bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Titers of Circulating Maternal Antibodies Suppress Effector and Memory B-Cell Responses Induced by an Attenuated Rotavirus Priming and Rotavirus-Like Particle-Immunostimulating Complex Boosting Vaccine Regimen
Authors: Nguyen Trang V. , Yuan Lijuan , Azevedo Marli S. P. , Jeong Kwang-il , Gonzalez Ana M. , Iosef Cristiana , Lovgren-Bengtsson Karin , Morein Bror , Lewis Peggy , Saif Linda J. 
Published: April 2006

ABSTRACT
We investigated maternal antibody (MatAb) effects on protection and immune responses to rotavirus vaccines. Gnotobiotic pigs were injected intraperitoneally at birth with pooled serum from sows hyperimmunized with human rotavirus (HRV); control pigs received no sow serum. Pigs with or without MatAbs received either sequential attenuated HRV (AttHRV) oral priming and intranasal boosting with VP2/VP6 virus-like particle (VLP)-immunostimulating complex (ISCOM) (AttHRV/VLP) or intranasal VLP-ISCOM prime/boost (VLP) vaccines at 3 to 5 days of age. Subsets of pigs were challenged at 28 or 42 days postinoculation with virulent Wa HRV to assess protection. Isotype-specific antibody-secreting cell (ASC) responses to HRV were quantitated by enzyme-linked immunospot assay to measure effector and memory B-cell responses in intestinal and systemic lymphoid tissues pre- and/or postchallenge. Protection rates against HRV challenge (contributed by active immunity and passive circulating MatAbs) were consistently (but not significantly) lower in the MatAb-AttHRV/VLP groups than in the corresponding groups without MatAbs. Intestinal B-cell responses in the MatAb-AttHRV/VLP group were most suppressed with significantly reduced or no intestinal immunoglobulin A (IgA) and IgG effector and memory B-cell responses or antibody titers pre- and postchallenge. This suppression was not alleviated but was enhanced after extending vaccination/challenge from 28 to 42 days. In pigs vaccinated with nonreplicating VLP alone that failed to induce protection, MatAb effects differed, with intestinal and systemic IgG ASCs and prechallenge memory B cells suppressed but the low intestinal IgA and IgM ASC responses unaffected. Thus, we demonstrate that MatAbs differentially affect both replicating and nonreplicating HRV vaccines and suggest mechanisms of MatAb interference. This information should facilitate vaccine design to overcome MatAb suppression.
The VR2 Epitope on the PorA P1.7-2,4 Protein Is the Major Target for the Immune Response Elicited by the Strain-Specific Group B Meningococcal Vaccine MeNZB
Authors: Martin D. R. , Ruijne N. , McCallum L. , O'Hallahan J. , Oster P. 
Published: April 2006

ABSTRACT
A protracted epidemic of group B meningococcal disease in New Zealand led to the testing of a strain-specific tailor-made vaccine, MeNZB. Immunogenicity levels achieved during age group trials enabled New Zealand's regulatory authority to grant licensure to deliver MeNZB to all individuals under age 20. During the trials target strains for serum bactericidal antibody measurements included the vaccine target strain NZ98/254 and two comparator epidemic-type strains (NZ94/167 and NZ02/09). In this study, 12 other strains differing variously from the vaccine strain by their capsular group, PorB type, and PorA variable region specificities, or PorA expression, were used as target strains. The PorA specificity of the serum bactericidal antibody responses to the vaccine was determined for 40 vaccinees. Sets of 10 pre- and postvaccination sera were chosen randomly from the young infant, older infant, toddler, and school-age group trials. Antibody recognition of linearized PorA proteins was also determined using immunoblotting. Across all age groups vaccine-induced serum bactericidal antibodies specifically targeted the VR2 P1.4 epitope of the PorA P1.7-2,4 protein irrespective of the PorB type and/or capsular type of the target strain. Deletion of amino acids within the VR2 epitope or replacement of the epitope through genetic exchange allowed strains variously to resist antibody-directed complement-mediated lysis and negated PorA-specific antibody recognition in immunoblots. The demonstration that the immunodominant antibody response was specifically for the VR2 P1.4 epitope of the PorA protein supports the public health decision to use a strain-specific vaccine for the control of New Zealand's epidemic of meningococcal disease.
Production of Soluble Triggering Receptor Expressed on Myeloid Cells by Lipopolysaccharide-Stimulated Human Neutrophils Involves De Novo Protein Synthesis
Authors: Mahdy Amr M. , Lowes Damon A. , Galley Helen F. , Bruce Jane E. , Webster Nigel R. 
Published: April 2006

