bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of the nuclease domain of ribonuclease III from M. tuberculosis at 2.1 Å
Authors: Akey David L. , Berger James M. 
Published: September 2005

AbstractRNase III enzymes are a highly conserved family of proteins that specifically cleave double‐stranded (ds)RNA. These proteins are involved in a diverse group of functions, including ribosomal RNA processing, mRNA maturation and decay, snRNA and snoRNA processing, and RNA interference. Here we report the crystal structure of the nuclease domain of RNase III from the pathogen Mycobacterium tuberculosis. Although globally similar to other RNase III folds, this structure has some features not observed in previously reported models. These include the presence of an additional metal ion near the catalytic site, as well as conserved secondary structural elements that are proposed to have functional roles in the recognition of dsRNAs.
Systematic review: treatment of chronic hepatitis B virus infection by pegylated interferon
Authors: HUI A. Y. , CHAN H. L.‐Y. , CHEUNG A. Y.‐K. , COOKSLEY G. , SUNG J. J.‐Y. 
Published: September 2005

SummaryBackground:  Pegylated interferon‐α has been shown to be more efficacious than conventional interferon in treating chronic hepatitis C. The use of peginterferon in chronic hepatitis B virus infection with positive hepatitis B e antigen has also been tested in a number of trials since 2003.Aim:  To systematically summarize and compare the results of these studies.Methods:  Four studies were identified from PubMed, Medline and reference lists. Data from the trials were extracted and analysed. Where appropriate, combined odds ratio of different trials was calculated. Safety data including serious adverse events and emergence of drug‐resistant mutants were recorded.Results:  Three of the four trials contained predominantly Asian patients. Peginterferon is found to be superior to lamivudine monotherapy and induced sustained biochemical and virological responses in about one‐thirds of patients after 12 months of therapy. Coadministration of lamivudine did not result in improvement in viral suppression. Peginterferon appears to reduce the emergence of YMDD mutation in the combination treatment groups. It was well tolerated with serious adverse events reported in <10% of patients in most trials.Conclusions:  Peginterferon‐α treatment of at least 6 months should be considered as one of the first‐line therapeutic options for hepatitis B virus infection.
Variation in practice of ileal intubation among diverse endoscopy settings: results from a national endoscopic database
Authors: HAREWOOD G. C. , MATTEK N. C. , HOLUB J. L. , PETERS D. , LIEBERMAN D. A. 
Published: September 2005

SummaryBackground:  Terminal ileum intubation rates at colonoscopy are variable. One of the major indications for terminal ileum intubation is to identify Crohn's disease. Signs and symptoms which raise a suspicion of Crohn's include abdominal pain/bloating, anaemia and diarrhoea.Aim:  To determine the proportion of terminal ileal intubation in patients undergoing evaluation of abdominal pain/bloating, anaemia or diarrhoea with normal endoscopic findings at colonoscopy.Methods:  The Clinical Outcomes Research Initiative national endoscopic database was analysed to determine the proportion of terminal ileum intubation in patients undergoing evaluation of either abdominal pain/bloating, anaemia or diarrhoea with normal endoscopic findings at colonoscopy and to characterize this population of patients. Patients with known or suspected inflammatory bowel disease were excluded from the analysis.Results:  Between January 2000 and December 2003, 21 638 patients underwent complete colonoscopy for evaluation of either abdominal pain/bloating, anaemia or diarrhoea with normal colon findings. Overall, 3858 patients (18%) underwent terminal ileum evaluation. Intubation rates differed according to procedure indication: abdominal pain (13%), anaemia (13%), diarrhoea (28%). Terminal ileum assessment declined with advancing patient age and was least frequent in Black patients (12% vs. 18% in non‐Blacks, P < 0.0001). Ileal intubation rates also varied among endoscopy site types: community (17%), academic (21%), Veterans Affairs Medical Centres (17%), P < 0.0001. Multiple logistic regression identified patients with the indication of diarrhoea (OR: 2.58) as more likely to undergo terminal ileum intubation when compared with those with abdominal pain/bloating. Patients in Veterans Affairs (OR: 1.26) and academic (OR: 1.29) sites were more likely to undergo terminal ileum intubation compared with community sites.Conclusion:  Less than one‐fifth of patients with either abdominal pain/bloating, anaemia or diarrhoea underwent ileal intubation in the setting of a normal colonoscopy. Significant practice variation was observed in rates of terminal ileum evaluation. Further study is required to determine whether terminal ileum examination impacts patient management or outcome.
Socioeconomic gradient in use of statins among Danish patients: population‐based cross‐sectional study
Authors: Thomsen Reimar W. , Johnsen Søren P. , Olesen Anne V. , Mortensen Jens T. , Bøggild Henrik , Olsen Jørn , Sørensen Henrik T. 
Published: September 2005

