bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of the T-SPOT.TB Assay to Detect Latent Tuberculosis Infection Among Rheumatic Disease Patients on Immunosuppressive Therapy
Authors: BEHAR SAMUEL M. , SHIN DANIEL S. , MAIER AGNES , COBLYN JONATHAN , HELFGOTT SIMON , WEINBLATT MICHAEL E. 
Published: October 2009

Objective.We evaluated the T-SPOT.TB assay to identify latent tuberculosis infection (LTBI) in patients with rheumatic disease receiving immunosuppressive medication including tumor necrosis factor (TNF) antagonists.Methods.A total of 200 patients seen in the Arthritis Center at Brigham and Women’s Hospital were enrolled for study. Most patients were US-born women with rheumatoid arthritis. A medical history was obtained using a questionnaire, whole blood was drawn for the T-SPOT.TB assay, and tuberculin skin testing (TST) was performed.Results.Both tests were performed on 179 subjects, who had no history of a positive TST. All subjects had a strong response to the T-SPOT.TB test positive control, and there were no indeterminate results. Among these 179 subjects, 2 had a positive TST and 10 had a positive T-SPOT.TB test. No subject was positive for both tests. Patients with a positive T-SPOT.TB test did not have typical risk factors for LTBI based on clinical evaluation.Conclusion.The lack of concordance between the TST and the T-SPOT.TB assay may indicate that the immunoassay is more sensitive, particularly in a patient population taking immunosuppressive medications. It is equally likely that the low prevalence of LTBI in this low-risk population led to an increase in the false-positive rate despite the high sensitivity and specificity of the T-SPOT.TB assay. In the context of our patient population, the T-SPOT.TB assay is likely to be most useful in evaluation of patients with a positive TST, since these patients have a higher pretest probability of having LTBI.
Prospective Randomized Trial of Limbal Relaxing Incisions Combined with Microincision Cataract Surgery
Authors: Ouchi Masayuki , Kinoshita Shigeru 
Published: October 2009

Purpose:
To evaluate clinical outcomes of limbal relaxing incision (LRI) combined with bimanual phacoemulsification and insertion of an intraocular lens (IOL) developed for bimanual microincision cataract surgery (MICS).

Methods:
In a prospective, single-center study, eyes with ≥0.75 diopters (D) of keratometric astigmatism were randomly assigned to two surgical techniques: 1) bimanual MICS (non-LRI group) or 2) LRI combined with bimanual MICS (LRI group). Postoperative uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), postoperative refractive error, corneal topography, and vector analysis of keratometric change between pre- and postoperative eyes were compared.

Results:

In all cases of astigmatism in the LRI group, incisions for phacoemulsification and IOL insertion did not overlap or affect the LRIs. Uncorrected distance visual acuity was significantly higher in the LRI group (mean: 0.94) than in the non-LRI group (mean: 0.71,
P
=.009), although no difference was seen in CDVA in either group. Postoperative cylindrical error was significantly lower in the LRI group than in the non-LRI group (0.56 D and 1.51 D, respectively,
P
=.0004). Cravy analysis showed that the vector change in cylinder was 1.44 D in the LRI group and 0.18 D in the non-LRI group (
P
=.0007).

Conclusions:
Limbal relaxing incision with bimanual MICS is an easy-to-follow combined surgery to correct preexisting astigmatism with predictable accuracy.
Functional Expression of Formyl Peptide Receptor Family in Human NK Cells
Authors: Kim Sang Doo , Kim Jung Mo , Jo Seong Ho , Lee Ha Young , Lee Sun Young , Shim Jae Woong , Seo Su-Kil , Yun Jeanho , Bae Yoe-Sik 
Published: October 2009

Abstract
We determined the expression of the formyl peptide receptor (FPR) family and the functional roles of the FPR family in NK cells. All tested human NK cells express two members of the FPR family (FPR1 and FPR2). The expression of FPR3 was noted to occur in a donor-specific manner. The stimulation of NK cells with FPR family-selective agonists (fMLF (N-formyl-Met-Leu-Phe), MMK-1, F2L, and WKYMVm (Trp-Lys-Tyr-Met-Val-d-Met)) elicited cytolytic activity in resting NK cells, but not in IL-2-activated NK cells; the cytolytic activity was not inhibited by pertussis toxin. The FPR family agonists also stimulated chemotactic migration of IL-2-activated NK cells, but not resting NK cells; the chemotactic migration was completely inhibited by pertussis toxin. WKYMVm stimulates ERK, p38 MAPK, and JNK activities in both resting and IL-2-activated NK cells. WKYMVm-induced chemotactic migration was partially inhibited by PD98059 (2′-amino-3′-methoxyflavone); however, the inhibition of JNK by its selective inhibitor (SP600125, anthra[1,9-cd]pyrazol-6(2H)-one) dramatically inhibited the WKYMVm-induced cytolytic activity. Furthermore, WKYMVm-induced chemotactic migration and cytolytic activity were partly inhibited by FPR family-selective antagonists (cyclosporin H and WRWWWW). Taken together, our findings indicate that human NK cells express functional members of the FPR family, and in turn the activation of the three members of the FPR receptor family elicit cytolytic activity in NK cells, thus suggesting that the receptors are potentially important therapeutic targets for the modulation of NK cell-mediated immune responses.
Anergic T Cells Are Metabolically Anergic
Authors: Zheng Yan , Delgoffe Greg M. , Meyer Christian F. , Chan Waipan , Powell Jonathan D. 
Published: October 2009

