bluuebunny/crossref_metadata_2025 huggingface dataset:
The C‐terminus of Bfa1p in budding yeast is essential to induce mitotic arrest in response to diverse checkpoint‐activating signals
Authors: Kim Junwon , Jeong John , Song Kiwon
Published: May 2004

During mitosis, genomic integrity is maintained by the proper coordination of anaphase entry and mitotic exit through mitotic checkpoints. In budding yeast, exit from mitosis is triggered by the activation of the small GTPase Tem1p. Bfa1p in association with Bub2p negatively regulates Tem1p in response to spindle damage, spindle misorientation, and DNA damage, resulting in cell cycle arrest. To delineate the Bfa1p domains that respond to distinct checkpoint signals, we constructed 13 Bfa1 deletion mutants. The C‐terminal 184 amino acids of Bfa1p (Bfa1‐D8391‐574) contained the entire capacity of Bfa1p to generate mitotic arrest in response to spindle damage, spindle misorientation, and DNA damage. This domain was also enough to interact with the mitotic exit network proteins Tem1p, Bub2p, and Cdc5p, and to localize to the spindle pole body (SPB). Over‐expression of Bfa1‐D8391‐574induced late anaphase arrest as efficient as the full‐length Bfa1p in a Bub2p‐dependent manner. In contrast, the N‐terminal portion of Bfa1p (Bfa1‐D161‐376) could not localize to SPB and did not block mitotic exit in response to diverse checkpoint signals. Bfa1‐D161‐376interacted with Tem1p but not with Bub2p and its over‐expression partially arrested cells in mitosis in the absence of Bub2p. By random mutagenesis of Bfa1‐D8391‐574with hydroxylamine, we isolated a point mutant of D8, D8E438K, which interacts with both Tem1p and Bub2p but cannot respond to checkpoint signals. This mutant also showed reduced efficiency in the localization to SPB. Taken together, our study demonstrated that various checkpoint signals are transmitted to the C‐terminal domain of Bfa1 (Bfa1‐D8391‐574) and that Bfa1p localization to SPB is necessary but not sufficient to regulate mitotic exit in response to various checkpoint signals.
Role of Herp in the endoplasmic reticulum stress response
Authors: Hori Osamu , Ichinoda Fusae , Yamaguchi Atsushi , Tamatani Takashi , Taniguchi Manabu , Koyama Yoshihisa , Katayama Taiichi , Tohyama Masaya , Stern David M. , Ozawa Kentaro , Kitao Yasuko , Ogawa Satoshi
Published: May 2004

Application of differential display to cultured rat astrocytes allowed cloning of Herp cDNA. Although Herp was strongly induced by endoplasmic reticulum (ER) stress, it decayed rapidly consequent to proteasome‐mediated degradation. To investigate the role of this molecule in terms of the stress response, Herp knockout cells were developed using F9 embryonic carcinoma cells. F9 Herp null cells were more vulnerable to ER stress compared with F9 wild‐type cells. In the early period of ER stress (0–8 h after tunicamycin treatment), Herp null cells displayed enhanced ER stress signalling and stabilization of an endogenous ERAD substrate, compared with wild‐type cells. In the intermediate period (8–20 h after tunicamycin treatment), Herp null cells displayed reduced ER stress signalling, whereas in the late period (20–40 h after tunicamycin treatment), Herp null cells manifested irreversible cellular changes that lead to apoptotic cell death. Transfection analysis revealed that the N‐terminal region, including the ubiquitin‐like domain of Herp, was required for the survival of F9 cells under ER stress. These results indicate that Herp is a short‐lived Ub‐like protein improving the balance of folding capacity and protein loads in the ER and plays crucial roles for the ER stress resistance in F9 cells.
Identification of cryptochrome DASH from vertebrates
Authors: Daiyasu Hiromi , Ishikawa Tomoko , Kuma Kei‐ichi , Iwai Shigenori , Todo Takeshi , Toh Hiroyuki
Published: May 2004

