bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Effect of Saturated and Unsaturated Free Fatty Acids on the Generation of Monocyte Adhesion and Chemotactic Factors by Adipocytes
Authors: Han Chang Yeop , Kargi Atil Y. , Omer Mohamed , Chan Christina K. , Wabitsch Martin , O'Brien Kevin D. , Wight Thomas N. , Chait Alan 
Published: November 2009

OBJECTIVEObesity is associated with monocyte-macrophage accumulation in adipose tissue. Previously, we showed that glucose-stimulated production by adipocytes of serum amyloid A (SAA), monocyte chemoattractant protein (MCP)-1, and hyaluronan (HA) facilitated monocyte accumulation. The current objective was to determine how the other major nutrient, free fatty acids (FFAs), affects these molecules and monocyte recruitment by adipocytes.RESEARCH DESIGN AND METHODSDifferentiated 3T3-L1, Simpson-Golabi-Behmel syndrome adipocytes, and mouse embryonic fibroblasts were exposed to various FFAs (250 μmol/l) in either 5 or 25 mmol/l (high) glucose for evaluation of SAA, MCP-1, and HA regulation in vitro.RESULTSSaturated fatty acids (SFAs) such as laurate, myristate, and palmitate increased cellular triglyceride accumulation, SAA, and MCP-1 expression; generated reactive oxygen species (ROS); and increased nuclear factor (NF) κB translocation in both 5 and 25 mmol/l glucose. Conversely, polyunsaturated fatty acids (PUFAs) such as arachidonate, eicosapentaenate, and docosahexaenate (DHA) decreased these events. Gene expression could be dissociated from triglyceride accumulation. Although excess glucose increased HA content, SFAs, oleate, and linoleate did not. Antioxidant treatment repressed glucose- and palmitate-stimulated ROS generation and NFκB translocation and decreased SAA and MCP-1 expression and monocyte chemotaxis. Silencing toll-like receptor-4 (TLR4) markedly reduced SAA and MCP-1 expression in response to palmitate but not glucose. DHA suppressed NFκB translocation stimulated by both excess glucose and palmitate via a peroxisome prolifterator–activated receptor (PPAR) γ–dependent pathway.CONCLUSIONSExcess glucose and SFAs regulate chemotactic factor expression by a mechanism that involves ROS generation, NFκB, and PPARγ, and which is repressed by PUFAs. Certain SFAs, but not excess glucose, trigger chemotactic factor expression via a TLR4-dependent pathway.
Role of Quantitative Bone Scanning in the Assessment of Bone Turnover in Patients With Charcot Foot
Authors: Bem Robert , Jirkovská Alexandra , Dubský Michal , Fejfarová Vladimira , Buncová Marie , Skibová Jelena , Jude Edward B. 
Published: November 2009

OBJECTIVE
To assess the new quantitative bone scan parameters as markers of Charcot neuroosteoarthropathy (CNO) activity.

RESEARCH DESIGN AND METHODS
Forty-two patients with acute (n = 21) and nonacute (n = 21) CNO underwent quantitative bone scanning. Patients with acute CNO were followed for 3–12 months and bone scans were repeated after treatment. New quantitative parameters were assessed and compared with markers of bone turnover and with skin temperature difference (STD).

RESULTS
Significant correlations between quantitative bone scan parameters and bone turnover markers were observed (all P &lt; 0.05). These parameters decreased after treatment of CNO, and its reduction to the baseline value correlated with differences of bone turnover markers and STD (all P &lt; 0.05).

CONCLUSIONS
Our study suggests that bone scanning can be used not only for diagnosis of CNO but also for monitoring disease activity by quantitative bone scan parameters.
A Non-invasive Methodology for Fetal Monitoring during Pregnancy
Authors: Karvounis E. C. , Tsipouras M. G. , Papaloukas C. , Tsalikakis D. G. , Naka K. K. , Fotiadis D. I. 
Published: November 2009

