bluuebunny/crossref_metadata_2025_split huggingface dataset:
Energy conservation: an alternative for investment in the oil sector for OPEC Member Countries
Authors: Zamani Mehrzad 
Published: June 2005

AbstractInvestment in the oil sector is the main policy of expanding net crude oil export capacity in OPEC Member Countries. The other alternative should be improving energy conservation policies. Since these countries benefit from cheap energy sources, it is reasonable to expect inefficient use of energy in their economies, resulting in relatively high energy intensity. This paper deals with the causality relationship between energy consumption and gross domestic product (GDP). First, stationary tests are run. Second, if there is a cointegrating relationship, an error correction model is applied; otherwise a standard Granger causality test is conducted. It was discovered that for all OPEC Member Countries we cannot statistically accept causality running from energy to GDP. Therefore, not only are proper conservation policies not a threat to economic growth, they also lead to an expansion of oil export capacity.
Inhibition of protein synthesis and activation of stress‐activated protein kinases by onnamide A and theopederin B, antitumor marine natural products
Authors: Lee Kun‐Hyung , Nishimura Shinichi , Matsunaga Shigeki , Fusetani Nobuhiro , Horinouchi Sueharu , Yoshida Minoru 
Published: June 2005

During the course of screening for the agents that activate transforming growth factor‐β (TGF‐β) signaling cascade, onnamide A and theopederin B, heterocyclic compounds related to mycalamides from a marine sponge, were found to induce plasminogen activator inhibitor‐1 (PAI‐1) promoter‐derived gene expression in Mv1Lu cells. The maximum induction of the PAI‐1 promoter by onnamide A and theopederin B was observed at the concentrations of 50 nM and 2 nM, respectively. These compounds strongly inhibited protein synthesis at the 50% inhibitory concentrations of 30 nM for onnamide A and 1.9 nM for theopederin B, and induced activation of p38 mitogen‐activated protein kinase and c‐Jun NH2‐terminal protein kinase (JNK). Anisomycin, a well‐known inducer of ribotoxic stress that inhibits protein synthesis and activates both p38 kinase and JNK, also activated PAI‐1 gene expression. Furthermore, PAI‐1 expression by onnamide A, theopederin B, and anisomycin was inhibited by SB202190 and SP600125, specific inhibitors of stress‐activated protein kinases. Onnamide A and theopederin B were cytotoxic to a variety of cell lines and strongly induced apoptosis in HeLa cells within 24 h, which was accompanied by the sustained activation of p38 kinase and JNK. These results suggest that onnamide A and theopedirin B trigger a ribotoxic stress‐like response, thereby inducing p38 kinase and JNK activation, the kinase‐dependent PAI‐1 gene expression, and apoptosis. (Cancer Sci 2005; 96: 357–364)
T cell-mediated immune responses in human newborns: ready to learn?
Authors: Marchant A , Goldman M 
Published: June 2005

SummaryInfections with intracellular pathogens are often more severe or more prolonged in young infants suggesting that T cell-mediated immune responses are different in early life. Whereas neonatal immune responses have been quite extensively studied in murine models, studies of T cell-mediated immunity in human newborns and infants are scarce. Qualitative and quantitative differences when compared with adult immune responses have been observed but on the other hand mature responses to certain vaccines and infectious pathogens were demonstrated during the postnatal period and even during foetal life. Herein, we review the evidence suggesting that under appropriate conditions of stimulation, protective T cell-mediated immune responses could be induced by vaccines in early life.
AcellularBordetella pertussisvaccine enhances mucosal interleukin-10 production, induces apoptosis of activated Th1 cells and attenuates colitis in Gαi2-deficient mice
Authors: Öhman L , Willén R , Hultgren O H , Hultgren Hörnquist E 
Published: June 2005