Abstract
Full T cell activation requires TCR engagement (signal 1) in the context of costimulation (signal 2). Costimulation is required for maximal expression of effector cytokines and prevention of T cell anergy. It has become increasingly clear that another major function of costimulation is to up-regulate the metabolic machinery necessary for T cell function. In this report we demonstrate that anergic T cells are metabolically anergic, in that upon full stimulation (signals 1 plus 2) they fail to up-regulate the machinery necessary to support increased metabolism. These findings suggest that one mechanism responsible for the maintenance of T cell anergy is failure to up-regulate the metabolic machinery. Furthermore, we demonstrate that by blocking leucine, glucose, and energy metabolism, T cell activation is mitigated. Additionally, inhibition of these metabolic pathways during T cell activation leads to anergy in Th1-differentiated cells. Overall, our findings extend the role of T cell metabolism in regulating T cell function.
Lymph Node Stromal Cells Support Dendritic Cell-Induced Gut-Homing of T Cells
Authors: Molenaar Rosalie , Greuter Mascha , van der Marel Arnold P. J. , Roozendaal Ramon , Martin Stefan F. , Edele Fanny , Huehn Jochen , Förster Reinhold , O'Toole Tom , Jansen Wendy , Eestermans Inge L. , Kraal Georg , Mebius Reina E. 
Published: October 2009

Abstract
T cells are imprinted to express tissue-specific homing receptors upon activation in tissue-draining lymph nodes, resulting in their migration to the site of Ag entry. Expression of gut-homing molecules α4β7 and CCR9 is induced by retinoic acid, a vitamin A metabolite produced by retinal dehydrogenases, which are specifically expressed in dendritic cells as well as stromal cells in mucosa-draining lymph nodes. In this study, we demonstrate that mesenteric lymph node stromal cell-derived retinoic acid can directly induce the expression of gut-homing molecules on proliferating T cells, a process strongly enhanced by bone marrow-derived dendritic cells in vitro. Therefore, cooperation of sessile lymph node stromal cells with mobile dendritic cells warrants the imprinting of tissue specific homing receptors on activated T cells.
Reduced Diabetes in btk-Deficient Nonobese Diabetic Mice and Restoration of Diabetes with Provision of an Anti-Insulin IgH Chain Transgene
Authors: Kendall Peggy L. , Moore Daniel J. , Hulbert Chrys , Hoek Kristen L. , Khan Wasif N. , Thomas James W. 
Published: October 2009

Abstract
Type 1 diabetes results from T cell-mediated destruction of insulin-producing β cells. Although elimination of B lymphocytes has proven successful at preventing disease, modulation of B cell function as a means to prevent type 1 diabetes has not been investigated. The development, fate, and function of B lymphocytes depend upon BCR signaling, which is mediated in part by Bruton’s tyrosine kinase (BTK). When introduced into NOD mice, btk deficiency only modestly reduces B cell numbers, but dramatically protects against diabetes. In NOD, btk deficiency mirrors changes in B cell subsets seen in other strains, but also improves B cell-related tolerance, as indicated by failure to generate insulin autoantibodies. Introduction of an anti-insulin BCR H chain transgene restores diabetes in btk-deficient NOD mice, indicating that btk-deficient B cells are functionally capable of promoting autoimmune diabetes if they have a critical autoimmune specificity. This suggests that the disease-protective effect of btk deficiency may reflect a lack of autoreactive specificities in the B cell repertoire. Thus, signaling via BTK can be modulated to improve B cell tolerance, and prevent T cell-mediated autoimmune diabetes.
Localization of Kv1.3 Channels in the Immunological Synapse Modulates the Calcium Response to Antigen Stimulation in T Lymphocytes
Authors: Nicolaou Stella A. , Neumeier Lisa , Steckly Ashleigh , Kucher Vladimir , Takimoto Koichi , Conforti Laura 
Published: October 2009

