bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression in germinated cysts of Phytophthora nicotianae
Authors: SHAN WEIXING , MARSHALL JERRY S. , HARDHAM ADRIENNE R. 
Published: July 2004

SUMMARYThe life cycle of Phytophthora species contains several distinct asexual developmental stages that are important for plant infection and disease development. These include vegetative growth of filamentous hyphae, production of multinucleate sporangia, motile, uninucleate zoospores and germinated cysts, the stage at which plant colonization is initiated. To understand mechanisms regulating molecular and cellular processes in germinated cysts, differential hybridization analysis of a cDNA library was used to identify genes up‐regulated after cyst germination in P. nicotianae. Arrays of 12 288 random cDNA clones derived from a germinated cyst cDNA library were screened with 32P‐labelled cDNA probes synthesized from mRNA isolated from four different developmental stages and tobacco tissues infected with P. nicotianae. The resultant expression profiles for each cDNA clone led to the identification of over 300 clones showing up‐regulated expression in germinated cysts compared with the other three stages. Sequencing of the 5′ end of 382 selected clones yielded 355 sequences representing 146 putative unigenes. Sequence analysis revealed similarities to genes encoding proteins involved in energy production, protein biosynthesis, signalling, cell‐wall biogenesis and transcription regulation. Novel genes putatively involved in cell adhesion, cell‐wall biogenesis and transcriptional regulation were identified. Thirty‐one cDNA clones were analysed by Northern blotting and for 28 the pattern of expression in the Northern blots was the same as that indicated by the macroarray screening, verifying the fidelity of the colony hybridization data.
Fungal dimorphism regulated gene expression in Ustilago maydis: II. Filament down‐regulated genes
Authors: GARCÍA‐PEDRAJAS MARÍA D. , GOLD SCOTT E. 
Published: July 2004

SUMMARY Ustilago maydis displays dimorphic growth alternating between a budding haploid form and a filamentous dikaryon resulting from mating of two haploid cells. This morphological switch plays a critical role in pathogenicity because only the filamentous dikaryon can infect corn plants. Previously, we identified a role for the cAMP signal transduction pathway in dimorphism and pathogenicity. The repression of a subset of genes in filamentous cells may be critical for programming virulence. To identify these filament down‐regulated genes and to understand better the role of wild‐type budding cells in the life and disease cycle of U. maydis in nature, we used suppression subtractive hybridization. We arrayed a library of approximately 5500 cDNA clones and showed by reverse Northern blot analysis that most, as expected, are down‐regulated during filamentous growth. By an iterative sequencing and hybridization process to eliminate previously determined sequences, we showed that > 88% of the clones detected as differential in the reverse Northern blot screening harbour sequences corresponding to 48 different genes. Differential expression was confirmed for 37 of these genes by Northern blot analysis. For eight of these confirmed differential genes, expression could only be detected in budding cells. For genes expressed in both growth forms, levels of differential expression varied from as much as 65‐fold to only two‐fold higher levels in budding cells. Twenty‐seven of the 37 genes confirmed to be differential had similarity to database sequences, and fell into several putative functional categories. In future studies we will produce deletion mutants in several highly differentially expressed genes to study their roles in morphogenesis and pathogenesis.
Identification of a lipopolysaccharide responsive erk‐like MAP kinase in tobacco leaf tissue
Authors: PIATER LIZELLE ANN , NÜRNBERGER THORSTEN , DUBERY IAN A. 
Published: July 2004

SUMMARYLipopolysaccharides (LPS) are indispensable cell surface components of Gram‐negative bacteria and have diverse roles in plant–microbe interactions. Treatment of Nicotiana tabacum with the LPS of an endophytic strain of Burkholderia cepacia results in an enhanced defensive capacity in the tissue. In this study the rapid and transient phosphorylation of an extracellular signal‐regulated (ERK)‐like mitogen‐activated protein (MAP) kinase in response to LPS from B. cepacia (LPSB.cep.) elicitation is reported. Based on in‐gel kinase assays it was found that this 43‐kDa LPSB.cep.‐responsive kinase is optimally activated following 7 min elicitation with 100 µg/mL LPS. Its identity as an ERK MAPK was supported by tyrosine‐phosphorylated association with induction, immunodetection with pTEpY‐specific MAPK antibodies and inhibition of phosphorylation by U0126, an upstream MAPKK inhibitor. The kinase utilized myelin basic protein, but not casein or histone, as substrate. Ca2+ did not modulate the phosphorylation, nor did wounding. To date, other MAP kinases have been shown to act either independently or upstream from reactive oxygen intermediates produced during the oxidative burst. It was found that hydrogen peroxide is either not generated in leaf tissue in response to LPS elicitation or, if generated, does not trigger the phosphorylation of the kinase. Physicochemical characterization of the ERK‐like MAPK indicated a molecular mass of 43 kDa and a pI of 6.3; two‐dimensional gel analysis indicated two charge isomers. This is the first demonstration of such an LPS‐responsive MAP kinase phosphorylation in plants.
Risk of vascular disease in adults with diagnosed coeliac disease: a population‐based study
Authors: West J. , Logan R. F. A. , Card T. R. , Smith C. , Hubbard R. 
Published: July 2004