Summary
Objectives: This paper describes a methodology for the monitoring of the fetal cardiac health status during pregnancy, through the effective and non-invasive monitoring of the abdominal ECG signals (abdECG) of the mother.
Methods: For this purpose, a three-stage methodology has been developed. In the first stage, the fetal heart rate (fHR) is extracted from the abdECG signals, using nonlinear analysis. Also, the eliminated ECG (eECG) is calculated, which is the abdECG after the maternal QRSs elimination. In the second stage, a blind source separation technique is applied to the eECG signals and the fetal ECG (fECG) is obtained. Finally, monitoring of the fetus is implemented using features extracted from the fHR and f ECG, such as the T/QRS ratio and the characterization of the fetal ST waveforms.
Results: The methodology is evaluated using a dataset of simulated multichannel abdECG signals: 94.79% accuracy for fHR extraction, 92.49% accuracy in T/QRS ratio calculation and 79.87% in ST waveform classification.
Conclusions: The novel non-invasive proposed methodology is advantageous since it offers automated identification of fHR and fECG and automated ST waveform analysis, exhibiting a high diagnostic accuracy.
Outcome of Unilateral Inferior Oblique Recession
Authors: Singh Vinita , Agrawal Saurabh , Agrawal Siddharth 
Published: November 2009

Purpose:
The aim of this study was to analyze the outcome of unilateral inferior oblique (IO) recession in patients with unilateral or asymmetrical IO overaction in terms of effectiveness, stability, and undesired effects.

Methods:
Fifteen patients with nonparalytic strabismus who underwent unilateral IO recession for unilateral or asymmetric IO overaction and horizontal muscle surgery were included in this study. Nine patients demonstrated asymmetric bilateral IO overaction, whereas 6 had unilateral overaction. All patients underwent IO recession to the Scheie Parks point in one eye, along with conventional horizontal muscle surgery. Clinical outcome assessment included changes in oblique muscle dysfunction in both eyes. Changes in horizontal deviation, V pattern, vertical deviation, and excyclotorsion were also studied.

Results:
Satisfactory outcome in terms of oblique muscle function, V pattern, vertical deviation, and cyclodeviation was achieved in all patients with unilateral IO overaction and 7 (77%) patients with bilateral IO over-action. Increased IO overaction in the other eye was noted in 2 patients. Satisfactory outcome in patients with bilateral overaction was related to degree of asymmetry in IO overaction between the 2 eyes.

Conclusion:
Unilateral IO recession is effective in patients with unilateral IO overaction and selected patients with largely asymmetrical bilateral IO overaction.

[J Pediatr Ophthalmol Strabismus 2009;46:350–357.]
Importance of the ‘Third Criterion’ for Retinopathy of Prematurity Screening in Developing Countries
Authors: Azad Rajvardhan , Chandra Parijat , Patwardhan Sourabh D. , Gupta Aparna 
Published: November 2009

Purpose:
Developing countries often need a modification of the American screening guidelines for retinopathy of prematurity.

Methods:
A total of 1,302 eyes in 651 infants with retinopathy of prematurity were analyzed by the parameters of gestational age and birth weight suggested by the American guidelines.

Results:
With the use of current gestational age and birth weight guidelines, 86 of 1,302 eyes (6.6%) were missed, and 38 of these eyes (2.9%) had potentially treatable or more severe retinopathy of prematurity and were in need of treatment.

Conclusion:
Use of the “third criterion” (ie, neonatologist referral of sick infants who were believed to be at high risk for retinopathy of prematurity), enabled larger infants who were otherwise missed by the American guidelines to be included for screening. Even when the parameters were increased, a relatively small number of infants was still missed. Therefore, in view of the limited resources and manpower in developing countries, the American screening guidelines are appropriate.

[J Pediatr Ophthalmol Strabismus 2009;46:332–334.]
Prolonged Constant Eye Misalignment Leads to Failure to Develop Binocular Vision in Childhood Ocular Myasthenia Gravis
Authors: Emoto Yuko , Emoto Hirofumi , Fujie Waki , Wakakura Masato 
Published: November 2009

Purpose:
Variable eye misalignment and blepharoptosis in childhood ocular myasthenia gravis can lead to permanent binocular visual loss. However, a standard ophthalmologic intervention for this condition has yet to be fully established. This study investigated the influence of variable eye misalignment and asymmetric blepharoptosis on the development of binocular vision in childhood ocular myasthenia gravis.

Methods:
The authors retrospectively reviewed clinical records of consecutive patients with childhood ocular myasthenia gravis whose age of onset was younger than 36 months and who had follow-up periods of more than 1 year. Five patients were enrolled and were treated medically with pyridostigmine or corticosteroids. Eye alignment, eye movements, and blepharoptosis were observed during the follow-up period. Stereoacuity was recorded before and at the end of follow-up using Titmus stereoscopic and major amblyoscopic tests.

