bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actin cytoskeletal dynamics in T lymphocyte activation and migration
Authors: Samstag Yvonne , Eibert Sybille M , Klemke Martin , Wabnitz Guido H 
Published: March 2003

Abstract
Dynamic rearrangements of the actin cytoskeleton are crucial for the function of numerous cellular elements including T lymphocytes. They are required for migration of T lymphocytes through the body to scan for the presence of antigens, as well as for the formation and stabilization of the immunological synapse at the interface between antigen-presenting cells and T lymphocytes. Supramolecular activation clusters within the immunological synapse play an important role for the initiation of T cell responses and for the execution of T cell effector functions. In addition to the T cell receptor/CD3 induced actin nucleation via Wasp/Arp2/3-activation, signals through accessory receptors of the T cell (i.e., costimulation) regulate actin cytoskeletal dynamics. In this regard, the actin-binding proteins cofilin and L-plastin represent prominent candidates linking accessory receptor stimulation to the rearrangement of the actin cytoskeleton. Cofilin enhances actin polymerization via its actin-severing activity, and as a long-lasting effect, cofilin generates novel actin monomers through F-actin depolymerization. L-plastin stabilizes acin filament structures by means of its actin-bundling activity.
Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response
Authors: Charbonnier Anne-Sophie , Hammad Hamida , Gosset Philippe , Stewart Geoffrey A , Alkan Sefik , Tonnel André-Bernard , Pestel Joël 
Published: March 2003

Abstract
Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)-sensitized allergic patients and in healthy donors, M-DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1-pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80, and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic naive CD4+ T cells from healthy donors, Der p 1-pulsed M-DC from allergic patients favored a Th1 profile [interferon (IFN)-γhigh/IL-4low] and Der p 1-pulsed P-DC, a Th2 profile (IFN-γlow/IL-4high). In healthy donors, no T cell polarization (IFN-γlow/IL-4low) was induced by Der p 1-pulsed M-DC or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led to an inhibition of IL-10 production by T cells and a polarization toward a type 1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P-DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors.
Interleukin-4 biases differentiation of B cells from Trypanosoma cruzi-infected mice and restrains their fratricide: role of Fas ligand down-regulation and MHC class II-transactivator up-regulation
Authors: Acosta Rodriguez E V , Zuñiga E , Montes C L , Gruppi A 
Published: March 2003

Abstract
In the present work, we demonstrate that interleukin (IL)-4 is able to rescue B cells from Trypanosoma cruzi-infected mice, counteracting the strong apoptotic signals that these cells received in vivo. We have observed that IL-4 restrains the apoptosis of immunoglobulin (Ig)M+ and IgG+ B cells from infected and normal mice without inducing them to proliferate. In addition, IL-4 does not modify the quantity or quality of the antibodies secreted by B cells from infected mice, as it blocks their terminal differentiation to plasma cells and favors memory pathway. It is interesting that the protective effect of IL-4 over B cells from infected mice is mediated, at least partly, by the down-regulation of Fas ligand (FasL) expression, which leads to interference in the apoptosis executed by these B cells through the Fas/FasL death pathway. Accordingly, a marked up-regulation of the “FasL gene repressor” class II transactivator was observed, suggesting that this would be one mechanism underlying the IL-4-mediated FasL down-regulation.
Cell type-dependent activation of 5-lipoxygenase by arachidonic acid
Authors: Bürkert Eva , Szellas Dagmar , Rådmark Olof , Steinhilber Dieter , Werz Oliver 
Published: March 2003

Abstract
5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory leukotrienes. We show that stimulation of polymorphonuclear leukocytes (PMNL), rat basophilic leukemia (RBL)-1, or transfected HeLa cells with arachidonic acid (AA) caused prominent 5-LO product formation that coincided with the activity of extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase. 5-LO product formation in AA-stimulated PMNL and RBL-1 cells was independent of Ca2+. However, in HeLa cells expressing a 5-LO mutant lacking potential 5-LO phosphorylation sites, removal of Ca2+ caused a prominent loss of 5-LO activity. For Mono Mac 6 (MM6) cells, A failed to activate ERKs, and AA-induced 5-LO product formation was only minute. Also, activation of ERKs by phorbol esters did not lead to prominent 5-LO product synthesis. Instead, 5-LO activation in MM6 cells required Ca2+ or alternative signaling pathways induced by hyperosmotic stress. In summary, mechanisms for activation of 5-LO differ considerably between cell types.
Human immunodeficiency virus type 1 (HIV-1) induces activation of multiple STATs in CD4+ cells of lymphocyte or monocyte/macrophage lineages
Authors: Kohler James J , Tuttle Daniel L , Coberley Carter R , Sleasman John W , Goodenow Maureen M 
Published: March 2003

