bluuebunny/crossref_metadata_2025 huggingface dataset:
Microparticles, malignancy and thrombosis
Authors: Zahra Sharon , Anderson Julia A. M. , Stirling David , Ludlam Christopher A.
Published: February 2011

Microparticles (MPs) are considered to be important biological effectors of several different physiological and pathological processes. There is increasing evidence of their role in haemostasis and thrombosis, and also of their importance in cancer cell survival, invasiveness and metastasis. The level of circulating MPs has been assessed in many different disease states, and there are reports that patients with malignancy and patients with thrombosis have increased levels of circulating MPs and MP‐dependent thrombogenic potential. Research into the function and effect of MPs is currently hampered by a lack of standardization in the methods used to identify and quantify them. As these methods improve it is likely that MP assays will be of use both diagnostically and therapeutically in the future.
Advances in understanding the pathogenesis of familial thrombocythaemia
Authors: Teofili Luciana , Larocca Luigi M.
Published: February 2011

Familial thrombocytosis can be divided into two broad categories. The first includes inherited syndromes that affect only the megakaryocytic lineage with Mendelian inheritance, high penetrance and polyclonal haematopoiesis. The second category includes inherited predisposition to true Philadelphia‐negative myeloproliferative neoplasms (MPN) and is characterized by low penetrance, clonal haematopoiesis and presence of somatic mutations such as JAK2 V617F. It must be underlined that these two categories represent two well separate entities, with different patterns of proliferation and different transmission modalities. This review will focus on the molecular pathogenesis of hereditary thrombocytosis, underlining those clinical pictures that are specifically associated with mutations in the genes of thrombopoietin or in its receptor. Moreover, we propose an approach for the diagnosis and therapy of these syndromes.
Familial haemophagocytic lymphohistiocytosis: advances in the genetic basis, diagnosis and management
Authors: Gholam C , Grigoriadou S , Gilmour K C , Gaspar H B
Published: February 2011

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive disorder of immune dysregulation associated with uncontrolled T cell and macrophage activation and hypercytokinaemia. The incidence of FHL is 0·12/100·000 children born per year, with a male to female ratio of 1:1. The disease is classified into six different types based on genetic linkage analysis and chromosomal localization; five specific genetic defects have been identified, which account for approximately 90% of all patients. Type 1 is due to an as yet unidentified gene defect located on chromosome nine. Type 2 is caused by mutations in the perforin (PRF1) gene, type 3 by mutations in the Munc-13–4 (UNC13D) gene, type 4 by mutations in the syntaxin 11 (STX11) gene and the recently described type 5 due to mutations in the gene encoding syntaxin binding protein 2 (STXBP-2). The incidence of the five types varies in different ethnic groups. The most common presenting features are pyrexia of unknown origin, pronounced hepatosplenomegaly and cytopenias. Neurological features tend to present later and are associated with poor prognosis. Absent or decreased lymphocyte cytotoxicity is the cellular hallmark of FHL. Biochemical features such as hyperferritinaemia, hypertriglyceridaemia and hypofibrinogenaemia are usually present, along with high levels of soluble interleukin 2 receptor in the blood and cerebrospinal fluid. Bone marrow aspirate may demonstrate the characteristic haemophagocytes, but initially is non-diagnostic in two-thirds of patients. Established international clinical, haematological and biochemical criteria now facilitate accurate clinical diagnosis. The disease is fatal unless a haematopoietic stem cell transplant (HSCT) is performed. The introduction of HSCT has dramatically improved the prognosis of the disease. However, the mortality of the disease is still significantly high and a number of challenges remain to be addressed. Active disease at the time of the transplant is the major significant poor prognostic factor. Delayed diagnosis, after irreversible organ damage has occurred, especially neurological damage, disease reoccurrence and pre-transplant mortality, remain a concern.
Elevated blood levels of inflammatory monocytes (CD14+CD16+) in patients with complex regional pain syndrome
Authors: Ritz B W , Alexander G M , Nogusa S , Perreault M J , Peterlin B L , Grothusen J R , Schwartzman R J
Published: February 2011

Complex regional pain syndrome (CRPS) is a chronic pain disorder. Although its pathophysiology is not completely understood, neurogenic inflammation is thought to play a significant role. Microglia and astrocytes are activated following tissue injury or inflammation and have been reported to be both necessary and sufficient for enhanced nociception. Blood-borne monocytes/macrophages can infiltrate the central nervous system (CNS) and differentiate into microglia resulting in hypersensitivity and chronic pain. The primary aim of this study was to evaluate the proportion of the proinflammatory CD14+CD16+ monocytes as well as plasma cytokine levels in blood from CRPS patients compared to age- and gender-matched healthy control individuals. Forty-six subjects (25 CRPS, 21 controls) were recruited for this study. The percentage of monocytes, T, B or natural killer (NK) cells did not differ between CRPS and controls. However, the percentage of the CD14+CD16+ monocyte/macrophage subgroup was elevated significantly (P < 0·01) in CRPS compared to controls. Individuals with high percentage of CD14+CD16+ demonstrated significantly lower (P < 0·05) plasma levels on the anti-inflammatory cytokine interleukin (IL)-10. Our data cannot determine whether CD14+CD16+ monocytes became elevated prior to or after developing CRPS. In either case, the elevation of blood proinflammatoty monocytes prior to the initiating event may predispose individuals for developing the syndrome whereas the elevation of blood proinflammatory monocytes following the development of CRPS may be relevant for its maintenance. Further evaluation of the role the immune system plays in the pathogenesis of CRPS may aid in elucidating disease mechanisms as well as the development of novel therapies for its treatment.
Smoking and periodontal disease: discrimination of antibody responses to pathogenic and commensal oral bacteria
Authors: Hayman L , Steffen M J , Stevens J , Badger E , Tempro P , Fuller B , McGuire A , Al-Sabbagh Mohanad , Thomas M V , Ebersole J L
Published: February 2011

