bluuebunny/crossref_metadata_2025_split huggingface dataset:
SpA: web-accessible spectratype analysis: data management, statistical analysis and visualization
Authors: He Min , Tomfohr John K. , Devlin Blythe H. , Sarzotti Marcella , Markert M. Louise , Kepler Thomas B. 
Published: July 2005

Abstract
Summary: SpA is a web-accessible system for the management, visualization and statistical analysis of T-cell receptor spectratype data. Users upload data from their spectratype analyzers to SpA, which saves the raw data and user-defined supplementary covariates to a secure database. The statistical engine performs several data analyses and statistical summaries. The visualization engine displays spectratype histograms in a Java applet and in an image file suitable for download. All of these results are also saved to the database and remain accessible to the user. Additional statistical tools specific to the analysis of multiple spectratypes are also available through the SpA interface.
Availability: The service is freely accessible via the web at http://www.duke.edu/~kepler/spa.html. Additional technical support and specialized statistical analysis and consultation are available by arrangement with the authors and, depending on the service requested, may be subject to fee.
Contact: kepler@duke.edu
Distinct patterns of gene expression in hepatocellular carcinomas and adjacent non‐cancerous, cirrhotic liver tissues in rats fed a choline‐deficient, l‐amino acid‐defined diet
Authors: Uematsu Fumiyuki , Takahashi Masakazu , Yoshida Midori , Igarashi Maki , Watanabe Naoto , Suzuki Noriko , Abe Masayoshi , Rusyn Ivan , Floyd Robert A. , Nakae Dai 
Published: July 2005

Gene expression profiles of HCC and surrounding non‐cancerous tissues in rats fed a CDAA diet for 70 weeks, as well as normal liver tissues, were explored using an oligonucleotide microarray for 3757 genes. A total of 146 genes were identified as differentially expressed; the affected functions including metabolism, apoptosis, cell cycling, RNA splicing, Wnt signaling, reactive oxygen species‐induced stress, and fibro/cirrhogenesis. The genes were found to fit into four distinct expression patterns after classification by hierarchical and k‐means clustering procedures. Notably, genes within the same functional category tended to be found within the same cluster, thus gene functions appeared to be related to their expression patterns. For example, genes encoding receptors (Fisher's exact test, P < 0.01) and cytokines (Fisher's exact test, P < 0.05) were both enriched in a cluster characterized by low expression in HCC compared to their surrounding tissues. While some of the receptors in this cluster had cell‐proliferative potential, others are known to be growth‐suppressive. It was noted, however, that four of the 10 receptor genes encode G‐protein‐coupled receptors, for which growth‐suppressive potential has been reported. The seven growth factors in the same cluster included two fibroblast growth factors. The current findings suggest the possibility that genes differentially expressed in this multistep carcinogenic model may be classified into relatively few clusters according to their expression patterns, and that these clusters may be associated with gene functional categories. (Cancer Sci 2005; 96: 414 – 424)
Dyspepsia consulters and patterns of management: a population‐based study
Authors: AHLAWAT S. K. , RICHARD LOCKE G. , WEAVER A. L. , FARMER S. A. , YAWN B. P. , TALLEY N. J. 
Published: July 2005

SummaryBackground:  Although dyspepsia is common, management patterns in the United States are unknown.Aim:  To determine the pattern of dyspepsia evaluation and treatment over 20 years in a population‐based cohort, and test the hypothesis that the management was influenced by dyspepsia subgroup and gender.Methods:  The validated Bowel Disease Questionnaire was mailed to a random sample of Olmsted County, Minnesota residents (1988–1990). Of the 835 survey respondents, 213 subjects were identified as having dyspepsia according to Rome I Criteria. The medical chart of each dyspeptic subject who had not denied research authorization (n = 206) was reviewed to identify all episodes of care for dyspepsia symptoms 10 years before and 10 years after the date the Bowel Disease Questionnaire was completed. Of these 206 subjects (mean age 47 years, 48% female), 34% had ulcer‐like dyspepsia, 32% had dysmotility‐like dyspepsia, and 37% had reflux‐like dyspepsia.Results:  Nearly half (n = 98, 48%) had episodes of care for dyspepsia symptoms over 20 years. Of these 98 subjects, 49% had upper gastrointestinal endoscopy, 4% motility studies and 12% were tested for Helicobacter pylori. At the first visit of the episode of care closest to Bowel Disease Questionnaire completion, 72% were seen in primary care, 16% in emergency medicine and 2% in gastroenterology. In addition, 13% were referred to gastroenterology clinic within this episode. During the study period, 70% were given an ‘acid’ diagnosis, 7% a ‘motility’ diagnosis and 54% a ‘functional’ diagnosis; 78% received acid suppression agents (28% proton pump inhibitors), 18% psychotropic agents and 7% prokinetic agents. No significant association was found between gender and test usage, specialty referral or type of treatment, although women were three times less likely to receive proton pump inhibitors (odds ratio 3.3, 95% CI: 1.2–9.1). Symptom severity, frequency and pattern were risk factors for health care seeking in dyspepsia.Conclusions:  Delivery of care for dyspepsia was similar among dyspepsia subgroups and in men and women.
Systematic review and meta‐analysis: proton‐pump inhibitor treatment for ulcer bleeding reduces transfusion requirements and hospital stay – results from the Cochrane Collaboration
Authors: LEONTIADIS G. I. , SHARMA V. K. , HOWDEN C. W. 
Published: July 2005

