bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is There an Urban-Rural Divide? Population Surveys of Rheumatic Musculoskeletal Disorders in the Pune Region of India Using the COPCORD Bhigwan Model
Authors: JOSHI VAIJAYANTI LAGU , CHOPRA ARVIND 
Published: October 2009

Objective.To estimate urban prevalence of rheumatic musculoskeletal (MSK) disorders and compare to an earlier rural regional study.Methods.We screened 8145 adults from a preselected urban locality in Pune, India, for MSK pain in a cross-sectional house-to-house survey (Stage I) over 20 weeks. The World Health Organization-International League of Associations for Rheumatology (WHO-ILAR) Community Oriented Program for Control of Rheumatic Diseases (COPCORD) Bhigwan model was used. Thirty trained community volunteers completed Phases I and II questionnaires, concurrent with rheumatology evaluation (Phase III). Clinical diagnosis was based on standard diagnosis/classification criteria. Point prevalence rates from our survey and the earlier Bhigwan village (Pune district) survey were standardized (adjusted age-sex to India population census 2001) and are reported for osteoarthritis (OA), rheumatoid arthritis (RA), seronegative spondyloarthritis (SSA), and inflammatory arthritis (IA).Results.One thousand one hundred fifty-two urban cases (65% women) were identified (14.1%, 95% confidence interval 13.4, 14.9). The self-reported pain sites (Phase II) were hip (0.4), knees (6.3), ankle (1.9), feet (0.7), shoulders (2), hands (1.3), wrist (1.2), neck (1.9), upper back (1.7), low back (5.5), thigh (1.5), calf (1.4), and sole (0.8); corresponding rural sites being hip (1.1), knees (13.7), ankle (7), feet (1.6), shoulders (7.9), hands (6.3), wrist (6.9), neck (6.8), upper back (8.4), low back (12.6), thigh (4.8), calf (7.1) and sole (2.2). OA disorders, soft tissue rheumatism (STR) and ill-defined aches and pains were predominant in both surveys; < 10% reported IA. The major disorders among urban cases were OA (4), STR (1.2), RA (0.2, ACR criteria 1988), undifferentiated IA (0.3), SSA (0.3), and gout (0.06); corresponding rates in Bhigwan were OA (6.3), STR (3.8), RA (0.5), undifferentiated IA (0.8), SSA (0.3), and gout (0.1). Infections were conspicuously absent.Conclusion.While similar in spectrum, standardized prevalence rates of self-reported pain sites and rheumatic MSK disorders were significantly lower in the urban (current Pune COPCORD surveys) versus rural (Bhigwan) community, and in both communities aches and pains that are poorly understood by modern science were predominant.
Evaluation of a Web-based Teaching Module on Examination of the Hand
Authors: AVERNS HENRY , MARASCHIELLO MARK , van MELLE ELAINE , DAY ANDREW 
Published: October 2009

Objective.To evaluate the effectiveness of an online module in the development of medical students’ clinical hand examination skills.Methods.We developed a Web-based module to teach examination of the hand to first-year medical students (n = 99) to address the core skills expected in undergraduate medical training in Canada. The module was compared to the standard recommended text and tutor-led teaching using a validated objective structured clinical examination (OSCE) and a written knowledge test.Results.A total of 17 students completed the OSCE from the book-based learning group, 18 from the tutor-led group, and 26 from the online module group. The average total OSCE score was significantly higher for students in the online module group compared to the textbook group (73.2% and 60.5%, respectively; p = 0.003). There was no significant difference between students in the online module and tutor-led groups (73.2% and 69.0%, respectively; p = 0.31). The online module group had a significantly higher mean total knowledge score than the textbook group (8.4 and 5.7, respectively; p < 0.001; maximum score 10) and the tutor-led group (8.4 and 7.4, respectively; p = 0.04).Conclusion.Our study provides evidence that a well designed Web-based module, supported by sound educational theory, is an effective tool in the teaching of musculoskeletal examination skills, and provides some advantages over tutor-led teaching in terms of knowledge retention.
Interpersonal Psychotherapy: A Treatment for Late-life Depression
Authors: Hinrichsen Gregory A. 
Published: October 2009