Smoking is an independent risk factor for the initiation, extent and severity of periodontal disease. This study examined the ability of the host immune system to discriminate commensal oral bacteria from pathogens at mucosal surfaces, i.e. oral cavity. Serum immunoglobulin (Ig)G antibody reactive with three pathogenic and five commensal oral bacteria in 301 current smokers (age range 21–66 years) were examined by enzyme-linked immunosorbent assay. Clinical features of periodontal health were used as measures of periodontitis. Antibody to the pathogens and salivary cotinine levels were related positively to disease severity; however, the antibody levels were best described by the clinical disease unrelated to the amount of smoking. The data showed a greater immune response to pathogens than commensals that was related specifically to disease extent, and most noted in black males. Significant correlations in individual patient responses to the pathogens and commensals were lost with an increasing extent of periodontitis and serum antibody to the pathogens. Antibody to Porphyromonas gingivalis was particularly distinct with respect to the discriminatory nature of the immune responses in recognizing the pathogens. Antibody responses to selected pathogenic and commensal oral microorganisms differed among racial groups and genders. The antibody response to the pathogens was related to disease severity. The level of antibody to the pathogens, and in particular P. gingivalis, was correlated with disease severity in black and male subsets of patients. The amount of smoking did not appear to impact directly serum antibody levels to these oral bacteria.
Expression and function of the autoimmune regulator (Aire) gene in non-thymic tissue
Authors: Eldershaw S A , Sansom D M , Narendran P
Published: February 2011

Educational immune tolerance to self-antigens is induced primarily in the thymus where tissue-restricted antigens (TRAs) are presented to T lymphocytes by cells of the thymic stroma – a process known as central tolerance. The expression of these TRAs is controlled in part by a transcription factor encoded by the autoimmune regulatory (Aire) gene. Patients with a mutation of this gene develop a condition known as autoimmune–polyendocrinopathy–candidiasis–ectodermal–dystrophy (APECED), characterized by autoimmune destruction of endocrine organs, fungal infection and dental abnormalities. There is now evidence for TRA expression and for mechanisms of functional tolerance outside the thymus. This has led to a number of studies examining Aire expression and function at these extra-thymic sites. These investigations have been conducted across different animal models using different techniques and have often shown discrepant results. Here we review the studies of extra thymic Aire and discuss the evidence for its expression and function in both human and murine systems.
Serum insulin‐like growth factor I and its binding protein 3 in their relation to intima–media thickness: results of the study of health in Pomerania (SHIP)
Authors: Spilcke‐Liss Elisabeth , Friedrich Nele , Dörr Marcus , Schminke Ulf , Völzke Henry , Brabant Georg , Nauck Matthias , Wallaschofski Henri
Published: February 2011

Objective Previous studies detected associations between lower insulin‐like growth factor I (IGF‐I) levels and increased risk of congestive heart failure or ischaemic heart disease. The aim of the present study was to assess the association of IGF‐I and its binding protein 3 (IGFBP‐3) with the carotid intima–media thickness (IMT) as marker of asymptomatic cardiovascular disease.

Design and population From the population‐based Study of Health in Pomerania (SHIP), a total of 2286 participants aged 45 years or older with readable ultrasound of the carotid arteries were available for the present analyses.

Methods and measurements Serum IGF‐I and IGFBP‐3 levels were categorized into three groups (low, moderate, high) according to the sex‐specific 10th and 90th percentile. Analyses of variance (anova) and logistic regression analyses adjusted for age, waist circumference, diabetes, hypertension and creatinine clearance were performed.

Results After adjusting for confounding factors, IGF‐I and the IGF‐I/IGFBP‐3 ratio were positively related to IMT inanova. Logistic regression analyses confirmed these findings and showed that high IGF‐I levels, a high IGF‐I/IGFBP‐3 ratio and low IGFBP‐3 levels were associated to higher odds of increased IMT.

Conclusion In conclusion, high IGF‐I or high IGF‐I/IGFBP‐3 ratio values and low IGFBP‐3 levels are associated with increased IMT. Therefore, systemic levels of the IGF axis or alterations in the balance of its components are associated with subclinical atherosclerotic disease.
Aromatase deficiency owing to a functional variant in the placenta promoter and a novel missense mutation in the CYP19A1 gene
Authors: Hauri‐Hohl Annik , Meyer‐Böni Monika , Lang‐Muritano Mariarosaria , Hauri‐Hohl Mathias , Schoenle Eugen J. , Biason‐Lauber Anna
Published: February 2011

Context  Aromatase deficiency in women is a rare 46, XX disorder of sex differentiation characterized by a defect in catalysing oestrogens from androgens.

Objective  To better understand this rare disorder, we searched for mutations in the CYP19A1 gene of an affected girl and analysed their functional consequences.

Design and patient  We examined a girl presenting with clitoral hypertrophy at birth and mild maternal virilization (acne) during pregnancy.

Main outcome measurement  A genotype–phenotype correlation was found.