Abstract
Human immunodeficiency virus type 1 (HIV-1) impacts the activation state of multiple lineages of hematopoietic cells. Chronic HIV-1 infection among individuals with progressive disease can be associated with increased levels of activated signal transducers and activators of transcription (STATs) in peripheral blood mononuclear cells. To investigate interactions between HIV-1 and CD4+ cells, activated, phosphorylated STAT proteins in nuclear extracts from lymphocytic and promonocytic cell lines as well as primary monocyte-derived macrophages were measured. Levels of activated STATs increased six- to tenfold in HUT78 and U937 cells within 2 h following exposure to virions. The response to virus was dose-dependent, but kinetics of activation was delayed relative to interleukin-2 or interferon-γ. Activation of STAT1, STAT3, and STAT5 occurred with diverse viral envelope proteins, independent of coreceptor use or viral replication. Envelope-deficient virions had no effect on STAT activation. Monoclonal antibody engagement of CD4 identified a novel role for CD4 as a mediator in the activation of multiple STATs. Results provide a model for HIV-1 pathogenesis in infected and noninfected hematopoietic cells.
Regulation of lymphocyte-mediated killing by GTP-binding proteins
Authors: Khurana Dianne , Leibson Paul J 
Published: March 2003

Abstract
Exocytosis of granules containing apoptosis-inducing proteins is one mechanism of target cell killing by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Granules containing perforin and granzymes are redistributed to the area of cell contact initiated by specific interactions between surface ligands on a target cell and receptors on an effector lymphocyte. The formation of a stable conjugate between a cytotoxic lymphocyte and its potential target cell, followed by the directed delivery of granule components to the target cell are prerequisites of lymphocyte-mediated killing. Critical to understanding the development of cytotoxic function by CTLs and NK cells is the delineation of the second messenger pathways that specifically control the reorganization of the actin cytoskeleton during cell-mediated cytotoxicity. The low molecular weight guanosine 5′-triphosphate-binding proteins of the Rho family play a central role in these regulatory events controlling cytotoxic lymphocyte activation.
Differential recruitment of α2β1 and α4β1 integrins to lipid rafts in Jurkat T lymphocytes exposed to collagen type IV and fibronectin
Authors: Holleran Brian J , Barbar Élie , Payet Marcel D , Dupuis Gilles 
Published: March 2003

Abstract
Collagen type IV (CnIV) and fibronectin (Fn) were used as ligands to study the distribution of α2β1 and α4β1 integrins in low-density, detergent-resistant microdomains (DRM) of Jurkat lymphocytes. CnIV-coated microspheres induced (optical trapping) the redistribution of GM1-associated fluorecence from the cell periphery to the area of contact. This was not observed in cells treated with β-methyl cyclodextrin (MCD). Fn- or bovine serum albumin-coated microspheres did not modify the peripheral distribution of fluorescence. These observations were confirmed by confocal microscopy. Western blot analysis of cells exposed to surfaces coated with CnIV revealed that the α2-subunit was initially present at low levels in DRM, became strongly associated after 40 min, and returned to basal levels after 75 min. Fn induced a slight recruitment of the β1-integrin α4-subunit in DRM after 5 and 10 min, followed by a return to basal levels. Neither CnIV nor Fn triggered significant changes in the distribution of the β1-subunit in DRM. Fn- and CnIV-coated microspheres or surfaces coated with these ligands triggered a MCD-sensitive mobilization of Ca2+. MCD did not alter the state of the Ca2+ reserves. The differential distributions of the α2β1 and α4β1 integrins in DRM may provide one additional step in the regulation of outside-in signaling involving these integrins.
Synergism of nitric oxide and maturation signals on human dendritic cells occurs through a cyclic GMP-dependent pathway
Authors: Paolucci Clara , Burastero Samuele E , Rovere-Querini Patrizia , De Palma Clara , Falcone Sestina , Perrotta Cristiana , Capobianco Annalisa , Manfredi Angelo A , Clementi Emilio 
Published: March 2003