A new type of cryptochrome, CRY‐DASH, has been recently identified. The CRY‐DASH proteins constitute the fifth subfamily of the photolyase/cryptochrome family. CRY‐DASHs have been identified from Synechocystis sp. PCC 6803, Vibrio cholerae, and Arabidopsis thaliana. The Synechocystis CRY‐DASH was the first cryptochrome identified from bacteria, and its biochemical features and tertiary structure have been extensively investigated. To determine how broadly the subfamily is distributed within living organisms, we searched for new CRY‐DASH candidates within several databases. We found five sequences as new CRY‐DASH candidates, which are derived from four marine bacteria and Neurospora crassa. We also found many CRY‐DASH candidates from the EST databases, which included sequences from fish and amphibians. We cloned and sequenced the cDNAs of the zebrafish and Xenopus laevis candidates, based on the EST sequences. The proteins encoded by the two genes were purified and characterized. Both proteins contained folate and flavin cofactors, and have a weak DNA photolyase activity. A phylogenetic analysis revealed that the seven candidates actually belong to the new type of cryptochrome subfamily. This is the first report of the CRY‐DASH members from vertebrates and fungi.
Autoantibodies from primary biliary cirrhosis patients with anti-p95c antibodies bind to recombinant p97/VCP and inhibitin vitronuclear envelope assembly
Authors: MIYACHI K , HIRANO Y , HORIGOME T , MIMORI T , MIYAKAWA H , ONOZUKA Y , SHIBATA M , HIRAKATA M , SUWA A , HOSAKA H , MATSUSHIMA S , KOMATSU T , MATSUSHIMA H , HANKINS R W , FRITZLER M J
Published: May 2004

We have reported previously that p95c, a novel 95-kDa cytosolic protein, was the target of autoantibodies in sera of patients with autoimmune hepatic diseases. We studied 30 sera that were shown previously to immunoprecipitate a 95 kDa protein from [35S]-methionine-labelled HeLa lysates and had a specific precipitin band in immunodiffusion. Thirteen sera were available to test the ability of p95c antibodies to inhibit nuclear envelope assembly in an in vitro assay in which confocal fluorescence microscopy was also used to identify the stages at which nuclear assembly was inhibited. The percentage inhibition of nuclear envelope assembly of the 13 sera ranged from 7% to 99% and nuclear envelope assembly and the swelling of nucleus was inhibited at several stages. The percentage inhibition of nuclear assembly was correlated with the titre of anti-p95c as determined by immunodiffusion. To confirm the identity of this autoantigen, we used a full-length cDNA of the p97/valosin-containing protein (VCP) to produce a radiolabelled recombinant protein that was then used in an immunoprecipitation (IP) assay. Our study demonstrated that 12 of the 13 (93%) human sera with antibodies to p95c immunoprecipitated recombinant p97/VCP. Because p95c and p97 have similar molecular masses and cell localization, and because the majority of sera bind recombinant p97/VCP and anti-p95c antibodies inhibit nuclear assembly, this is compelling evidence that p95c and p97/VCP are identical.
Heterogeneity in cellular and humoral immune responses againstToxoplasma gondiiantigen in humans
Authors: FATOOHI A F , COZON G J N , GONZALO P , MAYENCON M , GREENLAND T , PICOT S , PEYRON F
Published: May 2004

Protection against Toxoplasma gondii in infected patients is mainly attributed to cellular immunity. We here attempt to improve the characterization of the proteins that induce cellular immunity in naturally infected patients. Cellular immunity was evaluated by flow cytometry after 7 days of blood culture from 31 chronically T. gondii infected and 8 noninfected pregnant women, in the presence of soluble T. gondii antigen (ST-Ag) or fractionated proteins from ST-Ag, separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Blood cultures from infected patients with ST-Ag induced 39·5 ± 12·7% of activated (CD25+) CD4+ T cells using flow cytometry. This contrasts with the absence of activated CD4+ T cells after either culture with PBS or in blood cultures from noninfected women. The protein fraction between 21 and 41·9 kD induced the highest response (14·7 ± 10·0%). Blood samples from 20 infected and 5 uninfected women were cultured in presence of 12 protein subfractions of 2–208 kD. The highest frequencies of response among infected patients were seen with fractions (Fr) 26–31·9 kD (C.I. 85–100%) and Fr 32–36·9 kD (C.I. 77–100%). Although we note a good concordance between cellular and humoral response, Western blot analysis of ST-Ag does not completely predict the panel of proteins recognized by cellular immunity. Two-dimensional separation of the ST-Ag revealed more than 200 protein spots in these fractions. However, only two proteins in the 20–40 kD range induced a significant humoral response. Further studies are necessary to determine which proteins in the Fr 26–31·9 kD and 32–36·9 kD are superior immunogens for cellular responses.
A novel and effective approach of developing aggressive experimental autoimmune gastritis in neonatal thymectomized BALB/c mouse by polyinosinic:polycytidylic acid
Authors: KOBAYASHI Y , MURAKAMI H , AKBAR S M F , MATSUI H , ONJI M
Published: May 2004