ABSTRACT

The triggering receptor expressed on myeloid cells (TREM-1) is a recently identified receptor expressed on neutrophils and monocytes. Activation of the receptor induces neutrophils to release the enzyme myeloperoxidase and inflammatory cytokines such as interleukin-8. TREM-1 has an alternatively spliced variant that lacks the transmembrane region, resulting in the receptor being secreted in a soluble form (sTREM-1). Soluble TREM-1 has been detected in plasma during experimental and clinical sepsis and has been advocated as a diagnostic marker of infection for pneumonia and as a prognostic marker for patients with septic shock. We studied TREM-1 surface expression, using flow cytometry, and simultaneously measured sTREM-1 concentrations in culture supernatants of lipopolysaccharide (LPS)-stimulated neutrophils. TREM-1 surface expression was constitutive and was not upregulated upon LPS stimulation. However, sTREM-1 release from neutrophils was significantly upregulated by LPS stimulation (
P
< 0.0001), an effect that was abrogated by cycloheximide. Soluble TREM-1 is therefore secreted by human neutrophils in response to LPS challenge in a process involving de novo protein synthesis that is not accompanied by an upregulation of the TREM-1 receptor on the surfaces of the cells.
Abnormal Expression and Distribution of Heat Shock Protein 90: Potential Etiologic Immunoendocrine Mechanism of Glucocorticoid Resistance in Idiopathic Nephrotic Syndrome
Authors: Ouyang Juan , Jiang Tang , Tan Min , Cui Yinpeng , Li Xiaoyan 
Published: April 2006

ABSTRACTResistance to glucocorticoid (GC) treatment in some patients with idiopathic nephrotic syndrome (INS) is a significant clinical problem. Heat shock protein 90 (HSP90) is the chaperon protein of the GC receptor, which is supposed to be the key factor of GC response. Therefore, we conducted this study to define the mechanisms of GC resistance related to HSP90. INS patients and cell lines with differing GC responses were included in the present study. We found that the level of HSP90 mRNA expression in INS patients was significantly higher than that in healthy controls and that HSP90 expression in GC-resistant INS patients was higher than that in GC-sensitive INS patients. A confocal immunofluorescence test was performed to investigate the subcellular localization of HSP90, and we found that the distribution of HSP90 in the GC-resistant INS group was greater in the nuclei than that of the GC-sensitive INS group. When the function of HSP90 was blocked by the HSP90-specific inhibitor, the GC sensitivity of GC-sensitive cells decreased remarkably. These results indicate that HSP90 plays a vital role in GC response. In addition, the abnormality in the mRNA level and subcellular distribution of HSP90 in GC-resistant INS patients may be etiologically significant in terms of endogenous/synthetic GC resistance. On one hand, it may disturb immunoendocrine regulation via endogenous GC and immune homeostasis and thus be involved in the occurrence of the immune-mediated disease; on the other hand, it may influence the patient's response to synthetic GC treatment and result in treatment failure.
Associations of SF-36 mental health functioning and work and family related factors with intentions to retire early among employees
Authors: Harkonmäki K , Rahkonen O , Martikainen P , Silventoinen K , Lahelma E 
Published: April 2006

Objective:To examine the associations of mental health functioning (SF-36) and work and family related psychosocial factors with intentions to retire early.Methods:Cross sectional survey data (n = 5037) from the Helsinki Health Study occupational cohort in 2001 and 2002 were used. Intentions to retire early were inquired with a question: “Have you considered retiring before normal retirement age?” Mental health functioning was measured by the Short Form 36 (SF-36) mental component summary (MCS). Work and family related psychosocial factors included job demands and job control, procedural and relational justice, conflicts between work and family, and social network size. Multinomial regression models were used to analyse the data.Results:Poor mental health functioning, unfavourable psychosocial working conditions, and conflicts between work and family were individually related to intentions to retire early. After adjustments for all work and family related factors the odds ratio for low mental health functioning was halved (from OR = 6.05 to 3.67), but nevertheless the association between poor mental health functioning and strong intentions to retire early remained strong.Conclusions:These findings highlight not only the importance of low mental health and unfavourable working conditions but also the simultaneous impact of conflicts between work and family to employees’ intentions to retire early.
The frequency of workplace exacerbation among health maintenance organisation members with asthma
Authors: Henneberger P K , Derk S J , Sama S R , Boylstein R J , Hoffman C D , Preusse P A , Rosiello R A , Milton D K 
Published: April 2006

