. pteronyssinus allergens (nDer p 1, rDer p 2, nDer p 4, rDer p 5, rDer p 7, rDer p 8, rDer p 10 and rDer p 14) in RAST‐based dot blot assays.

Results  Using a combination of Der p 1 and Der p 2, at least 97% of the D. pteronyssinus‐allergic patients could be diagnosed in each of the HDM allergic populations. However, more than 50% of the patients also reacted with other allergens and significant variabilities regarding the frequencies of IgE reactivity to individual allergen molecules were found. Patients with a predominant storage mite allergy showed none or only very weak IgE reactivity to purified D. pteronyssinus allergens.

Conclusions  Purified Der p 1 and Der p 2 are sufficient for the diagnosis of ≥ 97% of D. pteronyssinus allergic patients in Europe, but other allergens may also play an important role for the diagnosis and treatment of HDM allergy.
Retinopathy in type 2 diabetes mellitus is associated with increased intima‐media thickness and endothelial dysfunction
Authors: Malecki M. T. , Osmenda G. , Walus‐Miarka M. , Skupien J. , Cyganek K. , Mirkiewicz‐Sieradzka B. , Damek‐Guzik T. A. , Guzik T. J. , Sieradzki J.
Published: November 2008

Background  Microangioathy and macroangiopathy in type 2 diabetes mellitus (T2DM) frequently coexist. Both types of vascular complications share traditional risk factors. It is not clear whether the presence of microangiopathy, such as diabetic retinopathy (DR), constitutes a predictor of atherosclerosis in T2DM. Here we described the search for the association between DR and intima‐media thickness (IMT) in T2DM. We also compared endothelial function in subjects with and without DR.

Material and methods  We examined 182 consecutive patients with T2DM for at least 5 years (mean age at examination 56·3 ± 6·52 years). We assessed (i) IMT of carotid artery by ultrasound and (ii) endothelial function by flow‐mediated dilatation (FMD) method as well as by measurement of concentrations of von Willebrand factor (vWF) and s‐ICAM‐1. All patients underwent ophthalmological examination. Statistical analysis included Student's, Mann–Whitney, chi‐square, Fisher tests and multiple regression.

Results  DR was found in 71 (39·0%) subjects. IMT was higher in patients with DR than those without DR (0·87 mm vs. 0·79 mm, respectively, P = 0·0001). FMD was lower in the complication group than in subjects without DR (8·38% vs. 10·45%, respectively, P = 0·0023). Concentrations of s‐ICAM‐1 and vWF were not different between the groups. In multiple regression analysis, DR was among the predictors of increased IMT (P = 0·016) and decreased FMD (P = 0·002). We did not find a significant association of DR with vWF and s‐ICAM‐1 (P = 0·09 and P = 0·11, respectively).

Conclusions  DR is associated with increased IMT and endothelial dysfunction in T2DM. Impaired endothelial function may be a common denominator of pathogenesis of microvascular complications and atherosclerosis in T2DM.
Water flow paths in soil control element exports in an Andean tropical montane forest
Authors: Boy J. , Valarezo C. , Wilcke W.
Published: November 2008

We tested the hypothesis that concentrations of chemical constituents in stream water can be explained by the depth of water flow through soil. Therefore, we measured the concentrations of total organic carbon (TOC), NO3‐N, NH4‐N, dissolved organic nitrogen (DON), P, S, K, Ca, Mg, Na, Al and Mn in rainfall, throughfall, stemflow, litter leachate, mineral soil solution and stream water of three 8–13 ha catchments on steep slopes (1900–2200 m above sea level) of the south Ecuadorian Andes, from April 1998 to April 2003. Peak C (14–22 mg litre−1), N (0.6–0.9 mg litre−1), K (0.5–0.7 mg litre−1), Ca (0.6–1.0 mg litre−1), Mg (0.3–0.5 mg litre−1), Al (110–390 μg litre−1) and Mn (3.9–8.4 μg litre−1) concentrations in stream water were associated with lateral flow (fast near‐surface flow in saturated topsoil) while the greatest P (0.1–0.3 mg litre−1), S (0.3–0.7 mg litre−1) and Na (3.0–6.0 mg litre−1) concentrations occurred during low baseflow conditions. All elements had greater concentrations in the organic layer than in the mineral soil, but only C, N, K, Ca, Mg, Al and Mn were flushed out during lateral‐flow conditions. Phosphorus, S and Na, in contrast, were mainly released by weathering and (re‐)oxidation of sulphides in the subsoil. Baseflow accounted for 32% to 61% of P export, while > 50% of S was exported during intermediate flow conditions (i.e. lateral flow at the depth of several tens of cm in the mineral soil). Near‐surface water flow through C‐ and nutrient‐rich topsoil during rainstorms was the major export pathway for C, N, Al and Mn (contributing > 50% to the total export of these elements). Near‐surface flow also accounted for one‐third of total base metal export. Our results demonstrate that near‐surface flow related to storm events markedly affects the cycling of many nutrients in steep tropical montane forests.
Carbon mineralization rates at different soil depths across a network of European forest sites (FORCAST)
Authors: Rey A. , Pegoraro E. , Jarvis P. G.
Published: November 2008

