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1.
Anal Verbal Behav ; 39(1): 86-98, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37397134

ABSTRACT

Although many neurotypical children acquire untaught word-object relations incidentally from naturally occurring environmental experiences, many children with and without developmental disabilities require specific intervention. This study examined the effects of rotating listener (match and point) and speaker (tact and intraverbal-tact) responses with added echoics during multiple exemplar instruction (MEI) with training sets of stimuli on the acquisition of Incidental Bidirectional Naming (Inc-BiN). Listener-speaker MEI procedures reported in Hawkins et al. European Journal of Behavior Analysis, 10(2), 265-273, (2009) were replicated with procedural modification, new instructors, and new participants (four preschoolers with and without disabilities). The listener-speaker MEI with added echoics consisted of rotating across four response operants: match-with-echoics, point-with-echoics, tact, and intraverbal-tact responses. We measured the establishment of Inc-BiN through the number of the correct untaught listener (point) and untaught speaker (intraverbal-tact) responses for untaught stimuli during the listener-speaker MEI with added echoics. We found that listener-speaker MEI with added echoics was effective in establishing Inc-BiN for 3 of 4 participants.

2.
J Am Acad Dermatol ; 58(4): 592-5, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18249469

ABSTRACT

Total skin electron beam radiation is an effective therapy for palliation of the cutaneous symptoms of the most common types of cutaneous T-cell lymphomas, mycosis fungoides and Sézary syndrome. We report 4 cases of patients with Sézary syndrome who had significant improvement in their blood burden of malignant cells in addition to complete cutaneous responses to total skin electron beam therapy. The data from these 4 patients illustrate the potential for total skin electron beam to be used as both a skin and blood tumor debulking agent, and not merely as a palliation for skin symptoms.


Subject(s)
Electrons , Lymphoma, T-Cell, Cutaneous/radiotherapy , Sezary Syndrome/radiotherapy , Skin Neoplasms/radiotherapy , T-Lymphocytes/radiation effects , Whole-Body Irradiation , CD4-CD8 Ratio , Combined Modality Therapy , Flow Cytometry , Humans , Lymphocyte Count , Mycosis Fungoides/radiotherapy
3.
J Invest Dermatol ; 128(2): 473-80, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17713571

ABSTRACT

IL-21, a common gamma-chain cytokine secreted by activated CD4+ T cells, influences both humoral and cell-mediated immune responses through the regulation of T, B, dendritic, and natural killer (NK) cells. Sézary syndrome is an advanced form of cutaneous T-cell lymphoma, a clonally derived malignancy of CD4+ T cells that is characterized by profound defects in host cellular immune function. As a modulator of both innate and adaptive immune responses, IL-21 could play an important role in augmenting cell-mediated immunity in these patients. Normal donor and Sézary syndrome patient peripheral blood mononuclear cells were cultured with IL-21 and tested for CD8+ T- and NK-cell activation, NK-cell cytotoxicity, and tumor cell proliferation and apoptosis. IL-21 resulted in a modest increase in CD8+ T- and NK-cell activation, associated with a marked increase in cytolytic activity against both K562 and malignant CD4+ T-cell targets. Although IL-21 failed to demonstrate pro-apoptotic effects on the malignant CD4+ T cells, it is noteworthy that it had no demonstrable proliferative effects on these cells. Thus, IL-21 may play an important role in enhancing the host immune response of Sézary syndrome patients through the increased cytolytic activity of T and NK cells.


Subject(s)
Interleukins/immunology , Sezary Syndrome/immunology , Sezary Syndrome/pathology , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , Apoptosis/immunology , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Cell Division/drug effects , Cell Division/immunology , Dipeptidyl Peptidase 4/metabolism , Humans , Interferon-gamma/metabolism , Interleukins/pharmacology , K562 Cells , Killer Cells, Natural/metabolism , Killer Cells, Natural/pathology , Lectins, C-Type , RNA, Messenger/metabolism , Receptors, Interleukin-21/genetics , Tumor Cells, Cultured , Up-Regulation/immunology
4.
Am J Hematol ; 82(9): 792-7, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17546636