SummaryMice deficient for the inhibitory G protein subunit α2 (Gαi2–/–) spontaneously develop a progressive inflammatory bowel disease resembling ulcerative colitis, and have a T helper 1 (Th1)-dominated immune response prior to onset of colitis, which is further augmented after the onset of disease. The present study was performed to investigate whether the Gαi2–/– mice were able to down-regulate the Th1-dominated inflammatory mucosal immune response and/or induce an anti-inflammatory Th2/T regulatory response and thereby diminish the severity of colitis following treatment with acellular Bordetella pertussis vaccine. The acellular vaccine against B. pertussis, the causative agent of whooping cough, has been demonstrated to induce a Th2-mediated response in both man and mice. We therefore treated Gαi2–/– mice intraperitoneally with a three-component acellular B. pertussis vaccine. The treated Gαi2–/– mice showed significantly increased interleukin (IL)-10 production in intestinal tissue, associated with significantly reduced colitis and decreased mortality, compared to untreated Gαi2–/– mice. The attenuation of colitis in Gαi2–/– mice was due, at least partly, to the B. pertussis surface antigen filamentous haemagglutinin (FHA), which almost completely inhibited proliferation of CD4+ T cells and stimulated apoptosis of activated CD4+ T helper 1 cells. In conclusion, the three-component acellular B. pertussis vaccine containing filamentous haemagglutinin increases the production of IL-10 in the intestinal mucosa, induces apoptosis of activated Th1 cells and attenuates colitis in Gαi2–/– mice.
Cross-reaction between antibodies to the major epitope of Ro60 kD autoantigen and a homologous peptide of Coxsackie virus 2B protein
Authors: Stathopoulou E A , Routsias J G , Stea E A , Moutsopoulos H M , Tzioufas A G 
Published: June 2005

Summary
Coxsackie virus RNA has recently been detected in biopsy specimens of minor salivary glands from patients with primary Sjögren's Syndrome (pSS). A peptide derived from Coxsackie virus 2B protein (pepCoxs) presents 87% sequence homology with the 222–229 region of the major linear B-cell epitope of  Ro60 kD  autoantigen  (pep216–232).  Synthetic  peptides  corresponding to pep216–232: 216KALSVETEKLLKYLEAV232 and pepCoxs: 31MVTSTITEKL LKNLVKI47, were prepared. Sera from 42 patients with pSS and 43 patients with systemic lupus erythematosus (SLE) as well as sera from 27 healthy individuals (normal controls) and sera from 30 patients with rheumatoid arthritis (disease controls) were tested against the two homologous peptides. Twenty-five percent of SLE sera and 33·3% of pSS sera reacted against pep216–232, whereas 28% of SLE sera and 37% of pSS sera recognized the pepCoxs. The sera reacting with pep216–232 were apparently the same as those reacting with pepCoxs. Normal sera and disease control sera presented only a limited reactivity against both peptides (ranging from 3·7% to 10%). Both peptides reacted more prominently with anti-Ro/La (+) sera from pSS patients. Thus, pep216–232 was recognized by 17% of the anti-Ro (+) sera and by 42% of the anti-Ro/La (+) sera, whereas pepCoxs was recognized by 28·5% and 38% of the a-Ro(+) and a-Ro/La(+) sera, respectively. Purified anti-pep216–232 antibodies readily reacted with both peptides while inhibition experiments revealed the specificity of this reaction. These results suggest a possible cross-reaction between antibodies to the major linear B-cell epitope of Ro60 kD autoantigen and the homologous pepCoxs in pSS patients. This cross-reaction might potentially play a role in autoantibody formation and the perpetuation of the autoimmune response against Ro/SSA and La/SSB.
Analysis of circulating γδ+ T cells in children affected by IgE-associated and non-IgE-associated allergic atopic eczema/dermatitis syndrome
Authors: Cairo C , Arabito E , Landi F , Casati A , Brunetti E , Mancino G , Galli E 
Published: June 2005

SummaryRecent studies have suggested that not only αβ+ T cells, but also the less common γδ+ T cells may play a role as effectors and immunoregolatory cells in the development and perpetuation of allergic inflammation. The objective of this study was to focus on the role of γδ+ T cells in atopic dermatitis (AD), a chronic relapsing inflammatory disease of the skin, often associated with allergic bronchial asthma. The present study employed flow cytometric analysis to compare numbers and phenotypic characteristics of γδ+ T cells in the peripheral blood of children with atopic dermatitis and age-matched healthy controls. The percentage of circulating Vγ 9Vδ2+ T lymphocytes was significantly increased in AD patients with respect to the age-matched controls, with a positive correlation with clinical score severity. The prevalent phenotype in both AD patients and controls was CD45RO+, with no differences observed in the percentage of Vδ2+ CD45RO+ between these groups. Conversely, memory CD45RO+ CD62L+ Vδ2+ lymphocytes were significantly lower in AD patients. Furthermore, naive circulating Vδ2+ T lymphocytes were significantly lower in AD children than in aged-matched controls. No correlation was observed between circulating Vγ 9Vδ2+ expansion and IgE serum levels. It was concluded that an association exists between the levels of circulating γδ+ T lymphocytes and atopic dermatitis, with a positive correlation with clinical score but no link with IgE serum levels. The pathophysiological role of γδ T lymphocytes in atopic dermatitis awaits further investigation.
TCR Vα14+ natural killer T cells function as effector T cells in mice with collagen-induced arthritis
Authors: Ohnishi Y , Tsutsumi A , Goto D , Itoh S , Matsumoto I , Taniguchi M , Sumida T 
Published: June 2005