AimsSocioeconomic inequalities in statin use are a public health concern but they may also confound observational studies of statins’ effectiveness. We conducted a population‐based cross‐sectional study in Denmark to examine the association between socioeconomic status (SES) and statin use.MethodsWe obtained data on socioeconomic status of all persons in North Jutland County, Denmark, between 1995 and 1999 from the Prevention Registry at Statistics Denmark. Data on filled statin prescriptions were identified through the County Prescription Database. We compared the 1‐year prevalence proportions of statin use for different socioeconomic groups, adjusted for age and urbanization. Separate analyses were done for patients with a history of cardiovascular disease as recorded in the County Hospital Discharge Registry.ResultsAmong men with cardiovascular disease, statin use in 1995 was higher in those with the highest socioeconomic status (adjusted relative prevalence proportion (RPP) among top managers 1.86, 95% CI: 1.17–2.96), and lower among retired men (RPP (95% CI) 0.63 [0.43–0.93] in old‐age pensioners, and 0.66 [0.45–0.98] in the early retired), when compared with basic‐level workers. The socioeconomic differences in statin use among men decreased in magnitude over time but remained throughout the study period. We found no clear social gradient in statin use among women.ConclusionsEven in a health care system that claims to ensure a high degree of equity in medical care, we found clear indications of a socioeconomic gradient in statin use among men in the years after the launching of these drugs.
Treatment‐related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992–2001
Authors: Christensen Merete Stubkjaer , Heyman Mats , Möttönen Merja , Zeller Bernward , Jonmundsson Gudmundur , Hasle Henrik ,   on behalf of the Nordic Society of Paediatric Haematology and Oncology (NOPHO)
Published: September 2005

SummaryDespite continuously more successful treatment of childhood acute lymphoblastic leukaemia (ALL), 2–5% of children still die of other causes than relapse. The Nordic Society of Paediatric Haematology and Oncology‐ALL92 protocol included 1652 patients ≤15 years of age with precursor B‐ and T‐cell ALL diagnosed between 1992 and 2001. Induction deaths and deaths in first complete remission (CR1) were included in the study. A total of 56 deaths (3%) were identified: 19 died during induction (1%) and 37 in CR1 (2%). Infection was the major cause of death in 38 cases. Five patients died of early death before initiation of cytotoxic therapy. Five patients died because of toxicity of inner organs and one of accidental procedure failures. Seven patients died of complications following allogenic haematopoietic stem cell transplantation (HSCT) in CR1. Girls were at higher risk of treatment‐related death (TRD) [relative risk (RR) = 2·2; 95% confidence interval (CI95%): 1·2–4·0, P < 0·01], mostly because of infections. Risk of TRD was also higher in children with Down syndrome (RR = 4·5; CI95%: 2·0–10·2, P < 0·00). In conclusion, 3% of children with ALL died of TRD, with bacterial infections as the most common cause of death. Girls and Down syndrome patients had a higher risk of TRD. Infections still remain a major challenge in childhood ALL.
The interactions between inflammation and coagulation
Authors: Esmon Charles T. 
Published: September 2005

SummaryInflammation initiates clotting, decreases the activity of natural anticoagulant mechanisms and impairs the fibrinolytic system. Inflammatory cytokines are the major mediators involved in coagulation activation. The natural anticoagulants function to dampen elevation of cytokine levels. Furthermore, components of the natural anticoagulant cascades, like thrombomodulin, minimise endothelial cell dysfunction by rendering the cells less responsive to inflammatory mediators, facilitate the neutralisation of some inflammatory mediators and decrease loss of endothelial barrier function. Hence, downregulation of anticoagulant pathways not only promotes thrombosis but also amplifies the inflammatory process. When the inflammation–coagulation interactions overwhelm the natural defence systems, catastrophic events occur, such as manifested in severe sepsis or inflammatory bowel disease.
Mannose-binding lectin 2 (MBL2) gene polymorphism in asthma and atopy among adults
Authors: Aittoniemi J , Soranummi H , Rovio A T , Hurme M , Pessi T , Nieminen M , Karjalainen J 
Published: September 2005