Abstract
Nitric oxide (NO), generated by phagocytes at inflammation sites, contributes to regulate immune responses through autocrine and paracrine actions on bystander cells. Among the latter are dendritic cells (DCs). Little is known about regulation of DC function by NO, especially in the human system. We exposed human monocyte-derived DCs to the NO donor (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino] diazen-1-ium-1,2 diolate (DETA-NO) during their maturation process induced by treatment with tumor necrosis factor α or lipopolysaccharide or by CD40 activation. We report here that after exposure to DETA-NO, DCs exhibit a significantly increased ability to activate T lymphocytes stimulated by mycobacterial antigens, Staphylococcus aureus Cowen strain B, allo-antigens, or cross-linking of the CD3–T cell receptor complex. This effect persists after removal of DETA-NO, depends on the generation of cyclic guanosine 5′-monophosphate, and is a result of enhanced release by DCs of soluble factors, in particular interleukin (IL)-12. This modulation of DC function is a result of a synergism between NO and the various maturation stimuli, as neither enhanced T cell activation nor IL-12 release was observed after DC exposure to DETA-NO only. These results provide the first evidence that NO acts as a cosignaling molecule regulating human DC response to maturation stimuli.
CBP Recruitment and Histone Acetylation in Differential Gene Induction by Glucocorticoids and Progestins
Authors: Lambert James R. , Nordeen Steven K. 
Published: March 2003

Abstract
We have analyzed histone acetylation at the steroid-responsive mouse mammary tumor virus (MMTV) promoter in five separate cell lines that express functional glucocorticoid and/or progesterone receptors. Chromatin immunoprecipitation assays reveal that glucocorticoid and progesterone receptors bind the MMTV promoter after hormone addition but that receptor binding is not associated with an increase in acetylation of histone H3 or H4. We have, however, found one exception to this rule. Previously we described a cell line [T47D(C&L)] that displayed a remarkable differential induction of MMTV by glucocorticoids and progestins. At one chromosomal locus (MMTV-luciferase), MMTV is preferentially induced by glucocorticoids, whereas at another locus within the same cell (MMTV-CAT), MMTV is activated by both glucocorticoids and progestins. Here we show that the glucocorticoid-mediated induction of MMTV-luciferase is accompanied by increased recruitment of CBP to the promoter and increased histone H3 and H4 acetylation, whereas the hormonal induction of MMTV-CAT in the same cell exhibits a more modest CBP recruitment without any increase in histone acetylation. These studies suggest that increased histone acetylation may serve a potentiating function for MMTV promoter activation at certain loci. However, increased histone acetylation is not requisite for steroid-mediated induction of transcription at all genes.
Analytical and clinical evaluation of CYFRA 21-1 by electrochemiluminescent immunoassay in head and neck squamous cell carcinoma
Authors: Deng Yan Fei , Chen Ping , Lin Yong Zhi , Le Jia Zhen , Wu Xiao Li , Yu Ming Qiang , Zhuang Pei Yun , Gao Ming Hua 
Published: March 2003

This paper attempts to evaluate the clinical usefulness of CYFRA 21-1 as a serum tumour marker in patients with head and neck squamous cell carcinoma (HNSCC).The serum concentration of CYFRA 21-1 was measured utilizing a new electrochemiluminescent immunoassay (ECLIA) in 142 patients with HNSCC before and after treatment, 68 patients with benign tumours of the head and neck, and 50 healthy controls.Serum levels of CYFRA 21-1 in patients with HNSCC were significantly higher than those of benign tumours and healthy controls (p < 0.001). The diagnostic sensitivity and specificity of CYFRA 21-1 for HNSCC were 62 per cent and 100 per cent, respectively. The positive rates of CYFRA 21-1 increased with progression of HNSCC, serum CYFRA 21-1 levels were related to the tumour stage expressed by primary tumour (T) and nodal status (N) (p < 0.001), but not related to patient age, gender, smoking and drinking habit, or histopathological grade (p > 0.05). Post-treatment levels of CYFRA 21-1 in HNSCC decreased significantly (p < 0.001). Among 38 patients with clinical or radiological evidence of a recurrence during follow-up, 78.9 per cent (30 of 38) showed an increase in CYFRA 21-1.The analytical ECLIA performance for serum CYFRA 21-1 provides a new means of clinical assessment for HNSCC. The results of ECLIA suggest that the serum marker CYFRA 21-1 is valuable not only for diagnosis but also for close monitoring of patients with HNSCC.
Cardiorespiratory Events Recorded on Home Monitors
Authors: Ramanathan Rangasamy , Corwin Michael J. , Hunt Carl E. , Lister George , Tinsley Larry R. , Baird Terry , Silvestri Jean M. , Crowell David H. , Hufford David , Martin Richard J. , Neuman Michael R. , Weese-Mayer Debra E. , Cupples L. Adrienne , Peucker Mark , Willinger Marian , Keens Thomas G. ,   for The Collaborative Home Infant Monitoring Evaluation (CHIME) Study Group
Published: March 2003