SummaryBackground : It has been suggested that vascular disease mortality may be reduced in coeliac disease because of lower levels of blood pressure, cholesterol and body mass.Aim : To examine whether people with coeliac disease are at reduced risk of various vascular diseases.Methods : We identified 3790 adults with diagnosed coeliac disease and 17 925 age‐ and sex‐matched controls in the General Practice Research Database. We estimated odds ratios for diagnosed hypertension, hypercholesterolaemia and atrial fibrillation and hazard ratios for myocardial infarction and stroke.Results : Adults with coeliac disease, compared with controls, were less likely to have had a diagnosis of hypertension [11% vs. 15%, odds ratio 0.68 (95% confidence interval: 0.60–0.76)] or hypercholesterolaemia [3.0% vs. 4.8%, odds ration 0.58 (95% confidence interval: 0.47–0.72)] but slightly more likely to have had atrial fibrillation [2.1% vs. 1.7%, odds ratio 1.26 (95% confidence interval: 0.97–1.64)]. The hazard ratio for myocardial infarction was 0.85 (95% confidence interval: 0.63–1.13), while the hazard ratio for stroke was 1.29 (95% confidence interval: 0.98–1.70).Conclusions : Although rates of myocardial infarction and stroke were not substantially different, adults with coeliac disease do have a lower prevalence of hypertension and hypercholesterolaemia compared with the general population. The effect of a gluten‐free diet on cardiovascular risk factors should be determined before any screening programmes for coeliac disease are instituted.
Azathioprine dose escalation in inflammatory bowel disease
Authors: Rayner C. K. , Hart A. L. , Hayward C. M. M. , Emmanuel A. V. , Kamm M. A. 
Published: July 2004

SummaryBackground : Forty per cent of patients with inflammatory bowel disease fail to respond to standard dose azathioprine (2 mg/kg/day).Aims : To evaluate the efficacy and safety of increasing the azathioprine dose according to a fixed schedule and guided by clinical response and adverse effects.Methods : We reviewed the records of all patients with inflammatory bowel disease treated by a single clinician over 6 years, unresponsive to at least 3 months treatment with standard dose azathioprine, and whose dose was subsequently increased.Results : Forty patients (27 male; 24 Crohn's, 16 ulcerative colitis) with chronic active disease or recurrent flares despite standard dose azathioprine for a median 8 months (range 3–114) increased their dose from a median 2.02 (1.61–3.19) mg/kg/day to 2.72 (2.37–3.99) mg/kg/day in one to four increments of 0.5 mg/kg/day, and were followed over a median6 (0.5–54) months. Eleven of the 40 patients (seven Crohn's, four ulcerative colitis) responded or had reduced frequency of flare‐ups at the end of follow‐up, while 17 of the 40 patients had no benefit. Response was more likely for maximum doses ≤2.5 mg/kg/day (six of 11 patients) than for doses >2.5 mg/kg/day (five of 29 patients) (P = 0.042). Twelve patients (11 of whom received maximum doses >2.5 mg/kg/day) were unable to maintain an increased azathioprine dose because of leukopenia in eight, nausea in three, and raised liver enzymes in one (all transient and reversible).Conclusions : Increasing the azathioprine dose up to 2.5 mg/kg/day appears beneficial in patients who have not responded to 2 mg/kg/day. Further increase above 2.5 mg/kg/day is less likely to be efficacious, and is associated with a substantial risk of adverse reactions.
Clinical and histological features of non‐alcoholic fatty liver disease in Hong Kong Chinese
Authors: Wong V. W.‐S. , Chan H. L.‐Y. , Hui A. Y. , Chan K.‐F. , Liew C.‐T. , Chan F. K.‐L. , Sung J. J.‐Y. 
Published: July 2004

