bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of PilZ domain proteins in the virulence of Xanthomonas campestris pv. campestris
Authors: MCCARTHY YVONNE , RYAN ROBERT P. , O'DONOVAN KAREN , HE YONG‐QIANG , JIANG BO‐LE , FENG JIA‐XUN , TANG JI‐LIANG , DOW J. MAXWELL 
Published: September 2008

SUMMARYCyclic di‐GMP [(bis‐(3′–5′)‐cyclic di‐guanosine monophosphate)] is an almost ubiquitous second messenger in bacteria that is implicated in the regulation of a range of functions that include developmental transitions, aggregative behaviour, adhesion, biofilm formation and virulence. Comparatively little is known about the mechanism(s) by which cyclic di‐GMP exerts these various regulatory effects. PilZ has been identified as a cyclic di‐GMP binding protein domain; proteins with this domain are involved in regulation of specific cellular processes, including the virulence of animal pathogens. Here we have examined the role of PilZ domain proteins in virulence and the regulation of virulence factor synthesis in Xanthomonas campestris pv. campestris (Xcc), the causal agent of black rot of crucifers. The Xcc genome encodes four proteins (XC0965, XC2249, XC2317 and XC3221) that have a PilZ domain. Mutation of XC0965, XC2249 and XC3221 led to a significant reduction of virulence in Chinese radish. Mutation of XC2249 and XC3221 led to a reduction in motility whereas mutation of XC2249 and XC0965 affected extracellular enzyme production. All mutant strains were unaffected in biofilm formation in vitro. The reduction of virulence following mutation of XC3221 could not be wholly attributed to an effect on motility as mutation of pilA, which abolishes motility, has a lesser effect on virulence.
Co‐administration of proton pump inhibitors delays elimination of plasma methotrexate in high‐dose methotrexate therapy
Authors: Suzuki Kunihiro , Doki Kosuke , Homma Masato , Tamaki Hirofumi , Hori Satoko , Ohtani Hisakazu , Sawada Yasufumi , Kohda Yukinao 
Published: September 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Co‐administration of proton pump inhibitors (PPIs) increases plasma methotrexate (MTX) concentration in cancer patients receiving high‐dose MTX (HDMTX) therapy.• There is controversy as to whether or not co‐administration of PPIs affects plasma MTX elimination in HDMTX therapy.• Inhibitory activity of PPIs on breast cancer resistance protein (BCRP) is a possible mechanism for the drug interaction between MTX and PPIs. WHAT THIS STUDY ADDS • Co‐administration of a PPI (omeprazole, lansoprazole, or rabeprazole) was more frequently observed in the delayed MTX elimination group than in the normal MTX elimination group.• Multiple logistic regression analysis with adjustment for significant covariates revealed that PPI co‐administration was a significant risk factor for delayed plasma MTX elimination.• The half‐maximal inhibitory concentration of each PPI in inhibiting BCRP function was much higher than the therapeutic unbound concentration in the plasma.AIMTo assess whether or not co‐administration of proton pump inhibitors (PPIs) is a risk factor for delayed elimination of plasma methotrexate (MTX) in high‐dose MTX (HDMTX) therapy for malignant diseases.METHODSTo assess the effects of PPI co‐administration on elimination of plasma MTX, we examined plasma MTX concentration data on 171 cycles of HDMTX therapy performed in 74 patients. We performed multiple logistic regression analysis to evaluate PPI co‐administration as a risk factor. Inhibitory potencies of omeprazole, lansoprazole, rabeprazole and pantoprazole on MTX transport via breast cancer resistance protein (BCRP, ABCG2) were also investigated in an in vitro study using membrane vesicles expressing human BCRP.RESULTSWe identified co‐administration of PPIs as a risk factor for delayed elimination (odds ratio 2.65, 95% confidence interval 1.03, 6.82) as well as renal and liver dysfunction. All four PPIs inhibited BCRP‐mediated transport of MTX, with half‐maximal inhibitory concentrations of 5.5–17.6 µM – considerably higher than the unbound plasma concentrations of the PPIs.CONCLUSIONSOur results support previous findings suggesting that PPI co‐administration is associated with delayed elimination of plasma MTX in patients with HDMTX therapy. This drug interaction, however, cannot be explained solely by the inhibitory effects of PPIs on BCRP‐mediated MTX transport.
Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II)
Authors: Gehring U. , Strikwold M. , Schram‐Bijkerk D. , Weinmayr G. , Genuneit J. , Nagel G. , Wickens K. , Siebers R. , Crane J. , Doekes G. , Di Domenicantonio R. , Nilsson L. , Priftanji A. , Sandin A. , El‐Sharif N. , Strachan D. , Van Hage M. , Von Mutius E. , Brunekreef B. ,   and the ISAAC Phase Two Study Group
Published: September 2008