SummaryMannose-binding lectin (MBL) insufficiency due to polymorphisms in the MBL2 gene causes an opsonization defect, which has been connected to infections and atopy. We investigated the significance of MBL2 genotypes with regard to persistent asthma and atopy among adults. The genotypes were determined in 243 adults with persistent asthma and 400 controls. Atopy was determined by skin-prick test. As a result, the carriage of −221 base pairs (bp) promoter region variant allele X (nucleotide change G→C; alleles Y→X, respectively) causing low MBL expression proved to be a significant risk factor for asthma in non-atopic males [odds ratio (OR) = 2·52, 95% confidence interval (CI) = 1·23–5·15; P = 0·01]. Furthermore, the X-allele carriage was associated with the decrease in lung function (forced expiratory volume at 1 s, FEV1) during follow-up in the patients with asthma (P = 0·033), the effect being strongest for non-atopic asthmatics (P = 0·042). The MBL2 genotype had no clear effect on the occurrence of atopy in adults. In conclusion, our results abrogate the previously suggested predisposing effect of MBL insufficiency on atopy at least in adults. However, as MBL is a complement component participating in immune defence against microbes, and as in the pathogenesis of non-atopic asthma infectious agents are probably involved, the gene–environment interactions between MBL and infections should be assessed further with regard to asthma.
Neutrophilic granulocytes are the predominant cell type infiltrating pancreatic islets in contact with ABO-compatible blood
Authors: Moberg L , Korsgren O , Nilsson B 
Published: September 2005

Summary
The poor outcome of intraportal islet transplantation may be explained by the instant blood-mediated inflammatory reaction (IBMIR), characterized by islet entrapment in blood clots, leucocyte infiltration and disruption of islet morphology. Here we employ a newly developed in vitro system to identify the blood cells involved in this process. Islets were mixed with ABO-compatible blood in heparinized tubes and incubated for various times up to 6 h. Clots were analysed immunohistochemically for detection of platelets (CD41a), leucocytes/lymphocytes (CD11b), granulocytes (CD16, lysozyme), neutrophilic granulocytes (neutrophil elastase), eosinophilic granulocytes (NaCN + H2O2), macrophages (CD68), dendritic cells (CD209/DC-SIGN), B cells (CD20) and T cells (CD4, CD8). Platelets were rapidly deposited around the islets in contact with the blood, reaching a maximum by 30 min. The first neutrophilic granulocytes appeared in the islets after 15 min, increased at 1 h and peaked at 2 h. Small numbers of macrophages were found infiltrating the islets already after 5 min, with a slight increase over time. However, control stainings of cultured islets and pancreas biopsies identified these cells as being largely of donor origin. No T cells, B cells, dendritic cells or eosinophilic granulocytes were detected during the 6 h observation time. Neutrophilic granulocytes were identified as the main infiltrating blood cell in islets exposed to blood, implying that these cells play a key role in clinical islet transplantation. Because islets are known to be exquisitely susceptible to oxidative stress, development of drugs targeting neutrophilic cytotoxicity could markedly improve the outcome of islet transplantation.
The β1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2β protein ofTrypanosoma cruziassociate with a specific pattern of epitope recognition
Authors: Bergami P Lopez , Gómez K A , Levy G V , Grippo V , Baldi A , Levin M J 
Published: September 2005

SummaryBALB/c mice immunized with recombinant Trypanosoma cruzi ribosomal P2β protein (TcP2β) develop a strong and specific antibody response against its 13 residue-long C-terminal epitope (peptide R13: EEEDDDMGFGLFD) that has a concomitant β1-adrenergic stimulating activity. However, other animals that undergo similar immunizations seem tolerant to this epitope. To evaluate further the antibody response against the ribosomal P proteins, 25 BALB/c and 25 Swiss mice were immunized with TcP2β. From the 50 animals, 31 developed a positive anti-R13 response, whereas 19 were non-responsive. From the 31 anti-R13 positive mice, 25 had anti-R13 antibodies that recognized the discontinuous motif ExDDxGF, and their presence correlated with the recording of supraventricular tachycardia. The other six had anti-R13 antibodies but with a normal electrocardiographic recording. These anti-R13 antibodies recognized the motif DDxGF shared by mammals and T. cruzi and proved to be a true anti-P autoantibody because they were similar to those elicited in Swiss, but not in BALB/c mice, by immunization with the C-terminal portion of the mouse ribosomal P protein. Our results show that the recognition of the glutamic acid in position 3 of peptide R13 defines the ability of anti-R13 antibodies to react with the motif AESDE of the second extracellular loop of the β1-adrenergic receptor, setting the molecular basis for their pathogenic β1 adrenoceptor stimulating activity.
Improvement of herpetic stromal keratitis with fumaric acid derivate is associated with systemic induction of T helper 2 cytokines
Authors: Heiligenhaus A , Li H , Schmitz A , Wasmuth S , Bauer D 
Published: September 2005