SummaryBackground: Non‐alcoholic fatty liver disease is prevalent in affluent countries and is a cause of cirrhosis and possibly hepatocellular carcinoma.Aim: To examine the clinical and histological features of biopsy‐proven non‐alcoholic fatty liver disease and investigate the predictors of severe histological disease in Chinese patients.Methods: Electronic records of all patients (n = 247) who underwent liver biopsy between 1996 and 2003 in our hospital were retrieved. Patients who had histological features of non‐alcoholic fatty liver disease were identified. The demographic, clinical, laboratory and histological (Brunt's criteria) parameters of these patients were analysed.Results: Forty‐two patients had histology‐proven non‐alcoholic fatty liver disease. The median age was 47 years (range 23–69). All except one patient had features of metabolic syndrome. The median alanine aminotransferase was 93 (range 24–270) IU/L. Thirty‐six (85.7%) patients had steatohepatitis and 11 (26.1%) also had fibrosis. Only one patient had stage 3 fibrosis. The presence of diabetes mellitus predicted higher grade steatohepatitis and fibrosis (P = 0.019) whereas alanine aminotransferase level had no correlation with histological severity of steatohepatitis. After a median follow‐up of 42 months, no patient developed hepatic decompensation.Conclusions: Most Chinese patients with non‐alcoholic fatty liver disease had features of the metabolic syndrome. Histological activity was generally mild. Diabetes mellitus was the most important predictor of severe histological disease.
Masking of 13C urea breath test by proton pump inhibitors is dependent on type of medication: comparison between omeprazole, pantoprazole, lansoprazole and esomeprazole
Authors: Levine A. , Shevah O. , Shabat‐Sehayek V. , Aeed H. , Boaz M. , Moss S. F. , Niv Y. , Avni Y. , Shirin H. 
Published: July 2004

SummaryBackground : The need to withhold acid suppression therapy while awaiting urea breath test results is a common clinical problem in symptomatic patients. It is unclear at present if the dose or type of proton pump inhibitor or the type of test meal govern the apparent masking effect of proton pump inhibitors on the urea breath test.Aim : To prospectively evaluate Helicobacter pylori detection rates during treatment with four different proton pump inhibitors, utilizing a high‐dose citric acid‐based 13C urea breath test.Methods : Patients positive for Helicobacter pylori by urea breath test were randomized to receive either omeprazole 20 mg/day, pantoprazole 40 mg/day, lansoprazole 30 mg/day or esomeprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 of treatment.Results : One hundred and seventy‐nine patients, mean age 45.8 ± 16.8, completed the study. Treatment with omeprazole or pantoprazole prior to urea breath test (UBT) was associated with low false negative results, while lansoprazole and esomeprazole caused clinically unacceptable high false negative rates (pantoprazole 2.2% vs. lansoprazole 16.6%, P = 0.02, vs. esomeprazole 13.6%, P = 0.05; omeprazole 4.1% vs. lansoprazole 16.6%, P = 0.05).Conclusions : Proton pump inhibitor‐induced false negative results on high‐dose citric acid based urea breath test vary with the type of proton pump inhibitor used. Selection of the appropriate test meal and proton pump inhibitor may allow symptomatic individuals to continue their proton pump inhibitors prior to performing a urea breath test.
Treatment of acute hepatitis C with interferon α‐2b: early initiation of treatment is the most effective predictive factor of sustained viral response
Authors: Delwaide J. , Bourgeois N. , Gérard C. , De Maeght S. , Mokaddem F. , Wain E. , Bastens B. , Fevery J. , Géhénot M. , Le Moine O. , Martinet J. P. , Robaeys G. , Servais B. , Van Gossum M. , Van Vlierberghe H. ,   the Belgian Association for the Study of the Liver (BASL)
Published: July 2004