SummaryBackground:  Proton‐pump inhibitors reduce re‐bleeding and surgical intervention, but not mortality, after ulcer bleeding.Aim:  To examine the effects of proton‐pump inhibitor treatment on transfusion requirements and length of hospital stay in patients with ulcer bleeding.Methods:  For the Cochrane Collaboration meta‐analysis of randomized‐controlled trials of proton‐pump inhibitor therapy for ulcer bleeding, outcomes of transfusion requirements and hospital stay were summarized, respectively, as mean (±s.d.) units transfused and hospital days. We calculated weighted mean difference with 95% confidence interval. We also performed subgroup analyses according to geographical origin of the randomized‐controlled trials.Results:  There was significant heterogeneity among randomized‐controlled trials for either outcome. Overall, proton‐pump inhibitor treatment marginally reduced transfusion requirements (WMD = −0.6 units; 95% CI: −1.1 to 0; P = 0.05) and length of hospitalization (WMD = −1.1 days; 95% CI: −1.5 to −0.7; P < 0.0001). Most of the randomized‐controlled trials did not state precise criteria for administering blood transfusion and discharging patients, thereby limiting the strength of conclusions on the pooled effects.Conclusions:  Proton‐pump inhibitor treatment for ulcer bleeding produces small, but potentially important, reductions in transfusion requirements and length of hospitalization.
Normal and leukaemic stem cells
Authors: Bonnet Dominique 
Published: July 2005

SummaryThe blood‐related cancer leukaemias were the first diseases where human cancer stem cells, or leukaemic stem cells (LSC), were isolated. The haematopoietic system is one of the best tissues for investigating cancer stem cells, because the developmental hierarchy of normal blood formation is well defined. Leukaemias can now be viewed as aberrant haematopoietic processes initiated by rare LSC that have maintained or reacquired the capacity for indefinite proliferation through accumulated mutations and/or epigenetic changes. Yet, despite their critical importance, much remains to be learned about the developmental origin of LSC and the mechanisms responsible for their emergence in the course of the disease. This report will review our current knowledge on normal and LSC development and examine the impact of these discoveries may have clinically and in our understanding of the leukaemogenic process.
High‐dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment‐related mortality in patients with multiple myeloma: results of a randomised study
Authors: Fenk R. , Schneider P. , Kropff M. , Huenerlituerkoglu A. N. , Steidl U. , Aul C. , Hildebrandt B. , Haas R. , Heyll A. , Kobbe G. ,   the West German Myeloma Study Group
Published: July 2005