SummaryNatural killer (NK) T cells are a unique, recently identified cell population and are suggested to act as regulatory cells in autoimmune disorders. In the present study, designed to investigate the role of NKT cells in arthritis development, we attempted to induce arthritis by immunization of type II collagen (CIA) in Jα281 knock out (NKT-KO) and CD1d knock out (CD1d-KO) mice, which are depleted of NKT cells. From the results, the incidence of arthritis (40%) and the arthritis score (1·5 ± 2·2 and 2·0 ± 2·7) were reduced in NKT-KO and CD1d-KO mice compared to those in respective wild type mice (90%, 5·4 ± 3·2 and 2·0 ± 2·7, P &lt; 0·01). Anti-CII antibody levels in the sera of NKT-KO and CD1d-KO mice were significantly decreased compared to the controls (OD values; 0·32 ± 0·16 and 0·29 ± 0·06 versus 0·58 ± 0·08 and 0·38 ± 0·08, P &lt; 0·01). These results suggest that NKT cells play a role as effector T cells in CIA. Although the cell proliferative response and cytokine production in NKT-KO mice after the primary immunization were comparable to those in wild type mice, the ratios of both activated T or B cells were lower in NKT-KO mice than wild type mice after secondary immunization (T cells: 9·9 ± 1·8%versus 16·0 ± 3·4%, P &lt; 0·01, B cells: 4·1 ± 0·5%versus 5·1 ± 0·7%, P &lt; 0·05), suggesting that inv-NKT cells contribute to the pathogenicity in the development phase of arthritis. In addition, IL-4 and IL-1β mRNA expression levels in the spleen during the arthritis development phase were lower in NKT-KO mice, while the IFN-γ mRNA expression level was temporarily higher. These results suggest that inv-NKT cells influence cytokine production in arthritis development. In conclusion, inv-NKT cells may promote the generation of arthritis, especially during the development rather than the initiation phase.
Increased monocyte transcription of the proteinase 3 gene in small vessel vasculitis
Authors: Ohlsson S , Hellmark T , Pieters K , Sturfelt G , Wieslander J , Segelmark M 
Published: June 2005

SummaryProteinase 3 (PR3) is a pleiotropic and destructive serine protease and it is also a major target for autoantibodies in systemic small vessel vasculitis. We have shown recently that patients in stable remission have increased circulating levels of PR3, independent of autoantibody titre, inflammation, neutrophil degranulation and renal function. Here we explore the possibility of increased PR3 gene transcription. RNA was purified from peripheral blood monocytes from vasculitis patients and controls. Specific mRNA was measured by TaqMan real-time polymerase chain reaction (PCR). The monocyte-like cell lines THP-1 and U937 and human peripheral blod monocytes from healthy controls were stimulated with cytokines and lipopolysaccharide (LPS) for different time periods. PR3 protein was measured in plasma with enzyme-linked immunosorbent assay (ELISA). The median result for PR3 mRNA was 9.6 (1.8–680) for 22 patients, compared to 1 (0.1–2.8) for the 15 healthy controls. Elastase expression was also significantly increased, whereas myeloperoxidase and interleukin-8 were not. Stimulation of monocytes with tumour necrosis factor (TNF)-α, interferon (IFN)-γ or LPS did not result in any increase of PR3 or elastase transcription, whereas interleukin (IL)-8 transcription was increased 10-fold. Circulating monocytes from patients with systemic vasculitis display increased PR3 gene transcription compared to healthy controls and patients with sytemic lupus erythematosus (SLE). This may be important for the development of vasculitis. Our results do not favour a role for cytokines, antineutrophil cytoplasmic antibodies (ANCA) or immunosuppressive medication in the upregulation of PR3 transcription in vasculitis.
Interleukin-4 induced down-regulation of skin homing receptor expression by human viral-specific CD8+ T cells may contribute to atopic risk of cutaneous infection
Authors: Seneviratne S L , Jones L , Bailey A S , Samuel R V , Black A P , Ogg G S 
Published: June 2005