SummaryAim : To evaluate the efficacy of early interferon α‐2b in non‐post‐transfusion acute hepatitis C virus: a prospective study with historical comparison.Patients : Group A: 28 patients prospectively treated for acute hepatitis C virus with daily regimen of interferon 5 million units for 2 months. Group B: historical series of 16 patients with untreated acute hepatitis C virus.Results : There was no significant difference between the two groups with regard to gender, age, icterus, alanine aminotransferase, or genotypes. In group B, hepatitis spontaneously resolved in three of 16 (19%) patients (follow‐up 1–7 years). In group A, 21 of 25 patients became sustained viral responders (75%; P = 0.0003 vs. group B). Factors include not predictive of sustained viral response: age, gender, sources of infection, presence of icterus, alanine aminotransferase peak, bilirubin peak, incubation period, presence of hepatitis C virus antibodies at presentation, or genotypes. The time from presentation to the start of therapy was, however, significantly shorter in sustained viral responders (43 ± 31 days) than in relapsers or non‐responders (88 ± 52 days) (P = 0.016).Conclusions : Early treatment of acute hepatitis C virus with interferon prevents chronicity. A short waiting time from presentation to treatment appears as the most relevant predictive factor for sustained response.
Therapeutic Arthritis Research and Gastrointestinal Event Trial of lumiracoxib – study design and patient demographics
Authors: Hawkey C. J. , Farkouh M. , Gitton X. , Ehrsam E. , Huels J. , Richardson P. 
Published: July 2004

SummaryBackground : Cyclooxygenase‐2 selective inhibitors were developed in order to reduce the incidence of life‐threatening gastrointestinal ulcer complications compared with non‐selective non‐steroidal anti‐inflammatory drugs. Previous outcomes studies have, variously, lacked power to investigate this endpoint, focused on broader outcomes, or been too small to quantify the influence of aspirin.Aim : To evaluate lumiracoxib, a novel cyclooxygenase‐2 selective inhibitor, vs. non‐selective non‐steroidal anti‐inflammatory drugs in an outcomes study of considerably increased size. This paper describes the study's methodology.Methods and patients : The Therapeutic Arthritis Research and Gastrointestinal Event Trial was a randomized, double‐blind, 52‐week study of lumiracoxib 400 mg once daily (two to four times the recommended dose for osteoarthritis) versus naproxen 500 mg twice daily or ibuprofen 800 mg three‐times daily in patients with osteoarthritis. Randomization was stratified for low‐dose aspirin use and age (≤ 64, 65–74, ≥ 75 years). The study was powered to investigate upper gastrointestinal ulcer complications (primary endpoint) in patients not taking aspirin and in the overall study population; other endpoints included cardiovascular, renal and hepatic measures.Conclusions : Therapeutic Arthritis Research and Gastrointestinal Event Trial was designed to provide definitive answers concerning the gastrointestinal safety of lumiracoxib, addressing the controversial issues arising from outcomes studies with other cyclooxygenase‐2 selective inhibitors.
Plasma levels of von Willebrand factor regulate ADAMTS‐13, its major cleaving protease
Authors: Mannucci Pier Mannuccio , Capoferri Cristina , Canciani Maria Teresa 
Published: July 2004

SummaryADAMTS‐13, the metalloprotease that disposes physiologically of the most thrombogenic multimers of von Willebrand factor (VWF), tends to be low in plasma when VWF is high. We evaluated the behaviour of these two proteins in naturally occurring, experimental and clinical situations associated with VWF levels spanning from undetectable to supranormal. ADAMTS‐13 was approximately 10% higher (and VWF 35% lower) in 65 healthy individuals of blood group O than in 65 individuals of groups A, B and AB. Thirty‐three patients with type 3 von Willebrand disease (VWD) with undetectable plasma VWF had approximately 35% higher levels of ADAMTS‐13 than a comparable group of healthy individuals with normal VWF. When VWF was raised to supranormal levels by desmopressin (DDAVP) in 10 healthy volunteers, ADAMTS‐13 decreased by approximately 20%, with no change of the protease in three patients with severe VWD who had no post‐DDAVP VWF rise. When VWF was raised from very low to normal levels by the infusion of VWF‐containing plasma concentrates in four patients with type 3 VWD and one with type 1 VWD plasma, ADAMTS‐13 decreased in parallel. These data show that throughout a large spectrum of plasma VWF levels there is a negative association between this protein and the activity of its major cleaving protease.
Haematogones in the peripheral blood of adults: a four‐colour flow cytometry study of 102 patients
Authors: Kroft Steven H. , Asplund Sheryl L. , McKenna Robert W. , Karandikar Nitin J. 
Published: July 2004