SummaryWe conducted a randomised trial comparing an intensified versus a standard conditioning regimen for high‐dose chemotherapy followed by autologous stem‐cell transplantation in patients with multiple myeloma. In this study, 56 patients were randomly assigned for high‐dose therapy with melphalan 200 mg/m2 or with idarubicin 42 mg/m2, melphalan 200 mg/m2 and cyclophosphamide 120 mg/kg. The primary objective was response rate. Acute toxicity, mainly because of infections, was higher in the intensified treatment arm with a treatment‐related mortality of 20%versus 0% in the standard arm. This lead to the early discontinuation of the study. Response rates did not differ significantly between both treatment arms {intensified versus standard: complete response + near complete remission 50% [95% confidence interval (CI) 26–74%] vs. 33% (95% CI 17–55%), partial remission 35% (95% CI 16–61%) vs. 50% (95% CI 30–70%)}. After a follow‐up of 5 years, the median time‐to‐progression and overall survival were not significantly different between both patient groups. Analysis restricted to patients surviving the first 100 d after transplant showed a better outcome for patients with ≥2 bad prognostic risk factors in the intensified treatment arm, however all treatment‐related deaths occurred within this group of patients. In conclusion, intensified conditioning for high‐dose therapy had intolerably high toxicity without improving outcome in patients with multiple myeloma.
Rapid and specific detection of clinically significant haemoglobinopathies using electrospray mass spectrometry–mass spectrometry
Authors: Daniel Yvonne A. , Turner Charles , Haynes Roberta M. , Hunt Beverley J. , Neil Dalton R. 
Published: July 2005

SummaryIncreasing demand for population screening for the haemoglobinopathies gives rise to a requirement for high throughput systems, which allow for cost effective, rapid, sensitive and specific screening of clinically significant haemoglobins. We have developed a practical and efficient approach using tryptic digestion and electrospray triple quadrupole mass spectrometry–mass spectrometry (MSMS) in multiple reaction monitoring acquisition mode for the identification of the clinically important haemoglobin variants, S, C, DPunjab, OArab, and E. A total of 200 blood samples, comprising 52 haemoglobin AA, 57 AS (sickle cell trait), 44 AC (C trait), 16 SC (SC disease), 14 SS (sickle cell disease), 10 AE (E trait), 2 ADPunjab (DPunjab trait) and 1 each of AOArab (OArab trait), CC (C disease), DPunjabDPunjab (DPunjab disease), OArabOArab (OArab disease), and EE (E disease), have been analysed in parallel with existing phenotype and molecular methods. All haemoglobin variants were correctly identified by MSMS, with no false positives or false negatives. The system detects both heterozygotes and homozygotes and has potential applications in neonatal and antenatal screening.
Soluble syndecan‐1 level at diagnosis is an independent prognostic factor in multiple myeloma and the extent of fall from diagnosis to plateau predicts for overall survival
Authors: Lovell Richard , Dunn Janet A. , Begum Gulnaz , Barth Nicola J. , Plant Tim , Moss Paul A. , Drayson Mark T. , Pratt Guy ,   on behalf of the Working Party on Leukaemia in Adults (part of the National Cancer Research Institute Haematological Oncology Clinical Studies Group)
Published: July 2005

SummarySyndecan‐1 (CD138) is a heparin sulphate proteoglycan that is over expressed on the surface of both normal and malignant plasma cells and actively shed from the cell surface (soluble syndecan‐1). Soluble syndecan‐1 has been shown to be an independent prognostic factor in myeloma but its role in prognostic classification requires further investigation. We have retrospectively measured soluble syndecan‐1 in 324 presentation samples and 154 plateau phase samples from the UK Medical Research Council Myeloma VIth trial. Log‐rank analysis showed that the presentation value of soluble syndecan‐1 is a highly significant prognostic factor when assessing survival from entry (χ2 = 14·92,P < 0·0001) and remains an important independent prognostic factor when considered in Cox regression models (P ≤ 0·02) with known independent factors. The magnitude of fall in soluble syndecan‐1 from presentation to plateau also had prognostic value when assessing overall survival from plateau (χ2 = 3·79,P = 0·05). In conclusion, this large study confirms that soluble syndecan‐1 level is a powerful independent prognostic factor both at diagnosis and at plateau phase.
Genotype–phenotype correlation in MYH9‐related thrombocytopenia
Authors: Dong Fan , Li Sufeng , Pujol‐Moix Núria , Luban Naomi L. C. , Shin Sang Won , Seo Jae Hong , Ruiz‐Saez Arlette , Demeter Judit , Langdon Scott , Kelley Michael J. 
Published: July 2005