SummaryBackground
Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent.Objectives
To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries.Methods
Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi‐centre cross‐sectional study of 840 children aged 9–12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end‐points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen‐specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure.Results
Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29–0.96) for endotoxin levels per m2 of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64–0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever.Conclusion
These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.
Should children with a history of anaphylaxis to foods undergo challenge testing?
Authors: Vlieg‐Boerstra B. J. , Duiverman E. J. , Van Der Heide S. , Bijleveld C. M. A. , Kukler J. , Dubois A. E. J. 
Published: September 2008

SummaryBackground
Data on the frequency of resolution of anaphylaxis to foods are not available, but such resolution is generally assumed to be rare.Objective
To determine whether the frequency of negative challenge tests in children with a history of anaphylaxis to foods is frequent enough to warrant challenge testing to re‐evaluate the diagnosis of anaphylaxis, and to document the safety of this procedure.Methods
All children (n=441) who underwent a double‐blind, placebo‐controlled food challenge (DBPCFC) between January 2003 and March 2007 were screened for symptoms of anaphylaxis to food by history. Anaphylaxis was defined as symptoms and signs of cardiovascular instability, occurring within 2 h after ingestion of the suspected food.Results
Twenty‐one children were enrolled (median age 6.1 years, range 0.8–14.4). The median time interval between the most recent anaphylactic reaction and the DBPCFC was 4.25 years, range 0.3–12.8. Twenty‐one DBPCFCs were performed in 21 children. Eighteen of 21 children were sensitized to the food in question. Six DBPCFCs were negative (29%): three for cows milk, one for egg, one for peanut, and one for wheat. In the positive DBPCFCs, no severe reactions occurred, and epinephrine administration was not required.Conclusions
This is the first study using DBPCFCs in a consecutive series of children with a history of anaphylaxis to foods, and no indications in dietary history that the food allergy had been resolved. Our study shows that in such children having specific IgE levels below established cut‐off levels reported in other studies predicting positive challenge outcomes, re‐evaluation of clinical reactivity to food by DBPCFC should be considered, even when there are no indications in history that anaphylaxis has resolved. DBPCFCs can be performed safely in these children, although there is a potential risk for severe reactions.
Changes in adiponectin multimer distribution in response to atorvastatin treatment in patients with type 2 diabetes
Authors: Von Eynatten M. , Liu D. , Bluemm A. , Schuster T. , Baumann M. , Lutz J. , Heemann U. , Dugi K. A. , Nawroth P. P. , Bierhaus A , Humpert P. M. 
Published: September 2008

SummaryObjective  Multimeric high molecular weight (HMW) forms of adiponectin were previously shown to be inversely associated with the extent of atherosclerosis in males and are down‐regulated in patients with the metabolic syndrome and type 2 diabetes. In this study, potential influences of atorvastatin therapy on adiponectin multimer distribution were studied in patients with type 2 diabetes.Design, patients and measurements  The effect of 40 mg atorvastatin on HMW, medium molecular weight (MMW), and low molecular weight (LMW) isoforms of adiponectin were investigated in 75 patients (23 females; 52 males) with type 2 diabetes in an 8‐week‐long, placebo‐controlled and randomized study. Adiponectin multimeric isoforms were detected by Western blot analysis.Results  After atorvastatin therapy the median serum concentration of HMW adiponectin increased significantly by 42·3% (1·68 vs. 2·39 µg/ml; P < 0·001), while concentrations of MMW adiponectin and LMW adiponectin significantly decreased by 20·8% and 23·2%, respectively (MMW: 3·31 vs. 2·62 µg/ml, P = 0·047; LMW: 0·56 vs. 0·43 µg/ml, P = 0·033). Median total adiponectin levels were not significantly altered by atorvastatin treatment (6·0 vs. 6·2 µg/ml, P = 0·898). Consequently, the HMW : total‐adiponectin ratio significantly increased by 25·0% (0·40 vs. 0·50; P = 0·013).Conclusions  Atorvastatin therapy is associated with significant changes in adiponectin multimer distribution in patients with type 2 diabetes. Since total adiponectin levels were not affected by intervention, atorvastatin may shift adiponectin size towards the HMW form.
Characterization of the recognition and functional heterogeneity exhibited by cytokine‐induced killer cell subsets against acute myeloid leukaemia target cell
Authors: Linn Yeh C. , Lau Siew Kee J. , Liu Bee H. , Ng Lee H. , Yong Hao X. , Hui Kam M. 
Published: September 2008

