bluuebunny/crossref_metadata_2025 huggingface dataset:
Home care during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation is advantageous compared with hospital care
Authors: Svahn Britt-Marie , Remberger Mats , Myrbäck Karl-Erik , Holmberg Katarina , Eriksson Britta , Hentschke Patrik , Aschan Johan , Barkholt Lisbeth , Ringdén Olle
Published: November 2002

After myeloablative treatment and allogeneic stem cell transplantation (SCT), patients are kept in isolation rooms in the hospital to prevent neutropenic infections. During a 3-year period, patients were given the option of treatment at home after SCT. Daily visits by an experienced nurse and daily phone calls from a physician from the unit were included in the protocol. We compared 36 patients who wished to be treated at home with 18 patients who chose hospital care (control group 1). A matched control group of 36 patients treated in the hospital served as control group 2. All home care patients had hematologic malignancies and 19 were in first remission or first chronic phase. Of the donors, 25 were unrelated. The patients spent a median of 16 days at home (range, 0-26 days). Before discharge to the outpatient clinic after SCT, patients spent a median of 4 days (range, 0-39 days) in the hospital. In the multivariate analysis, the home care patients were discharged earlier (relative risk [RR] 0.33, P = .03), had fewer days on total parenteral nutrition (RR 0.24, P < .01), less acute graft-versus-host disease (GVHD) grades II-IV (RR 0.25,P = .01), lower transplantation-related mortality rates (RR 0.22, P = .04), and lower costs (RR 0.37, P < .05), compared with the controls treated in the hospital. The 2-year survival rates were 70% in the home care group versus 51% and 57% (not significant) in the 2 control groups, respectively (P < .03). To conclude, home care after SCT is a novel and safe approach. This study found it to be advantageous, compared with hospital care.
SH2-containing inositol phosphatase (SHIP-1) transiently translocates to raft domains and modulates CD16-mediated cytotoxicity in human NK cells
Authors: Galandrini Ricciarda , Tassi Ilaria , Mattia Gianfranco , Lenti Luisa , Piccoli Mario , Frati Luigi , Santoni Angela
Published: November 2002

Membrane recruitment of the SH2containing 5′ inositol phosphatase 1 (SHIP-1) is responsible for the inhibitory signals that modulate phosphatidylinositol 3-kinase (PI3K)–dependent signaling pathways. Here we have investigated the molecular mechanisms underlying SHIP-1 activation and its role in CD16-mediated cytotoxicity. We initially demonstrated that a substantial fraction of SHIP-1–mediated 5′ inositol phosphatase activity associates with CD16 ζ chain after receptor cross-linking. Moreover, CD16 stimulation on human primary natural killer (NK) cells induces the rapid and transient translocation of SHIP-1 in the lipid-enriched plasma membrane microdomains, termed rafts, where it associates with tyrosine-phosphorylated ζ chain and shc adaptor protein. As evaluated by confocal microscopy, CD16 engagement by reverse antibody-dependent cellular cytotoxicity (ADCC) rapidly induces SHIP-1 redistribution toward the area of NK cell contact with target cells and its codistribution with aggregated rafts where CD16 receptor also colocalizes. The functional role of SHIP-1 in the modulation of CD16-induced cytotoxicity was explored in NK cells infected with recombinant vaccinia viruses encoding wild-type or catalytic domain–deleted mutant SHIP-1. We found a significant SHIP-1–mediated decrease of CD16-induced cytotoxicity that is strictly dependent on its catalytic activity. These data demonstrate that CD16 engagement on NK cells induces membrane targeting and activation of SHIP-1, which acts as negative regulator of ADCC function.
Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4–stimulated B cells
Authors: Suto Akira , Nakajima Hiroshi , Hirose Koichi , Suzuki Kotaro , Kagami Shin-ichiro , Seto Yohei , Hoshimoto Aihiro , Saito Yasushi , Foster Donald C. , Iwamoto Itsuo
Published: November 2002

Interleukin 21 (IL-21) has recently been identified as a multifunctional cytokine that induces the proliferation of T cells and B cells and differentiation of natural killer cells. To determine whether IL-21 regulates IL-4–mediated immune responses, we examined the effect of IL-21 on antigen-specific IgE production in mice. We also examined the effect of IL-21 on IL-4–induced IgE production from B cells and antigen-induced T-helper 2 (Th2) cell differentiation. The in vivo injection of IL-21 prevented antigen-specific IgE but not IgG2a production on immunization. IL-21 did not affect Th2 cell differentiation or IL-4 production from CD4+ T cells but directly inhibited IL-4–induced IgE production from B cells at single-cell levels. Moreover, IL-21 inhibited IL-4–induced germ line Cε transcription in B cells without the inhibition of signal transducer and activator of transcription 6 (Stat6) activation. Taken together, these results indicate that IL-21 down-regulates IgE production from IL-4–stimulated B cells through the inhibition of germ line Cε transcription and thus suggest that IL-21 may be useful for the treatment of IgE-dependent allergic diseases.
Real-time T-cell profiling identifies H60 as a major minor histocompatibility antigen in murine graft-versus-host disease
Authors: Choi Eun Young , Christianson Gregory J. , Yoshimura Yoshitaka , Jung Nadja , Sproule Thomas J. , Malarkannan Subramaniam , Joyce Sebastian , Roopenian Derry C.
Published: November 2002

