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Biomedical subjects

R Edelson

Publications and source records attributed to R Edelson.

At least 19 recordsLinked to original sources
PubMed1992

Correlations of unique clinical, immunotypic, and histologic findings in cutaneous gamma/delta T-cell lymphoma.

Cutaneous T-cell lymphoma is a malignancy of T cells that express a clone-specific heterodimer T-cell receptor for antigen. The second recognized case of an epidermotropic malignancy of T-cells expressing gamma/delta T-cell receptor-expressing cells is reported. The immunophenotype of the malignant T-cells was CD3+, CD2+, CD7+, gamma/delta T-cell receptor+, CD4-, CD8-, and alpha/beta T-cell receptor-. The clinical features were remarkable for extreme epidermotropism with a scant dermal lymphomatous infiltrate. Profound keratinocyte necrosis occurred in areas of malignant skin infiltrates. Despite cutaneous lesions covering more than 50% of the skin surface of the patient, no adenopathy or splenomegaly was detected. The intense epidermotropism of this patient's gamma/delta T-cell receptor-expressing cells and the putative cytolytic properties of CD4- CD8- gamma/delta contributed to the destruction of epidermis. Remission was induced with a combination of electron beam and extracorporeal photochemotherapy.

Antigens, CD↗
PubMed1992

Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy.

BACKGROUND: This original cohort of patients with erythrodermic cutaneous T-cell lymphoma (CTCL) was reported to have clinical improvement with photopheresis during the 12 months of the original study. No long-term follow-up data have been available to examine the impact of this therapy on the disease. OBJECTIVE: Our purpose was to provide long-term follow-up on the original 29 erythrodermic CTCL patients treated with photopheresis and to compare these results with historical controls. METHODS: Files of patients from the original photopheresis study centers were reviewed and their current status was documented. RESULTS: The median survival of the treated patients was 60.33 months from the date of diagnosis and 47.9 months from the date of the start of photopheresis therapy. A complete remission has been maintained in four of the six patients who achieved complete responses in the original study. The best responses were seen in patients with a lower CD4/CD8 ratio in the peripheral blood at the start of therapy. CONCLUSION: Photopheresis can influence the natural history of erythrodermic CTCL by inducing remissions and prolonging survival with minimal toxicity.

CD4-CD8 Ratio↗
PubMed1991

Endocytosis of the TCR/CD3 complex and the class-I major histocompatibility complex in a human T cell line.

We investigated the expression of the T cell receptor (TCR)/CD3 complex on a CD4-positive human T cell lymphoma cell line treated with phorbol myristate acetate (PMA) and/or CA2+ ionophore using fluorescence flow cytometry and fluorescence microscopic analysis. PMA induced a significant decrease in the expression of the CD3 complex on the cell membranes. Fluorescence microscopy confirmed that the down regulation is due to internalization of the antigens. Ca2+ ionophore treatment had no effect on the internalization of the CD3 complex. Double staining revealed that the vesicles containing the internalized CD3 complex and those containing intra-cytoplasmic class I major histocompatibility complex antigen had similar distribution in the PMA-stimulated cells, implying coexistence of these two antigens in a cytoplasmic perinuclear distribution.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Phototoxic liposomes coupled to an antibody that alone cannot modulate its cell-surface antigen kill selected target cells.

Molecules such as antibodies that bind to cell surfaces can be used to deliver cytotoxic drugs to selected cells. To be effective the drug must usually be taken into the cells by endocytosis. In this study a T-cell line (CCRF-CEM) was effectively killed by liposomes carrying a photosensitizer and bearing the antibody OKT4 (anti-CD4). The unconjugated antibody does not induce antigenic modulation in the target cells, an indication of the absence of endocytosis, and would therefore not normally have been selected as an agent for drug delivery. It cannot, however, be concluded with certainty that the conjugates act at the cell surface and several alternative explanations of their efficacy are offered.

Animals↗
PubMed1990

Inhibition of autoimmune disease in a murine model of systemic lupus erythematosus induced by exposure to syngeneic photoinactivated lymphocytes.

MRL/l mice develop progressive, virulent autoimmune disease that has many of the features of systemic lupus erythematosus. Prophylactic treatment of MRL/l mice with syngeneic photoinactivated autoimmune splenocytes improves survival and inhibits the fulminant hyperproliferation of abnormal T cells and the production of high titer anti-DNA antibody invariably found in untreated mice. The proliferation of Thy 1+ splenic T cells was significantly decreased, and prolonged retention of the response to T-cell mitogen was found in treated mice. Treatment with unmodified cells induced a partial inhibition of disease features which did not prolong survival rates. These results suggest that phototherapy potentiates a normal immunoregulatory process which enables suppression of the development of abnormal cell populations in young MRL/l mice with relatively intact immune systems.