Most of the carbon (C) in terrestrial ecosystems is stored in the mineral soil layers. Thus, the response of the mineral soil to potential increases in temperature is crucial for the prediction of the impact of climate change on terrestrial ecosystems. Samples from three mineral soil layers were collected from eight mature forest sites in the European network CARBOEUROFLUX and were incubated at four temperatures (4, 10, 20 and 30°C) forc. 270 days. Carbon mineralization rates were related to soil and site characteristics. Soil water holding capacity, C content, nitrogen (N) content and organic matter all decreased with soil depth at all sites, with significantly larger amounts of organic matter, C and N in the top 0–5 cm of mineral soil than in the deeper layers. The conifer forest soils had significantly lower pH, higher C/N ratios and carbon contents in the top 5 cm than the broadleaf forest soils. Carbon mineralization rates decreased with soil depth and time at all sites but increased with temperature, with the highest rates measured at 30°C for all sites. Between 50 and 70% of the total C respired after 270 days of incubation came from the top 5 cm. The percentage C loss was small in all cases, ranging from 1 to 10%. A two‐compartment model was fitted to all data to derive the labile/active and slow/recalcitrant fractions, as well as their decomposition constants. Although the labile fraction was small in all cases, we found significantly larger amounts of labile C in the broadleaf forest soils than in the conifer forest soils. No statistically significant differences were found in the temperature sensitivity parameterQ10among sites, soil layers or between conifer and broadleaf soils. The averageQ10for all soils was 2.98 (± 0.10). We found that despite large differences among sites, C mineralization can be successfully predicted as a combined function of site leaf area index, mean annual temperature and content of labile carbon in the soil (R2 = 0.93).
Distribution of polycyclic aromatic hydrocarbons in particle‐size separates and density fractions of typical agricultural soils in the Yangtze River Delta, east China
Authors: Ni J. Z. , Luo Y. M. , Wei R. , Li X. H.
Published: November 2008

Soil organic matter can be divided into different organic carbon (C) pools with different turnover rates. The organic pollutants in soils associated with these organic C pools may have different bioavailability and environmental risks during the decomposition of soil organic matter. We studied the distribution patterns of 15 USEPA priority polycyclic aromatic hydrocarbons (PAHs) in different particle‐size separates (clay, fine silt, coarse silt, fine sand and coarse sand) and density fractions (light and heavy fractions) of nine agricultural topsoils (0–20 cm depth) from a contaminated area in the Yangtze River Delta region of east China. There was a decreasing trend in PAH concentration in particle‐size separates with decreasing particle size. However, the different particle‐size separates had similar PAH composition. The concentration of PAHs in the light fraction ranged from 13 037 to 107 299 μg kg−1, far higher than in the heavy fraction, which ranged from 222 to 298 μg kg−1. Although the light fraction accounted for only 0.4–2.3% of the soils, it was associated with 31.5–69.5% of soil PAHs. The organic matter in coarse silt had the strongest capacity for enrichment with PAHs. Combining the distributions of PAHs and the turnover rates of organic matter in different soil fractions, the environmental risks of PAH‐polluted soils may be due mainly to the PAHs associated with sand and the light fraction.
Soil hydrophobicity: a contribution of diuron sorption experiments
Authors: Chaplain V. , Brault A. , Tessier D. , Défossez P.
Published: November 2008