Neonatal thymectomy induces autoimmune gastritis (AIG) in 40–70% of BALB/c mice. We presumed that induction of autoimmunity by polyinosinic:polycytidylic acid (poly I:C) might allow development of a more aggressive model of AIG. A group of BALB/c mice were thymectomized on day 3 after birth. Neonatal thymectomized mice were either injected with poly I:C or phosphate-buffered saline (PBS). Non thymectomized neonatal BALB/c mice were injected with only poly I:C. All neonatal thymectomized mice injected with poly I:C developed 3 cardinal features of AIG: (1) moderate to severe degree gastritis (2) presence of autoantibody to H+/K+ ATPase and (3) loss of parietal cells. However, only 70% of the PBS-treated neonatal thymectomized BALB/c mice developed some, but not, all features of AIG. A mild degree of AIG was seen in 12 of 31 nonthymectomized BALB/c mice administered with only poly I:C. Administration of poly I:C in neonatal thymectomized BALB/c mice in the first and second week appeared to be the most effective for induction of aggressive AIG. The levels of interleukin (IL)-6, IL-12p70, interferon-γ and tumour necrosis factor-α were significantly higher in poly I:C-injected thymectomized mice compared to PBS-injected neonatal thymectomized mice (P < 0·05). The frequencies of CD4+CD25+ regulatory T cells in the spleen were significantly decreased in neonatal thymectomized mice administered with poly I:C compared to PBS-treated neonatal thymectomized mice (P < 0·01). Taken together, these results suggest that induction of inflammatory cytokines and reduction of regulatory T cells by poly I:C might contribute to the development of an aggressive model of AIG in neonatal thymectomized BALB/c mice.
Thymic volume is associated independently with the magnitude of short- and long-term repopulation of CD4+ T cells in HIV-infected adults after highly active antiretroviral therapy (HAART)
Authors: RUIZ-MATEOS E , RUBIO A , VALLEJO A , DE LA ROSA R , SANCHEZ-QUIJANO A , LISSEN E , LEAL M
Published: May 2004

Age is one of the main factors involved in the rapidity and the magnitude of CD4+ T cell repopulation in human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treatment (HAART). Improved thymic function has been suggested as the main factor associated with CD4+ T cell restoration after HAART. This work was undertaken to determine, among host factors, the predictor variable at baseline involved in the magnitude of short- and long-term recovery of CD4+ T cells after HAART. HIV-RNA levels and CD4+ T cell numbers were determined in 54 HIV-infected adults at baseline and at weeks 4, 12, 48 and 96 after HAART. T cell subpopulations were determined by flow cytometry, thymic volume by computed tomography, T cell receptor excision circle (TREC)-bearing cells by quantitative polymerase chian reaction (PCR) and interleukin (IL)-7 levels by enzyme linked immunosorbent assay at baseline. The phenotype of patients’ isolates was determined by infecting GHOST cells expressing CCR5 and CXCR4. The possible interference of phenotype with thymic function was also analysed. Baseline thymic volume was associated independently with the magnitude of short- and long-term recovery of CD4+ T cells after HAART, despite the patients’ viral phenotype. The measurement of thymic volume before therapy may predict the magnitude of T cell increase. This result could have important clinical implications not only in HIV-infected patients, but also in other scenarios of T cell depletion such as bone marrow transplantation and chemotherapy.
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

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 < 0·0001) and between the soluble TNFRs and ALT levels (P < 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 < 0·01). Baseline IL-10 levels correlated with TNFR-p75 (P < 0·01) and with treatment response (P < 0·05) and a significant IL-10 reduction from baseline was observed from day 3 among responders, irrespective of the type of treatments (P < 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

Intramuscular 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

Both 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

Proteinase‐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

Exogenous 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

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

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

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

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.
Growth and Yield Performance of Some Cotton Cultivars in Xinjiang, China, An Arid Area with Short Growing Period
Authors: Wang C. , Isoda A. , Wang P.
Published: May 2004

Eleven cotton (Gossypium hirsutum L.) cultivars were evaluated for their growth and yield performance in Shihezi, Xinjiang, China, an area in Central Asia with short growing period in 1999 and 2000. In each cultivar the number of bolls per plant was low and the number of bolls per unit area was high. Each cultivar showed rather high seed and lint yields. The highest lint yield was Xinluzao 10 in both years with 1761 and 1809 kg ha−1. High yield ability of the cultivars in this study was attributed to large number of bolls per unit area with high lint percentage. Seed and lint yields had significant positive correlations with mean net assimilation rate, ratio of reproductive to vegetative organs and mean boll weight at earlier stages of boll growth, suggesting that early boll formation and successive partitioning of dry matter into bolls were important factors for boll growth in this study area.
Evaluation of Fibre Flax (Linum usitatissimum L.) Performance under Minimal and Zero Tillage in Eastern Canada
Authors: Couture S. J. , DiTommaso A. , Asbil W. L. , Watson A. K.
Published: May 2004