Results  By direct sequencing of the CYP19A1 gene, we identified a heterozygous A>G mutation (c. A1374G) mutation in exon IX, leading to the missense p.N411S in the P450Aro protein and a heterozygous placenta promoter variant −41 base pairs upstream of exon I.1. Aromatase enzyme activity was completely lost when the mutant p.N411S protein was expressed in COS‐1 cells. The placenta promoter variant had a significantly reduced (−50%) transactivation ability compared to wild‐type.

Conclusion  Our data describe a novel loss‐of‐function missense mutation in CYP19A1 combined with the first‐described variant of the placenta promoter with a significant reduction in function, likely to be the molecular basis of this rare 46, XX disorder of sex development. This seems to represent a unique case of aromatase deficiency occurring in utero only.
Hollow spheroids in ascites of ovarian clear cell carcinoma: how are they formed and how do they behave?
Authors: Kato N. , Narutomi K. , Fukase M. , Motoyama T.
Published: February 2011

N. Kato, K. Narutomi, M. Fukase and T. Motoyama

Hollow spheroids in ascites of ovarian clear cell carcinoma: how are they formed and how do they behave?

Objective:  Although the multicellular aggregates (spheroids) in malignant ascites are usually solid throughout, they sometimes have acellular hollow spaces, especially in ascites of ovarian clear cell carcinoma. The purpose of this study is to analyse the origin and behaviour of hollow spheroids.

Methods:  Archival cytological and histological specimens of 32 ovarian carcinomas, including 12 clear cell carcinomas, were reviewed. HAC‐2, a clear cell carcinoma cell line, was injected into the abdominal cavity of nude mice for direct comparison of ascitic cytology and tumour histology. Spheroids that were collected from nude mice ascites were cultured in vitro to observe their behaviour.

Results:  Five of six clear cell carcinomas with hollow spheroids showed spherule‐like hyaluronan‐rich stroma in their tumour tissue, whereas those without hollow spheroids did not. After heterotransplantation, both ascites and tumour imprints showed small or large hollow spheroids. Hyaluronan was detected in the former but not in the latter. The abdominal tumours showed compact spherule‐like hyaluronan‐rich stroma, enlarged oedematous stroma or intermediate stroma. In both size and hyaluronan status, small and large hollow spheroids were approximately comparable to spherule‐like hyaluronan‐rich stroma and oedematous stroma, respectively. During culture in vitro, hollow spheroids were maintained as hollow spheroids in suspension, and produced daughter hollow spheroids.

Conclusions:  The hollow space in the spheroids originates from spherule‐like hyaluronan‐rich stroma, where water trapping by hyaluronan causes enlargement of the space. The matrix within the hollow space serves as a scaffold that regulates cell polarity and matrix production.
GrazeIn: a model of herbage intake and milk production for grazing dairy cows. 3. Simulations and external validation of the model
Authors: Delagarde R. , Valk H. , Mayne C. S. , Rook A. J. , González‐Rodríguez A. , Baratte C. , Faverdin P. , Peyraud J. L.
Published: February 2011

GrazeIn is a model for predicting herbage intake and milk production of grazing dairy cows. The objectives of this paper are to test its robustness according to a planned arrangement of grazing and feeding scenarios using a simulation procedure, and to investigate the precision of the predictions from an external validation procedure with independent data. Simulations show that the predicted effects of herbage allowance, herbage mass, herbage digestibility, concentrate supplementation, forage supplementation and daily time at pasture are consistent with current knowledge. The external validation of GrazeIn is investigated from a large dataset of twenty experiments representing 206 grazing herds, from five research centres within Western Europe. On average, mean actual and predicted values are 14·4 and 14·2 kg DM d−1 for herbage intake and 22·7 and 24·7 kg d−1 for milk production, respectively. The overall precision of the predictions, estimated by the mean prediction error, are 16% (i.e. 2·3 kg DM d−1) and 14% (i.e. 3·1 kg d−1) for herbage intake and milk production, respectively. It is concluded that the GrazeIn model is able to predict variations in herbage intake and milk production of grazing dairy cows in a realistic manner over a wide range of grazing management practices, rendering it suitable as a basis for decision support systems.
GrazeIn: a model of herbage intake and milk production for grazing dairy cows. 1. Prediction of intake capacity, voluntary intake and milk production during lactation
Authors: Faverdin P. , Baratte C. , Delagarde R. , Peyraud J. L.
Published: February 2011

The prediction of both food intake and milk production constitutes a major issue in ruminants. This article presents a model predicting voluntary dry matter intake and milk production by lactating cows fed indoors. This model, with an extension to predict herbage intake at grazing presented in a second article, is used in the Grazemore decision support system. The model is largely based on the INRA fill unit system, consisting of predicting separately the intake capacity of the cows and the fill value (ingestibility) of each feed. The intake capacity model considers potential milk production as a key component of voluntary feed intake. This potential milk production represents the energy requirement of the mammary gland, adjusted by protein supply when the protein availability is limiting. Actual milk production is predicted from the potential milk production and from the nutritional status of the cow. The law of response of milk production is a function of the difference between energy demand and actual energy intake, modulated by protein intake level. The simulation of experimental data from different feeding trials illustrates the performance of the model. This new model enables dynamic simulations of intake and milk production sensitive to feeding management during the whole lactation period.
Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection
Authors: Dulgerian Laura R. , Garrido Vanina V. , Stempin Cinthia C. , Cerbán Fabio M.
Published: February 2011