SummaryThe polyclonal cytokine‐induced killer (CIK) cells exhibit potent cytotoxicity against a variety of tumour cells including autologous and allogeneic acute myeloid leukaemic (AML) targets. At maturity, three lymphocyte subsets: CD3− CD56+, CD3+ CD56− and CD3+ CD56+, constitute the bulk of the CIK cell culture. The CD3− CD56+ subset behaves like classical natural killer (NK) cells where cytotoxicity is potentiated by blocking the human leucocyte antigen Class I molecules in the AML targets. Both the CD3+ CD56+ and CD3+ CD56− subsets, though known to kill autologous and allogeneic targets to a comparable degree and therefore non‐major histocompatibility complex (MHC)‐restricted, nevertheless require the presence of the MHC molecule on the target, which interacts with their CD3–T‐cell receptor complex. Although CIK cells are often termed ‘NK‐like’ T cells, we have demonstrated that the well‐characterized NK receptors KIR, NKG2C/E, NKG2D and DNAM‐1 are not involved in the process of AML recognition for the CD3+ CD56− and CD3+ CD56+ subsets. The CD3+ CD56+ and CD3+ CD56− subsets express a polyclonal and comparable TCRVβ repertoire in a Gaussian distribution. The CD3+ CD56+ subset kills AML targets more efficiently than its CD3+ CD56− counterpart because of the presence of a higher proportion of CD8+ cells. The CD3+ CD56+ subset comprise more terminally differentiated late effector T cells that bear the CD27+ CD28− or CD27− CD28− phenotype, with a higher granzyme A content. In comparison, the phenotype of the CD3+ CD56− subset is consistent with early effector T cells that are CD27+ CD28+ and CD62L+, known to be less cytotoxic but possess greater proliferative potential.
Toll‐like receptor ligand activation of murine bone marrow‐derived dendritic cells
Authors: Dearman Rebecca J. , Cumberbatch Marie , Maxwell Gavin , Basketter David A. , Kimber Ian 
Published: September 2008

SummaryDendritic cells (DCs) are required for the initiation of primary immune responses. The pattern of Toll‐like receptor (TLR) expression on various subsets of these cells has been shown to differ, suggestive of distinct roles in influencing immune responses. We have examined here the responses of immature DCs derived from murine bone marrow (BMDCs) to a range of TLR ligands. BMDCs cultured for 6 days in the presence of granulocyte–macrophage colony‐stimulating factor were stimulated for 24 hr with ligands to TLR1‐2 [Pam3Cys‐Ser‐(Lys)4 (PAM)], TLR2‐6 (macrophage‐activating lipopeptide‐2 (MALP‐2); zymosan or peptidoglycan (PG)], TLR3 (polyinosinic‐polycytidylic acid), TLR4 [lipopolysaccharide R515 (LPS)], TLR5 (flagellin), TLR7 (polyuridylic acid) and TLR9 [CpG ODN2395 (CpG)]. DC activation was monitored using membrane marker expression and analysis of culture supernatants for cytokine/chemokine release. Ligands to TLR3 and TLR7 failed to activate BMDCs. All other TLR ligands caused elevated expression of membrane markers. PAM, MALP‐2 and LPS induced high‐level expression of proinflammatory cytokines and chemokines. Treatment with CpG was associated with a preferential type 1 cytokine and chemokine profile. Zymosan and PG were proinflammatory but also skewed towards a type 2 pattern of cytokines and chemokines. In contrast, flagellin did not cause marked secretion by BMDCs of cytokines or chemokines. These data for BMDCs are largely consistent with the reported TLR repertoire of freshly isolated murine Langerhans cells. In addition, murine BMDCs show selective responses to TLR ligands with respect to general activation, with differentiated cytokine patterns suggestive of potential priming for divergent immune responses.
Polymorphism of HLA‐DRB1, ‐DQB1 and ‐DPB1 genes in Bai ethnic group in southwestern China
Authors: Hu W. , Tang L. , Wang J. , Wang B. , Li S. , Yu H. , Tang W. , Li H. , Tan S. , Shou W. , Xiao C. 
Published: September 2008