Abstract
The immunological synapse (IS), a highly organized structure that forms at the point of contact between a T cell and an APC, is essential for the proper development of signaling events, including the Ca2+ response. Kv1.3 channels control Ca2+ homeostasis in human T cells and move into the IS upon Ag presentation. However, the process involved in channel accumulation in the IS and the functional implications of this localization are not yet known. Here we define the movement of Kv1.3 into the IS and study whether Kv1.3 localization into the IS influences Ca2+ signaling in Jurkat T cells. Crosslinking of the channel protein with an extracellular Ab limits Kv1.3 mobility and accumulation at the IS. Moreover, Kv1.3 recruitment to the IS does not involve the transport of newly synthesized channels and it does not occur through recycling of membrane channels. Kv1.3 localization in the IS modulates the Ca2+ response. Blockade of Kv1.3 movement into the IS by crosslinking significantly increases the amplitude of the Ca2+ response triggered by anti-CD3/anti-CD28-coated beads, which induce the formation of the IS. On the contrary, the Ca2+ response induced by TCR stimulation without the formation of the IS with soluble anti-CD3/anti-CD28 Abs is unaltered. The results presented herein indicate that, upon Ag presentation, membrane-incorporated Kv1.3 channels move along the plasma membrane to localize in the IS. This localization is important to control the amplitude of the Ca2+ response, and disruption of this process can account for alterations of downstream Ca2+-dependent signaling events.
Ligand Binding but Undetected Functional Response of FcR after Their Capture by T Cells via Trogocytosis
Authors: Hudrisier Denis , Clemenceau Béatrice , Balor Stéphanie , Daubeuf Sandrine , Magdeleine Eddy , Daëron Marc , Bruhns Pierre , Vié Henri 
Published: October 2009

Abstract
Intercellular transfer of cell surface proteins by trogocytosis is common and could affect T cell responses. Yet, the role of trogocytosis in T cell function is still elusive, and it is unknown whether a molecule, once captured by T cells, harbors the same biological properties as in donor APC. In this study, we showed that FcγR as well as the associated FcRγ subunit could be detected at high levels on murine and human T cells after their intercellular transfer from FcγR-expressing APC. Capture of FcγR occurred during coculture of T cells with FcγR-expressing APC upon Ab- or Ag-mediated T cell stimulation. Once captured by T cells, FcγR were expressed in a conformation compatible with physiological function and conferred upon T cells the ability to bind immune complexes and to provision B cells with this source of Ag. However, we were unable to detect downstream signal or signaling-dependent function following the stimulation of FcγR captured by T cells, and biochemical studies suggested the improper integration of FcγR in the recipient T cell membrane. Thus, our study demonstrates that T cells capture FcγR that can efficiently exert ligand-binding activity, which, per se, could have functional consequences in T cell-B cell cooperation.
Absence of Mature Peripheral B Cell Populations in Mice with Concomitant Defects in B Cell Receptor and BAFF-R Signaling
Authors: Hoek Kristen L. , Carlesso Gianluca , Clark Emily S. , Khan Wasif N. 
Published: October 2009

AbstractGeneration of mature B lymphocytes from early (T1) and late transitional (T2) precursors requires cooperative signaling through BCR and B cell-activating factor receptor 3 (BR3). Recent studies have shown that BCR signaling positively regulates NF-κB2, suggesting BCR regulation of BR3 signaling. To investigate the significance of signal integration from BCR and BR3 in B cell development and function, we crossed Btk-deficient mice (btk−/−), which are developmentally blocked between the T2 and the mature follicular B cell stage as a result of a partial defect in BCR signaling, and A/WySnJ mice, which possess a mutant BR3 defective in propagating intracellular signals that results in a severely reduced peripheral B cell compartment, although all B cell subsets are present in relatively normal ratios. A/WySnJ × btk−/− mice display a B cell-autonomous defect, resulting in a developmental block at an earlier stage (T1) than either mutation alone, leading to the loss of mature splenic follicular and marginal zone B cells, as well as the loss of peritoneal B1 and B2 cell populations. The competence of the double mutant T1 B cells to respond to TLR4 and CD40 survival and activation signals is further attenuated compared with single mutations as evidenced by severely reduced humoral immune responses in vivo and proliferation in response to anti-IgM, LPS, and anti-CD40 stimulation in vitro. Thus, BCR and BR3 independently and in concert regulate the survival, differentiation, and function of all B cell populations at and beyond T1, earliest transitional stage.
Potent High-Affinity Antibodies for Treatment and Prophylaxis of Respiratory Syncytial Virus Derived from B Cells of Infected Patients
Authors: Collarini Ellen J. , Lee F. Eun-Hyung , Foord Orit , Park Minha , Sperinde Gizette , Wu Hai , Harriman William D. , Carroll Stephen F. , Ellsworth Stote L. , Anderson Larry J. , Tripp Ralph A. , Walsh Edward E. , Keyt Bruce A. , Kauvar Lawrence M. 
Published: October 2009