The programmed death ligands 1 (PD‐L1) and 2 (PD‐L2) that bind to programmed death 1 (PD‐1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypanosoma cruzi infection. We have studied the role of PD‐L1 and PD‐L2 in T. cruzi infection and their importance in arginase/inducible nitric oxide synthase (iNOS) balance in the immunomodulatory properties of macrophages (Mφ). In this work, we have demonstrated that expression of the PD‐1/PD‐L pathway is modified during T. cruzi infection on Mφs obtained from peritoneal cavity. The Mφs from T. cruzi‐infected mice suppressed T‐cell proliferation and this was restored when anti‐PD‐1 and anti‐PD‐L1 antibodies were added. Nevertheless, anti‐PD‐L2 antibody treatment did not re‐establish T‐cell proliferation. PD‐L2 blockade on peritoneal cells from infected mice showed an increase in arginase expression and activity and a decrease in iNOS expression and in nitric oxide (NO) production. Additionally, interleukin‐10 production increased whereas interferon‐γ production was reduced. As a result, this microenvironment enhanced parasite proliferation. In contrast, PD‐1 and PD‐L1 blockage increased iNOS expression and NO production on peritoneal Mφs from T. cruzi‐infected mice. Besides, PD‐L2 knockout infected mice showed an increased in parasitaemia as well as in arginase activity, and a reduction in NO production. Taken together, our results demonstrate that PD‐L2 is involved in the arginase/iNOS balance during T. cruzi infection having a protective role in the immune response against the parasite.
The alveolar bone height of the primary and first permanent molars in healthy 6‐ to 9‐year‐old Jordanian children
Authors: Al Jamal Ghaida , Al‐Batayneh Ola B , Hamamy Dima
Published: February 2011

Aim

To establish a threshold cemantoenamel junction (CEJ)–alveolar bone crest (ABC) distance in healthy 6‐ to 9‐year‐old Jordanian children and determine the effect of pathological changes, physiological changes, gender, and age on the CEJ–ABC distance.

Design

Bitewing radiographs were made for 539 6‐ to 9‐year‐old children. Plaque index (PI), gingival index (GI), calculus index (CI), DMFS score, and pocket depth were all assessed through clinical examination. CEJ–ABC distance was measured from radiographs at the mesial surface of permanent first molars (PFM), and the mesial and distal surfaces of primary molars.

Results

The CEJ–ABC distance ranged from 0.00 to 4.49 mm, the mean for all surfaces was 0.84 ± 0.44 mm, no gender or age group differences were found. The mesial surface of the PFMs had the smallest mean CEJ–ABC distance. The CEJ–ABC distances were greater in the maxilla than in the mandible. No significant effect of PI, GI or CI on CEJ–ABC distance was found. Caries, faulty restorations, exfoliation, and partial eruption adjacent to measured surfaces had significant effect on the CEJ–ABC distance.

Conclusion

The mean CEJ–ABC distance was <1 mm. Threshold CEJ–ABC distances of 1.0 and 1.5 mm for PFMs and primary molars, respectively, are suggested to be used in 6‐ to 9‐year‐old children.
Adaptive divergence for a fitness‐related trait among invasiveAmbrosia artemisiifoliapopulations in France
Authors: CHUN YOUNG JIN , LE CORRE VALÉRIE , BRETAGNOLLE FRANÇOIS
Published: February 2011

The impact of natural selection on the adaptive divergence of invasive populations can be assessed by testing the null hypothesis that the extent of quantitative genetic differentiation (QST) would be similar to that of neutral molecular differentiation (FST). Using eight microsatellite loci and a common garden approach, we comparedQSTandFSTamong ten populations of an invasive speciesAmbrosia artemisiifolia(common ragweed) in France. In a common garden study with varying water and nutrient levels, we measuredQSTfor five traits (height, total biomass, reproductive allocation, above‐ to belowground biomass ratio, and days to flowering). Although lowFSTindicated weak genetic structure and strong gene flow among populations, we found significant diversifying selection (QST > FST) for reproductive allocation that may be closely related to fitness. It suggests that abiotic conditions may have exerted selection pressure onA. artemisiifoliapopulations to differentiate adaptively, such that populations at higher altitude or latitude evolved greater reproductive allocation. As previous studies indicate multiple introductions from various source populations ofA. artemisiifoliain North America, our results suggest that the admixture of introduced populations may have increased genetic diversity and additive genetic variance, and in turn, promoted the rapid evolution and adaptation of this invasive species.
A new family of quorum sensing pheromones synthesized using S‐adenosylmethionine and Acyl‐CoAs
Authors: Winans Stephen C.
Published: February 2011

It is now widely accepted that populations of bacterial cells often co‐ordinate their behaviour via diffusible chemical signals. Many different signals have been documented, but they fall into a relatively small number of families. One such signal, CAI‐1, from Vibrio cholerae consists of a substituted 13‐carbon alkane. In this issue, Bassler and colleagues provide evidence that CAI‐1 exemplifies an entirely new class of pheromones. They also show that one species of Vibrio synthesizes and detects just one such pheromone, while another species synthesizes and detects several. Bioinformatics and data from another group indicate that this new class of signals may be widespread among beta‐ and gamma‐proteobacteria.
Cannabinoid‐induced delayed gastric emptying is selectively increased upon intermittent administration in the rat: role of CB1 receptors
Authors: Abalo R. , Cabezos P. A. , Vera G. , López‐miranda V. , Herradón E. , Martín‐fontelles M. I.
Published: February 2011

Background  Cannabinoids acutely administered depress central, cardiovascular and gastrointestinal functions. These effects might be modified upon repeated administration. Compared to the effects induced by daily administration, those induced by intermittent administration are less known. The effect of intermittent treatment with the CB1/CB2 cannabinoid agonist WIN55,212‐2 (WIN) was studied in the rat.