AbstractIn this work, polymorphism of human leukocyte antigen (HLA)‐DRB1, ‐DQB1 and ‐DPB1 genes was detected using polymerase chain reaction–sequence‐based typing method in 128 healthy unrelated volunteers from the Bai ethnic group of Yunnan province of southwest China. Among all the 28 alleles detected for the DRB1 gene, the most common allele was DRB1*120201 with a frequency of 16.41%, followed by DRB1*090102, DRB1*080302, DRB1*1404, DRB1*150101, DRB1*140101 and DRB1*160201, with frequencies of 10.16%, 9.77%, 9.38%, 8.98%, 8.59% and 8.21%, respectively. Among 19 DQB1 alleles detected, the most frequent allele was DQB1*030101/0309 (35.94%), followed by DQB1*050201 (11.33%), DQB1*060101/060103 (10.54%) and DQB1*0401 (10.16%). For the DPB1 locus, the most common alleles were DPB1*0501 (42.19%), DPB1*1301 (13.28%), DPB1*020102 (10.93%) and DPB1*040101 (9.77%). The comparison of HLA class II allele frequencies of Bais with those of other Chinese populations suggested that the Bai ethnic group belonged to the southern group of Chinese.
Influences on medical students' decisions to study at a rural clinical school
Authors: Spencer Ryan J. , Cardin Anthony J. , Ranmuthugala Geetha , Somers George T. , Solarsh Barbara 
Published: September 2008

AbstractObjective:  To identify factors that influenced medical students at Monash University to undertake their first year of clinical training (third year of the medical course) at a rural clinical school (RCS). Design:  Third‐year Monash University medical students undertaking clinical placements at a RCS were surveyed in 2005. A semistructured questionnaire was used to ask students to rate the influence of a list of factors on their decision to undertake their year‐long placement at a RCS. Results:  Under half (48%) of students studying at an RCS reported that they were of rural background. All surveyed items were identified as having had a positive influence. Greater clinical experience, learning opportunities and patient access were identified as having the greatest positive influence followed closely by free accommodation and other financial and supportive incentives. Future rural career intention was eight times more likely to be a positive influence in rural compared with urban background students. Conclusion:  The most important positive influence on Monash third‐year medical students' decision to study at an RCS is the perception of high‐quality clinical experiences and education. This perception arises from rural exposure during pre‐clinical years.
Geographical variation of incidence of cutaneous melanoma in Queensland
Authors: Buettner Petra Gertraud , MacLennan Robert 
Published: September 2008

AbstractObjective:  The study investigated geographical differences and time trends of incidence rate and body site distribution of cutaneous melanoma in Queensland. Design:  Analysis of data recorded by Queensland Cancer Registry. Patients:  Analysis included 34 021 patients with invasive and 10 710 patients with in situ melanoma diagnosed between 1982 and 2002.Main outcome measures:  Age‐standardised incidence rates (world standard population) per 100 000 inhabitants of cutaneous melanoma and annual percentage change (APC). Results:  Yearly age‐standardised incidence rates of invasive melanoma averaged over the 21 years of observation were highest in the south‐eastern part of the state, notably in the statistical division Moreton for men (54.2) and in Fitzroy for women (51.4). Inland divisions had on average lower rates than coastal areas. For both men and women, age‐standardised incidence rates of invasive and of in situ melanoma increased between 1982 and 2002 for Queensland as a whole and for almost all its statistical divisions. For invasive cancer, the increase was strongest for Moreton (APC men: 5.4%; women: 4.5%; P < 0.001, respectively). APCs were higher for in situ melanoma compared with invasive melanoma for all statistical divisions and both genders. In both genders, the increase in invasive rates was most pronounced for the trunk (APC men: 3.2%, P = 0.040; women: 2.3%; P = 0.306).Conclusions:  The south‐eastern corner of Queensland endured the main burden of melanoma. Behavioural and lifestyle choices might create the observed differences between statistical divisions. The increase in trunk melanomas is discussed with respect to aetiology.
IgG subclass distribution, affinity of anti‐myeloperoxidase antibodies in sera from patients with Wegener's granulomatosis and microscopic polyangiitis
Authors: LIU LI‐JUN , CHEN MIN , YU FENG , ZHAO MING‐HUI , WANG HAI‐YAN 
Published: September 2008