Although CD8 T cells are thought to be a principal effector population of graft-versus-host disease (GVHD), their dynamics and specificity remain a mystery. Using a mouse model in which donor and recipient were incompatible at many minor histocompatibility antigens (minor H Ags), the CD8 T-cell response was tracked temporally and spatially through the course of GVHD. Donor CD8 T cells in the circulation, spleen, lung, and liver demonstrated virtually identical kinetics: rapid expansion and then decline prior to morbidity. Remarkably, up to one fourth of the CD8 T cells were directed against a single minor antigen, H60. Extreme H60 immunodominance occurred regardless of sampling time, site, and genetic background. This study is the first to analyze the T cells participating in GVHD in “real-time,” demonstrates the exceptional degree to which immunodominance of H60 can occur, and suggests that such superdominant minor H Ags could be risk factors for GVHD.
Interleukin-10–mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen
Authors: Hall Andrew M. , Ward Frank J. , Vickers Mark A. , Stott Lisa-Marie , Urbaniak Stanislaw J. , Barker Robert N.
Published: November 2002

Regulatory T cells have been shown to control animal models of immune-mediated pathology by inhibitory cytokine production, but little is known about such cells in human disease. Here we characterize regulatory T-cell responses specific for a human red blood cell autoantigen in patients with warm-type autoimmune hemolytic anemia. Peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia were found either to proliferate and produce interferon-γ or to secrete the regulatory cytokine interleukin 10 when stimulated in vitro with a major red blood cell autoantigen, the RhD protein. Flow cytometric analysis confirmed that the majority of the responding cells were of the CD4+phenotype. Serial results from individual patients demonstrated that this bias toward proliferative or interleukin-10 responses was unstable over time and could reverse in subsequent samples. Epitope mapping studies identified peptides from the sequence of the autoantigen that preferentially induced interleukin-10 production, rather than proliferation, and demonstrated that many contain naturally processed epitopes. Responses to such peptides suppressed T-cell proliferation against the RhD protein, an inhibition that was mediated largely by interleukin 10 and dependent on cytotonic T lymphocyte–associated antigen (CTLA-4) costimulation. Antigenic peptides with the ability to stimulate specific regulatory cells may represent a new class of therapeutic agents for immune-mediated disease.
A novel diagnostic screen for defects in the Fanconi anemia pathway
Authors: Shimamura Akiko , de Oca Rocio Montes , Svenson John L. , Haining Nicholas , Moreau Lisa A. , Nathan David G. , D'Andrea Alan D.
Published: November 2002

Fanconi anemia (FA) is an autosomal recessive chromosomal instability syndrome characterized by congenital abnormalities, progressive bone marrow failure, and cancer predisposition. Although patients with FA are candidates for bone marrow transplantation or gene therapy, their phenotypic heterogeneity can delay or obscure diagnosis. The current diagnostic test for FA consists of cytogenetic quantitation of chromosomal breakage in response to diepoxybutane (DEB) or mitomycin C (MMC). Recent studies have elucidated a biochemical pathway for Fanconi anemia that culminates in the monoubiquitination of the FANCD2 protein. In the current study, we develop a new rapid diagnostic and subtyping FA assay amenable for screening broad populations at risk of FA. Primary lymphocytes were assayed for FANCD2 monoubiquitination by immunoblot. The absence of the monoubiquitinated FANCD2 isoform correlated with the diagnosis of FA by DEB testing in 11 known patients with FA, 37 patients referred for possible FA, and 29 healthy control subjects. Monoubiquitination of FANCD2 was normal in other bone marrow failure syndromes and chromosomal breakage syndromes. A combination of retroviral gene transfer and FANCD2 immunoblotting provides a rapid subtyping assay for patients newly diagnosed with FA. These new FA screening assays would allow efficient testing of broad populations at risk.
Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm
Authors: Fröhling Stefan , Schlenk Richard F. , Breitruck Jochen , Benner Axel , Kreitmeier Sylvia , Tobis Karen , Döhner Hartmut , Döhner Konstanze
Published: November 2002

To assess the prognostic relevance of activating mutations of theFLT3 gene in homogeneously treated adults 16 to 60 years of age with acute myeloid leukemia (AML) and normal cytogenetics, pretreatment samples from 224 patients entered into 2 consecutive multicenter treatment trials were analyzed for FLT3internal tandem duplications (ITDs) and Asp835 mutations. Treatment included intensive double-induction therapy and postremission therapy with high cumulative doses of high-dose cytarabine. ITDs were detected in 32% of the patients and were related to de novo AML and to high white blood cell (WBC) counts, percentages of peripheral blood (PB) and bone marrow (BM) blasts, and serum lactate dehydrogenase levels. Asp835 mutations were present in 14% of the patients and were associated with WBC counts and percentages of PB and BM blasts that were higher than those of patients without FLT3mutations. With a median follow-up of 34 months, remission duration and overall survival (OS) were significantly shorter for patients with Asp835 mutations or an ITD than for those without FLT3 mutations (P = .03 and P = .0004, respectively). These results were attributable mainly to the negative prognostic effect of FLT3 ITDs. On multivariate analysis, mutantFLT3 was an independent marker affecting remission duration and OS (hazard ratio, 2.35 and 2.11, respectively). Fluorescence in situ hybridization did not detect monoallelicFLT3 deletions in ITD-positive patients. FLT3mutations identify a subset of young AML patients with normal cytogenetics who do not benefit from intensive chemotherapy, including double-induction and postremission therapy with high-dose cytarabine.
Myeloid progenitors protect against invasive aspergillosis andPseudomonas aeruginosa infection following hematopoietic stem cell transplantation
Authors: BitMansour Andrew , Burns Stacy M. , Traver David , Akashi Koichi , Contag Christopher H. , Weissman Irving L. , Brown Janice M. Y.
Published: November 2002