Methods  Male rats received saline, vehicle or WIN at 0.5 (low‐WIN) or 5 (high‐WIN) mg kg−1 week−1 for 4 weeks. WIN effects on the central nervous system (cannabinoid tetrad tests), cardiovascular function and gastrointestinal motor function were evaluated after the first and last doses, and, where appropriate, 1 week after the last dose. To determine the involvement of CB1 receptors in the chronic effect of WIN, the CB1 receptor antagonist/inverse agonist AM251 (1 mg kg−1) was used.

Key Results  High‐ (but not low‐) WIN induced the four signs of the cannabinoid tetrad, and reduced gastrointestinal motility, but did not alter cardiovascular parameters. Upon chronic intermittent administration, tolerance did not clearly develop to WIN effects. Quite the opposite, depression of gastric emptying was intensified. No effect was long‐lasting. Repeated administration of AM251 was more efficacious than single administration to block WIN chronic central effects, but the opposite occurred regarding lower intestinal motility.

Conclusions & Inferences  Upon intermittent administration, hypersensitization may develop to some effects (particularly delayed gastric emptying) induced by cannabinoid agonists. CB1 antagonists/inverse agonists may show different efficacy upon repeated or single administration to block cannabinoid‐induced central and gastrointestinal effects. Thus, cannabinoid effects are dependent on the pattern of drug administration.
Different serum cytokine levels in chronic vs. acute Anisakis simplex sensitization‐associated urticaria
Authors: DASCHNER A. , RODERO M. , DE FRUTOS C. , VALLS A. , VEGA F. , BLANCO C. , CUÉLLAR C.
Published: February 2011

The knowledge on immune mechanisms of chronic urticaria (CU) at the cytokine level is widely scarce. We compared pro‐ and anti‐inflammatory as well as Th1‐ and Th2‐associated serum cytokine levels in two phenotypes of CU: associated with (CU+) and without (CU−) sensitization against Anisakis simplex, a ubiquitous fish parasite, that has been associated with acute urticaria in gastro‐allergic anisakiasis (GAA) and with CU+. Thirteen CU+ and 19 CU− patients were compared with 13 GAA patients and 15 control subjects for cytokines, measured by cytometric bead array. Urticaria activity score was positively correlated with IL‐6 in CU−. Serum levels of IL‐10 were lower in CU+ and CU− with respect to the control group. Median IFN‐γ was lower in all urticaria groups. Patients with previous parasitism by A. simplex displayed higher TGF‐β levels than subjects without previous parasitism. The main finding was lower levels of IL‐17 in CU+ with respect to GAA or controls, with a further tendency to even lower levels in CU−. Different urticaria phenotypes are associated with distinct serum cytokine levels.
Donor risk score and baseline biopsy CADI value predict kidney graft outcome
Authors: Kahu Jaanus , Kyllönen Lauri , Räisänen‐Sokolowski Anne , Salmela Kaija
Published: February 2011

Kahu J, Kyllönen L, Räisänen‐Sokolowski A, Salmela K. Donor risk score and baseline biopsy CADI value predict kidney graft outcome. Clin Transplant 2011: 25: E276–E283. © 2011 John Wiley & Sons A/S.

Abstract:  Different donor parameters and baseline biopsy have been used to assess the quality of donor organs. There is, however, no consensus which risk factors and chronic changes in the donor kidney can be accepted for transplantation. The study included 481 deceased organ donors and their 829 kidney recipients transplanted during 1995–2005. The biopsies were re‐evaluated according to the Banff 97 classification. The prognostic significance of donor risk factors and Chronic Allograft Damage Index (CADI) was analyzed. We propose a new donor risk score, calculated as the count of positive risk factors from a defined set of factors in the medical history of the donor. This donor risk score predicts histological quality of the kidney, graft function, and survival. Transplantations from donors with donor risk score >4 had significantly decreased graft survival compared to those with donor risk scores 0–4; the five‐yr death‐censored graft survivals were 83% vs. 93%, respectively. High donor CADI score (>3) was associated with worse graft function and survival. Three‐yr glomerular filtration rate declined from 82 to 49 mL/min with donor CADI increase from 0 to ≥4. Our results show that high donor risk score and CADI value reflect low functional reserve and risk for poor graft outcome.
Surveillance of megakaryocytic function by measurement of CD61‐exposing microparticles in allogeneic hematopoietic stem cell recipients
Authors: Rank Andreas , Nieuwland Rienk , Delker Ruth , Pihusch Verena , Wilkowski Ralf , Toth Bettina , Kolb Hans‐Jochem , Pihusch Rudolf
Published: February 2011

Rank A, Nieuwland R, Delker R, Pihusch V, Wilkowski R, Toth B, Kolb H‐J, Pihusch R. Surveillance of megakaryocytic function by measurement of CD61‐exposing microparticles in allogeneic hematopoietic stem cell recipients. Clin Transplant 2011: 25: E233–E242. © 2011 John Wiley & Sons A/S.