CME Educational Objectives

1.
Identify that interpersonally relevant stressors are a potential cause and consequence of depression in later life.

2.
Explain the basic structure of interpersonal psychotherapy (IPT) in the treatment of depression.

3.
Express that IPT has been found useful in the treatment of late life depression.
Psychotherapy as End-of-life Care: Special Considerations for the Older Patient
Authors: Scalmati Alessandra , Kennedy Gary J. 
Published: October 2009

CME Educational Objectives

1.
List at least three presenting problems in the psychiatric consultation for older patients at the end of life.

2.
State the psychotherapeutic modalities studied in geriatric end-of-life care and describe their efficacy.

3.
Name at least two common conter-transference responses to working with aged patients at the end of life, and how to address them.
1,25-Dihydroxyvitamin D3 and IL-2 Combine to Inhibit T Cell Production of Inflammatory Cytokines and Promote Development of Regulatory T Cells Expressing CTLA-4 and FoxP3
Authors: Jeffery Louisa E. , Burke Fiona , Mura Manuela , Zheng Yong , Qureshi Omar S. , Hewison Martin , Walker Lucy S. K. , Lammas David A. , Raza Karim , Sansom David M. 
Published: October 2009

Abstract
The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has potent immunomodulatory properties that have promoted its potential use in the prevention and treatment of infectious disease and autoimmune conditions. A variety of immune cells, including macrophages, dendritic cells, and activated T cells express the intracellular vitamin D receptor and are responsive to 1,25(OH)2D3. Despite this, how 1,25(OH)2D3 regulates adaptive immunity remains unclear and may involve both direct and indirect effects on the proliferation and function of T cells. To further clarify this issue, we have assessed the effects of 1,25(OH)2D3 on human CD4+CD25− T cells. We observed that stimulation of CD4+CD25− T cells in the presence of 1,25(OH)2D3 inhibited production of proinflammatory cytokines including IFN- γ, IL-17, and IL-21 but did not substantially affect T cell division. In contrast to its inhibitory effects on inflammatory cytokines, 1,25(OH)2D3 stimulated expression of high levels of CTLA-4 as well as FoxP3, the latter requiring the presence of IL-2. T cells treated with 1,25(OH)2D3 could suppress proliferation of normally responsive T cells, indicating that they possessed characteristics of adaptive regulatory T cells. Our results suggest that 1,25(OH)2D3 and IL-2 have direct synergistic effects on activated T cells, acting as potent anti-inflammatory agents and physiologic inducers of adaptive regulatory T cells.
Analysis of the Role of Tripeptidyl Peptidase II in MHC Class I Antigen Presentation In Vivo
Authors: Kawahara Masahiro , York Ian A. , Hearn Arron , Farfan Diego , Rock Kenneth L. 
Published: October 2009

Abstract
Previous experiments using enzyme inhibitors and RNA interference in cell lysates and cultured cells have suggested that tripeptidyl peptidase II (TPPII) plays a role in creating and destroying MHC class I-presented peptides. However, its precise contribution to these processes has been controversial. To elucidate the importance of TPPII in MHC class I Ag presentation, we analyzed TPPII-deficient gene-trapped mice and cell lines from these animals. In these mice, the expression level of TPPII was reduced by &gt;90% compared with wild-type mice. Thymocytes from TPPII gene-trapped mice displayed more MHC class I on the cell surface, suggesting that TPPII normally limits Ag presentation by destroying peptides overall. TPPII gene-trapped mice responded as well as did wild-type mice to four epitopes from lymphocytic choriomeningitis virus. The processing and presentation of peptide precursors with long N-terminal extensions in TPPII gene-trapped embryonic fibroblasts was modestly reduced, but in vivo immunization with recombinant lentiviral or vaccinia virus vectors revealed that such peptide precursors induced an equivalent CD8 T cell response in wild-type and TPPII-deficient mice. These data indicate that while TPPII contributes to the trimming of peptides with very long N-terminal extensions, TPPII is not essential for generating most MHC class I-presented peptides or for stimulating CTL responses to several Ags in vivo.
CD4+ T Cells and Lactobacillus casei Control Relapsing Colitis Mediated by CD8+ T Cells
Authors: Hacini-Rachinel Feriel , Nancey Stephane , Boschetti Gilles , Sardi Fatima , Doucet-Ladevèze Remi , Durand Pierre-Yves , Flourié Bernard , Kaiserlian Dominique 
Published: October 2009