Animals↗
PubMed1989

Inhibition of antiskin allograft immunity by infusions with syngeneic photoinactivated effector lymphocytes.

Induction of tolerance for skin allotransplantation requires selective suppression of the host response to foreign histocompatibility antigens. This report describes a new approach that employs pretreatment of effector cells with 8-methoxy-psoralen (8-MOP) and ultraviolet A light (UVA) to render the effector cells of graft rejection immunogenic for the syngeneic recipient. Reinfusion of photodamaged cells resulted in an immunosuppressive host response that permitted prolonged retention of histoincompatible skin grafts and specifically inhibited in vitro and in vivo responses that correlate with allograft rejection. Eight days after BALB/c mice received CBA/j skin grafts, their splenocytes served as a source of alloreactive effector cells. The splenocytes were treated with 100 ng/ml 8-MOP and 1 J/cm2 UVA before reinfusion into naive BALB/c recipients. Recipient mice were tested for tolerance to alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), delayed type hypersensitivity assays (DTH), and challenge with a fresh CBA/j graft. Splenocytes from BALB/c recipients of photoinactivated splenocytes containing the effector cells of CBA/j alloantigen rejection proliferated poorly in MLC and generated lower cytotoxic T cell responses to CBA/j alloantigens in comparison with sensitized and naive controls. Splenocytes from these hyporesponsive mice suppressed the MLC and CTL response to alloantigen from sensitized and naive BALB/c mice. In vivo the DTH response was specifically suppressed to the relevant alloantigen in comparison with controls. Moreover, BALB/c mice treated in this fashion retained a CBA/j skin graft for up to 42 d posttransplantation without visual evidence of rejection. These results indicate that the in vivo and in vitro response to alloantigen can be attenuated by pretreating the host with photoinactivated splenocytes containing the effector cells of alloantigen rejection.

Animals↗
PubMed1989

Molecular cloning of CD1a (T6), a human epidermal dendritic cell marker related to class I MHC molecules.

To investigate the structure, function, and control of CD1a, we have cloned a 1.6-kbp cDNA which encodes the expressed CD1a protein and includes untranslated 5' and 3' sequences and the poly-A tail. As the protein recognized by the monoclonal antibody OKT6, CD1a is a useful marker for Langerhans cells (LC). CD1a is found on these cells and on thymocytes, suggesting an important immunologic role for this molecule. We constructed a cDNA library in lambda gt10 using mRNA from MOLT-4, a cell line that expresses the CD1a surface antigen. We then screened the library with an oligonucleotide synthesized according to a known partial sequence for CD1a, and subcloned the cDNA and its restriction fragments into pGEM for sequencing and probe production. Based on this sequence the CD1a protein is predicted to consist of three extracellular domains (alpha 1-3), a hydrophobic transmembrane region, and a cytoplasmic tail. DNA 5' to the alpha 1 region may undergo alternative exon splicing. There is high sequence identity between the beta-2 microglobulin binding region of MHC I molecules and CD1a. The secondary structure predicted for CD1a is very similar to the actual structure of HLA-A2, a classical MHC I molecule. The similarity includes the beta pleated sheets and alpha helices which form the antigen binding groove of the alpha-1 and alpha-2 domains. The homology predicted between CD1a and HLA-A2 in these regions appears to exist on the level of secondary structure despite low primary nucleotide and amino acid sequence identity. The structural data and probes we have developed should facilitate studies of the function of CD1a as well as novel investigations of LC.

Amino Acid Sequence↗
PubMed1987

Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results.

Systemically disseminated cutaneous T-cell lymphoma is generally resistant to chemotherapy and radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links DNA. After oral administration of methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative erythroderma, and 20 of 28 whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.

Administration, Oral↗
PubMed1987

Selective killing of T lymphocytes by phototoxic liposomes.

Two-fold specificity in drug delivery obtained through the localized activation of drugs by physical means and the attachment of drugs to proteins that bind to target cells might be used for highly selective cancer chemotherapy or for immunosuppression. Toward this end, a monoclonal antibody against an antigen on the surface of T lymphocytes was covalently attached to liposomes containing a phototoxic drug, pyrene, bound to the lipid bilayer. When unfractionated peripheral blood lymphocytes, or B- and T-cell lines, were irradiated after treatment with these liposomes, T cells were killed while B cells were spared, demonstrating the validity of the approach in a simple in vitro assay.

Antibodies, Monoclonal↗
PubMed1987

Chest-wall deformity following soft-tissue expansion for breast reconstruction.