Abstract
Native human Abs represent attractive drug candidates; however, the low frequency of B cells expressing high-quality Abs has posed a barrier to discovery. Using a novel single-cell phenotyping technology, we have overcome this barrier to discover human Abs targeting the conserved but poorly immunogenic central motif of respiratory syncytial virus (RSV) G protein. For the entire cohort of 24 subjects with recent RSV infection, B cells producing Abs meeting these stringent specificity criteria were rare, &lt;10 per million. Several of the newly cloned Abs bind to the RSV G protein central conserved motif with very high affinity (Kd 1–24 pM). Two of the Abs were characterized in detail and compared with palivizumab, a humanized mAb against the RSV F protein. Relative to palivizumab, the anti-G Abs showed improved viral neutralization potency in vitro and enhanced reduction of infectious virus in a prophylaxis mouse model. Furthermore, in a mouse model for postinfection treatment, both anti-G Abs were significantly more effective than palivizumab at reducing viral load. The combination of activity in mouse models for both prophylaxis and treatment makes these high-affinity human-derived Abs promising candidates for human clinical testing.
IL-33 Amplifies the Polarization of Alternatively Activated Macrophages That Contribute to Airway Inflammation
Authors: Kurowska-Stolarska Mariola , Stolarski Bartosz , Kewin Peter , Murphy Grace , Corrigan Christopher J. , Ying Sun , Pitman Nick , Mirchandani Ananda , Rana Batika , van Rooijen Nico , Shepherd Malcolm , McSharry Charlie , McInnes Iain B. , Xu Damo , Liew Foo Y. 
Published: October 2009

Abstract
Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity. Mice deficient in ST2, a receptor for the latest member of the IL-1 family, IL-33, have impaired type 2 immune responses. We therefore reasoned that IL-33/ST2 signaling may be involved in the differentiation and activation of AAM during airway inflammation. We report here that IL-33 changed the quiescent phenotype of alveolar macrophages toward an AAM phenotype that expressed mannose receptor, IL-4Rα, and produced high levels of CCL24 and CCL17 in an IL-13-dependent manner during IL-33-induced airway inflammation. Neutralization of AAM-derived CCL24 led to an amelioration of IL-33-induced eosinophilia in the lungs. Moreover, depletion of alveolar macrophages reduced IL-33-induced airway inflammation. Additionally, the attenuated OVA-induced airway inflammation in ST2−/− mice was associated with a decrease in AAM differentiation. In vitro, IL-33 amplified IL-13-induced polarization of alveolar- and bone marrow-derived macrophage toward an AAM phenotype by increasing the expression of arginase I, Ym1, as well as the production of CCL24 and CCL17. IL-13/IL-4Rα signaling was crucial for IL-33-driven AAM amplification by inducing the expression of ST2L. Finally, we showed that IL-33 was more abundantly expressed in the lung epithelial cells of asthma patients than those from healthy controls, suggesting that IL-33 may be involved in lung macrophage activation in clinical asthma. Taken together, we demonstrate here that IL-33/ST2 plays a significant role in the amplification of AAM polarization and chemokine production which contribute to innate and Ag-induced airway inflammation.
The Proteasome Inhibitor Bortezomib Enhances the Susceptibility to Viral Infection
Authors: Basler Michael , Lauer Christoph , Beck Ulrike , Groettrup Marcus 
Published: October 2009

Abstract
The proteasome, a multicatalytic protease, is responsible for the generation of most MHC class I ligands. Bortezomib, a proteasome inhibitor, is clinically approved for treatment of multiple myeloma and mantle cell myeloma. In the present study, we investigated the effect of bortezomib on viral infection. Infection of bortezomib-treated mice with the lymphocytic choriomeningitis virus (LCMV) led to a decreased cytotoxic T cell response to several LCMV-derived CD8+ T cell epitopes. Bortezomib treatment caused a reduced expansion of CD8+ T lymphocytes and increased viral titers in LCMV-infected mice. Administration of bortezomib during expansion of CD8+ T cells had no influence on the cytotoxic T cell response, suggesting that bortezomib interferes with priming of naive T cells. Indeed, determination of Ag load in spleen 4 days post infection, revealed a reduced presentation of LCMV-derived cytotoxic T cell epitopes on MHC class I molecules. In summary, we show that proteasome inhibition with bortezomib led to an increased susceptibility to viral infection, and demonstrate for the first time, that proteasome inhibitors can alter Ag processing in vivo.
Human γδ T Cells: A Lymphoid Lineage Cell Capable of Professional Phagocytosis
Authors: Wu Yin , Wu Wutian , Wong Wai Man , Ward Eliot , Thrasher Adrian J. , Goldblatt David , Osman Mohamed , Digard Paul , Canaday David H. , Gustafsson Kenth 
Published: October 2009