Results:
None of the patients had amblyopia or anisometropia, but all had blepharoptosis that improved within 2 weeks after medication was administered. There was only one case in which stereoacutiy failed to develop, and this patient had a long period of constant exotropia lasting 48 months. In the remaining four cases, there was constant exotropia lasting less than 4 months or intermittent exotropia throughout the follow-up period. All of these patients regained or maintained binocular vision.

Conclusion:
Prolonged constant eye misalignment may be attributable to impaired binocular vision, and prompt eye alignment may be necessary in childhood ocular myasthenia gravis. Therefore, treatment based on precise assessment by a neuro-ophthalmologist or pediatric ophthalmologist that evaluates even slight eye misalignment is essential in ensuring normal development of binocular vision.

[J Pediatr Ophthalmol Strabismus 2009;46:358–361.]
Modulation of Allergenicity of Major House Dust Mite Allergens Der f 1 and Der p 1 by Interaction with an Endogenous Ligand
Authors: Takai Toshiro , Kato Takeshi , Hatanaka Hideki , Inui Kyoko , Nakazawa Takuya , Ichikawa Saori , Mitsuishi Kouichi , Ogawa Hideoki , Okumura Ko 
Published: November 2009

AbstractAlthough many allergens bind endogenous molecules other than Abs in the human body, whether the interaction can modulate allergenicity has been unknown. Here, we investigated the effect of the interaction of recombinant major mite group 1 allergens (Der f 1 and Der p 1), which belong to the papain-like cysteine protease family, with an endogenous protease inhibitor, cystatin A, on their allergenicity. Cystatin A bound reduced forms of the allergens, in which the cysteine residue at the catalytic center of the protease activity was reduced by treatment with l-cysteine, but did not bind oxidized forms. Cystatin A partially inhibited the binding of IgE in mite-allergic volunteers’ sera to the reduced forms, but unexpectedly enhanced the basophil histamine-releasing activity. A catalytic site-mutant of Der f 1 behaved in terms of histamine release, similarly to the reduced form. Molecular modeling showed that cystatin A interacts with the allergens within a narrow area. The results indicate that interaction with cystatin A reduces the limited number of IgE epitopes of the allergens but enhances their biological activity to release histamine, suggesting a new concept, that interaction between allergens and their endogenous ligands modulates the allergenicity even toward enhancement in the effector phase. On the other hand, i.p. immunization without alum of mice with cystatin A-treated reduced Der f 1 induced less serum Der f 1-specific IgE than immunization with reduced Der f 1 alone, suggesting that endogenous protease inhibitors suppress the induction of allergen-specific IgE, which is dependent on the enzymatic activity of cysteine protease-allergens, in the sensitization process.
The Yellow Fever Virus Vaccine Induces a Broad and Polyfunctional Human Memory CD8+ T Cell Response
Authors: Akondy Rama S. , Monson Nathan D. , Miller Joseph D. , Edupuganti Srilatha , Teuwen Dirk , Wu Hong , Quyyumi Farah , Garg Seema , Altman John D. , Del Rio Carlos , Keyserling Harry L. , Ploss Alexander , Rice Charles M. , Orenstein Walter A. , Mulligan Mark J. , Ahmed Rafi 
Published: November 2009

Abstract
The live yellow fever vaccine (YF-17D) offers a unique opportunity to study memory CD8+ T cell differentiation in humans following an acute viral infection. We have performed a comprehensive analysis of the virus-specific CD8+ T cell response using overlapping peptides spanning the entire viral genome. Our results showed that the YF-17D vaccine induces a broad CD8+ T cell response targeting several epitopes within each viral protein. We identified a dominant HLA-A2-restricted epitope in the NS4B protein and used tetramers specific for this epitope to track the CD8+ T cell response over a 2 year period. This longitudinal analysis showed the following. 1) Memory CD8+ T cells appear to pass through an effector phase and then gradually down-regulate expression of activation markers and effector molecules. 2) This effector phase was characterized by down-regulation of CD127, Bcl-2, CCR7, and CD45RA and was followed by a substantial contraction resulting in a pool of memory T cells that re-expressed CD127, Bcl-2, and CD45RA. 3) These memory cells were polyfunctional in terms of degranulation and production of the cytokines IFN-γ, TNF-α, IL-2, and MIP-1β. 4) The YF-17D-specific memory CD8+ T cells had a phenotype (CCR7−CD45RA+) that is typically associated with terminally differentiated cells with limited proliferative capacity (TEMRA). However, these cells exhibited robust proliferative potential showing that expression of CD45RA may not always associate with terminal differentiation and, in fact, may be an indicator of highly functional memory CD8+ T cells generated after acute viral infections.
Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani
Authors: Sharma Ankur , Madhubala Rentala 
Published: November 2009

