ABSTRACT
The Acne-Specific Quality of Life Questionnaire (Acne-QoL) was developed to measure the impact of facial acne across four dimensions of patient quality of life. The main objective of the current study was to evaluate the responsiveness of this instrument. Secondarily, this study provided an opportunity to extend the developer's psychometric validation. The Acne-QoL was utilized in two randomized, double-blind, placebo-controlled studies of the efficacy of Estrostep (norethindrone acetate/ethinyl estradiol) in the treatment of facial acne; a total of 296 Estrostep and 295 placebo patients were evaluated. The Acne-QoL was completed at the beginning, middle (cycle 3), and end (cycle 6) of the 6-month treatment period. The responsiveness of the Acne-QoL was demonstrated through its ability to detect both small (baseline to mid-study) and moderate (baseline to study end) treatment advantages for Estrostep patients. Confirmatory factor analysis supported the subscale structure, and internal consistency estimates were excellent. Convergent and discriminant validity were supported by correlations between Acne-QoL scores and clinical measures that were both in the direction and relative magnitude hypothesized. Finally, item response theory analyses confirmed that each item is highly related to its subscale's latent construct and that each subscale is sensitive across a broad range of the underlying continuum. The results of this evaluation confirm that the Acne-QoL is responsive, internally consistent, and valid.
Subject(s)
Acne Vulgaris/psychology , Quality of Life , Sickness Impact Profile , Surveys and Questionnaires , Adolescent , Adult , Controlled Clinical Trials as Topic , Double-Blind Method , Female , Humans , Male , Patient Participation , Placebos , Psychometrics , United StatesABSTRACT
Regulation of gene activation by the estrogen receptor (ER) is complex and involves co-regulatory proteins, oncoproteins (such as Fos and Jun), and phosphorylation signaling pathways. Here we report the cloning and initial characterization of a novel protein, Brx, that contains a region of identity to the oncogenic Rho-guanine nucleotide exchange (Rho-GEF) protein Lbc, and a unique region capable of binding to nuclear hormone receptors, including the ER. Western and immunohistochemistry studies showed Brx to be expressed in estrogen-responsive reproductive tissues, including breast ductal epithelium. Brx bound specifically to the ER via an interaction that required distinct regions of ER and Brx. Furthermore, overexpression of Brx in transfection experiments using an estrogen-responsive reporter revealed that Brx augmented gene activation by the ER in an element-specific and ligand-dependent manner. Moreover, activation of ER by Brx could be specifically inhibited by a dominant-negative mutant of Cdc42Hs, but not by dominant negative mutants of RhoA or Rac1. Taken together, these data suggest that Brx represents a novel modular protein that may integrate cytoplasmic signaling pathways involving Rho family GTPases and nuclear hormone receptors.
Subject(s)
Oncogene Proteins/metabolism , Proto-Oncogene Proteins , Receptors, Estrogen/metabolism , A Kinase Anchor Proteins , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Animals , Breast/metabolism , Breast/pathology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cloning, Molecular , DNA, Complementary , Female , GTP-Binding Proteins/genetics , GTP-Binding Proteins/metabolism , Guanine Nucleotide Exchange Factors , Humans , Male , Minor Histocompatibility Antigens , Molecular Sequence Data , Mutagenesis , Oncogene Proteins/classification , Oncogene Proteins/genetics , Rabbits , Receptors, Estrogen/physiology , Retroviridae Proteins, Oncogenic , Sequence Homology, Amino Acid , Testis/immunology , Testis/pathology , Tissue Distribution , Tumor Cells, Cultured , cdc42 GTP-Binding ProteinABSTRACT
The T-lymphocyte subset interactions in the cell-mediated response to Epstein-Barr virus (EBV) were studied in an in vitro system in which the ability of T lymphocytes to inhibit outgrowth of autologous EBV-transformed B lymphocytes is assessed. Inhibition could be demonstrated within lymphocytes of both the T4 and T8 surface phenotypes. Outgrowth inhibition was observed more frequently when the effector T-cell population contained cells of both surface phenotypes. In blocking experiments the OKT3 antibody completely prevents development of outgrowth inhibitory activity; the OKT4 and OKT8 antibodies were less effective in interfering with outgrowth inhibitory function. Maximal blocking activity occurred when antibody addition occurred in the early phase of generation of suppressor function. Pharmacologically achievable concentrations of interferon-alpha restored outgrowth inhibitory activity after blocking with monoclonal antibody. EBV reactivation was easily demonstrable in a group of 10 renal allograft recipients who received OKT3 antibody for treatment of acute rejection. These studies suggest that the immunoregulatory control of proliferation of EBV-transformed B lymphocytes is complex, and involves a collaborative interaction of lymphocytes of both the T4 and T8 surface phenotypes.