Abstract
Professional phagocytosis in mammals is considered to be performed exclusively by myeloid cell types. In this study, we demonstrate, for the first time, that a mammalian lymphocyte subset can operate as a professional phagocyte. By using confocal microscopy, transmission electron microscopy, and functional Ag presentation assays, we find that freshly isolated human peripheral blood γδ T cells can phagocytose Escherichia coli and 1 μm synthetic beads via Ab opsonization and CD16 (FcγRIII), leading to Ag processing and presentation on MHC class II. In contrast, other CD16+ lymphocytes, i.e., CD16+/CD56+ NK cells, were not capable of such functions. These findings of distinct myeloid characteristics in γδ T cells strongly support the suggestion that γδ T cells are evolutionarily ancient lymphocytes and have implications for our understanding of their role in transitional immunity and the control of infectious diseases and cancer.
Uniform Distribution of Fractional Parts Related to Pseudoprimes
Authors: Banks William D. , Garaev Moubariz Z. , Luca Florian , Shparlinski Igor E. 
Published: October 2009

Abstract.We estimate exponential sums with the Fermat-like quotientswhere g and n are positive integers, n is composite, and P (n) is the largest prime factor of n. Clearly, both fg (n) and hg (n) are integers if n is a Fermat pseudoprime to base g, and if n is a Carmichael number, this is true for all g coprime to n. Nevertheless, our bounds imply that the fractional parts ﹛ fg (n)﹜ and ﹛hg (n)﹜ are uniformly distributed, on average over g for fg (n), and individually for hg (n). We also obtain similar results with the functions and .
Girsanov Transformations for Non-Symmetric Diffusions
Authors: Chen Chuan-Zhong , Sun Wei 
Published: October 2009

Abstract.Let X be a diffusion process, which is assumed to be associated with a (non-symmetric) strongly local Dirichlet form (ℰ, 𝓓 (ℰ)) on L2(E ;m). For u ∈ 𝓓(ℰ)e, the extended Dirichlet space, we investigate some properties of the Girsanov transformed process Y of X . First, let be the dual process of X and Ŷ the Girsanov transformed process of . We give a necessary and sufficient condition for (Y , Ŷ to be in duality with respect to the measure e2um. We also construct a counterexample, which shows that this condition may not be satisfied and hence (Y , Ŷ ) may not be dual processes. Then we present a sufficient condition under which Y is associated with a semi-Dirichlet form. Moreover, we give an explicit representation of the semi-Dirichlet form.
Convex Subordination Chains in Several Complex Variables
Authors: Ian Graham  , Hamada Hidetaka , Kohr Gabriela , Pfaltzgraff John A. 
Published: October 2009

Abstract.In this paper we study the notion of a convex subordination chain in several complex variables. We obtain certain necessary and sufficient conditions for a mapping to be a convex subordination chain, and we give various examples of convex subordination chains on the Euclidean unit ball in ℂn. We also obtain a sufficient condition for injectivity off(z/‖z‖, ‖z‖) onBn\ ﹛0﹜, wheref(z,t) is a convex subordination chain over (0, 1).
Generalized Polynomials and Mild Mixing
Authors: McCutcheon Randall , Quas Anthony 
Published: October 2009

Abstract.An unsettled conjecture of V. Bergelson and I. Håland proposes that if (X ,A, μ, T ) is an invertible weak mixing measure preserving system, where μ(X ) < ∞, and if p1, p2, … , pk are generalized polynomials (functions built out of regular polynomials via iterated use of the greatest integer or floor function) having the property that no pi, nor any pi−pj, i ≠ j, is constant on a set of positive density, then for any measurable sets A0, A1, … , Ak, there exists a zero-density set E ⊂ Zsuch thatWe formulate and prove a faithful version of this conjecture for mildly mixing systems and partially characterize, in the degree two case, the set of families ﹛p1, p2, … , pk﹜ satisfying the hypotheses of this theorem.