Objectives:Workplace conditions can potentially contribute to the worsening of asthma, yet it is unclear what percentage of adults with asthma experience workplace exacerbation of symptoms. The objective of this investigation was to determine the prevalence of workplace exacerbation of asthma (WEA).Methods:Adults with asthma aged 18–44 were enrolled into the baseline survey of a longitudinal study. Members of a health maintenance organisation were considered candidates for participation if they fulfilled membership, diagnostic, and treatment criteria based on automated review of electronic billing, claims, and pharmacy records. Diagnosis and treatment were confirmed by manual review of medical records. A telephone questionnaire was administered. A work related symptom score was assigned to each participant based on responses to questions about work related asthma symptoms, medication use, and symptom triggers. Blinded to participants’ answers to these questions, two researchers independently reviewed the self-reported work histories and assigned exposure ratings. A final exposure score was then calculated. Participants with sufficient evidence for work related symptoms and exposure were classified as having WEA.Results:Of the 598 participants with complete data, 557 (93%) were working, and 136 (23%) fulfilled the criteria for WEA. Those with WEA were more likely to be male and to report that they had been bothered by asthma symptoms during the past seven days.Conclusions:Workplace exacerbation of asthma was common in this study population, occurring in over a fifth of these adults with asthma. Physicians should consider that work can contribute to the exacerbation of symptoms when treating adults with asthma.
Expression of protein kinase C isoforms in cardiac hypertrophy and heart failure due to volume overload
Authors: Sentex Emmanuelle , Wang Xi , Liu Xueliang , Lukas Anton , Dhalla Naranjan S. 
Published: April 2006

The present study determined whether changes in the activity and isoforms of protein kinase C (PKC) are associated with cardiac hypertrophy and heart failure owing to volume overload induced by aortocaval shunt (AVS) in rats. A significant increase in Ca2+-dependent and Ca2+-independent PKC activities in the homogenate and particulate fractions, unlike the cystolic fraction, of the hypertrophied left ventricle (LV) were evident at 2 and 4 weeks after inducing the AVS. This increase coincided with increases in PKC-α and PKC-ζ contents at 2 week and increases in PKC-α, PKC-β1, PKC-β2, and PKC-ζ contents at 4 weeks in the hypertrophied LV. By 8 and 16 weeks of AVS, PKC activity and content were unchanged in the failing LV. On the other hand, no increase in the PKC activity or isoform content in the hypertrophied right ventricle (RV) was observed during the 16 weeks of AVS. The content of Gαq was increased in the LV at 2 weeks but then decreased at 16 weeks, whereas Gαq content was increased in RV at 2 and 4 weeks. Our data suggest that an increase in PKC isoform content neither plays an important role during the development of cardiac hypertrophy nor participates in the phase leading to heart failure owing to volume overload.
Comparison of folic acid uptake characteristics by human placental choriocarcinoma cells at acidic and physiological pH
Authors: Keating Elisa , Lemos Clara , Azevedo Isabel , Martel Fátima 
Published: April 2006

The aim of this work was to characterize the placental uptake of folic acid from the maternal circulation. Using 2 human trophoblast cell lines (BeWo and JAR), we verified that uptake of3H-folic acid was pH-dependent, increasing significantly with decreasing extracellular pH. In BeWo cells, uptake of3H-folic acid at pH 5.5 was (i) Na+-independent; (ii) inhibited by folic acid, 5-methyltetrahydrofolate (5-MTHF), and methotrexate (MTX); (iii) inhibited by the anion transport inhibitors 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) and 4-acetamido-4′-isothiocyano-2,2′-disulfonic acid stilbene (SITS); (iv) inhibited by the proton ionophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP); (v) not inhibited by blockers of receptor-mediated endocytosis (cytochalasin D and monensin); (vi) trans-inhibited by MTX and folic acid; and (vii) not affected by an anti-reduced folate transporter-1 (RFC) antibody. At pH 7.5, uptake of3H-folic acid was (i) Na+-independent; (ii) inhibited by folic acid and MTX, but not by 5-MTHF; (iii) inhibited by SITS, but not by DIDS; (iv) not affected by FCCP; (v) inhibited by monensin (but not by cytochalasin D); (vi) trans-inhibited by folic acid (but not by MTX); and (vii) inhibited by an anti-RFC antibody. In conclusion, in BeWo cells, both RFC and receptor-mediated endocytosis seem to be involved in3H-folic acid uptake at pH 7.5, whereas at pH 5.5, RFC and (or) a low pH-operating transporter distinct from RFC are involved.
Gender differences in the cardiac response to dietary conjugated linoleic acid isomers
Authors: Tappia Paramjit S. , Mangat Rabban , Gabriel Cindy , Dent Melissa R. , Aroutiounova Nina , Weiler Hope 
Published: April 2006