The feasibility of producing fibre flax in minimum tillage or zero tillage (ZT) systems was investigated. The results were variable between the sites, which differed in soil type and previous cropping history. Tillage regime had no impact on fibre flax phenological development including number of days to emergence, days to flowering and days to harvest at either site. However, tillage regime had a significant effect on mean stem diameter, dry matter content and plant height at all three sampling dates at the sandy loam site, and a significant effect on mid‐season plant height at the clay site. At the sandy loam site, ZT plots had the highest populations of plants with the finest stem diameters, the lowest branching ratios, but the shortest plants by the end of the season. Overall, plant densities were greater, stem diameters thinner, and biomass production higher in the heavier soil of the clay site. These results indicate that under the growing conditions present in 1998, fibre flax can successfully be grown in minimum or ZT systems on different soil types in Eastern Canada. Moreover, the growth of fibre flax in these systems does not compromise the proportion of tall plants having thin stems and minimal branching, a critical quality parameter for fibre flax production.
Differences in Starch Characteristics of Rice Strains Having Different Sensitivities to Maturation Temperatures
Authors: Suzuki Y. , Sano Y. , Ishikawa T. , Sasaki T. , Matsukura U. , Hirano H.‐Y.
Published: May 2004

The amylose synthesis in rice with Wxb is affected by environmental temperature during seed development. We previously isolated a mutant candidate (coi) in which amylose synthesis is insensitive to a cool temperature. Here, the effects of maturation temperature (21 °C vs. 28 °C) on the starch characteristics of coi and its original strain 76‐3/T65 were studied. Amylose contents and gelatinization properties of 76‐3/T65 were affected by maturation temperatures, while coi was less affected. The amylopectin chain length distributions were almost the same between the two strains maturated at both temperatures. Gelatinization onset (To), peak (Tp), conclusion temperatures (Tc) and enthalpies (ΔH) decreased with environmental temperatures, and Tp, Tc and ΔH of coi at 21 °C were significantly higher than those of 76‐3/T65. Thus, the coi mutant, less affected by maturation temperature than that of 76‐3/T65, may be a useful strain in understanding biochemical and genetic starch biosynthesis response to slight changes in temperature.
Alfalfa Phytoestrogen Content: Impact of Plant Maturity and Herbage Components
Authors: Seguin P. , Zheng W. , Souleimanov A.
Published: May 2004

Legumes contain a range of non‐nutritional phytochemicals that may have health‐promoting effects in humans. In this study, we determined the concentrations of four phytoestrogens (coumestrol, apigenin, luteolin and quercetin) in field‐grown alfalfa (Medicago sativa L.). Differences between plants of different stages of maturity, between plant parts, and different canopy segments were assessed. The concentration of individual phytoestrogen in whole herbage varied between 15 and 225 μg g−1 dry matter (DM) and was strongly affected by stage of maturity. Coumestrol and apigenin concentrations were highest at early vegetative stages, luteolin and quercetin at early vegetative and late flowering stages. All phytoestrogens were found in lowest concentrations at the early flowering stage (average 68 μg g−1 DM); stage at which alfalfa is usually harvested when used as a forage source for animals. At vegetative stages, apigenin was the predominant phytoestrogen in herbage followed by coumestrol, the reverse being observed upon initiation of flowering; luteolin and quercetin were found at all stages in similarly lower concentrations. Concentrations of luteolin, quercetin and apigenin were 225, 410 and 690 % greater, respectively, in flowers than in leaves or stems; coumestrol concentration was similar between plant parts. In flowers and stems the predominant phytoestrogens were apigenin and quercetin, followed by coumestrol and luteolin. Similar concentrations (average 26 μg g−1 DM) of each of the four phytoestrogens were found in leaves. Concentrations through the herbage canopy varied and were greatest at >60 cm from the soil surface for apigenin and coumestrol, but greatest at >60 and 0–20 cm for quercetin and at 0–20 cm for luteolin. The results suggest that if alfalfa is to be used as a source of phytoestrogens and is harvested for the production of herbal supplements or nutraceuticals, management will need to be adapted.
Managing as carers of stroke survivors: Strategies from the field
Authors: O'Connell Bev , Baker Linda
Published: May 2004

