bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of soluble tumour necrosis factor (TNF)-α receptors and cytokines in the early phase of treatment for chronic hepatitis C: comparison between interferon (IFN)-α alone, IFN-α plus amantadine or plus ribavirin
Authors: TORRE F , ROSSOL S , PELLI N , BASSO M , DELFINO A , PICCIOTTO A 
Published: May 2004

SUMMARY
We have previously studied the effect of three different treatment regimens with interferon (IFN)-α alone or in combination with amantadine or ribavirin on viral kinetics in the first month of therapy. To understand the regulation of cytokine immune response during early inhibition of HCV replication, we analysed the longitudinal profile of proinflammatory markers (soluble TNFRs), of type 1 cytokines [IFN-γ and interleukin (IL-12)], and of a type 2 cytokine (IL-10). Twenty-two chronic hepatitis C patients received daily therapy for 6 months. Sera were collected at baseline, at 6, 12, 24, 30 and 48 h and at the 3rd, 7th, 15th and 30th days of treatment. All cytokines and receptors were evaluated by enzyme linked immunosorbent assay (ELISA). At baseline, a correlation was found between the two soluble TNFRs (P &lt; 0·0001) and between the soluble TNFRs and ALT levels (P &lt; 0·003), as shown previously. Regardless of the type of treatment, lower levels of soluble TNFR-p75 were present from day 3 in patients who had significant virus decay at day 30 (P &lt; 0·01). Baseline IL-10 levels correlated with TNFR-p75 (P &lt; 0·01) and with treatment response (P &lt; 0·05) and a significant IL-10 reduction from baseline was observed from day 3 among responders, irrespective of the type of treatments (P &lt; 0·05). IL-12 and IFN-γ levels did not differ according to treatment or outcome. These findings suggest a pivotal role for IL-10 in orchestrating the antiviral immune response. Its early decline can favour the shift from a Th2 to a Th1 immune response, which has been shown to be associated with a long-term virological response to treatment.
Induction of hyperthyroidism in mice by intradermal immunization with DNA encoding the thyrotropin receptor
Authors: BARRETT K , LIAKATA E , RAO P V , WATSON P F , WEETMAN A P , LYMBERI P , BANGA J P , CARAYANNIOTIS G 
Published: May 2004

SUMMARYIntramuscular injection with plasmid DNA encoding the human thyrotropin receptor (TSHR) has been known to elicit symptoms of Graves’ disease (GD) in outbred but not inbred mice. In this study, we have examined, firstly, whether intradermal (i.d.) injection of TSHR DNA can induce hyperthyroidism in BALB/c mice and, secondly, whether coinjection of TSHR- and cytokine-producing plasmids can influence the outcome of disease. Animals were i.d. challenged at 0, 3 and 6 weeks with TSHR DNA and the immune response was assessed at the end of the 8th or 10th week. In two experiments, a total of 10 (67%) of 15 mice developed TSHR-specific antibodies as assessed by flow cytometry. Of these, 4 (27%) mice had elevated thyroxine (TT4) levels and goitrous thyroids with activated follicular epithelial cells but no evidence of lymphocytic infiltration. At 10 weeks, thyroid-stimulating antibodies (TSAb) were detected in two out of the four hyperthyroid animals. Interestingly, in mice that received a coinjection of TSHR- and IL-2- or IL-4-producing plasmids, there was no production of TSAbs and no evidence of hyperthyroidism. On the other hand, coinjection of DNA plasmids encoding TSHR and IL-12 did not significantly enhance GD development since two out of seven animals became thyrotoxic, but had no goitre. These results demonstrate that i.d. delivery of human TSHR DNA can break tolerance and elicit GD in inbred mice. The data do not support the notion that TSAb production is Th2-dependent in murine GD but they also suggest that codelivery of TSHR and Th1-promoting IL-12 genes may not be sufficient to enhance disease incidence and/or severity in this model.
Sequence‐specific binding of normal serum immunoglobulin M to exposed protein C‐termini
Authors: Sokoloff Alex V. , Puckett Marissa , Ludtke James J. , Fetterly Bryan 
Published: May 2004