Abstract:  Increasing evidence suggests that circulating microparticles (MP) exposing CD61 originate predominantly from megakaryocytes. Dramatic changes in megakaryocytic homeostasis are regularly observed following allogeneic hematopoietic stem cell transplantation (HSCT) and associated with transplantation‐associated complications. We studied MP plasma levels prospectively in healthy subjects (n = 10) and allogeneic HSCT recipients (n = 19) twice weekly from the start of conditioning therapy up to day 30. A total of 224 measurement points were evaluated. MP were isolated, double‐stained with annexin V and anti‐CD61, and analyzed by flow cytometry. In uncomplicated HSCT, we found a correlation between platelet and CD61‐exposing MP count, which resulted in a constant ratio of MP per platelet. The ratio was increased in patients with active hematological malignancies before transplantation and normalized during conditioning therapy. After take, the MP ratio increased, whereas infections and microangiopathic hemolytic anemia did not affect the ratio. In patients with GvHD, a decreased MP ratio was observed depending on the grade of GvHD, possibly indicating megakaryocytic damage. The MP ratio was able to discriminate between toxic, septic, and GvHD‐induced hyperbilirubinemia. We first describe CD61+ MP levels during allogeneic HSCT and postulate that the MP ratio might be a useful biomarker for the surveillance of megakaryocytes during HSCT.
Long‐term effects on renal function of dose‐reduced calcineurin inhibitor and sirolimus in cardiac transplant patients
Authors: Khandhar Sameer J. , Shah Hemal V. , Shullo Michael A. , Zomak Rachelle , Navoney Michelle , McNamara Dennis M. , Kormos Robert L. , Toyoda Yoshiya , Teuteberg Jeffrey J.
Published: February 2011

Khandhar SJ, Shah HV, Shullo MA, Zomak R, Navoney M, McNamara DM, Kormos RL, Toyoda Y, Teuteberg JJ. Long‐term effects on renal function of dose‐reduced calcineurin inhibitor and sirolimus in cardiac transplant patients.  Clin Transplant 2012: 26: 42–49.  © 2011 John Wiley & Sons A/S.

Abstract:  Calcineurin inhibitor (CNI)‐associated renal insufficiency is common after cardiac transplantation (CTX); however, the addition of sirolimus allows for CNI dose reduction and this strategy may limit CNI renal toxicity. This study examines the long‐term effects of such a strategy.

Methods:  Patients from a single center who had CTX from 1990 to 2007 and who were converted to sirolimus and a dose‐reduced CNI were compared to group‐matched controls maintained on CNI and an antiproliferative agent.

Results:  One hundred and fifty‐five patients (79 sirolimus and 76 controls) were included and had similar baseline characteristics. Sirolimus was started a mean of 1429 d post‐CTX and maintained for a mean of 823 d. Reason for conversion to sirolimus was renal insufficiency (34%), vasculopathy (29%), recurrent rejection (19%), and other (18%). The eGFR was not different between groups at baseline (44.7 mL/min/1.73 m2 vs. 46.0, p = 0.64) or at any point during follow‐up: 90 d, 180 d, 1 yr, 2 yr, and 3 yr.

Conclusion:  Patients converted to a regimen of sirolimus and a dosed‐reduced CNI have stable renal function over the following three yr, but do not have an improvement in renal outcomes compared to patients maintained on full dose CNI.
Geographic variation in the flood‐induced fluctuating temperature requirement for germination in Setaria parviflora seeds
Authors: Mollard F. P. O. , Insausti P.
Published: February 2011

Our aim was to search for specific seed germinative strategies related to flooding escape in Setaria parviflora, a common species across the Americas. For this purpose, we investigated induction after floods, in relation to fluctuating temperature requirements for germination in seeds from mountain, floodplain and successional grasslands. A laboratory experiment was conducted in which seeds were imbibed or immersed in water at 5 °C. Seeds were also buried in flood‐prone and upland grasslands and exhumed during the flooding season. Additionally, seeds were buried in flooded or drained grassland mesocosms. Germination of exhumed seeds was assayed at 25 °C or at 20 °C/30 °C in the dark or in the presence of red light pulses. After submergence or soil flooding, a high fraction (>32%) of seeds from the floodplain required fluctuating temperatures to germinate. In contrast, seeds from the mountains showed maximum differences in germination between fluctuating and constant temperature treatment only after imbibition (35%) or in non‐flooded soil conditions (40%). The fluctuating temperature requirement was not clearly related to the foregoing conditions in the successional grassland seeds. Maximum germination could also be attained with red light pulses to seeds from mountain and successional grasslands. Results show that the fluctuating temperature requirement might help floodplain seeds to germinate after floods, indicating a unique feature of the dormancy of S. parviflora seeds from floodplains, which suggests an adaptive advantage aimed at postponing emergence during inundation periods. In contrast, the fluctuating temperature required for germination among seeds from mountain and successional grasslands show its importance for gap detection.
Persistence of sunflower crop traits and fitness in Helianthus petiolaris populations
Authors: Gutierrez A. , Cantamutto M. , Poverene M.
Published: February 2011

Transgenic plants have increased interest in the study of crop gene introgression in wild populations. Genes (or transgenes) conferring adaptive advantages persist in introgressed populations, enhancing competitiveness of wild or weedy plants. This represents an ecological risk that could increase problems of weed control. Introgression of cultivar alleles into wild plant populations via crop–wild hybridisations is primarily governed by their fitness effect. To evaluate this, we studied the second generation of seven wild–crop interspecific hybrids between weedy Helianthus petiolaris and cultivated sunflower, H. annuus var. macrocarpus. The second generation comprised open‐pollinated progeny and backcrosses to the wild parent, mimicking crosses that occur in natural situations. We compared a number of morphological, life history and fitness traits. Multivariate analysis showed that the parental species H. annuus and H. petiolaris differed in a number of morphological traits, while the second hybrid generation between them was intermediate. Sunflower crop introgression lowered fitness of interspecific hybrids, but fitness parameters tended to recover in the following generation. Relative frequency of wild/weedy and introgressed plants was estimated through four generations, based on male and female parent fitness. In spite of several negative selection coefficients observed in the second generation, introgressed plants could be detected in stands of <100 weedy H. petiolaris populations. The rapid recovery of fecundity parameters leads to prediction that any trait conferring an ecological advantage will diffuse into the wild or weedy population, even if F1 hybrids have low fitness.
The βI‐galactosidase of Cicer arietinum is located in thickened cell walls such as those of collenchyma, sclerenchyma and vascular tissue
Authors: Martín I. , Jiménez T. , Hernández‐Nistal J. , Dopico B. , Labrador E.
Published: February 2011