SummaryMutation of the non‐muscle myosin heavy chain type II‐A results in MYH9‐related hereditary macrothrombocytopenia (HMTC), including four autosomal dominant platelet disorders: May‐Hegglin anomaly (MHA), Sebastian (SBS), Fechtner (FS) and Epstein (EPS) syndrome. Denaturing high‐performance liquid chromatography (DHPLC) was optimised for rapid screening of the seven exons harbouring all but one of the previously reported mutations of MYH9. Individuals from 13 families with phenotypes suggestive of MYH9‐related HMTC were screened for mutations by DHPLC followed by direct sequencing of samples with aberrant column retention time. Mutations were identified in all 13 families. Six distinct missense heterozygous mutations were found in 10 families, including six families with MHA or SBS (E1841K, D1424N), three families with FS (R702H, R1165C, and D1424Y), and one family with EPS (S96L). A truncating mutation (R1933X) was found in three MHA families. A review of all published mutations suggests that mutation in the C‐terminal coiled coil region or truncation of the tailpiece is associated with haematological‐only phenotype, while mutation of the head ATPase domain frequently is associated with nephropathy and/or hearing loss. Mutations of other regions have intermediate expression of non‐haematological characteristics. Further study is required to confirm these associations and understand the molecular basis for this genotype–phenotype relationship.
The prognostic value of CD38 expression in chronic lymphocytic leukaemia patients studied prospectively at diagnosis: a single institute experience
Authors: Gentile Massimo , Mauro Francesca Romana , Calabrese Elisabetta , Propris Maria Stefania De , Giammartini Elena , Mancini Francesca , Milani Maria Laura , Guarini Anna , Foà Robin 
Published: July 2005

SummaryThe purpose of this study was to assess in chronic lymphocytic leukaemia (CLL) patients the prevalence and clinical impact of CD38 expression, evaluated prospectively at disease presentation, and to verify whether this parameter changes over time. In 242 consecutive and untreated CLL patients, the percentage of CD38+cases, according to the 7%, 20% and 30% cut‐off points, was 21%, 17% and 14%, respectively. Using the 7% threshold, CD38 positivity correlated with male sex, intermediate and high‐risk (Rai I–IV) disease, lower Hb and platelet levels, and higher lymphocyte count. Furthermore, patients with a CD38 expression ≥7% showed a significantly lower 3‐year probability of treatment‐free survival (TFS) than CD38−patients (P < 0·0001). At multivariate analysis, CD38 expression remained significantly associated to TFS, together with stage, lymphocyte count and morphology. Also, in the 146 patients with stage 0 CLL a CD38 expression ≥7% identified a subgroup of patients with a significantly lower 3‐year probability of TFS (P = 0·0005). Furthermore, this parameter did not change in 30 of 31 (97%) re‐evaluated patients. In conclusion, this study indicates that, when tested at diagnosis and on fresh material, a CD38 expression ≥7% is an important parameter for the identification of early CLL patients with more aggressive disease and that its expression remains stable over time.
Iron acquisition mechanisms of Flavobacterium psychrophilum
Authors: Møller J D , Ellis A E , Barnes A C , Dalsgaard I 
Published: July 2005

AbstractForty strains of Flavobacterium psychrophilum were tested for the production of siderophores using the universal Chrome Azurol S (CAS) assay. The majority of the strains (85%) were CAS positive (CAS+) and some (15%) were CAS negative (CAS−). The cryptic plasmid pCP1 was carried by all positive strains and was lacking from negative strains. While a weak catechol reaction was detectable in CAS+ culture supernatants, the CAS reaction was, to some extent, heat sensitive, questioning whether the positive reaction was caused only by siderophores. The ability to grow in vitro under iron‐restricted conditions did not correlate with the CAS reactivity, as growth of both CAS+ and CAS− strains was similarly impaired under iron restriction induced by 2,2 dipyridyl. Suppressed growth under these conditions was restored by addition of FeCl3, haemoglobin and transferrin for both CAS+ and CAS− strains.
Potential use of a Yersinia ruckeri O1 auxotrophic aroA mutant as a live attenuated vaccine
Authors: Temprano A , Riaño J , Yugueros J , González P , de Castro L , Villena A , Luengo J M , Naharro G 
Published: July 2005

AbstractThe aroA gene of Yersinia ruckeri, which encodes 5‐enolpyruvylshikimate 3‐phosphate synthase, was insertionally inactivated with a DNA fragment containing a kanamycin resistance determinant and reintroduced by allelic exchange into the chromosome of Y. ruckeri 21102 O1 by means of the suicide vector pIVET8. The Y. ruckeri aroA::Kanr mutant was highly attenuated when inoculated intraperitoneally into rainbow trout, with a 50% lethal dose of >5 × 107 CFU. The mutants were not recoverable from the internal organs 48 h post‐inoculation or later. The vaccination of rainbow trout with the AroA mutant as a live vaccine conferred significant protection (relative percentage survival = 90%) against the pathogenic wild‐type strain of Y. ruckeri.
European eels, Anguilla anguilla (L.), infected with Anguillicola crassus exhibit a more pronounced stress response to severe hypoxia than uninfected eels
Authors: Gollock M J , Kennedy C R , Brown J A 
Published: July 2005