SummaryBoth the timely clearance of degraded endogenous structures and the presence of secreted natural immunoglobulin M (IgM) are needed to avoid autoimmunity. These requirements may be causally related provided that natural IgM preferentially reacts with degraded antigens and, by activating complement, mediates their non‐inflammatory clearance through complement receptors. We have previously shown that normal serum IgM reacts in vivo and in vitro with virtually all randomly generated C‐terminal peptides displayed on T7 phage. The resultant multivalent IgM–peptide complexes activate complement and are detected by a loss of phage infectivity. A striking feature of these reactions is that different C‐terminal peptides (? 3–4 amino acids) specifically react with different ‘C‐terminal’ IgM (C‐IgM) antibodies. This suggests that degraded supramolecular structures, expressing elevated levels of identical C‐termini as a result of proteolysis, denaturation and abnormal exposure of repetitive protein constituents, may be preferential targets of C‐IgM‐mediated complement activation in the physiological environment. The specificity of C‐IgM–peptide reactions is much higher than one would expect, assuming that normal serum IgM mostly comprises polyspecific natural antibodies. However, it is possible that polyspecific IgM is not adequately registered by our ‘functional’ phage‐inactivation assays. In this study, we resolve the issue of C‐IgM specificity by directly characterizing the binding reactivity of normal serum IgM with phage‐displayed C‐terminal peptides.
Tethered ligand‐derived peptides of proteinase‐activated receptor 3 (PAR3) activate PAR1 and PAR2 in Jurkat T cells
Authors: Hansen Kristina K. , Saifeddine Mahmoud , Hollenberg Morley D. 
Published: May 2004

SummaryProteinase‐activated receptors (PARs) can activate a number of signalling events, including T‐cell signal‐transduction pathways. Recent data suggest that the activation of PARs 1, 2 and 3 in Jurkat T‐leukaemic cells induces tyrosine phosphorylation of the haematopoietic signal transducer protein, VAV1. To activate the PARs, this study used the agonist peptides SFLLRNPNDK, SLIGKVDGTS and TFRGAPPNSF, which are based on the sequences of the tethered ligand sequences of human PARs 1, 2 and 3, respectively. Here, we show that peptides based on either the human or murine PAR3‐derived tethered ligand sequences (TFRGAP‐NH2 or SFNGGP‐NH2) do not activate PAR3, but rather activate PARs 1 and 2, either in Jurkat or in other PAR‐expressing cells. Furthermore, whilst thrombin activates only Jurkat PAR1, trypsin activates both PARs 1 and 2 and also disarms Jurkat PAR1 for thrombin activation. We conclude therefore that in Jurkat or related T cells, signalling via PARs that can affect VAV1 phosphorylation is mediated via PAR 1 or 2, or both, and that distinct serine proteinases may potentially differentially affect T‐cell function in the settings of inflammation.
Efficient scavenger receptor‐mediated uptake and cross‐presentation of negatively charged soluble antigens by dendritic cells
Authors: Shakushiro Kohsuke , Yamasaki Yasuomi , Nishikawa Makiya , Takakura Yoshinobu 
Published: May 2004

SummaryExogenous antigens endocytosed in large amounts by antigen‐presenting cells (APC) are presented on major histocompatibility complex (MHC) class I molecules as well as on class II molecules, a process called cross‐presentation. Among APC, dendritic cells (DC) play a key role in cross‐presentation by transporting internalized antigen to the cytosol. The present study shows that ovalbumin (OVA) introduced with negative charges by succinylation (Suc‐OVA), maleylation (Mal‐OVA) or cis‐aconitylation (Aco‐OVA) was efficiently taken up by DC via scavenger receptors (SR). Mal‐OVA and Aco‐OVA were efficiently cross‐presented by DC, while cross‐presentation of Suc‐OVA was hardly observed. MHC class I presentation of acylated OVA introduced directly into the cytosol was inefficient and presentation of exogenous native OVA but not of Aco‐OVA was markedly augmented by chloroquine, an inhibitor of endosomal acidification, suggesting that deacylation in endosomes or lysosomes is necessary for cross‐presentation of acylated OVA. MHC class I presentation of exogenous native OVA and Aco‐OVA by DC was blocked by lactacystin and brefeldin A, demonstrating that exogenous antigens taken up by DC are cross‐presented through the conventional cytosolic pathway. Therefore, SR‐mediated delivery of antigen to DC leads to efficient cross‐presentation, although the pathway of chemical modification should be considered.
Isolated PACNS‐like presentation of a systemic vasculitis complicating a myelodysplastic syndrome
Authors: Incalzi R. A. , Arena V. , Capelli A. , Gambassi G. 
Published: May 2004