SummaryHaematogones have been extensively characterized in bone marrow, but not in the peripheral blood (PB). We studied 102 PB samples from adult patients with a sensitive flow cytometry method. Sixty‐six of 102 samples (65%) contained detectable haematogones, ranging from 0·01% to 1·3% of white blood cells (median 0·06%, mean 0·13%). Of 66 cases with complete blood count data, 51 had absolute haematogone counts of 0·00037–0·105 × 109/l (median 0·0054 × 109/l, mean 0·012 × 109/l). PB haematogones belonged exclusively to the most mature maturational stage. These findings have implications for PB analysis of minimal residual disease in acute lymphoblastic leukaemia and follicular lymphoma.
Fanconi anaemia and leukaemia – clinical and molecular aspects
Authors: Tischkowitz Marc , Dokal Inderjeet 
Published: July 2004

SummaryFanconi anaemia (FA) is an autosomal recessive chromosomal instability disorder, which is characterized by congenital abnormalities, defective haemopoiesis and a high risk of developing acute myeloid leukaemia and certain solid tumours. It can be caused by mutations in at least eight different genes. Molecular studies have established that a common pathway exists, both between the FA proteins and other proteins involved in DNA damage repair such as NBS1, ATM, BRCA1 and BRCA2. This review summarizes the general clinical and specific haematological features and the current management of FA. Recent molecular advances will also be discussed in the context of the cellular and clinical FA phenotype, with particular emphasis on the haematological aspects of the condition.
Identification of protein Sα gene mutations including four novel mutations in eight unrelated patients with protein S deficiency
Authors: Okada Hiromi , Takagi Akira , Murate Takashi , Adachi Tatsuya , Yamamoto Koji , Matsushita Tadashi , Takamatsu Junki , Sugita Kanji , Sugimoto Mitsuhiko , Yoshioka Akira , Yamazaki Tomio , Saito Hidehiko , Kojima Tetsuhito 
Published: July 2004

SummaryEight distinct and potentially causative mutations were identified in eight unrelated Japanese patients with protein S (PS) deficiency, by direct DNA sequencing of the protein Sα (PSα) gene‐specific polymerase chain reaction products of all 15 exons and exon/intron boundaries. There were five missense mutations, including two novel mutations (Cys80Tyr and Arg314His), and three showed a major impact on the expected gene products: novel mutations of a 5‐bp deletion (delCTCTG887:Cys206Stop) and a nonsense mutation (Glu208Stop), as well as a previously reported splice site (exon 10 +5 A→G) mutation. One of the patients showed compound heterozygosity for delCTCTG887 and 732A→G. Investigation for the cosegregation state of these two mutations with PS deficiency in the patient's family suggested that the delCTCTG887 mutation was responsible for the abnormal phenotype and that the 732A→G (Lys155Glu) mutation did not appear to play a key role. However, we also identified the same 732A→G (Lys155Glu) mutation in an unrelated patient with apparent PS deficiency with severe pulmonary embolism, and found that this mutation seemed to cosegregate with a PS‐deficient state in her family members. These data implied that unknown factor(s) other than the 732A→G mutation itself might influence phenotypic expression of PS status in different individuals.
Ocular presentation of primary central nervous system lymphoma: diagnosis and treatment
Authors: Hormigo Adília , Abrey Lauren , Heinemann Murk‐Hein , DeAngelis Lisa M. 
Published: July 2004

SummaryPrimary ocular lymphoma (POL), a lymphoma of the globe, is a restricted form of primary central nervous system lymphoma (PCNSL) that often progresses to the brain and meninges; frequently it is misdiagnosed until central nervous system (CNS) lymphoma develops. The optimal treatment has not yet been identified. We retrospectively reviewed the course and the treatment of POL in 31 patients. Seventeen patients were treated for isolated POL (group A) and 14 were treated only after CNS disease was diagnosed (group B). The treatment in both groups consisted of systemic chemotherapy, chemotherapy plus radiotherapy (RT) or RT alone. In group A, nine patients (53%) developed CNS progression and five (29%) had ocular recurrence. In group B, seven (50%) had CNS progression and three (21%) ocular relapse. To control for diagnostic lead time, median survival was calculated from initial ocular symptoms and was 60 months in group A and 35 months in group B (P < 0·05). Ocular lymphoma responds to a variety of therapies but treatment with chemotherapy and/or ocular radiotherapy (ORT) failed to prevent CNS progression. Patients whose ocular disease was identified and treated before CNS progression had a significantly improved survival.