AbstractThe parasite, Anguillicola crassus is a non‐native species that infects naive European eels, Anguilla anguilla, and causes pathological damage to the swimbladder, potentially compromising their ability to cope with hypoxic conditions. This study aimed to elucidate whether anguillicolosis exacerbates the stress responses to exposure to hypoxic water, conditions that have been implicated in mass mortalities of wild infected European eels. Blood parameters in infected and uninfected eels were measured during exposure to severe hypoxia over an 8‐h period. Infected fish showed significantly higher levels of plasma cortisol compared with uninfected eels after 4 h of hypoxia. Uninfected fish showed an almost twofold increase in plasma glucose after 8‐h exposure to hypoxia but infected fish showed no significant change, so that the plasma glucose concentration was significantly higher in uninfected eels than in infected eels. Both groups showed similar elevations in blood haematocrit, suggesting a similar catecholamine response in infected and uninfected eels. The lack of a hyperglycaemic response in infected eels, despite indirect evidence of a catecholamine response to hypoxia, may reflect an increase in glucose turnover. The data suggest that anguillicolosis results in a significantly greater corticosteroid stress response to hypoxia accompanied by a higher metabolic cost.
Different proteins bind to the butyrolactone receptor protein ARE sequence located upstream of the regulatory ccaR gene of Streptomyces clavuligerus
Authors: Santamarta Irene , Pèrez‐Redondo Rosario , Lorenzana Luis M. , Martìn Juan F. , Liras Paloma 
Published: July 2005

SummaryCell‐free extracts from Streptomyces clavuligerus, purified by elution from heparin‐agarose with an ARE‐containing DNA fragment or by salt elution chromatography, bind to a 26 nt ARE sequence, for butyrolactone receptor proteins (AREccaR). This sequence is located upstream of the ccaR gene, encoding the activator protein CcaR required for clavulanic acid and cephamycin C biosynthesis. The binding is specific for the ARE sequence as shown by competition with a 34 nt unlabelled probe identical to the ARE sequence. A brp gene, encoding a butyrolactone receptor protein, was cloned from S. clavuligerus. Sixty‐one nucleotides upstream of brp another ARE sequence (AREbrp) was found, suggesting that Brp autoregulates its expression. Pure recombinant rBrp protein binds specifically to the ARE sequences present upstream of ccaR and brp. A brp‐deleted mutant, S. clavuligerus Δbrp::neo1, produced 150–300% clavulanic acid and 120–220% cephamycin C as compared with the parental strain, suggesting that Brp exerts a repressor role in antibiotic biosynthesis. EMSA assays using affinity chromatography extracts from the deletion mutant S. clavuligerus Δbrp::neo1 lacked a high‐mobility band‐shift due to Brp but still showed a slow‐mobility band‐shift observed in the wild‐type strain. These results indicate that two different proteins bind specifically to the ARE sequence and modulate clavulanic acid and cephamycin C biosynthesis by its action on ccaR gene expression.
Weapons of mass retraction
Authors: Burrows Lori L. 
Published: July 2005

SummaryTwitching motility is a unique form of bacterial propulsion on solid surfaces associated with cycles of extension, tethering and retraction of type IV pili (T4P). Although investigations over the last two decades in a number of species have identified the majority of the genes involved in this process, we are still learning how these pili are assembled and the mechanics by which bacteria use T4P to drag themselves from one place to another. Among the puzzles that remain to be solved is the mechanism by which hydrolysis of ATP is coupled to pilus assembly and disassembly, and how the cell envelope structure is modified to accommodate the passage of the pilus through the periplasm. Unravelling of these and other enigmas in the T4P system will not only teach us more about these important colonization and virulence factors, but also help us to understand related processes such as type II secretion, which relies on a set of proteins homologous to those in the T4P system, and bacterial conjugation, involving retractable pili belonging to the F‐like subgroup of the type IV secretion family. This review focuses on recent discoveries relating to the assembly and function of T4P in generation of twitching motility.