We report localisation of the chickpea βI‐Gal, a member of the chickpea β‐galactosidase family, which contains at least four members. After generation of specific antibodies, the distribution and cellular immunolocalisation of the protein in different organs and developmental stages of the plant was studied. βI‐Gal protein is much longer than the other chickpea β‐galactosidases because of the presence of a lectin‐like domain in the carboxyl terminus of the protein. Western blot experiments indicated that the active βI‐Gal retains this lectin‐like domain for its function in the plant. The βI‐Gal protein was mainly detected in cell walls of elongating organs, such as seedling epicotyls and stem internodes. An immunolocation study indicated a very good correlation between the presence of this βΙ‐galactosidase and cells whose walls are thickening, not only in aged epicotyls and mature internodes in the final phase of elongation, but mostly in cells with a support function, such as collenchyma cells, xylem and phloem fibres and a layer of sclerenchyma cells surrounding the vascular cylinder (perivascular fibres). These results could suggest a function for the βI‐Gal in modification of cell wall polymers, leading to thicker walls than the primary cell walls.
Transcriptional regulation of two RTE‐like genes of carnation during flower senescence and upon ethylene exposure, wounding treatment and sucrose supply
Authors: Yu Y. , Wang H. , Liu J. , Fu Z. , Wang J. , Liu J.
Published: February 2011

RTE1 (REVERSION‐TO‐ETHYLENE SENSITIVITY1) was identified as a positive regulator of ETR1 (ethylene resistant1) function in Arabidopsis; RTEs are a small gene family. Ethylene plays a crucial role in the senescence of carnation (Dianthus caryophyllus L.) flowers. Two cDNA clones encoding putative RTE‐like protein (DCRTE1 and DCRTH1) were obtained from total RNA isolated from senescing carnation petals using RT‐PCR and RACE techniques. The predicted proteins of DCRTE1 and DCRTH1 consist of 228 and 233 amino acids, respectively. Interestingly, the deduced DCRTE1 protein, like most other RTEs, includes two putative transmembrane domains, while the deduced DCRTH1 protein includes five putative transmembrane domains, according to the TMHMM database. Northern blots showed that the level of DCRTE1 mRNA in petals first decreased then increased remarkably after ethylene production started, and DCRTE1 expression showed an increasing trend in ovaries during natural flower senescence. The amount of DCRTH1 transcripts increased gradually in both petals and ovaries during natural senescence. Exogenous ethylene increased transcript abundance of DCRTE1 and DCRTH1 to various degrees in both petals and ovaries. STS treatment decreased the level of DCRTH1 mRNA in petals and ovaries compared with the control. DCRTE1 and DCRTH1 showed a rapid increase and then a decrease in mRNA accumulation in leaves after wounding. These results suggest that both DCRTE1 and DCRTH1 could play important roles in flower senescence‐related signalling. Sucrose treatment did not remarkably affect the amount of DCRTE1 and DCRTH1 mRNAs.
For she that hath, to her shall be given…Implications of flowering in Anemone nemorosa L.
Authors: Pontoppidan M.‐B. , Petersen P. M. , Philipp M.
Published: February 2011

We looked for life‐history trade‐offs between flowering, vegetative growth and somatic maintenance in the common woodland herb Anemone nemorosa. A. nemorosa forms a horizontal rhizome system consisting of previously formed annual segments and terminated by a flowering or non‐flowering shoot. Resources acquired by the aboveground parts are used for flowering, seed production, storage and growth of the annual segments. Resources stored in the rhizome during the growing period are used for preformation of buds, somatic maintenance between two growing periods and development of aboveground parts in the following spring. We hypothesised that the decision to invest in flower buds depends on the amount of resources stored in the recently formed annual segment. We also hypothesised a trade‐off between flowering and segment growth and, finally, as a consequence, we expected individual rhizomes to alternate between the flowering and the non‐flowering state. We found that segments producing flower buds were significantly longer than non‐flowering segments, indicating that resource level influences the function of the preformed buds. Contrary to our expectations, we found flowering rhizomes produced longer annual segments than non‐flowering rhizomes. We suggest the larger leaf area of flowering rhizomes and occasional abortion of flowers or seeds as possible mechanisms behind this pattern. Our study shows that even though the decision to produce a flower bud is taken in another time‐frame than that in which the actual flowering and fruiting takes place, an ostensibly inexpedient decision is changed to a neutral or even an advantageous incident.
Amlodipine ameliorates endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats
Authors: He Xi , Zhang Hong‐Li , Zhao Ming , Yang Jun‐Lu , Cheng Gong , Sun Lei , Li Dong‐Ling , Jiang Hong‐Ke , Zhao Qiang , Yu Xiao‐Jiang , Zang Wei‐Jin
Published: February 2011

1. Endothelial dysfunction plays a critical role in the development and progression or pathogenesis of hypertension. Amlodipine, a calcium channel blocker, is an effective antihypertensive agent. We investigated the effects of amlodipine on endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats (SHR).