SUMMARY:Aim:  Our previous study suggested that patients with MPO‐ANCA (myeloperoxidase antineutrophil cytoplasmic autoantibodies)‐positive Wegener's granulomatosis (WG) were common in Chinese, indicating that patients with MPO‐ANCA could manifest as either WG or microscopic polyangiitis (MPA). The aim of this study was to compare the immunological characteristics of MPO‐ANCA in patients with WG and MPA.Methods:  Fifteen patients with WG and 21 patients with MPA were enrolled in the current study. Anti‐MPO IgG subclasses and their titres were detected by antigen‐specific enzyme‐linked immunosorbent assays (ELISA); affinity was assessed by antigen‐inhibition ELISAs. The sera from all patients were employed to inhibit biotin conjugated affinity‐purified human anti‐MPO antibodies (Probe‐biotin), from plasma exchange of a patient with MPA, in a competitive inhibition ELISAs system.Results:  All four anti‐MPO subclasses could be detected in sera from patients with WG and MPA. The titres of anti‐MPO IgG4 subclass in patients with WG were significantly higher than those with MPA (1:1878 vs 1:218, P < 0.005). The affinity constants of MPO‐ANCA were comparable between patients with WG and MPA (0.3–70/M vs 0.3–140/M respectively). Eleven out of the 15 sera and 18 out of the 21 sera could inhibit the binding of the Probe‐biotin in patients with WG and MPA respectively. The average inhibition rate was 47.7% ± 11.5% and 61.7% ± 14.5% respectively (P < 0.05).Conclusion:  MPO‐ANCA IgG4 subclass might play a role in the development of WG. The MPO‐ANCA in WG and MPA might recognize overlapping but different epitopes on native MPO molecule. The difference in immunological characteristics of MPO‐ANCA might contribute to different disease entities.
Facial wrinkles as a predictor of decreased renal function
Authors: PARK BYUNG‐HYUN , LEE SIK , PARK JIN‐WOO , KIM KYUNG‐AH , KIM HAN‐UK , LEE JU‐HYUNG , KOH DAI‐HA , YOUM JUNG‐HO , YOO NINA , PARK SUE‐KYUNG , KWON KEUN‐SANG 
Published: September 2008

SUMMARY:Aims:  Oxidative stress generated either by exogenous or endogenous sources can lead to progressive organ damage and skin ageing over a long period of time. Moreover, some dermatological signs are independent of chronological ageing, and may reflect the long‐term redox state of internal organs. Therefore, we hypothesized that there might be an association between facial wrinkles and decreased renal function, an oxidative stress‐related disease.Methods:  A cross‐sectional study was carried out in a Korean population of 264 adults aged 30 years and older. Facial wrinkle scores in the crow's‐foot area were estimated using a standardized form of visual assessment. As an index of renal function, we determined estimated glomerular filtration rate (eGFR). Lipid hydroperoxide (LPO) assay was performed to measure the levels of oxidative stress.Results:  After adjusting for possible confounders, lower eGFRs and higher LPO levels were found in those with severe facial wrinkles.Conclusion:  We conclude that severe facial wrinkles might be used as a predictive marker of decreased renal function, independently of age, gender and other established risk factors.
Molecular analysis of the SMN and NAIP genes in Iranian spinal muscular atrophy patients
Authors: Omrani Omid , Bonyadi Morteza , Barzgar Mohammad 
Published: September 2008

AbstractBackground:  Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal cord anterior horn cells, leading to muscular atrophy. SMA is clinically classified into three subgroups based on the age of onset and severity. The majority of patients with SMA have homozygous deletions of exons 7 and 8 of the survival motor neuron (SMN) gene. The purpose of the present study was to determine the frequency of SMN and neuronal apoptosis inhibitory protein (NAIP) gene deletions in Iranian SMA patients. Experience in prenatal diagnosis of SMA in this population is also reported.Methods:  To study the frequency of deletions of SMN and NAIP genes in an Iranian sample group, 75 unrelated SMA patients (54 type I, eight type II and 13 type III) were analyzed according to the methods described by van der Steege et al and Roy et al.Results:  Homozygous deletion of SMN1 exons 7 and/or 8 were identified in 68 out of 75 patients (90%). Deletion of exon 5 of the NAIP gene was found in 40/54 of type I, 2/8 of type II and 1/13 of type III patients.Conclusions:  Deletion of the SMN1 gene is a major cause of SMA in Iran, and NAIP gene deletions were common in the present patients with type I SMA. Also, the incidence of NAIP deletion is higher in more severe SMA.