Myelotoxic treatments for oncologic diseases are often complicated by neutropenia, which renders patients susceptible to potentially lethal infections. In these studies of murine hematopoietic stem cell transplantation (HSCT), cotransplantation of lineage-restricted progenitors known as common myeloid progenitors (CMP) and granulocyte-monocyte progenitors (GMP) protects against death following otherwise lethal challenge with either of 2 pathogens associated with neutropenia: Aspergillus fumigatus and Pseudomonas aeruginosa. Cotransplantation of CMP/GMP resulted in a significant and rapid increase in the absolute number of myeloid cells in the spleen, most of which were derived from the donor CMP/GMP. Despite persistent peripheral neutropenia, improved survival correlated with the measurable appearance of progenitor-derived myeloid cells in the spleen. A marked reduction or elimination of tissue pathogen load was confirmed by culture and correlated with survival. Localization of infection by P aeruginosa and extent of disease was also assessed by in vivo bioluminescent imaging using a strain ofP aeruginosa engineered to constitutively express a bacterial luciferase. Imaging confirmed that transplantation with a graft containing hematopoietic stem cells and CMP/GMP reduced the bacterial load as early as 18 hours after infection. These results demonstrate that enhanced reconstitution of a tissue myeloid pool offers protection against lethal challenge with serious fungal and bacterial pathogens.
Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation
Authors: DiNubile Mark J. , Stossel Thomas P. , Ljunghusen Olof C. , Ferrara James L. M. , Antin Joseph H.
Published: November 2002

The idiopathic pneumonia syndrome (IPS) represents a common and often fatal complication of hematopoietic stem cell transplantation (HSCT). Gelsolin is a highly conserved actin-binding protein normally present in plasma that may serve a basic physiological role in limiting acute lung injury of diverse etiologies. We hypothesized that depletion of circulating gelsolin following HSCT might play a permissive role in the pathogenesis of IPS. Plasma gelsolin levels were measured by immunoblotting in frozen samples obtained weekly from 24 patients undergoing allogeneic HSCT. Patients with and without IPS were similar with respect to age, diagnosis, histocompatibility differences between donor and recipient, and conditioning regimen. Mean gelsolin levels in the 9 patients with rapidly fatal IPS were significantly lower than those in patients without this complication by week 3 after HSCT (101 ± 61 mg/L versus 221 ± 54 mg/L; P = .0002). Seven (88%) of the 8 patients with gelsolin levels of less than 100 mg/L in the first month after HSCT died from IPS within 3 months; conversely, gelsolin levels fell to less than 100 mg/L in 7 (78%) of the 9 patients who died from IPS within 3 months of HSCT (P = .0007). These findings suggest that gelsolin levels shortly after allogeneic HSCT can predict the later development of fatal IPS. Gelsolin replacement in selected transplant patients may offer a novel strategy to prevent or reverse IPS.
Discordant expression of selectin ligands and sialyl Lewis x–related epitopes on murine myeloid cells
Authors: Kobzdej Marcin M. A. , Leppänen Anne , Ramachandran Vishwanath , Cummings Richard D. , McEver Rodger P.
Published: November 2002

Murine leukocytes are thought to express α2-3-sialylated and α1-3-fucosylated selectin ligands such as sialyl Lewis x (sLex), although monoclonal antibodies (mAbs) to sLex or Lex reportedly do not bind to murine leukocytes. We observed that P- and E-selectin bound to pronase-sensitive ligands on murine monocytic WEHI-3 cells and murine neutrophils, indicating that the ligands for both selectins are glycoproteins. CSLEX-1, HECA-452, and other widely used mAbs to sLex and Lex did not bind to WEHI-3 cells and bound at very low levels to murine neutrophils. Only the anti-sLex mAbs 2H5 and KM93, which also recognize nonfucosylated glycans, bound to WEHI-3 cells. 2H5 and KM93 bound to pronase-resistant structures, indicating that the mAbs did not identify selectin ligands. Treatment of WEHI-3 cells with glycosidases or chlorate demonstrated that sialic acid modifications, α1-3-galactosylation, or sulfation did not mask epitopes for mAbs to sLex or Lex. Compared to human promyelocytic HL-60 cells, WEHI-3 cells and murine neutrophils expressed low α1-3-fucosyltransferase activities. Consistent with very low endogenous fucosylation, forced fucosylation of intact WEHI-3 cells or murine neutrophils by exogenous α1-3-fucosyltransferase FTVI and GDP-fucose created many new epitopes for anti-sLexmAbs such as HECA-452 and CSLEX-1. Nevertheless, forced fucosylation of intact cells did not significantly augment their ability to bind to fluid-phase P- or E-selectin or to roll on immobilized P- or E-selectin under flow. These data suggest that murine myeloid leukocytes fucosylate only a few specific glycans, which interact preferentially with P- and E-selectin.
Prolonged Survival After Complete Resection of Disseminated Melanoma and Active Immunotherapy With a Therapeutic Cancer Vaccine
Authors: Hsueh Eddy C. , Essner Richard , Foshag Leland J. , Ollila David W. , Gammon Guy , O’Day Steven J. , Boasberg Peter D. , Stern Stacey L. , Ye Xing , Morton Donald L.
Published: November 2002

PURPOSE: The curative effect of surgery in certain patients with metastatic melanoma suggests the presence of endogenous antitumor responses. Because melanoma is immunogenic, we investigated whether a therapeutic cancer vaccine called Canvaxin (CancerVax Corporation, Carlsbad, CA) could enhance antitumor immune responses and thereby prolong survival.