ContextHome monitors designed to identify cardiorespiratory events are frequently used in infants at increased risk for sudden infant death syndrome (SIDS), but the efficacy of such devices for this use is unproven.ObjectiveTo test the hypothesis that preterm infants, siblings of infants who died of SIDS, and infants who have experienced an idiopathic, apparent life-threatening event have a greater risk of cardiorespiratory events than healthy term infants.DesignLongitudinal cohort study conducted from May 1994 through February 1998.SettingFive metropolitan medical centers in the United States.ParticipantsA total of 1079 infants (classified as healthy term infants and 6 groups of those at risk for SIDS) who, during the first 6 months after birth, were observed with home cardiorespiratory monitors using respiratory inductance plethysmography to detect apnea and obstructed breathing.Main Outcome MeasuresOccurrence of cardiorespiratory events that exceeded predefined conventional and extreme thresholds as recorded by the monitors.ResultsDuring 718 358 hours of home monitoring, 6993 events exceeding conventional alarm thresholds occurred in 445 infants (41%). Of these, 653 were extreme events in 116 infants (10%), and of those events with apnea, 70% included at least 3 obstructed breaths. The frequency of at least 1 extreme event was similar in term infants in all groups, but preterm infants were at increased risk of extreme events until 43 weeks' postconceptional age.ConclusionsIn this study, conventional events are quite common, even in healthy term infants. Extreme events were common only in preterm infants, and their timing suggests that they are not likely to be immediate precursors to SIDS. The high frequency of obstructed breathing in study participants would likely preclude detection of many events by conventional techniques. These data should be important for designing future monitors and determining if an infant is likely to be at risk for a cardiorespiratory event.
Management of Chronic Tension-Type Headache With Tricyclic Antidepressant Medication, Stress Management Therapy, and Their Combination
Authors: Holroyd Kenneth A. , O'Donnell Francis J. , Stensland Michael , Lipchik Gay L. , Cordingley Gary E. , Carlson Bruce W. 
Published: March 2003

ContextChronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects.ObjectiveTo evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches.Design and SettingRandomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio.ParticipantsTwo hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo).InterventionsParticipants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53).Main Outcome MeasuresMonthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating ≥5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group.ResultsTricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (≥50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P = .006), stress management therapy (35%; P = .003), or placebo (29%; P = .001). On other measures the combined therapy and its 2 component therapies produced similar outcomes.ConclusionsOur results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.
Prevalence of C282Y and H63D Mutations in the Hemochromatosis (HFE) Gene in the United States
Authors: Steinberg Karen K. , Cogswell Mary E. , Chang Joy C. , Caudill Samuel P. , McQuillan Geraldine M. , Bowman Barbara A. , Grummer-Strawn Laurence M. , Sampson Eric J. , Khoury Muin J. , Gallagher Margaret L. 
Published: March 2003

ContextPopulation-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening.ObjectiveTo estimate the prevalence of the HFE mutations C282Y and H63D in the US population.DesignCross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994.Setting and ParticipantsGenotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis.Main Outcome MeasuresEstimates of the prevalence of C282Y and H63D mutations.ResultsThe prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation.ConclusionsEstimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.
Maternal Immunity and Prevention of Congenital Cytomegalovirus Infection
Authors: Fowler Karen B. , Stagno Sergio , Pass Robert F. 
Published: March 2003

ContextVaccine development to prevent congenital cytomegalovirus (CMV) infection has been impeded by the uncertainty over whether maternal immunity protects the fetus.ObjectiveTo determine whether the presence of maternal antibodies to CMV significantly reduces the risk of congenital CMV infection in future pregnancies.Design, Setting, and ParticipantsCohort study of 3461 multiparous women from a population with a high rate of congenital CMV infection who delivered newborns screened for congenital CMV infection between 1993 and 1998, and whose cord serum specimen from a previous delivery could be retrieved and tested for antibody to CMV.Main Outcome MeasureCongenital CMV infection according to maternal immune status, age, race, parity, and socioeconomic status.ResultsOf 604 newborns born to initially seronegative mothers, congenital CMV infection occurred in 18 (3.0%). In contrast, of 2857 newborns born to immune mothers, congenital CMV infection occurred in 29 (1.0%) Two factors, preconception maternal immunity (adjusted risk ratio, 0.31; 95% confidence interval, 0.17-0.58) and maternal age of 25 years or older (adjusted risk ratio, 0.19; 95% confidence interval, 0.07-0.49), were highly protective against congenital CMV infection. No other factors were associated with a reduction in the risk of congenital CMV infection.ConclusionNaturally acquired immunity results in a 69% reduction in the risk of congenital CMV infection in future pregnancies.