The present study was undertaken to assess the heart function, by the in vivo catheterization technique, of healthy male and female Sprague–Dawley rats fed different conjugated linoleic acid (CLA) isomers, (cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12)) individually and in combination (50:50 mix as triglyceride or fatty acids) from 4 to 20 weeks of age. Whereas the triglyceride form of the CLA isomer mix lowered the heart rate, the rate of contraction (+dP/dt) and rate of relaxation (–dP/dt), systolic and diastolic pressures, mean arterial pressure, and the left ventricular systolic pressure were higher in male rats as compared with all the other dietary groups. In contrast, there were no significant effects in the cardiac function of the female rats in response to the CLA isomer mix in triglyceride form. Whereas the heart rate, +dP/dt, and left ventricular systolic pressure were lower in male rats fed the t10,c12 CLA isomer alone, the heart rate of the female rats was higher, but the systolic pressure, +dP/dt, and mean arterial pressure were lower compared with the control group. Also, the left ventricular end-diastolic pressure was specifically higher in the female rats in response to free fatty acids-containing CLA mix. Furthermore, an additive effect of the free fatty acids-containing CLA mix was seen in the +dP/dt and –dP/dt of female rats compared with the control group. These results indicate that CLA isomers exert differential effects on heart function and suggest the need for a complete evaluation of the benefits, interactions, and potential side effects of each isomer.
Epigallocatechin gallate preserves endothelial function by reducing the endogenous nitric oxide synthase inhibitor level
Authors: Tang Wei-Jun , Hu Chang-Ping , Chen Mei-Fang , Deng Pan-Yue , Li Yuan-Jian 
Published: April 2006

Asymmetric dimethylarginine (ADMA), the endogenous nitric oxide synthase inhibitor, is thought to be a key factor contributing to endothelial dysfunction. Tea catechins can cause an endothelium-dependent vasorelaxation. The present study examined the effect of epigallocatechin gallate (EGCG), the major component of tea catechins, on endothelial dysfunction induced by native low density lipoprotein (LDL) in rats and oxidized LDL (ox-LDL) in cultured endothelial cells, and whether the protective effect of EGCG is related to reduction of ADMA level. A single injection of LDL (4 mg·kg–1, i.v.) markedly reduced endothelium-dependent relaxation and the serum nitrite/nitrate (NO) level, and increased serum concentrations of ADMA, malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α). EGCG (10 or 50 mg·kg–1, i.p.) significantly attenuated the inhibition of vasodilator response to acetylcholine and the decreased serum nitrite/nitrate level, and reduced the elevated levels of ADMA, MDA, and TNF-α. Exposure of endothelial cells to ox-LDL (100 μg·mL–1) for 24 h markedly increased the medium levels of lactate dehydrogenase (LDH), ADMA, TNF-α, and MDA, and decreased the level of nitrite/nitrate in the medium and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in the endothelial cells. EGCG (10 and 100 μg·mL–1) significantly decreased the levels of LDH, ADMA, TNF-α, and MDA, and increased the level of nitrite/nitrate and the activity of DDAH. These results suggest that EGCG protects endothelial dysfunction induced by native LDL in vivo or by ox-LDL in endothelial cells, and the protective effect of EGCG on the endothelium is related to decrease in ADMA level via increasing of DDAH activity.
The modulatory effect of leptin on the overall insulin production in ex-vivo normal rat pancreas
Authors: Haddad N. , Howland R. , Baroody G. , Daher C. 
Published: April 2006

Leptin has a modulator effect on glucose-stimulated insulin secretion. To define the influences of different glucose (4, 8, 12, and 16 mmol/L) and leptin (5, 10, 15, and 20 nmol/L) concentrations on total insulin release in ex vivo pancreatic preparations, a customized perfusion technique was used. Such a profile of concentration brought about an index for the combined effect of leptin and glucose on the production of insulin. Insulin output was measured by radioimmunoassay. Stimulated by glucose alone in the control group, insulin secretion confirmed a bi-phasic pattern. Addition of leptin in the experimental group suppressed insulin secretion compared with control. A U-shape pattern of suppression was observed when the leptin and stimulatory glucose concentrations were combined. At 12 mmol/L glucose, leptin showed maximal insulin suppression. Leptin’s effect on insulin was glucose dependent and showed a reproducible U-shaped pattern of suppression, which implicated possible direct dose-dependent interaction between leptin and glucose on insulin secretion.
ADAPTIVE ROLES OF PROGRAMMED CELL DEATH DURING NERVOUS SYSTEM DEVELOPMENT
Authors: Buss Robert R. , Sun Woong , Oppenheim Ronald W. 
Published: April 2006