PATIENTS AND METHODS: Of 263 patients who underwent complete resection of American Joint Committee on Cancer stage IV melanoma, 150 received postoperative adjuvant vaccine therapy and 113 did not. The overall survival (OS) for the two groups was compared by Cox regression. Further survival analysis was performed by matched-pair analysis according to three prognostic variables: sex, metastatic site, and number of tumor-involved organ sites.

RESULTS: Five-year OS rates were 39% for vaccine and 19% for nonvaccine patients. On multivariate analysis, vaccine therapy was the most significant prognostic variable in this cohort (P = .0001). Analysis of 107 matched pairs of vaccine and nonvaccine patients revealed a significant OS advantage for vaccine therapy (P = .0009): 5-year OS was 39% for vaccine patients versus 20% for nonvaccine patients. There was a significant delayed-type hypersensitivity (DTH) response to adjuvant vaccine therapy (P = .0001), and OS was significantly correlated with DTH to vaccine (P = .0001) but not with DTH to purified protein derivative (PPD), a control antigen.

CONCLUSION: Prolonged survival was observed in patients who received postoperative active immunotherapy with Canvaxin therapeutic cancer vaccine. The correlation of survival with vaccine-DTH responses but not PPD-DTH indicates a treatment-specific effect. These findings suggest that adjuvant active specific immunotherapy should be considered after cytoreductive surgery for advanced melanoma.
Music and social identity: Stylistic identification as a response to musical style
Authors: Tekman Hasan Gürkan , Hortaçsu Nuran
Published: November 2002

One function of music is considered to be defining social identity for oneself and for others. This aspect of musical styles was investigated in the light of Social Identity Theory by examining how a college student population described fans of different musical styles. Respondents were questioned about their perception of listeners of six musical styles, two of which were indigenous to Turkey. Three basic dimensions that described the listeners of these styles emerged as the result of factor and scale reliability analyses. These dimensions were labelled the sophisticated, the sprightly, and the loser. Respondents associated these features with fans of different styles to different extents. The sprightly dimension characterized listeners of pop, rock, and rap best. The sophisticated dimension was most closely associated with listeners of classical and Turkish folk music. Listening to Arabesk, which is a style that is specific to Turkey, was most closely associated with the loser dimension. Consistent with the predictions of Social Identity Theory, evaluations by a person were affected by the attitude of that person towards a style in the cases of rock and Turkish folk music. Especially on the sophisticated dimension, respondents who liked rock or Turkish folk music rated the listeners of these styles closer to the ideal than respondents who disliked them. However, the self‐evaluations of these groups were similar. Furthermore, respondents typically described themselves as being closer to the ideal value on the three dimensions than the listeners of musical styles they liked. These results provide considerable support for the idea that liking a musical style shows characteristics of group membership according to Social Identity Theory.
Self‐reported emotional intelligence: Construct similarity and functional dissimilarity of higher‐order processing in Iran and the United States
Authors: Ghorbani Nima , Davison H. Kristl , Bing Mark N. , Watson P.J. , Mack Dan A.
Published: November 2002

This study employed the Trait Meta‐Mood Scale (TMMS) to assess self‐reported emotional intelligence cross‐culturally as an input (attention to emotions), process (clarity of emotions), and output (repair of emotions) information‐processing system. Iranian (N = 231) and American (N = 220) university students responded to the TMMS along with measures of alexithymia, public and private self‐consciousness, depression, anxiety, self‐esteem, and perceived stress. Negative correlations with alexithymia and expected linkages with all other variables documented the validity of the TMMS in both cultures. Most of the other measures correlated similarly in the two samples. However, private and public self‐consciousness displayed a stronger positive association in Iran. These two scales were also more predictive of adjustment in Iran and of maladjustment in the United States. This difference perhaps reflected a poorer integration of the two dimensions of self‐consciousness within a presumably more individualistic American society. Confirmatory factor analyses and measurement invariance procedures revealed cross‐cultural similarities in the fit of an a priori higher‐order factor structure to the obtained data, but subsequent structural equation modelling techniques uncovered cross‐cultural dissimilarities in the actual processing of emotional information. Specifically, the higher‐order factors of emotional intelligence were similar, but the interrelationships among those higher‐order factors were not. As expected, Iranians displayed positive relationships among the input, processing, and output activities of the information‐processing model. For the Americans, however, greater input was associated with diminished processing and output. This unanticipated relative contrast seemed congruent with speculation that the historical American emphasis on the self and individualism promotes positive, optimistic thinking. Overall, these data most importantly suggested that subtle cultural differences might exist in the processing of emotional information.
From “blame by praise” to “praise by blame”: Analysis of vocal patterns in ironic communication
Authors: Anolli Luigi , Ciceri Rita , Infantino Maria Giaele
Published: November 2002