ABSTRACT

The malignant cells in Sezary syndrome express the skin trafficking molecules' cutaneous lymphocyte associated antigen (CLA) and chemokine receptor 4 (CCR4). High levels of the CCR4 ligand, thymus, and activation-regulated chemokine (TARC), have been reported in the blood and skin of patients. The rexinoid X-receptor specific retinoid, bexarotene, has contributed to the resolution of cutaneous disease among patients. To evaluate the effects of bexarotene on skin trafficking molecule expression and chemotaxis, peripheral blood mononuclear cells from Sezary syndrome patients and healthy controls were treated with bexarotene in vitro. CCR4 and CLA expression levels and chemotaxis in response to TARC (6.25 ng/ml) were evaluated among lymphocytes before and after treatment with bexarotene (10 microM). Flow cytometric analysis was performed to evaluate CD4, CD26, CLA, and CCR4 cell surface expression. Transwell migration assays were performed to evaluate chemotaxis to TARC. Prior to treatment, malignant cells exhibited higher CCR4 expression (45-90%) and greater than four times more chemotaxis to TARC compared with healthy controls. After treatment with bexarotene for 36-96 hr, a 28% reduction in CCR4 expression was noted (P < 0.05) among the malignant population with an associated 9% decrease in chemotaxis to TARC (P < 0.05). Our results show that bexarotene may inhibit malignant cell trafficking to the skin through an ability to suppress CCR4 expression among Sezary syndrome lymphocytes.


Subject(s)
Anticarcinogenic Agents/pharmacology , Chemokines, CC/immunology , Chemotaxis, Leukocyte/drug effects , Receptors, Chemokine/immunology , Sezary Syndrome/drug therapy , Tetrahydronaphthalenes/pharmacology , Aged , Bexarotene , Case-Control Studies , Cells, Cultured , Chemokine CCL17 , Chemokines, CC/metabolism , Drug Evaluation, Preclinical , Female , Flow Cytometry , Humans , Leukocytes, Mononuclear/drug effects , Male , Middle Aged , Receptors, CCR4 , Receptors, Chemokine/metabolism , Sezary Syndrome/immunology , Sezary Syndrome/metabolism , Time Factors
6.
Clin Lymphoma Myeloma ; 7(3): 226-32, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17229339

ABSTRACT

PURPOSE: The goal of this study was to evaluate the clinical response rate of patients with Sézary syndrome (SS) to multimodality immunomodulatory therapy consisting of extracorporeal photopheresis in combination with >/= 2 systemic biologic response modifiers (interferon-, interferon-, retinoids, and/or sargramostim) and psoralen plus UV-A. PATIENTS AND METHODS: Twenty-eight patients who met established criteria for SS were treated with multimodality immunomodulatory therapy at the Hospital of the University of Pennsylvania between January 2000 and December 2002. All patients received > 6 cycles of extracorporeal photopheresis. Patients were categorized into groups based on their response to therapy. RESULTS: An overall clinical response of 89% was achieved with multimodality immunomodulatory therapy. Twenty-nine percent of patients exhibited a complete response, characterized by no evidence of cutaneous disease and a Sézary count 5%. Sixty-one percent exhibited a partial response. Eleven percent were nonresponders. CONCLUSION: Based on our experience, multimodality immunomodulatory therapy is an exceptionally effective treatment for SS. The durability of response and impact on overall survival remains to be determined; however, this approach offers an appealing alternative to treatments associated with higher morbidity rates.


Subject(s)
Immunotherapy/methods , Lymphoma, T-Cell, Cutaneous/therapy , Sezary Syndrome/therapy , Skin Neoplasms/therapy , Aged , Aged, 80 and over , Combined Modality Therapy/methods , Dendritic Cells/metabolism , Female , Humans , Interferon-alpha/metabolism , Interferon-gamma/metabolism , Lymphocytes/metabolism , Lymphoma, T-Cell, Cutaneous/immunology , Male , Middle Aged , Skin Neoplasms/immunology , Treatment Outcome
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