SummaryFumaric acid derivates have been shown to stimulate T helper-2-cytokines (interleukin (IL)-4, -5) without affecting the T-helper-1-cytokine (IL-2, interferon (IFN)-γ)-response. Herein, the influence of systemic treatment with the fumaric acid derivate dimethylfumarate (DMF) on the secretion of T helper-cytokines and the development of HSV-1 stromal keratitis (HSK) was studied in mice. The corneas from BALB/c mice were infected with 105 PFU of HSV-1 (KOS strain). While one group of mice was treated intraperitoneally with PBS, another group of mice received DMF at 15 mg/kg of body weight. Expression of IL-2, -4, -10 and IFN-γ was analysed in HSV-1 activated lymphocytes by ELISA. The severity of epithelial and stromal herpetic keratitis was investigated clinically. Corneas were studied for the inflammatory cell infiltration, and the CD3-, CD4- and CD8-positive cells were analysed by immunohistochemistry. The IL-2, -4, 10 and IFN-γ content was measured in the corneas. Virus replication in the eyes was analysed by a plaque-assay. The DTH-response, the HSV-specific T cell proliferation and the serum neutralizing antibody-titres were investigated. DMF increased IL-4 and IL-10, but not IL-2 and IFN-γ, secretion in activated lymphocytes from the spleen. Incidence and severity of stromal HSV-1 keratitis was reduced in the DMF group (P &lt; 0·01). In the corneas from DMF-treated mice, the numbers of CD3+ and CD4+ cells were decreased and IL-4 was increased. Severity of epithelial disease and the virus-clearance from the eyes did not differ between the PBS and DMF group of mice. DTH, HSV-specific T cell proliferation and the neutralizing antibody-titres were not impaired. DMF increased the T helper-2-cytokine secretion in activated lymphocytes. After corneal HSV-1 infection, corneas from DMF treated mice had increased IL-4 content. This is associated with an improvement of herpetic stromal keratitis and reduced corneal T cell infiltration. DMF did not impair the systemic antiviral response.
Reduced blood BDCA-2+ (lymphoid) and CD11c+ (myeloid) dendritic cells in systemic lupus erythematosus
Authors: Migita K , Miyashita T , Maeda Y , Kimura H , Nakamura M , Yatsuhashi H , Ishibashi H , Eguchi K 
Published: September 2005

SummaryType 1 IFN is thought to be implicated in the autoimmune process of SLE. Plasmacytoid dendric cells (DC), which are natural IFN-α producing cells, play a pivotal epipathogenic role in SLE. The present study was undertaken to investigate the phenotypic characteristics of peripheral blood DC in SLE patients in comparison with those of healthy controls. Samples from 20 SLE patients and 18 healthy controls were studied. Three-colour flow cytometry was performed to identify myeloid DC, as CD11c+ lineage marker–, and HLA-DR+ cells and plasmacytoid DC, as BDCA-2+ linage marker–, and HLA-DR+ cells. We used the whole blood ‘lyse/no-wash’ procedure, which allows precise counting of peripheral blood DC. BDCA-2+ plasmacytoid DC and CD11c+ myeloid DC were reduced in SLE patients compared with controls. Similarly, BDCA-3+ DC were reduced in SLE patients. These results indicated that SLE patients had a reduced number of both BDCA-2+ plasmacytoid DC and CD11c+ myeloid DC. These alternations of the DC subset may drive the autoimmune response in SLE.
GnRH-I and GnRH-II have differential modulatory effects on human peripheral blood mononuclear cell proliferation and interleukin-2 receptor γ-chain mRNA expression in healthy males
Authors: Tanriverdi F , Gonzalez-Martinez D , Hu Y , Kelestimur F , Bouloux P M G 
Published: September 2005