From a communication psychology point of view, irony is not only a rhetorical figure or a cunning linguistic device, but also an articulated strategy for a flexible negotiation of meaning, as well as for establishing and maintaining relations with others. Within the “irony family” phenomena our attention is focused on the sarcastic irony generated in a conflict context (“praise by blame”) and on the kind irony produced in a cooperation context (“blame by praise”). The effects of the variability of contextual cues on the vocal variables (Fo, energy, time) of irony were studied. Through the analysis of the vocal features of standard phrases in a conflict or cooperation context, an ironic dominant pattern has been found consisting of caricatured vocal traits, although differences referring to the two ironic expressions came out. From a subject‐by‐subject analysis, four ironic patterns were obtained: (1) in the cooperation context (a) a rather high and changeable pitch and strong energy (“bantering” joy) were observed, as well as (b) a low and monotone pitch and strong energy (emphatic mark of tenderness); (2) in the conflict context (a) a very high and changeable pitch, strong energy, and slow rate of articulation (“accented banter”) were found, as well as (b) a low and not very changeable pitch, slow rate of articulation, and steadily soft energy (like scorn and cold anger). Following these four vocal patterns, the ironic voice could be defined as a “voice of banter.” In such a way, irony appears as a method used to manipulate the weight of indirect speech, which allows the efficacy of the word and the innocence of silence. Moreover, the ironist can be described as an able director of his own image, able to play with the voice. Within social relationships, in fact, he can use his own voice for calibrating strategically his ways of (un)masking himself to the others.
The role of psychological defences in moderating between trauma and post‐traumatic symptoms among Palestinian men
Authors: Punamäki Raija‐Leena , Kanninen Katri , Qouta Samir , El‐Sarraj Eyad
Published: November 2002

Psychological defences are conceptualized as protective processes that help individuals to maintain their integrity in the face of threat and danger. Accordingly, their role in defending trauma victims from post‐traumatic symptoms was examined. The sample consisted of 128 Palestinian male political ex‐prisoners who had reported various degrees of torture and ill‐treatment. The first aim was to analyze the dimensionality and distribution of different defence mechanisms. The second was to examine which defences would moderate the association between the reported torture and ill‐treatment and the post‐traumatic symptoms (PTS). Third, the direct associations between reported torture and ill‐treatment and defences and between the defences and symptoms were explored. Defence mechanisms were assessed by a 40‐item version of the Defense Style Questionnaire (DSQ), and Post‐traumatic symptoms by the Harvard Trauma Questionnaire (HTQ), and experiences of torture and ill‐treatment by a scale developed for that purpose. The results show, first, that the men used predominantly mature defences such as anticipation, sublimation, suppression, and rationalization, but also relatively frequently somatization and dissociation, which are characteristic responses among trauma victims. Second, the principal component analysis revealed four defence dimensions, differentiated by the level of maturity and the approach to reality: the mature reality‐based, the consciousness‐limiting, the immature reality‐escaping, and the immature reality‐distorting defences. Third, against our hypothesis, the moderating analyses indicated that the reported torture and ill‐treatment were relatively more associated with vigilance, avoidance, and intrusion symptoms if men used consciousness‐limiting defences. Yet as expected, the mature reality‐based defences did not show a protective effect. Furthermore, a high level of reported torture and ill‐treatment was associated with a low level of the mature reality‐based defences, but not with a high level of immature defences. Last, similarly to earlier studies, the immature reality‐distorting and immature reality‐escaping defences associated directly with high, and mature reality‐based defences with low, levels of PTS‐symptoms.
Influence of opioid peptides on human neutrophil apoptosis and activation in vitro
Authors: Sulowska Zofia , Majewska Ewa , Krawczyk Katarzyna , Klink Magdalena , Tchórzewski Henryk
Published: November 2002

Background: It has been shown that cells of the immune system release opioid peptides and possess receptors for them. The concentrations of opioid peptides in the peripheral circulation rapidly increase during inflammation and acute stress response.

Aims: The effect of opioid peptides Met‐enkephalin (M‐ENK) and beta‐endorphin (β‐END) on the oxidative metabolism of normal human neutrophils and their death by apoptosis in vitro was investigated.

Methods: Isolated from peripheral blood, neutrophils were incubated in the presence or absence of 10-6 to 10-10 M of M‐ENK and β‐END for 12 and 18 h. Apoptosis of neutrophils was determined in vitro by flow cytometric analysis of cellular DNA content and Annexin V‐FITC protein binding to the cell surface. The MTT‐reduction assay was employed to estimate the oxidative metabolism of neutrophils.

Results: Treatment with M‐ENK caused a significant increase in apoptotic cells after 18 h of culture: ∗0
M (control) versus 10-10 M, p ≤ 0.02; ∗∗10−10 M versus 10-10 M, p ≤ 0.02. Treatment with β‐END caused a significant increase in apoptotic cells after 12 h of culture: 0 M versus 10-8 M,
p ≤ 0.03; ∗∗0M
M versus 10-10 M,
p ≤ 0.04. We found the significant increase in MTT reduction by neutrophils in the presence of M‐ENK and β‐END both before and after the culture. However, the ability of neutrophils to reduce the MTT salt to formazan decreased significantly after the culture.