Abstract.Myelodysplastic syndromes (MDS) are a series of haematological malignancies ranging from chronic refractory anaemia to leukaemia. There is increasing recognition of immunological abnormalities in patients with MDS, including few reports of cutaneous vasculitis; in no instance, a cerebral localization has been ascertained. Here, the case of a patient with MDS who presented exclusively with neurological signs that were considered indicative of a primary, isolated central nervous system vasculitis (PACNS) is reported. Although histological findings on brain tissue confirmed a small‐vessel vasculitis, this had to be considered in the context of a systemic vasculitis. In fact, at autopsy, an involvement of skin, myocardium, lungs, liver, kidney and bone marrow was also found. An autoimmune vasculitis should be included in the differential diagnosis of acute‐onset, isolated, cerebral symptoms complicating the course of MDS.
A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma
Authors: Landgren O. , Björkholm M. , Konradsen H. B. , Söderqvist M. , Nilsson B. , Gustavsson A. , Axdorph U. , Kalin M. , Grimfors G. 
Published: May 2004

Abstract.Background.  Splenectomy is accompanied by a life‐long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23‐valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune‐mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA).Methods.  A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti‐PS antibody levels measured by enzyme‐linked immunosorbent assay technique the patients were revaccinated with 23‐valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month ± 2 weeks (peak), and after 1 year ± 6 months (follow‐up). Patient files, a national population‐based database, and microbiological databases were checked for 124 HL patients to identify OPSI.Results.  A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow‐up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle‐aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7‐year period.Conclusions.  A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype‐specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1–5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.
Readmissions and adverse drug reactions in internal medicine: the economic impact
Authors: Dormann H. , Neubert A. , Criegee‐Rieck M. , Egger T. , Radespiel‐Tröger M. , Azaz‐Livshits T. , Levy M. , Brune K. , Hahn E.G. 
Published: May 2004

Abstract.Background.  Recent studies show that nearly half of the hospitalized patients are readmitted within 6 months from discharge. No data exist about the relationship between adverse drug reactions (ADRs) and readmittance to a department of internal medicine.Objectives.  The primary aims of the study were to determine if ADRs could be used as predictors for recurrent hospitalizations in internal medicine and to evaluate the economic impact of ADRs on hospitalization costs.Design  and setting.  A cohort‐based, prospective, 18‐month pharmacoepidemiological survey was conducted in the Department I of Internal Medicine at the University Hospital of Erlangen. All patients were intensively monitored for ADRs by a pharmacoepidemiological team. ADRs were evaluated for their offending drugs, probability, severity, preventability and classified by WHO‐ART. During a 6‐month period ADR‐positive patients were matched to non‐ADR patients applying diagnosis‐related group categorization in order to measure the impact of ADRs on the duration and frequency of hospitalization.Results.  Of 1000 admissions 424 patients had single admissions and 206 patients had recurrent readmissions (min 1, max 9). The prevalence of readmissions was 37% (n = 370). In 145 (23%) of 630 patients, 305 ADRs were observed. The ADR incidence was similar in first admissions and readmissions. ADRs were not found to predict further readmissions and lack of ADRs did not preclude readmissions. ADRs caused hospitalizations in 6.2% of first admissions and in 4.2% of readmissions. According to the Schumock algorithm 135 (44.3%) ADRs were found to be preventable. The occurrence and numbers of ADRs per admission were found to prolong hospitalization period significantly (r = 0.48 and 0.51, P < 0.001, n = 135). Of 9107 treatment days 20% were caused by in‐house (1130 days) and community‐acquired ADRs (669 days). In admissions and readmissions 11% (>973 days) of all treatment days were judged to be preventable.Conclusions.  Intensified drug monitoring supported by information technology in internal medicine is essential for early detecting and prevention of ADRs and saving hospital resources.
The platelet polymorphism PlA2 is a genetic risk factor for myocardial infarction
Authors: Grove E. L. , Ørntoft T. F. , Lassen J. F. , Jensen H. K. , Kristensen S. D. 
Published: May 2004