The programmed cell death (PCD) of developing cells is considered an essential adaptive process that evolved to serve diverse roles. We review the putative adaptive functions of PCD in the animal kingdom with a major focus on PCD in the developing nervous system. Considerable evidence is consistent with the role of PCD in events ranging from neurulation and synaptogenesis to the elimination of adult-generated CNS cells. The remarkable recent progress in our understanding of the genetic regulation of PCD has made it possible to perturb (inhibit) PCD and determine the possible repercussions for nervous system development and function. Although still in their infancy, these studies have so far revealed few striking behavioral or functional phenotypes. “Death opens unknown doors.” – John Masefield, 1910
Activin Receptor-Like Kinase 7 Induces Apoptosis through Up-Regulation of Bax and Down-Regulation of Xiap in Normal and Malignant Ovarian Epithelial Cell Lines
Authors: Xu Guoxiong , Zhou Hong , Wang Qinghua , Auersperg Nelly , Peng Chun 
Published: April 2006

Abstract
Transforming growth factor-β superfamily has been implicated in tumorigenesis. We have recently shown that Nodal, a member of transforming growth factor-β superfamily, and its receptor, activin receptor-like kinase 7 (ALK7), inhibit proliferation and induce apoptosis in human epithelial ovarian cancer cell lines. In this study, we further investigated the cellular mechanisms underlying the apoptotic action of ALK7 using an immortalized ovarian surface epithelial cell line, IOSE397, and an epithelial ovarian cancer cell line, OV2008. Infection of these cells with an adenoviral construct carrying constitutively active ALK7 (Ad-ALK7-ca) potently induced cell death; all cells died after 3 and 5 days of Ad-ALK7-ca infection in IOSE397 and OV2008 cells, respectively. ALK7-ca induced the expression of proapoptotic factor Bax but suppressed the expression of antiapoptotic factors Bcl-2, Bcl-XL, and Xiap. Silencing of Bax by small interfering RNA in IOSE397 cells significantly reduced ALK7-ca-induced apoptosis as measured by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay but partially blocked ALK7-ca-induced caspase-3 activation and did not affect the down-regulation of Xiap by ALK7-ca. Dominant-negative Smad2, Smad3, and Smad4 blocked ALK7-ca-regulated Xiap and Bax expression and caspase-3 activation. Thus, ALK7-induced apoptosis is at least in part through two Smad-dependent pathways, Bax/Bcl-2 and Xiap. (Mol Cancer Res 2006;4(4):235–46)
Transforming Growth Factor-β–Induced Expression of the Apolipoprotein E Gene Requires c-Jun N-Terminal Kinase, p38 Kinase, and Casein Kinase 2
Authors: Singh Nishi N. , Ramji Dipak P. 
Published: April 2006

Objective—The cytokine transforming growth factor-β (TGF-β) and apolipoprotein E (apoE) play potent antiatherogenic roles. Despite such importance, the mechanisms underlying the regulation of apoE expression by TGF-β have not been characterized and were therefore investigated.Methods and Results—Using THP-1 cell line as a model system, with key findings confirmed in primary cultures, we show that TGF-β induces the expression of apoE, and this is prevented by pharmacological inhibitors of c-Jun N-terminal kinase (JNK), p38 kinase, and casein kinase 2 (CK2). In support for an important role for these pathways, TGF-β activates JNK, p38 kinase, and CK2, and dominant-negative (DN) forms of these proteins inhibit the cytokine-induced apoE expression. TGF-β also increases the phosphorylation and expression of c-Jun, a downstream target for JNK action and a component of activator protein-1 (AP-1), and DN c-Jun inhibits the induction of apoE expression in response to the cytokine. AP-1 DNA binding was also induced by TGF-β, and the action of p38 kinase, JNK, and CK2 converged on the activation of c-Jun/AP-1.Conclusions—These studies reveal a novel role for JNK, p38 kinase, CK2, and c-Jun/AP-1 in the TGF-β–induced expression of apoE.