Conclusions: We observed that the in vitro effect of opioid peptides on the neutrophil survival and their functional state was time and dose dependent. The presence of antioxidants in the culture medium modifies neutrophil survival.
Interference of a short‐term exposure to nitrogen dioxide with allergic airways responses to allergenic challenges in BALB/c mice
Authors: Proust Barbara , Lacroix Ghislaine , Robidel Franck , Marliere Maryse , Lecomte Anthony , Vargaftig B. Boris
Published: November 2002

Nitrogen dioxide (NO2) is a common indoor and outdoor air pollutant whose role in the induction of asthma is unclear. We investigated the effects of NO2 on the development of asthma‐like responses to allergenic challenge in BALB/c mice. Ovalbumin (OVA)‐immunized mice were intranasally challenged with OVA or saline solution just before starting a 3 h exposure to 5 or 20 ppm NO2 or air. Twenty parts per million of NO2 induced a significant increase of bronchopulmonary hyperreactivity in OVA‐challenged mice and of permeability according to the fibronectin content of the bronchoalveolar lavage fluid (BALF) 24 h after exposure, as compared with air or 5 ppm NO2. Eosinophilia (cell counts in the BALF and eosinophil peroxidase of lung tissue) was detected at 24 and 72 h with similar levels for air and 20 ppm NO2, whereas a marked reduction was unexpectedly observed for 5 ppm NO2. At 24 h, interleukin‐5 in the BALF was markedly reduced at 5 ppm compared with 20 ppm NO2 and was also more intense for 20 ppm NO2 than for the air group. In contrast to specific IgG1 titers, anti‐OVA IgE titers and interleukin‐4 in the BALF were not affected by NO2 exposure. Irrespective of the concentration of NO2, OVA‐challenged mice did not develop late mucosal metaplasia compared with those exposed to OVA‐air. These results indicate that a short exposure to NO2 can exacerbate or inhibit some features of the development of allergic disease in mice and may depend on the concentration of pollutant.
The effect of high dose digoxin on cytokines in healthy dogs
Authors: Dülger Haluk , Şekeroğlu Mehmet Ramazan , Eryonucu Beyhan , Noyan Tevfik , Alici Süleyman
Published: November 2002

Background: Tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β are pro‐inflammatory cytokines, causing myocardial dysfunction and a negative inotropic effect. The drugs used to treat heart failure affect the production of cytokines. Digoxin, on which this study was focused, is one of the drugs for the treatment of heart failure.

Aim: The present study was designed to examine the early effects of high doses of digoxin on the production of cytokines in healthy dogs.

Methods: Digoxin was given parenterally to dogs at 0.15 mg/kg. IL‐1β and TNF‐α production and levels of digoxin in the serum were measured 0, 12, 24, 48, and 72 h following administration of digoxin.

Results: As the levels of serum digoxin taken at 12, 24, 48, and 72 h of administration were considered significantly high compared with preceding values
(p < 0.001),
no notable change in serum IL‐1β and TNF‐α levels was observed.

Conclusions: These results suggest that high doses of digoxin do not cause a significant cytokine production in heart muscle in the early phase.
Blood serotonin and joint pain in seropositive versus seronegative rheumatoid arthritis
Authors: Kopp Sigvard , Alstergren Per
Published: November 2002

Aim: To investigate whether blood serotonin (5‐hydroxytryptamine) (5‐HT) modulates musculoskeletal pain differently in seropositive and seronegative rheumatoid arthritis (RA).

Methods: Patients with temporomandibular joint (TMJ) involvement of seropositive RA (33 patients) or seronegative RA (28 patients) and 26 healthy individuals were included. TMJ pain, general musculoskeletal pain, plasma and serum 5‐HT, acute phase reactants and thrombocyte count were investigated.

Results: The patients with seropositive RA had higher serum (median = 1130 nmol/l) and plasma (55 nmol/l) levels of 5‐HT than the healthy individuals (704 nmol/l, p = 0.044 and 23 nmol/l, p < 0.001, respectively), and higher plasma levels of 5‐HT than the seronegative patients (14 nmol/l, p < 0.001). There was no significant correlation between serum and plasma levels of 5‐HT in any group.

In the seropositive RA patients, positive correlations were found between serum levels of 5‐HT and the number of painful mandibular movements
(rs = 0.36, n = 33, p = 0.042), as well as pain on maximum mouth opening (rs = 0.41, n = 24, p = 0.047) and tenderness to digital palpation (rs = 0.49, n = 33, p = 0.003).

In the healthy individuals, there was a negative correlation between plasma level of 5‐HT and the TMJ pressure pain threshold
(rs = −0.47
, n = 20
, p = 0.037).

Conclusion: Peripheral serotonergic pain mechanisms seem to be activated by blood 5‐HT in patients with seropositive RA, in contrast to seronegative patients.
Increased apoptosis of peripheral blood mononuclear cells in patients with perennial allergic asthma/rhinitis: relation to serum markers of apoptosis
Authors: Grzegorczyk Janina , Kowalski Marek L. , Pilat Anna , Iwaszkiewicz Jolanta
Published: November 2002

Background: The goal of our study was to examine spontaneous and stimulated apoptosis of peripheral blood MNC from allergic patients, sensitized to Der p I antigen as compared to cells from non‐atopic subjects. Furthermore we aimed to investigate which populations of mononuclear cells (lymphocytes, monocytes) undergo the apoptosis and to determine relations between apoptosis and serum levels of sFas/APO‐1, ICE/caspase‐1 or TNF‐α.