Abstract
Evidence that CD4+ regulatory T cells can control Ag-specific CD8+ T cell-mediated colitis in immunocompetent mice is poorly documented. To examine the potential of CD4+ T cells to control colitis, we used our model of CD8+ T cell-mediated colitis induced by intracolonic sensitization followed by challenge with the hapten 2,4-dinitrobenzene sulfonic acid. The defect of CD4+ T cells in MHC class II-deficient (Aβ°/°) mice allowed priming of 2,4-dinitrobenzene sulfonic acid-specific IFN-γ-producing CD8 colitogenic effectors and development of colitis in the otherwise resistant C57BL/6 strain. Cotransfer experiments in RAG2°/° mice and ex vivo studies showed that CD4+CD25+ T cells completely prevented CD8+ T cell-mediated colitis and controlled CD8+ T cell activation, respectively. In the susceptible BALB/c strain, Ab depletion revealed that lack of CD4+ regulatory T cells resulted in 1) acute colitis elicited by a suboptimal dose of hapten challenge and 2) more severe relapsing episodes of colitis induced by effector/memory CD8+ T cell-mediated colitis at an optimal dose of hapten challenge, even when CD4 depletion was performed just before the second challenge. Oral administration of the probiotic strain Lactobacillus casei DN-114 001 alleviated colitis and increased the suppressive function of Foxp3+CD4+ regulatory T cells of colon lamina propria. These data demonstrate that CD4+ regulatory T cells exert a protective effect on colitis by controlling colitogenic effector/memory CD8+ T cells during the effector (symptomatic) phase of acute and relapsing colitis, respectively. Probiotics with natural adjuvant effects on mucosal regulatory T cells may represent a valuable approach to alleviate the colitogenic effect of Tc1-type CD8+ effectors.
Protein Kinase B/Akt Signals Impair Th17 Differentiation and Support Natural Regulatory T Cell Function and Induced Regulatory T Cell Formation
Authors: Pierau Mandy , Engelmann Swen , Reinhold Dirk , Lapp Thabo , Schraven Burkhart , Bommhardt Ursula H. 
Published: October 2009

Abstract
Protein kinase B (PKB)/Akt signals control T cell proliferation and differentiation but their effect on the generation and function of regulatory T cells (Treg) and Th17 cells is not well understood. In this study, we show that elevated PKB signals antagonize the immunosuppressive effect of TGF-β1 on cell size, CD25 and CD98 expression, and proliferation of CD3-stimulated naive CD4+ T cells from wild-type and CD28-deficient mice. Conventional CD4+ T cells expressing active PKB are less susceptible to suppression by natural regulatory T cells. Although PKB signals do not affect the development of natural regulatory T cells, they enhance their suppressor capacity. Upon TCR triggering and TGF-β1 costimulation, wild-type and CD28-deficient CD4+ T cells transgenic for PKB readily express Foxp3, thereby acquiring suppressor capacity. These effects of elevated PKB signals on T cell function involve a marked and sustained activation of STAT5 and Foxp3 and reduction in nuclear NFATc1 levels. In contrast, PKB signals impair TGF-β1/IL-6-mediated differentiation of naive CD4+ T cells into the Th17 lineage. This correlates with an increased signaling of ERK, STAT5, and STAT6. Finally, elevated PKB signals reduced the severity of experimental autoimmune encephalomyelitis in wild-type mice but induced experimental autoimmune encephalomyelitis in mice deficient for CD28. Altogether, these data indicate an important role of PKB signals on control of TGF-β1-mediated T cell responses and, thereby, on tolerizing and inflammatory immune processes.
Phenotypical Characterization of Human Th17 Cells Unambiguously Identified by Surface IL-17A Expression
Authors: Brucklacher-Waldert Verena , Steinbach Karin , Lioznov Michael , Kolster Manuela , Hölscher Christoph , Tolosa Eva 
Published: October 2009