Abstract.Objectives.  Platelet glycoprotein (GP) receptor IIb/IIIa plays a key role in the development of myocardial infarction (MI), and PlA2 is a polymorphism in the gene encoding this receptor. The prevalence of PlA2 shows pronounced geographical variation and has to our knowledge not been presented for a Scandinavian population before. Platelets from PlA2‐positive individuals show increased aggregability compared with platelets from PlA2‐negative individuals, and PlA2 genotypes might be associated with MI. The purpose of this study was to investigate the relation between the PlA2 polymorphism and MI in a large Scandinavian population.Design.  Case–control study. We included patients with angiographically verified CAD with and without previous MI and a group of healthy individuals matched for age, race, and sex.Results.  We studied the frequency of PlA2 in 1191 healthy individuals and 1019 patients with coronary artery disease (CAD). Amongst these patients, 529 subjects had suffered an MI previously. PlA2 was present in 28% of healthy individuals, 28% of patients with CAD but no MI, and in 35% of patients with CAD and MI. The difference between healthy individuals and MI patients was significant (P = 0.002). Furthermore, a graded relationship between the number of PlA2 alleles and the risk of MI was seen (P = 0.011). Associations between PlA2 and traditional cardiovascular risk factors as well as mean platelet volume were investigated. We found a significant interaction between PlA2 and serum cholesterol.Conclusion.  In our Scandinavian study population the common platelet polymorphism PlA2 is significantly associated with an increased risk of MI, but not of CAD. Clinically, typing for PlA2 might have implications for antiplatelet therapy of patients with MI.
Eosinophil traffic in the circulation following allergen challenge
Authors: Sklar L. A. , Tsuji H. , Edwards B. S. , Larson R. S. , Schuyler M. 
Published: May 2004

Background:  Eosinophils contribute to the pathogenesis of asthma and localize to the lung after allergen exposure by uncertain mechanisms.Methods:  We used intrabronchial instillation of allergen to model the interaction between inhaled allergen and the lung. We measured the number of peripheral blood leukocytes and the expression of VLA‐4 (CD49d), Mac‐1 (CD11b) and PSGL‐1 (CD162) up to 4 h after instillation of allergen into a bronchus of eight atopic asthmatics. For controls, we instilled normal saline into a subset of the asthmatic subjects, and allergen into nonatopic, nonasthmatic subjects.Results:  There were changes of total leukocyte number, number of polymorphonuclear leukocytes, lymphocytes, monocytes and eosinophils in all three groups (atopic asthmatics instilled with allergen, atopic asthmatics instilled with saline, nonatopic nonasthmatic subjects instilled with allergen), which were likely related to bronchoscopy. However, the decrease of eosinophils was significant only in the atopic asthmatics instilled with allergen. The remaining eosinophils in the allergen challenged asthmatics were not activated as defined by cell density or change of expression of VLA‐4, Mac‐1 and PSGL‐1.Conclusions:  While eosinophils rapidly and specifically leave the circulation after allergen challenge of atopic asthmatics, the remaining circulating eosinophils are not activated.
Allergy, asthma and markers of infections among Albanian migrants to Southern Italy
Authors: Ventura M. T. , Munno G. , Giannoccaro F. , Accettura F. , Chironna M. , Lama R. , Hoxha M. , Panetta V. , Ferrigno L. , Rosmini F. , Matricardi P. M. , Barbuti S. , Priftanji A. , Bonini S. , Tursi A 
Published: May 2004