Methods: The study included 17 patients with perennial, allergic asthma and/or allergic rhinitis [6 male and 11 female; mean age 29,5 years; (range 15‐49)].

Apoptosis was assessed by fluorescence technique and confirmed by flow‐cytometric method and DNA ladder. Serum levels of sFas, ICE/caspase‐1 or TNF‐α were determined by immunoassays (ELISA).

Results: Apoptotic index of unfractionated mononuclear cells (MNC) and lymphocytes (but not monocytes) were significantly higher in allergic patients as compared to non‐allergic subjects after 48 and 72 hours of culture (p < 0.05). Incubation of cells with ConA (10 μg/ml) resulted in a significant increase in the proportion of apoptotic cells in all populations once the apoptotic index for MNC and lymphocytes (but not monocytes) was again significantly higher in allergic as compared to non‐allergic subjects after 24, 48 and 72 hour of culture.

In allergic patients, mean serum sFas level, was significantly lower then in non‐allergic group (mean value 624.8 pg/ml ± 25.67 versus 802.0 pg/ml ± 31.91; p = 0.003)
and in both groups sFas level correlated inversely with apoptosis of MNC. The mean ICE/caspase‐1 concentration was significantly higher in sera of allergic patients as compared to non‐allergic group (mean value 27.71 pg/ml ± 3.79 vs 23.54 pg/ml respectively; p < 0.01).
ICE/caspase‐1 levels in allergic patients correlated with apoptotic index of mononuclear cells (r = 0.57
; p < 0.001).

Conclusions: An increased spontaneous and mitogen‐induced apoptosis of MNC from peripheral blood of atopic patients as well as different serum levels of sFas and ICE/caspase‐1 correlating with apoptosis, suggest different regulation of apoptotic process in peripheral blood mononuclear cells of patients with allergic asthma and/or rhinitis.
Cytokine profile of Ehrlich ascites tumor treated with Bothrops jararaca venom
Authors: da Silva Reinaldo J. , da Silva Márcia G. , Vilela Lízia C. , Fecchio Denise
Published: November 2002

We previously demonstrated that Bothrops jararaca venom (BjV) has an antitumor effect on Ehrlich ascites tumor (EAT) cells and induces an increase of polymorphonuclear leukocytes in early stages of tumor growth. It has been reported that this venom presents an important inflammatory effect when inoculated in animal models and in human snakebites, and that cytokine levels have been detected in these cases. To evaluate whether the cytokines can be involved with the suppression of the tumoral growth, we evaluate the cytokine profile in the peritoneal cavity of mice inoculated with EAT cells and treated with BjV. Swiss mice were inoculated with EAT cells by the intraperitoneal route and treated with BjV venom (0.4 mg/kg, intraperitoneally), on the 1st, 4th, 7th, 10th, and 13th day. Mice were evaluated for cytokine levels on the 2nd, 5th, 8th, 11th and 14th day. Analysis was performed using an enzyme‐linked immunosorbent assay for interleukin (IL)‐1α, IL‐2, IL‐4, IL‐6, IL‐10, IL‐13, and tumor necrosis factor‐α (TNF‐α) levels in the peritoneal washing supernatant. Results were analyzed statistically by the Kruskal‐Wallis and Dunn′s tests at the 5% level of significance. We observed that EAT implantation induces IL‐6 production on the 11th and 14th days of tumor growth, IL‐10 on the 11th day and TNF‐α on the 14th day. The treatment with BjV suppresses production of these cytokines. In addition, IL‐13 was produced by animals that were inoculated only with venom on the 11th and 14th days, and by the group inoculated with EAT cells and treated with venom on the 2nd and 14th days. Furthermore, we suggest that the IL‐6 detected in the present study is produced by the EAT cells and the suppression of its production could be associated with the antitumor effect of BjV.
Inhibitory action of a macrolide antibiotic, roxithromycin, on co‐stimulatory molecule expressions in vitro and in vivo
Authors: Suzuki Mayumi , Asano Kazuhito , Yu Mei , Hisamitsu Tadashi , Suzaki Harumi
Published: November 2002

Objective: The influence of a macrolide antibiotic, roxithromycin (RXM), on co‐stimulatory molecule expression was examined in vitro and in vivo.

Materials and methods: Spleen cells obtained from BALB/c mice 10 days after immunization with 8.0 μg of hemocyanin absorbed to 4.0 mg of aluminum hydroxide were cultured in the presence of 100.0 μg/ml of hemocyanin and various concentrations of RXM. We first examined the influence of RXM on cell activation by examining the proliferative response of cells and cytokine production. We also examined the influence of RXM on co‐stimulatory molecule (CD40, CD80 and CD86) expressions on cultured splenic B‐lymphocytes induced by
in vitro antigenic stimulation using flow cytometry. In the second part of experiments, non‐immunized and immunized mice were treated orally with 2.5 mg/kg of RXM once a day for 4 or 8 weeks. Splenic B lymphocytes were obtained from these mice 24 h after antigenic challenge, and co‐stimulatory molecule expressions were examined by flow cytometer.