Abstract
Th17 cells are involved in the defense against bacteria and fungi and play a prominent role in the pathogenesis of autoimmune diseases, but research on human Th17 cells is hindered due to the lack of a surface marker. In this study, we report that a subset of human and mouse CD4+ T cells as well as human Th17 T cell clones express IL-17A on their surface upon stimulation. Correlation of surface IL-17A expression with intracellular IL-17A production and with RORγt mRNA expression identified surface IL-17A as a specific marker for human and mouse Th17 cells. Phenotype characterization of ex vivo CD4+ IL-17A+ cells showed that the chemokines CCR6 and CCR4, costimulatory molecules, as well as CD2 and CD49d were more prominently expressed on these cells than in surface IL-17A− cells, supporting the concept of Th17 cells as a potent inflammatory effector subtype. In addition, we generated human Th1, Th1/17 (producing both IFN-γ and IL-17A), and Th17 T cell clones based on single cell sorting of surface IL-17A−, IL-17Aint, and IL-17Ahigh CD4+ T cells, respectively, and showed the plasticity of the double producing clones to the cytokine milieu. The identification of surface IL-17A as a marker for Th17 cells should facilitate research on this subset.
Responsiveness of Stromal Fibroblasts to IFN-γ Blocks Tumor Growth via Angiostasis
Authors: Lu Yu , Yang Wei , Qin Chuan , Zhang Lianfeng , Deng Jingjing , Liu Shubai , Qin Zhihai 
Published: October 2009

Abstract
The importance of stromal cells for tumor is akin to soil for seed. However, the interaction among these cells is far from understood. In this study, we show that stromal fibroblasts exist not only during tumor progression but also during regression stage, together with immune effector cells. Coinjection of stromal fibroblasts with tumor cells often promotes tumor growth. However, the presence of IFN-γ significantly impairs the ability of these cells to promote tumor growth due to a reduced angiogenesis. The mechanism relies mainly on the IFN-γ-mediated down-regulation of vascular endothelial growth factor production by fibroblasts. The results reveal a novel link between immune cells and nonbone marrow-derived stromal cells, and define stromal fibroblasts as the main targets of IFN-γ in tumor immunity.
The Activation Threshold of CD4+ T Cells Is Defined by TCR/Peptide-MHC Class II Interactions in the Thymic Medulla
Authors: Stephen Tom Li , Tikhonova Anastasia , Riberdy Janice M. , Laufer Terri M. 
Published: October 2009