SummaryGnRH-I and its receptor (GnRHR-I) have previously been demonstrated and shown to be biologically active in the immune system, notably within peripheral lymphocytes. Recently however, a second form of GnRH (GnRH-II) has been described in the human. The functions of both these neuropeptides in PMBCs have not been understood yet. The present study was therefore designed to investigate the effects of GnRH-I and/or GnRH-II on human PMBC proliferation in males. Secondly, the effects of GnRH-I and GnRH-II on IL-2 dependent lymphocyte proliferation were examined. Finally, we analysed the role of GnRH-I and GnRH-II in IL-2R γ-chain expression. Peripheral venous blood samples were obtained from six male healthy volunteers (Mean age 27·75 ± 1·5). Non-radioactive cell proliferation assay was used for proliferation studies and we used quantitative real-time RT-PCR to examine the role of GnRH-I and GnRH-II on IL-2R γ-chain expression in PMBCs. Treatment of PMBCs with GnRH-I (10−9 M and 10−5 M) and with interleukin-2 (IL-2) (50 U/ml) resulted in a significant increase in cell proliferation compared with the untreated control. PMBCs cotreated with IL-2 and GnRH-I demonstrated higher proliferative responses than IL-2 treatment alone, the enhancement of GnRH-I on IL-2 response being significant only at GnRH-I concentration of 10−5 M. Co-incubation of IL-2+ GnRH 10−5 M with a GnRH antagonist (Cetrorelix; 10−6 M) significantly decreased the proliferation. GnRH-II did not affect the proliferation of PMBCs alone, and did not alter the proliferative response to IL-2. The proliferative responses to GnRH-I (alone and with IL-2) were significantly attenuated by GnRH-II coincubation (each in equal molar concentrations; 10−9 M to 10−5 M). It was found that GnRH-I increased the expression of IL-2Rγ mRNA in a dose dependent manner, with a significant increase of percentage 162·3 ± 14 of control at 10−5 M. In contrast, IL-2Rγ expression was significantly decreased in all concentrations of GnRH-II (10−9 M to10−5 M), and the maximum decrease was detected at 10−5 M, with percentage 37·7 ± 6·6 of control. All these findings strongly suggest that regulation of IL-2R expression may therefore be an important target for GnRH-I and GnRH-II in PMBCs in males. In summary, present study clearly demonstrates the differential effects of GnRH-I and GnRH-II on PMBC proliferation, IL-2 proliferative response, and IL-2Rγ expression in PMBCs in males. To our knowledge, our observations provide the first evidence for the interactions of these local neuropeptides at lymphocyte level. Further experimental data in human are warranted to explore the clinical implications of these data.
An atypical protein kinase C, PKC ζ, regulates human eosinophil effector functions
Authors: Kato Masahiko , Yamaguchi Takafumi , Tachibana Atsushi , Suzuki Masato , Izumi Takashi , Maruyama Kenichi , Hayashi Yasuhide , Kimura Hirokazu 
Published: September 2005

SummaryProtein kinase (PK) C comprises a family of isoenzymes that play key roles in downstream signalling and cell functions. We studied PKC ζ participation in the effector functions of human eosinophils stimulated with platelet‐activating factor (PAF) or complement (C) 5a. After pretreating eosinophils with a myristoylated specific PKC ζ inhibitor; bisindlolylmaleimide I (BisI), an inhibitor of conventional and novel PKCs; or rottlerin, a PKC δ inhibitor, we examined PAF‐ and C5a‐evoked functions. Induced PKC translocation was characterized by confocal laser scanning microscopy. The PKC ζ inhibitor blocked PAF‐ or C5a‐induced eosinophil superoxide anion generation as effectively as BisI or rottlerin. The PKC ζ inhibitor also attenuated PAF‐ or C5a‐induced eosinophil degranulation and adhesion. In contrast, the PKC ζ inhibitor did not affect PAF‐ or C5a‐induced CD11b expression. Finally, both eosinophil shape changes and the translocation of PKC ζ and p47phox, a component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, to the plasma membrane induced by PAF or C5a were completely inhibited by the PKC inhibitor. Thus, the atypical PKC ζ regulates human eosinophil adhesion and effector functions.