Background:  Studies of immigrants represent an useful tool to determine the relative relevance of environmental vs genetic factors in causing the reported rapid increase of the prevalence of sensitization and allergic diseases.Methods:  A total of 152 Albanian migrants to Southern Italy responded to a questionnaire based on the European Community Respiratory Health Survey (ECRHS) and 139 of them underwent skin prick test, and 61 serological assays for total IgE and IgG antibodies against Toxoplasma gondii (TG), herpes simplex virus 1 (HSV‐1), hepatitis A virus (HAV) and Helicobacter pylori (HP).Results:  Reported asthma was rare (2/152; 1.3%) and reported nasal allergies rather frequent (24/152; 15.8%). Sensitization to common inhalant allergens occurred in 27/139 (19.4%) subjects. The frequency of skin sensitization to pollen (P = 0.003) and that of hay fever (P = 0.004) increased with the time spent in Apulia. All the 61 sera had antibodies against HAV, 59/61 (96.7%) against HSV‐1, 48/61 (78.7%) against HP and 34/61 (55.7%) against TG. The prevalence of skin sensitization and hay fever symptoms were correlated to the duration of residence in Southern Italy.Conclusions:  Data presented indicate that Albanian migrants to Italy, in spite of the low prevalence of allergic diseases and sensitization in their country of origin, manifest with time an increasing prevalence of sensitization to local allergens and nasal symptoms after immigration to Italy. This would suggest a permanent role of allergen exposure and lifestyle factors in influencing the appearance of sensitization and symptoms of allergic diseases.
Comparison of local risk factors for children's atopic symptoms in Hanoi, Vietnam
Authors: Chai S. K. , Nga N. N. , Checkoway H. , Takaro T. K. , Redding G. J. , Keifer M. C. , Trung L. V. , Barnhart S. 
Published: May 2004

Background:  A 1999 study in Hanoi, Vietnam using the International Study on Asthma and Allergies in Childhood (ISAAC) questionnaire showed a high prevalence of atopic symptoms. Identifying risk factors for symptoms in these children may help in understanding the causes for these high estimates.Methods:  An ISAAC questionnaire with supplemental questions on environmental variables was distributed to 5495 school children in Hanoi and a suburban district, Dong Anh. The response rate was 65.7%.Results:  In Dong Anh, the following were among the significant age and gender adjusted associations: pig ownership [odds ratio (OR) (95% confidence interval), OR = 1.79 (1.18–2.70) for doctor‐diagnosed asthma (DDA), OR = 1.72 (1.08–2.78) for doctor diagnosed hay fever (DDHF)] and farming [OR = 1.67 (1.27–2.19) for ever asthma, OR = 1.51 (1.09–2.09) for DDHF]. In multivariate models, tuberculosis (TB) was a significant predictor of atopic symptoms [Hanoi: OR = 3.09 (1.10–8.70) for DDA, Dong Anh: OR = 3.71 (1.40–9.84) for DDA, OR = 4.66 (1.88–11.57) for DDHF].Conclusions:  These findings are contrary to the ‘hygiene hypothesis’. Recent immunologic and epidemiologic studies refute the inverse association between allergy and TB and may be one explanation for the positive association in this study. The positive association with pig ownership and farming may be because of exposures on farms in a developing country that may be different from exposures in farms of developed countries.
Macrophage mannose receptor in chronic sinus disease
Authors: Claeys S. , De Belder T. , Holtappels G. , Gevaert P. , Verhasselt B. , Van Cauwenberge P. , Bachert C. 
Published: May 2004

Background:  The role of infectious agents in the onset and maintenance of chronic sinus disease is still not fully understood. Macrophage mannose receptor (MMR), an innate pattern recognizing receptor, capable of phagocytosis of invaders and signal transduction for proinflammatory mechanisms, might be of importance in immune interactions in chronic sinus disease.Objective:  We examined the MMR in sinonasal airway mucosa to evaluate its possible role in chronic rhinosinusitis (CS) and nasal polyposis (NPs).Methods:  Surgical samples from patients with sinonasal disease were investigated with real‐time RT‐PCR for quantification of MMR mRNA expression, and the presence and location of MMR‐positive cells was analysed by immunohistochemistry.Results:  Quantification of MMR mRNA showed a statistically significant higher expression in NPs compared to CS without NP and controls. Immunohistochemistry revealed expression of MMR in all tissue samples; however, in NP we found an enhanced positive cellular staining including cell aggregates.Conclusions:  We could demonstrate for the first time that the expression of MMR is significantly upregulated in NP compared to patients with CS without NP or turbinate tissue of controls. Macrophages expressing MMR, accumulated in cell aggregates in NPs, play a possible key role in pathogen–macrophage interaction in NP disease.