Retention processes play a major role in the fate and impact of organic contaminants in soils. The main goal of this study was to determine the influence of soil hydrophobic properties on the retention of diuron by using plots of a long‐term experiment in Versailles. We selected seven plots with pH 3.4 to 8.2 and low organic content. Sorption isotherms were obtained on soil slurries and kinetic measurements of diuron sorption were performed on undisturbed soil samples. The results showed that the Freundlich coefficient kf decreased as pH increased and that the Koc coefficient, kf/TOC, was linearly related to the contact angle measured on the clay fraction over a wide range of pH. A low initial adsorption rate and low adsorption equilibrium were observed for the plot treated with NaNO3. In this case, the structure in micro‐aggregates was assumed to limit the accessibility of adsorption sites. The CaCO3 and CaO treated plots had similar organic matter contents, pHs, CECs and bulk densities, although their < 2 μm:C ratio differed. The higher retention of diuron in the CaCO3 plot is attributed to the higher hydrophobicity of the < 2 μm fraction, probably masking part of the permanent clay negative charges. Thus, in addition to the different treatments, organic matter composition and distribution should also be included as specific soil properties. We conclude that the sorption properties of pesticides such as diuron can be a good tool to obtain greater understanding of soil properties and the degree of soil hydrophobicity/hydrophilicity in particular.
Evaluation of phosphorus mobilization potential in rewetted fens by an improved sequential chemical extraction procedure
Authors: Zak D. , Gelbrecht J. , Wagner C. , Steinberg C. E. W.
Published: November 2008

After rewetting of peatlands, phosphorus (P) pore‐water concentrations were up to three orders of magnitude greater than under pristine conditions. It was hypothesized that different mobilization processes such as ion‐exchange reactions, biotic/abiotic redox reactions, acidification and ongoing anaerobic decomposition of particulate organic matter by hydrolytic cleavage and fermentation might be responsible. To identify P pools in peat samples of varying degrees of decomposition, we modified and improved a sequential chemical extraction method that allowed conclusions on potential mobilization mechanisms in rewetted peatlands. The results indicated that the earlier drainage of rewetted fens strongly increased the P mobilization potential in the upper decomposed peat layers. Accordingly, the amount of P bound to redox‐sensitive (bicarbonate/dithionite soluble) compounds (BD‐P) was, on average, one order of magnitude greater in decomposed peat of rewetted fens (5.4–14.3 μmol P g−1 dry matter or DM) than in underlying less‐decomposed peat layers (0.2–1.9 μmol P g−1 DM) or slightly decomposed peat derived from pristine fens (0.4–2.0 μmol P g−1 DM). The BD‐P fraction found in the upper very decomposed peat layers appears to be most important for P mobilization in rewetted fens and accounted for 85% of the variability of P mobilization rates. Despite uncertainties regarding P diagenetic processes in peat, as well as the development of microbial decomposition processes, in the long‐term, high pore‐water P concentrations can be expected in rewetted fens for decades to come.
NaOH‐extractable organic matter of andic soils from Galicia (NW Spain) under different land use regimes: a pyrolysis GC/MS study
Authors: Verde J. R. , Buurman P. , Martínez‐Cortizas A. , Macías F. , Camps Arbestain M.
Published: November 2008

The objective of this study was to determine to what extent the attenuation or loss of andic soil properties caused by land use change – from forest (FOR, average C content 118.2 ± 23.7 g kg−1) to agricultural land (AGR, average C content 55.7 ± 16.7 g kg−1) use – is reflected in soil organic matter (SOM) at the molecular level. For this, NaOH‐extractable SOM of A horizons from 17 soils developed on amphibolitic parent material in NW Spain was studied by pyrolysis gas chromatography spectrometry (Py‐GC/MS). We also included two buried andic A horizons (PAL, 2200 cal yr BP in age) on the same parent material, as a reference for the molecular composition of SOM from soils without recent litter additions. Organic matter of PAL soils had a composition largely different from that of superficial soils (FOR and AGR), with an important relative contribution of microbial polysaccharides and N‐compounds, and an absence of compounds that characterize fresh plant litter (e.g. lignins). In the superficial soils, the relative contribution of lignin‐derived compounds was greater in AGR than in FOR soils. Differences were also observed in the relative contribution of aliphatic compounds, FOR soils being enriched in this type of components compared with AGR soils. The results indicated that land use change from FOR to AGR, which was accompanied by a decrease in total SOM, resulted in an enrichment in primary SOM. The smaller relative abundance of primary SOM derivatives in andic FOR soils indicates that these compounds were quickly degraded in Andisols.