SummaryFactors controlling the expression of cutaneous lymphocyte-associated antigen (CLA) by T cells are poorly understood, but data from murine and human CD4+ T cell systems have suggested that cytokines play an important role. However, there are no data examining the influence of cytokines on the expression of CLA by human antigen-specific CD8+ T cells. Peripheral blood mononuclear cells (PBMC) were isolated from 10 HLA-A*0201-positive healthy individuals. Using HLA-peptide tetrameric complexes refolded with immunodominant peptides from Epstein–Barr virus (EBV), cytomegalovirus (CMV) and influenza A virus, we investigated the temporal associations of CLA expression by viral-specific CD8+ T cells following stimulation with antigen. Ex vivo influenza matrix-specific CD8+ T cells expressed significantly (P &lt; 0·05) greater levels of CLA than EBV BMLF1 and CMV pp65-specific CD8+ T cells (mean 9·7% influenza matrix versus 1·4% BMLF1 versus 1·1% pp65) and these differences were sustained on culture. However, regardless of viral specificity, interleukin (IL)-12 and IL-4 induced significant (P &lt; 0·05) dose-dependent up-regulation and down-regulation of CLA expression, respectively, with IL-4 showing a dominant negative effect. In many cases, IL-4 resulted in complete abrogation of detectable CLA expression by the viral-specific CD8+ T cells. Overall these data demonstrate that CLA expression by human viral-specific CD8+ T cells is highly dynamic and that IL-4 causes significant down-regulation. Disorders associated with a type 2 cytokine shift may reduce the efficiency of skin homing by viral-specific CD8+ T cells. Furthermore, the ability to modify the local and systemic microenvironment may offer novel therapeutic strategies that influence tissue-specific T cell homing.
Diminished cytokine signalling against bacterial components in mononuclear leucocytes from ulcerative colitis patients after leukocytapheresis
Authors: Mitsuyama K , Suzuki A , Matsumoto S , Tomiyasu N , Takaki K , Takedatsu H , Masuda J , Handa K , Harada K , Nishida H , Toyonaga A , Sata M 
Published: June 2005

SummaryInfiltration by circulating inflammatory cells is a prominent local inflammatory feature of ulcerative colitis (UC). Several trials have suggested that leukocytapheresis by filtration can benefit patients with active UC. We investigated how this therapy might modulate the inflammatory response. Patients with active UC who were beginning repeated filtration leukocytapheresis were studied. Mononuclear cell preparations were obtained from blood before and after the first treatment, and expression of cytokine signalling components and the cell-proliferative response were analysed in vitro. Leukocytapheresis reduced lipopolysaccharide-induced production of proinflammatory cytokines (interleukin-1, -6, -8 and tumour necrosis factor-α, P &lt; 0·05 for all) and activation of intracellular signalling components (nuclear factor-κB, mitogen-activated protein kinases, and signal transducer and activator of transcription-3), as well as surface expression of toll-like receptor-4 (P &lt; 0·05) in mononuclear cells. The therapy also reduced the cell-proliferative response by mononuclear cells stimulated with sonicated bacterial preparations from autologous intestine (P &lt; 0·05). These results indicate that activated mononuclear cells in the peripheral blood of patients with active UC are removed by leukocytapheresis and replaced by cells with a lower activation status. This replacement may partly explain the therapeutic benefit.
Engineering and functional evaluation of a single-chain antibody against HIV-1 external glycoprotein gp120
Authors: Wang H W , Cole D , Jiang W Z , Jin H T , Fu N , Chen Z L , Jin N Y 
Published: June 2005