Family members are required to provide increasingly complex care to relatives in the home. Stroke is a major cause of disability and there is increasing pressure being placed on carers to provide on‐going support to stroke survivors living in the community. This study involved interviewing carers to determine their perspectives on the support and educational needs they require and the coping strategies they used. Data analysis revealed that carers experienced considerable uncertainty about their role as carers and their future and that they used a number of coping strategies to manage in their caring role. The coping strategies adopted by the carers included remaining positive, adapting to change, comparing their situation with others who were worse off, changing their employment status, humour, switching off and using family support. It is important for health care professionals to understand the complex role of the carers and to advise them on strategies they can use to assist managing this role.
Human leukocyte antigen‐DQB1 alleles are not associated with schizophrenia in Kuwaiti Arabs
Authors: HAIDER MOHAMMAD Z. , ZAHID MOHAMMAD A.
Published: May 2004

Abstract  Schizophrenia is among the most severe and debilitating of psychiatric disorders and has a complex mode of inheritance. A susceptibility locus has been identified on chromosome 6 and some association studies involving human leukocyte antigen (HLA) genes have reported diverse results. The objective of the present study was to determine if there is an association between HLA‐DQB1 alleles and schizophrenia in Kuwaiti Arabs. The frequency of HLA‐DQB1 alleles was determined in a cohort of 195 Kuwaiti Arabs consisting of 81 schizophrenia patients and 114 ethnically matched healthy controls, using a polymerase chain reaction–sequence specific primers method. A total of nine DQB1 alleles were identified in this Kuwaiti cohort. The most prevalent DQB1 alleles in Kuwaiti schizophrenia patients were *0601 (28%), *0201 (23%) and *0501 (16%), respectively. However, no significant difference in the allele frequency was detected between schizophrenia patients and the controls. The DQB1*0602 allele, which has been negatively associated in African–Americans in previous reports, was not detected in the present Kuwaiti schizophrenia patients or controls.
Role and attitude of companions on geriatric psychiatry outpatient visits in Taiwan
Authors: CHEN CHING‐YEN , CHEN YING‐JEN , JUANG YEONG‐YUH , LIU CHIA‐YIH , HUNG CHING‐I
Published: May 2004

Abstract  The purpose of the present paper was to investigate the role and attitude of people who accompanied geriatric patients to an outpatient psychiatric clinic. The study was conducted at a large university hospital in Taiwan. Participants included 108 patients aged 65 years and older who were seen for their initial psychiatric visit; 81 patients were accompanied. All accompanying people were interviewed to obtain their assumed role and attitude during the visit. Data were gathered prospectively; statistical analyses were performed using SPSS‐PC. Accompanied patients (75% of participants) were older than those in the unaccompanied group. Most patients (53.1%) were accompanied by adult children who lived with them. Of the accompanying spouses, 48% were described as a supporter, and 60% showed a positive attitude. Most of the accompanying children acted as critics and speakers. Accompanying people whose responsible patients reported insomnia and suicide attempts showed a significantly positive attitude, whereas people who accompanied alcoholic patients were more negative and assumed a critic role. Many accompanying people requested further examination and drug treatment and expressed concern that the patient may be mentally ill. The role and attitude of accompanying people on the geriatric patient encounter are important factors in promoting patient–doctor communication and trust.
Neurological soft signs in schizophrenic patients with obsessive–compulsive disorder
Authors: SEVINCOK LEVENT , AKOGLU AYBARS , TOPALOGLU BEYZA , ASLANTAS HULYA
Published: May 2004

Abstract  The purpose of this study was to examine neurological soft signs (NSS) in schizophrenic patients with obsessive–compulsive disorder (OCD). Neurological soft signs were assessed in 15 schizophrenic patients with OCD (OCD‐schizophrenia), 38 schizophrenia patients without OCD (non‐OCD‐schizophrenia), and 24 healthy controls (HC) by means of the Neurological Evaluation Scale (NES). The OCD‐schizophrenia group had significantly higher scores on total and subscales of ‘sensory integration’ and ‘others’ of NES than the HC group. Subscale scores of ‘sequencing of motor acts’ in‐non‐OCD‐schizophrenia patients were significantly higher compared to OCD‐schizophrenia patients. Total NES scores of both groups were significantly correlated with Scale for the Assessment of Negative Symptoms (SANS) scores. Only the subscale of ‘sequencing of motor acts’ was significantly correlated with SANS within the OCD‐schizophrenia group. These results suggest that NSS do not significantly differ between schizophrenia patients with and without OCD, contrary to expectations. The NES scores in OCD‐schizophrenic patients do not appear to be related to a more severe form of schizophrenia. Neurological signs and negative symptoms in schizophrenia patients with and without OCD may be considered as neurodevelopmental predisposing factors. Further research is required in schizophrenia patients with OCD to investigate the relationships between NSS and several neuroimaging or neuropsychological findings, constituting a subgroup within the schizophrenia spectrum.