Results: Cell activation induced by in vitro antigenic stimulation was suppressed by RXM when cells were cultured in the presence of more than 5.0 μg/ml of the agent. Addition of RXM at a concentration of 5.0 μg/ml into cell cultures also suppressed co‐stimulatory molecule (CD40, CD80 and CD86) expressions on splenic B lymphocytes, which was enhanced by antigenic stimulation in vitro. Oral RXM administration for 4 weeks clearly suppressed the enhancement of CD40 and CD86 (but not CD80) expressions on splenic B lymphocytes induced by antigenic stimulation in vivo. This suppressive activity of RXM on co‐stimulatory molecule (CD40 and CD86) expressions was further strengthened by the treatment of mice for 8 weeks. Long‐term treatment with oral RXM also suppressed CD80 expressions, which was not suppressed by 4‐week treatment.

Conclusion: The present results suggest that RXM exerts its immunomodulating effects through suppression of both cell activation and co‐stimulatory molecule expressions induced by antigenic stimulation. These suppressive activities of RXM might contribute, in part, to the therapeutic mode of action of RXM on inflammatory diseases.
Green functions and fluctuation spectra for thermal modes in isotropic solid films
Authors: M C Oliveros  , D R Tilley
Published: November 2002

Green functions and fluctuation power spectra are calculated for entropy and temperature in thermally isolated solid thin films and semi-infinite media. The fluctuations are described by the heat diffusion equation, and only variations normal to the surface are considered. The Green functions are used in a calculation of the inelastic light (Rayleigh) scattering cross section for normally incident light. The most striking result is a omega-1/2divergence in the cross section for back-scattering off an opaque semi-infinite medium.
IT tools in personnel training in small enterprises: results of Project “Apply”
Authors: Kekäle Tauno , Pirolt Karin , Falter Claudia
Published: November 2002

This paper describes the findings of an European four‐country study that attempted to pinpoint the practical impediments the small enterprises face when attempting to use information technology (IT) as an aid in their personnel training. The study was made using the Delphi technique, interviewing 120 specialists (company owners, software and IT producers, training providers) in four countries. The results suggest that most of the small companies are not yet ready to use the latest IT technologies in their personnel training, but there may be a “trickle‐down” effect from the bigger companies in some countries. The results furthermore suggest that the new IT solutions seldom deliver what they promise for the small companies. It seems that the significant impediments are the factors that the IT solutions were supposed to solve, namely freedom of time, space and pre‐described content. It seems that not many of the IT training solutions are developed with the small companies’ needs in sight, and a more close cooperation between the actors and tailoring of the IT products are often needed when planning this kind of training.
Team self‐assessment: problem solving for small workgroups
Authors: LoBue Robert
Published: November 2002

The “team self‐assessment” is introduced here as an effective mechanism for front‐line supervisors to develop new procedures and process improvements directed at accomplishing strategic, as well as tactical, organizational objectives. It is shown in a handful of organizational environments to be an effective tool for encouraging employee participation in instigating creative ideas and reengineered process approaches. It can be used to address seemingly intractable process issues and repeated errors and is specifically constructed for employment by small workgroups and employee teams with direct responsibility for day‐to‐day line and staff tasks. The team self‐assessment also is shown to contain a measure of consistency with the theoretical and practical principles of the control self‐assessment, Belbin’sTM team roles, and Anderson and West’s team climate Inventory.
Research and the pedagogics of work and learning
Authors: Spencer Bruce
Published: November 2002

This paper argues that workplace learning is a problematic activity that may not result in the celebration of employee empowerment and autonomy that is often claimed but in the reverse: the entrenchment of existing power relations. It argues for an understanding of workplace learning within a broader economic and social context and for researchers and adult educators to acknowledge their historic responsibilities to argue for socially responsible adult education.
Spin-Flip Symmetry and Synchronization
Authors: Hoyweghen Clarissa Van , Naudts Bart , Goldberg David E.
Published: November 2002

In the context of optimization by evolutionary algorithms (EAs), epistasis, deception, and scaling are well-known examples of problem difficulty characteristics. The presence of one such characteristic in the representation of a search problem indicates a certain type of difficulty the EA is to encounter during its search for globally optimal configurations. In this paper, we claim that the occurrence of symmetry in the representation is another problem difficulty characteristic and discuss one particular form, spin-flip symmetry, characterized by fitness invariant permutations on the alphabet. Its usual effect on unspecialized EAs, premature convergence due to synchronization problems, is discussed in detail. We discuss five different ways to specialize EAs to cope with the symmetry: adapting the genetic operators, changing the fitness function, using a niching technique, using a distributed EA, and attaching a highly redundant genotype-phenotype mapping.
Embedded Landscapes
Authors: Heckendorn Robert B.
Published: November 2002

In this paper we introduce embedded landscapes as an extension of NK landscapes and MAXSAT problems. This extension is valid for problems where the representation can be expressed as a simple sum of subfunctions over subsets of the representation domain. This encompasses many additive constraint problems and problems expressed as the interaction of subcomponents, where the critical features of the subcomponents are represented by subsets of bits in the domain. We show that embedded landscapes of fixed maximum epistasis K are exponentially sparse in epistatic space with respect to all possible functions. We show we can compute many important statistical features of these functions in polynomial time including all the epistatic interactions and the statistical moments of hyperplanes about the function mean and hyperplane mean. We also show that embedded landscapes of even small fixed K can be NP-complete. We can conclude that knowing the epistasis and many of the hyperplane statistics is not enough to solve the exponentially difficult part of these general problems and that the difficulty of the problem lies not in the epistasis itself but in the interaction of the epistatic parts.