Abstract
Immature thymocytes that are positively selected based upon their response to self-peptide-MHC complexes develop into mature T cells that are not overtly reactive to those same complexes. Developmental tuning is the active process through which TCR-associated signaling pathways of single-positive thymocytes are attenuated to respond appropriately to the peptide-MHC molecules that will be encountered in the periphery. In this study, we explore the mechanisms that regulate the tuning of CD4+ single-positive T cells to MHC class II encountered in the thymic medulla. Experiments with murine BM chimeras demonstrate that tuning can be mediated by MHC class II expressed by either thymic medullary epithelial cells or thymic dendritic cells. Tuning does not require the engagement of CD4 by MHC class II on stromal cells. Rather, it is mediated by interactions between MHC class II and the TCR. To understand the molecular changes that distinguish immature hyperactive T cells from tuned mature CD4+ T cells, we compared their responses to TCR stimulation. The altered response of mature CD4 single-positive thymocytes is characterized by the inhibition of ERK activation by low-affinity self-ligands and increased expression of the inhibitory tyrosine phosphatase SHP-1. Thus, persistent TCR engagement by peptide-MHC class II on thymic medullary stroma inhibits reactivity to self-Ags and prevents autoreactivity in the mature repertoire.
A NUP98-HOXD13 Fusion Gene Impairs Differentiation of B and T Lymphocytes and Leads to Expansion of Thymocytes with Partial TCRB Gene Rearrangement
Authors: Choi Chul Won , Chung Yang Jo , Slape Christopher , Aplan Peter D. 
Published: October 2009

Abstract
Expression of a NUP98-HOXD13 (NHD13) fusion gene leads to myelodysplastic syndrome in mice. In addition to ineffective hematopoiesis, we observed that NHD13 mice were lymphopenic; the lymphopenia was due to a decrease in both T and B lymphocytes. Although the pro-B cell (B220+/CD43+) populations from the NHD13 and wild-type mice were similar, the NHD13 mice showed decreased pre-B cells (B220+/CD43−), indicating impaired differentiation at the pro-B to pre-B stage. Thymi from NHD13 mice were smaller and overexpressed Hoxa cluster genes, including Hoxa7, Hoxa9, and Hoxa10. In addition, the NHD13 thymi contained fewer thymocytes, with an increased percentage of CD4−/CD8− (double-negative (DN)) cells and a decreased percentage of CD4+/CD8+ (double-positive) cells; the DN1/DN2 population was increased and the DN3/DN4 population was decreased, suggesting a partial block at the DN2 to DN3 transition. To determine clonality of the thymocytes, we used degenerate RT-PCR to identify clonal Tcrb gene rearrangements. Five of six NHD13 thymi showed an unusual Tcrb gene rearrangement pattern with common, clonal DJ rearrangements, but distinct V-D junctions, suggesting a marked clonal expansion of thymocytes that had undergone a DJ rearrangement, but not completed a VDJ rearrangement. Taken together, these findings demonstrate that expression of the NHD13 transgene inhibits lymphoid as well as myeloid and erythroid differentiation, results in overexpression of Hoxa cluster genes, and leads to a precursor T cell lymphoblastic leukemia/lymphoma.
A2A Adenosine Receptor May Allow Expansion of T Cells Lacking Effector Functions in Extracellular Adenosine-Rich Microenvironments
Authors: Ohta Akio , Ohta Akiko , Madasu Manasa , Kini Radhika , Subramanian Meenakshi , Goel Nipun , Sitkovsky Michail 
Published: October 2009

AbstractImmunosuppressive signaling via the A2A adenosine receptor (A2AR) provokes a mechanism that protects inflamed tissues from excessive damage by immune cells. This mechanism is desirable not only for preventing uncontrolled tissue destruction by overactive immune responses, but also for protecting tumor tissues from antitumor immune responses. In aforementioned circumstances, T cell priming may occur in an environment containing high concentrations of extracellular adenosine. To examine qualitative changes in T cells activated in the presence of adenosine, we asked whether different functional responses of T cells are equally susceptible to A2AR agonists. In this study, we demonstrate that A2AR signaling during T cell activation strongly inhibited development of cytotoxicity and cytokine-producing activity in T cells, whereas the inhibition of T cell proliferation was only marginal. Both CD8+ and CD4+ T cells proliferated well in the presence of A2AR agonists, but their IFN-γ-producing activities were susceptible to inhibition by cAMP-elevating A2AR. Importantly, the impaired effector functions were maintained in T cells even after removal of the A2AR agonist, reflecting T cell memory of the immunoregulatory effect of adenosine. Thus, although the adenosine-rich environment may allow for the expansion of T cells, the functional activation of T cells may be critically impaired. This physiological mechanism could explain the inefficiency of antitumor T cells in the tumor microenvironment.
IL-27 Directly Restrains Lung Tumorigenicity by Suppressing Cyclooxygenase-2-Mediated Activities
Authors: Ho Ming-Yi , Leu Shr-Jeng Jim , Sun Guang-Huan , Tao Mi-Hua , Tang Shye-Jye , Sun Kuang-Hui 
Published: October 2009