AbstractResistance of Leishmania donovani to sodium antimony gluconate has become a critical issue in the current, prolonged epidemic in India. Hence, there is an urgent need for a vaccine that is protective against both antimony-susceptible and -resistant strains of L. donovani. The multigene LD1 locus located on chromosome 35 of Leishmania is amplified in ∼15% of the isolates examined. The open reading frame F (ORFF), a potential vaccine candidate against visceral leishmaniasis, is part of the multigene LD1 locus. ORFF was expressed as a chimeric conjugate of ubiquitin to elicit an Ag-specific cell-mediated immune response. Analysis of the cellular immune responses of ubiquitin-conjugated ORFF (UBQ-ORFF) DNA-immunized, uninfected BALB/c mice demonstrated that the vaccine induced enhanced IFN-γ-producing CD4+ and CD8+ T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-γ and the low levels of IL-4 and IL-10 further indicated that the immune responses with UBQ-ORFF were mediated toward the Th1 rather than Th2 type. Infection of immunized mice with either the antimony-susceptible (AG83) or -resistant (GE1F8R) L. donovani strain showed that UBQ-ORFF DNA vaccine induced higher protection when compared with ORFF DNA. UBQ-ORFF DNA-immunized and -infected mice showed a significant increase in IL-12 and IFN-γ and significant down-regulation of IL-10. High levels of production of nitrite and superoxide, two macrophage-derived oxidants that are critical in controlling Leishmania infection, were observed in protected mice. The feasibility of using ubiquitinated-conjugated ORFF DNA vaccine as a promising immune enhancer for vaccination against both antimony-susceptible and -resistant strains of L. donovani is reported.
The IL-27 p28 Subunit Binds Cytokine-Like Factor 1 to Form a Cytokine Regulating NK and T Cell Activities Requiring IL-6R for Signaling
Authors: Crabé Sandrine , Guay-Giroux Angélique , Tormo Aurélie Jeanne , Duluc Dorothée , Lissilaa Rami , Guilhot Florence , Mavoungou-Bigouagou Ulrick , Lefouili Fouad , Cognet Isabelle , Ferlin Walter , Elson Greg , Jeannin Pascale , Gauchat Jean-François 
Published: November 2009

AbstractIL-27 is formed by the association of a cytokine subunit, p28, with the soluble cytokine receptor EBV-induced gene 3 (EBI3). The IL-27R comprises gp130 and WSX-1. The marked difference between EBI3−/− and WSX-1−/− mice suggests that p28 has functions independent of EBI3. We have identified an alternative secreted complex formed by p28 and the soluble cytokine receptor cytokine-like factor 1 (CLF). Like IL-27, p28/CLF is produced by dendritic cells and is biologically active on human NK cells, increasing IL-12- and IL-2-induced IFN-γ production and activation marker expression. Experiments with Ba/F3 transfectants indicate that p28/CLF activates cells expressing IL-6Rα in addition to the IL-27R subunits. When tested on CD4 and CD8 T cells, p28/CLF induces IL-6Rα-dependent STAT1 and STAT3 phosphorylation. Furthermore, p28/CLF inhibits CD4 T cell proliferation and induces IL-17 and IL-10 secretion. These results indicate that p28/CLF may participate in the regulation of NK and T cell functions by dendritic cells. The p28/CLF complex engages IL-6R and may therefore be useful for therapeutic applications targeting cells expressing this receptor. Blocking IL-6R using humanized mAbs such as tocilizumab has been shown to be beneficial in pathologies like rheumatoid arthritis and juvenile idiopathic arthritis. The identification of a new IL-6R ligand is therefore important for a complete understanding of the mechanism of action of this emerging class of immunosuppressors.
TLR2 Engagement on Dendritic Cells Promotes High Frequency Effector and Memory CD4 T Cell Responses
Authors: Chandran Smita S. , Verhoeven David , Teijaro John R. , Fenton Matthew J. , Farber Donna L. 
Published: November 2009