2. Eight‐week‐old SHR were treated with amlodipine (10 mg/kg per day) for 8 weeks. Control SHR and Wistar‐Kyoto (WKY) rats were treated with saline. Systolic blood pressure (SBP) was measured by the tail‐cuff method. Isometric tension changes of isolated mesenteric arterial rings were recorded continuously by a myograph system. Serum contents of malondialdehyde (MDA) and total nitrate/nitrite (NOx) were determined. Vascular superoxide anion production was analysed with dihydroethidium (DHE) fluorescence.

3. The contractile responses to KCl and phenylephrine were greater in untreated SHR than in WKY. Acetylcholine (ACh)‐induced relaxation was significantly impaired in untreated SHR. Amlodipine treatment reduced the contractions and improved relaxation to ACh. In WKY, relaxation to ACh was inhibited by NG‐nitro‐l‐arginine methyl ester (l‐NAME) and not changed by ascorbic acid. In untreated SHR, the response to ACh was unaffected by l‐NAME, whereas it was improved by ascorbic acid. Amlodipine restored the inhibitory effect of l‐NAME on ACh‐induced relaxation, but ascorbic acid no longer exerted its facilitating effect. Amlodipine prevented the rise in SBP and ameliorated abnormalities in serum MDA and NO in untreated SHR. DHE assay showed an increased intravascular superoxide generation in untreated SHR, which was abrogated by amlodipine.

4. Treatment of SHR with amlodipine resulted in amelioration of endothelial dysfunction by anti‐oxidant activity and improvement in NO availability.
Serum pepsinogen II: A neglected but useful biomarker to differentiate between diseased and normal stomachs
Authors: He Cai‐yun , Sun Li‐ping , Gong Yue‐hua , Xu Qian , Dong Nan‐nan , Yuan Yuan
Published: February 2011

Background and Aim:  Serum pepsinogen II (sPGII) is underutilized and considered an inconspicuous biomarker in clinical practice. We refocused on this neglected but novel biomarker and conducted the present study, aiming to elucidate the normal level of sPGII in healthy Chinese patients and to investigate the clinical utility of sPGII for gastric disease screening.

Methods:  In 2008–2009, a total of 2022 participants from northern China were selected and enrolled in the study. sPGII and Helicobacter pylori (H. pylori)–immunoglobulin G were measured with ELISA.

Results:  sPGII showed a normal value of 6.6 microg/L in a total of 466 patients with endoscopically‐ and histologically‐normal stomachs. A small sex difference was observed: the average value of sPGII was 7 microg/L and 6 microg/L in males and females, respectively (P < 0.001). In the differentiation between healthy and diseased (endoscopically‐diseased stomach or gastritis/atrophic gastritis in endoscopic biopsies) stomach mucosae, the best sPGII cut‐off value was 8.25 microg/L (sensitivity 70.6%, specificity 70.8%). In screening the H. pylori seropositivity, the optimum cut‐off sPGII value was 10.25 microg/L (sensitivity 71.6%, specificity 70.1%).

Conclusions:  We demonstrated that the mean values of sPGII in a healthy Chinese population are 7 microg/L and 6 microg/L for males and females, respectively. sPGII significantly increases in diseased and H. pylori‐infected stomach, and the best sPGII cut‐off value is 8.25 microg/L in the differentiation between patients with healthy and diseased stomach mucosae. Furthermore, Chinese patients with sPGII greater than 10.25 microg/L are at greater risk of various H. pylori‐related gastropathies, and are therefore prior candidates for gastro‐protection therapy.
Primary retroperitoneal dysgerminoma presenting as an adrenal tumor: A case report and literature review
Authors: Yoo Su Hyun , Kim Kyu‐Rae , Hong Suk Jun , Cho Kyung‐Ja
Published: February 2011

Primary extragonadal germ cell tumors are rare and mostly occur in young men with predominance of nonseminomatous histology. We report an undescribed case of primary retroperitoneal dysgerminoma presenting as an adrenal tumor in a 17‐year‐old girl. Surgery was performed on a 10 × 9.5 cm sized adrenal gland tumor and the resected tumor showed unequivocal histological features of dysgerminoma. The diagnosis was confirmed by the tumor's germ cell immunophenotype. Postoperative ultrasonography, CT and PET over a 6‐month period revealed no evidence of ovarian lesion. The patient is stable, but with a suspicious residual tumor after adjuvant chemotherapy.
Genetic predisposition to diffuse panbronchiolitis
Authors: KEICHO NAOTO , HIJIKATA MINAKO
Published: February 2011

Diffuse panbronchiolitis is characterized by chronic inflammation in respiratory bronchioles and sinobronchial infection. The pathophysiology accompanying the persistent bacterial infection is noteworthy for the accumulation of lymphocytes and foamy macrophages around the small airways, for mucus hypersecretion, and for the number of neutrophils in the large airways. Until the establishment of long‐term macrolide therapy, the prognosis was generally poor. Case studies of diffuse panbronchiolitis in East Asians, including Japanese, Koreans and Chinese, have frequently been reported, and genetic predisposition to the disease has been assumed in Asians. Immunogenetic studies revealed a strong association with human leukocyte antigen (HLA)‐B54 in Japanese, whereas an association with HLA‐A11 was reported in Koreans. These findings imply that a major susceptibility gene may be located between the HLA‐A and HLA‐B loci on the short arm of human chromosome 6. We have recently cloned novel mucin‐like genes in this candidate region. In addition to accumulated knowledge of classical HLA genes and mucin genes, further analysis of newly identified genes may provide insights into the pathogenesis of the disease.