SummaryThe HIV-1 envelope glycoprotein surface subunit gp120 is an attractive target for molecular intervention. This is because anti-HIV-1 gp120 neutralizing antibodies display the potential ability to inhibit HIV-1 infection. The present investigation describes the construction of a genetically engineered single chain antibody (scFv102) against HIV-1 gp120, its expression and functional evaluation. The parental hybridoma cell line (102) produces an immunoglobulin directed against the conserved CD4-binding region of gp120. cDNAs encoding the variable regions of the heavy (VH) and light (VL) chains were prepared by reverse transcription PCR and linked together with an oligonucleotide encoding a linker peptide (Gly4Ser)3 to produce a single chain antibody gene. The resulting DNA construct was cloned into a prokaryotic expression vector (pET28) and recombinant scFv102 was expressed in Eserichia coli as an insoluble protein. The denatured scFv102 was refolded and purified by immobilized metal ion affinity chromatography. Purified scFv102 had the same specificity as the intact IgG in immuno-blotting assays and immuno-fluorescence (IF) detection, but ELISA analyses demonstrated the affinity of scFv102 to be 5-fold lower than that of the parental monoclonal antibody. In neutralization assays, scFv102 at concentrations lower than 40 µg/ml exhibited efficient interference with viral replication and inhibition of viral infection (90%) across a range of primary isolates of subtype B HIV-1. These results suggest that the constructed anti-HIV-1 gp120 scFv102 has good biological activity and can potentially be used for in vitro diagnostic and in vivo therapeutic applications.
Expression of tumour necrosis factor receptor and Toll-like receptor 2 and 4 on peripheral blood leucocytes of human volunteers after endotoxin challenge: a comparison of flow cytometric light scatter and immunofluorescence gating
Authors: Wittebole X , Coyle S M , Kumar A , Goshima M , Lowry S F , Calvano S E 
Published: June 2005

Summary
Toll-like receptors (TLRs) are involved in the recognition of bacterial products and thus participate in the induction of the inflammatory cascade. However, much less is known about the evolution of leucocyte TLR expression during human inflammatory stress. We hypothesized that a decrease in leucocyte TLRs could account for the so-called tolerance or hyporesponsiveness state to subsequent stimulation with bacteria-derived products. Because of the profound monocytopenia that ensues after in vivo lipopolysaccharide (LPS) challenge, we also compared monocyte TLR expression using two different techniques of flow cytometric gating. In a first set of experiments, 17 healthy volunteers underwent LPS challenge. Blood was drawn at different time-points and analysed by flow cytometry using light scatter gating and one-colour analysis to assess the expression of the tumour necrosis factor receptor (TNFR) and TLR2 and TLR4 on both monocytes and granulocytes. In a second set of experiments, the assessment of those receptors was made using a more specific gating method that utilized light scatter and CD14 immunofluorescence in a two-colour analysis. This was performed using whole blood drawn from five healthy volunteers and incubated ex vivo for different time periods with or without LPS and in 12 volunteers who underwent LPS challenge in vivo. The pattern of expression for monocyte TNFR was similar for both types of gating. Using only the light scatter gating, an initial drop of TLR 2 and 4 was observed on monocytes. By contrast, when using light scatter × immunofluorescence gating, an up-regulation of these two receptors following both in vivo and in vitro LPS exposure was observed. LPS up-regulates the expression of TLRs on monocytes and granulocytes. Depending upon the methodology utilized, contrasting results were obtained with respect to TLR2 and TLR4 expression. The flow cytometric gating technique used is of importance in determining cellular TLR2 and TLR4 expression, especially in blood samples exhibiting significant monocytopenia.
Immunogenicity and protective efficacy of the Mycobacterium tuberculosis fadD26 mutant
Authors: Infante E , Aguilar L D , Gicquel B , Pando R Hernandez 
Published: June 2005

Summary
The Mycobacterium tuberculosis fadD26 mutant has impaired synthesis of phthiocerol dimycocerosates (DIM) and is attenuated in BALB/c mice. Survival analysis following direct intratracheal infection confirmed the attenuation: 60% survival at 4 months post-infection versus 100% mortality at 9 weeks post-infection with the wild-type strain. The fadD26 mutant induced less pneumonia and larger DTH reactions. It induced lower but progressive production of interferon (IFN)-γ, interleukin (IL)-4 and tumour necrosis factor (TNF)-α. Used as a subcutaneous vaccine 60 days before intratracheal challenge with a hypervirulent strain of M. tuberculosis (Beijing code 9501000), the mutant induced a higher level of protection than did Bacille Calmette–Guérin (BCG). Seventy per cent of the mice vaccinated with the fadD26 mutant survived at 16 weeks after challenge compared to 30% of those vaccinated with BCG. Similarly, there was less tissue damage (pneumonia) and lower colony-forming units (CFU) in the mice vaccinated with the fadD26 mutant compared to the findings in mice vaccinated with BCG. These data suggest that DIM synthesis is important for the pathogenicity of M. tuberculosis, and that inactivation of DIM synthesis can increase the immunogenicity of live vaccines, and increase their ability to protect against tuberculosis.