AbstractLigation of TLR by distinct pathogen components provides essential signals for T cell priming, although how individual TLR engagement affects primary and memory T cell responses is not well defined. In this study, we demonstrate distinct effects of TLR2 vs TLR4 engagement on primary and memory CD4 T cell responses due to differential effects on APC. Priming of influenza hemagglutinin (HA)-specific naive CD4 T cells with HA peptide and the TLR2 agonist Pam3CysK in vivo resulted in a high frequency of activated HA-specific CD4 T cells that predominantly produced IL-2 and IL-17, whereas priming with HA peptide and the TLR4 agonist LPS yielded a lower frequency of HA-specific CD4 T cells and predominant IFN-γ producers. TLR2 agonist priming depended on TLR2 expression by APC, as wild-type CD4 T cells did not expand in response to peptide and Pam3CysK in TLR2-deficient hosts. TLR2-mediated priming also led to an increased frequency of Ag-specific memory CD4 T cells compared with TLR4 priming and mediated enhanced secondary responses to influenza challenge. Our results show that TLR engagement on APC influences both primary and secondary CD4 T cell responses, and suggest that long-term functional capacities of T cells are set by innate signals during early phases of an infection.
Signal-Transducing Adaptor Protein-2 Regulates Stromal Cell-Derived Factor-1α-Induced Chemotaxis in T Cells
Authors: Sekine Yuichi , Ikeda Osamu , Tsuji Satoshi , Yamamoto Chikako , Muromoto Ryuta , Nanbo Asuka , Oritani Kenji , Yoshimura Akihiko , Matsuda Tadashi 
Published: November 2009

AbstractSignal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin and Src homology 2-like domains, as well as a YXXQ motif in its C-terminal region. Our previous studies revealed that STAP-2 regulates integrin-mediated T cell adhesion. In the present study, we find that STAP-2 expression affects Jurkat T cell migration after stromal cell-derived factor-1α (SDF-1α)-treatment. Furthermore, STAP-2-deficient T cells exhibit reduced cell migration after SDF-1α-treatment. Importantly, overexpression of STAP-2 in Jurkat T cells induces activation of small guanine triphosphatases, such as Rac1 and Cdc42. Regarding the mechanism for this effect, we found that STAP-2 associates with Vav1, the guanine-nucleotide exchanging factor for Rac1, and enhances downstream Vav1/Rac1 signaling. These results reveal a novel STAP-2-mediated mechanism for the regulation of SDF-1α-induced chemotaxis of T cells via activation of Vav1/Rac1 signaling.
β-Defensins 2 and 3 Together Promote Resistance toPseudomonas aeruginosaKeratitis
Authors: Wu Minhao , McClellan Sharon A. , Barrett Ronald P. , Zhang Yunfan , Hazlett Linda D. 
Published: November 2009

AbstractDefensins play an important role in both innate and adaptive immunity due to their antimicrobial, regulatory, and chemotactic effects. Nonetheless, the role of murine β-defensins (mBD) 3 and 4, the murine homologs of human β-defensins (hBD) 2 and 3, remains unknown in Pseudomonas aeruginosa keratitis. This study explored their role in corneal infection and potential synergy with mBD2, a defensin associated with better outcome in this disease. Immunostaining and real-time RT-PCR data demonstrated that mBD3 and mBD4 expression was inducible and differentially regulated in the infected cornea of resistant BALB/c vs susceptible C57BL/6 (B6) mice. Knockdown studies using small interfering RNA treatment indicated that mBD3, but not mBD4, is required in ocular defense. Moreover, in vivo studies demonstrated individual and combined effects of mBD2 and mBD3 that modulate bacterial load, polymorphonuclear neutrophil (PMN) infiltration, and production of IFN-γ, MIP-2, IL-1β, TNF-α, inducible NO synthase (iNOS), TLR2, TLR4, MyD88, and NF-κB. Most notably, bacterial load was increased at 5 days postinfection by silencing either mBD2 or mBD3, but it was elevated at both 1 and 5 days postinfection when silencing both defensins. PMN infiltration was increased at 1 day postinfection by silencing both defensins or mBD3, but not mBD2 alone. iNOS expression was elevated by silencing mBD2, but it was reduced after silencing mBD3 or both defensins. Additionally, cell sources of mBD2 (macrophages, PMN and fibroblasts) and mBD3 (PMN) in corneal stroma were identified by dual label immunostaining after infection. Collectively, the data provide evidence that mBD2 and mBD3 together promote resistance against corneal infection.