Abstract
Gene transfer of IL-27 to tumor cells has been proven to inhibit tumor growth in vivo by antiproliferation, antiangiogenesis, and stimulation of immunoprotection. To investigate the nonimmune mechanism of IL-27 that suppresses lung cancer growth, we have established a single-chain IL-27-transduced murine Lewis lung carcinoma (LLC-1) cell line (LLC-1/scIL-27) to evaluate its tumorigenic potential in vivo. Mice inoculated with LLC/scIL-27 displayed retardation of tumor growth. Production of IL-12, IFN-γ, and cytotoxic T cell activity against LLC-1 was manifest in LLC/scIL-27-injected mice. Of note, LLC-1/scIL-27 exhibited decreased expression of cyclooxygenase-2 (COX-2) and PGE2. On the cellular level, the LLC/scIL-27 transfectants had reduced malignancy, including down-regulation of vimentin expression and reduction of cellular migration and invasion. The suppression of tumorigenesis by IL-27 on lung cancer cells was further confirmed by the treatment with rIL-27 on the murine LLC-1 and human non-small cell lung carcinoma (NSCLC) cell lines. PGE2-induced vimentin expression, movement, and invasiveness were also suppressed by the treatment with rIL-27. Our data show that IL-27 not only suppresses expression of COX-2 and PGE2 but also decreases the levels of vimentin and the abilities of cellular migration and invasion. Furthermore, inoculation of LLC/scIL-27 into immunodeficient NOD/SCID mice also exhibited reduced tumor growth. Our data indicate that IL-27-induced nonimmune responses can contribute to significant antitumor effects. Taken together, the results suggest that IL-27 may serve as an effective agent for lung cancer therapy in the future.
IDO Mediates TLR9-Driven Protection from Experimental Autoimmune Diabetes
Authors: Fallarino Francesca , Volpi Claudia , Zelante Teresa , Vacca Carmine , Calvitti Mario , Fioretti Maria C. , Puccetti Paolo , Romani Luigina , Grohmann Ursula 
Published: October 2009

Abstract
Originally predicated on the recognition of an increasing prevalence of allergy, the hygiene hypothesis was later found to accommodate the contrasting epidemiologic trends in developed countries for infectious vs autoimmune diseases. Experimentally, reduced exposure to infections will increase the risk of disease in several models of experimental autoimmunity. Although TLRs were initially considered as stimulatory molecules capable of activating early defense mechanisms against invading pathogens, emerging data suggest that they can also exert a regulatory function. In the present study, we evaluated whether TLR3 and TLR9, recognizing microbial dsDNA and CpG-containing DNA sequences, respectively, play a role in the protection from experimental autoimmune diabetes induced in C57BL/6 mice by streptozotocin. In wild-type animals, the disease was accompanied by up-regulation of IDO in pancreatic lymph nodes and would be greatly exacerbated by in vivo administration of an IDO inhibitor. Conversely, administration of a CpG-containing oligodeoxynucleotide greatly attenuated the disease in an IDO-dependent fashion. TLR9-, but not TLR3-deficient mice developed a more robust disease, an event accompanied by lack of IDO induction in pancreatic lymph nodes. Thus, our data suggest that the TLR9-IDO axis may represent a valuable target in the prevention/therapy of type 1 diabetes.