Tumor-specific Th17-polarized cells eradicate large established melanoma.

CD4+ T cells can differentiate into multiple effector subsets, but the potential roles of these subsets in anti-tumor immunity have not been fully explored. Seeking to study the impact of CD4+ T cell polarization on tumor rejection in a model mimicking human disease, we generated a new MHC class II-restricted, T-cell receptor (TCR) transgenic mouse model in which CD4+ T cells recognize a novel epitope in tyrosinase-related protein 1 (TRP-1), an antigen expressed by normal melanocytes and B16 murine melanoma. Cells could be robustly polarized into Th0, Th1, and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles and by surface markers, suggesting the potential for differential effector function in vivo.

Brief assessment of motor function: content validity and reliability of the fine motor scale.

Purpose: The Brief Assessment of Motor Function Fine Motor Scale (FMS) allows rapid assessment, independent of age. This study was done to establish content validity of the FMS and to demonstrate FMS reliability.

Methods: A standard questionnaire ("Disagree" to "Agree," 1-4) was emailed to 28 expert panel members.

Oxygen-uptake efficiency slope as a determinant of fitness in overweight adolescents.

Purpose: Peak oxygen uptake (VO2peak) is frequently difficult to assess in overweight individuals; therefore, submaximal measures that predict VO2peak are proposed as substitutes. Oxygen uptake efficiency slope (OUES) has been suggested as a submaximal measurement of cardiorespiratory fitness that is independent of exercise intensity. There are few data examining its value as a predictor of V O2peak in severely overweight adolescents.

Toll-like receptors in tumor immunotherapy.

Lymphodepletion with chemotherapeutic agents or total body irradiation (TBI) before adoptive transfer of tumor-specific T cells is a critical advancement in the treatment of patients with melanoma. More than 50% of patients that are refractory to other treatments experience an objective or curative response with this approach. Emerging data indicate that the key mechanisms underlying how TBI augments the functions of adoptively transferred T cells include (a) the depletion of regulatory T cells (T(reg)) and myeloid-derived suppressor cells that limit the function and proliferation of adoptively transferred cells; (b) the removal of immune cells that act as "sinks" for homeostatic cytokines, whose levels increase after lymphodepletion; and (c) the activation of the innate immune system via Toll-like receptor 4 signaling, which is engaged by microbial lipopolysaccharide that translocated across the radiation-injured gut.

Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus.

Oncolytic adenoviruses as a treatment for cancer have demonstrated limited clinical activity. Contributing to this may be the relevance of preclinical animal models used to study these agents. Syngeneic mouse tumor models are generally non-permissive for adenoviral replication, whereas human tumor xenograft models exhibit attenuated immune responses to the vector.

Mobilization, collection, and immunomagnetic selection of peripheral blood CD34 cells in recovered aplastic anemia patients.

Background: Most patients with severe aplastic anemia (sAA) respond to immunosuppression, but a significant number relapse or develop clonal abnormalities such as paroxysmal nocturnal hemoglobinuria, myelodysplasia, or leukemia. In principle, patients without matched sibling donors and older patients might benefit from transplantation of autologous hematopoietic peripheral blood progenitor cells (PBPCs) obtained during remission. Even patients who have clinically recovered from aplastic anemia have diminished hematopoietic progenitor cells, so the practicability of PBPC mobilization in these individuals is unknown.

Performance on a virtual reality spatial memory navigation task in depressed patients.

Objective: Findings on spatial memory in depression have been inconsistent. A navigation task based on virtual reality may provide a more sensitive and consistent measure of the hippocampal-related spatial memory deficits associated with depression.

Method: Performance on a novel virtual reality navigation task and a traditional measure of spatial memory was assessed in 30 depressed patients (unipolar and bipolar) and 19 normal comparison subjects.

CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) maintains peripheral tolerance by suppressing T-cell activation and proliferation but its precise role in vivo remains unclear. We sought to elucidate the impact of CTLA-4 expression on self/tumor-reactive CD8(+) T cells by using the glycoprotein (gp) 100-specific T-cell receptor (TCR) transgenic mouse, pmel-1. pmel-1 CLTA-4(-/-) mice developed profound, accelerated autoimmune vitiligo.

The New York Heart Association Classes and functional status: what are we really measuring?

The New York Heart Association (NYHA) Classes are used to appraise the status of patients with heart disease and evaluate treatment outcomes in clinical and research settings. Ambiguity exists concerning the construct the Classes represent and the optimal way to capture and interpret the information. This article examines the NYHA Classes within the context of a published functional status framework by Leidy.

Apparent hemolysis following intravenous antithymocyte globulin treatment in a patient with marrow failure and a paroxysmal nocturnal hemoglobinuria clone.

Background: Antithymocyte globulin (ATG) is a commonly used medication in the treatment of aplastic anemia. Although serum sickness has been described with the use of ATG, few cases of acute intravascular hemolysis have been reported. We report a case of apparent ATG-related hemolysis in a patient with aplastic anemia and a paroxysmal nocturnal hemoglobinuria (PNH) clone.

Adoptive immunotherapy for cancer: building on success.

Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic environment enables tumour-reactive T cells to destroy large burdens of metastatic tumour and how the state of differentiation of the adoptively transferred T cells can affect the outcome of treatment. We also discuss how the translation of these new findings might further improve the efficacy of adoptive cell transfer through the use of vaccines, haematopoietic-stem-cell transplantation, modified preconditioning regimens, and alternative methods for the generation and selection of the T cells to be transferred.

Navicular drop measurement in people with rheumatoid arthritis: interrater and intrarater reliability.

Background And Purpose: Navicular drop (ND) measurement may be a valuable examination technique for patients with rheumatoid arthritis (RA). However, no data exist on reliability for this technique in patients with RA. The purposes of this study were: (1) to determine interrater and intrarater reliability of ND measurements in people with RA, (2) to compare ND values of people with RA with published normative data, and (3) to investigate ND measurement error associated with the use of skin markings.

CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2.

CD4+CD25+ T regulatory (Treg) cells control immunologic tolerance to self-antigens and play a role in suppressing antitumor immune responses, but the mechanism of suppression in vivo remains uncertain. Recently, signaling through the high-affinity interleukin-2 (IL-2) receptor has been shown to be critical for Treg cell differentiation and survival in vivo. Mice deficient in IL-2 or its receptor (CD25 or CD122) or deficient in downstream signaling molecules, including JAK-3 and STAT-5, do not develop a stable population of Treg cells and subsequently acquire lymphoproliferative disease and autoimmunity.