We have presented a case in which the presumed pressure effects of tissue expansion caused multiple nondisplaced rib fractures of the anterior thorax in a patient undergoing breast reconstruction. Although the deformity was severe, a satisfactory cosmetic result was obtained and there have been no clinically significant sequelae during a 1-year follow-up period. The degree of bony deformation was most likely enhanced by the combination of this patient's severe osteoporosis, chronic steroid use, and peripheral vascular disease. The fragility and ease of fracture in the bones of osteoporotic postmenopausal females and the long-term effects of steroids on tissues is well known. We believe this observation to be important, since many reconstructed patients are postmenopausal and have variable degrees of osteoporosis. Many undergo adjuvant chemotherapy with steroids and antihormonal agents, and this group of women may therefore be at a greater risk for the occurrence of pressure deformities. The incidence and long-term significance of such deformities are not known. The reconstructive surgeon should be alert to the possibility of this phenomenon occurring as a result of tissue expansion in the patient with severe osteoporosis, peripheral vascular disease, or chronic steroid use.

Breast↗
PubMed1987

Induction of an immature T-cell phenotype in malignant helper T cells by cocultivation with epidermal cell cultures.

The possible inductive effect of epidermal cells on T-cell maturation has been examined employing an in vitro cocultivation technique. Mononuclear cells from 6 patients with cutaneous T-cell lymphoma (CTCL) and from 12 healthy volunteers were studied. In the 6 CTCL patients, all showed an expansion of the helper T-cell subpopulation and in one patient with leukemic CTCL, there was almost complete replacement of peripheral blood mononuclear cells by malignant cells with a helper T-cell phenotype. Epidermal cells derived from normal human skin were cultured to confluent monolayers, and were cocultivated with the mononuclear cells from CTCL patients or normal controls for 48 h at a density of 10(6)/ml. Following cocultivation, the surface phenotype of the cells from the 12 healthy volunteers and 5 of the patients with CTCL showed no significant phenotypic change. In the patient with leukemic CTCL, however, the surface phenotype of the malignant T cells had changed, with the acquisition of the T6 antigen by the majority of the cells. Cells cocultivated in medium alone and with human fibroblast monolayers showed no change in surface phenotype. The malignant T cells from the leukemic CTCL patient failed to react in a mixed lymphocyte culture to lymphocytes from 2 different healthy donors, and showed no phenotypic change following culture with these lymphocytes, indicating that the phenotypic change seen was not due to allogeneic stimulation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Reactivity of monoclonal antibody BE 2 in different stages of mycosis fungoides and in benign dermal infiltrates.

The cutaneous infiltrate in mycosis fungoides (MF) is predominantly composed of T4-positive T-cells. Attempts to distinguish the early stages of this condition from benign inflammatory infiltrates using anti-T3, T4 and other T-cell-associated antibodies have hitherto been unsuccessful. Recently a monoclonal antibody BE 2 has been described as selectively reacting against leukemic cells in patients with cutaneous T-cell lymphoma. To investigate whether the BE 2 antigen is differentially expressed in different stages of MF and benign dermatoses, thus facilitating diagnosis, especially of early MF, the reactivity of monoclonal antibody BE 2 against cutaneous infiltrates from such conditions was assessed. In the early stages of MF only a small number of reactive cells was present. In benign inflammatory infiltrates, especially in those that clinically and histologically were hardly distinguishable from early MF, BE 2 reactivity was essentially the same as in eczematous-stage MF. Lesions from plaque and tumor stage MF contained large numbers of BE 2-reactive cells. Our results indicate that expression of BE 2 is associated with the stage of a given MF lesion and is essentially identical in early MF and eczematous lesions with a similar histopathological appearance.

Antibodies, Monoclonal↗
PubMed1979

Concanvalin-A-binding proteins on the surface of human malignant and normal lymphocytes.

The concanavalin-A-binding cell surface glycoproteins from normal and certain leukaemic human lymphocytes were radiolabelled and then solubilized with detergent, isolated by affinity chromatography on Con A insolubilized on agarose beads, and subsequently analysed by SDS-polyacrylamide gel electrophoresis. Leukaemic T cells from patients with Sezary syndrome were found to express major concanavalin-A-binding glycoproteins on their outer surface similar to those of normal T lymphocytes. Leukaemic B cells from patients with chronic lymphocytic leukaemia expressed Con-A-binding proteins similar to those of B-cell lines. HLA antigens were predominant among the major Con-A-binding proteins on the surface of the normal and the malignant T cells studied. Human Ia-like antigens, HLA antigens, and the cell surface immunoglobulins IgD and IgM represented the major Con-A-binding proteins on the B cells studied. beta 2-microglobulin was found associated with HLA antigens on both leukaemic and non-leukaemic T and B cells. The presence of additional Con-A-binding proteins expressed on the surface of the different cell types studied is discussed along with some physical characteristics of the human Ia-like antigens isolated.

B-Lymphocytes↗