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Biomedical subjects

D N Sauder

Publications and source records attributed to D N Sauder.

At least 163 records · Page 9Linked to original sources
PubMed1983

Ultraviolet radiation inhibits alloantigen presentation by epidermal cells: partial reversal by the soluble epidermal cell product, epidermal cell-derived thymocyte-activating factor (ETAF).

It has been postulated that ultraviolet radiation (UVR) alters antigen presentation by macrophages. This is thought to be due, in part, to inhibition of macrophage-derived interleukin 1 (IL-1), which is a hormone-like factor with immunoregulatory functions. Conventional stimulator cells for antigen presentation are macrophages; however, other cell types such as epidermal Langerhans cells are capable of antigen presentation. Keratinocytes also play a role in the immune system by providing a factor with IL-1-like activity, termed Epidermal cell-derived Thymocyte-Activating Factor (ETAF). The purpose of this study was to determine whether UVR affects alloantigen presentation by epidermal cells and if so, whether the UV-induced change is due to UVR alteration in ETAF activity. Epidermal cells from UV-treated BALB/c mice (UV-EC) or from non-UV-treated mice (EC) were x-irradiated and then cocultured for 5 days with allogeneic T cells from C57Bl/6 mice. UV-EC caused less T-cell stimulation than did EC from non-UV-treated animals. When chromatography purified fractions of ETAF were added to cultured UV-EC, partial restoration of T-cell stimulation was seen. These results suggest that this UV-induced defect in alloantigen presentation is due, in part, to decreased ETAF activity.

Animals↗
PubMed1983

Strain variation in the induction of tolerance by epicutaneous application of trinitrochlorobenzene.

It has been postulated that a relationship exists between the density of epidermal Langerhans cells and the capacity of the epidermis to promote the induction of contact sensitization. This postulate was developed, in part, because (1) mouse tail epidermis contains fewer ATPase-positive (presumably Langerhans) cells than does abdominal epidermis, and (2) when tails of C57Bl/6 mice were painted with dinitrofluorobenzene (DNFB), the mice were less sensitive than those painted on the abdomen. In addition, tail-painted mice were shown to be tolerant to subsequent attempts at sensitization with DNFB. In this study we found that by painting the tails of mice with the hapten trinitrochlorobenzene (TNCB), sensitization was induced in certain mouse strains (BALB/c, A/J, and CBA--haplotypes H-2d, H-2a, H-2k, respectively), but tolerance resulted from painting the tails of other strains (C57Bl/6, C57Bl/10, and AB.Y--haplotype H-2b). The ability to become sensitive or tolerant is not related to Langerhans cell density as detected by ATPase staining. While the mechanism for this strain difference in the induction of tolerance is unknown, tolerance induced in C57Bl/6 mice is mediated in part by the generation of suppressor cells.

Adenosine Triphosphatases↗
PubMed1983

Neoplastic cells obtained from Hodgkin's disease are potent stimulators of human primary mixed lymphocyte cultures.

Neoplastic cells obtained from the pleural effusion of a patient with Hodgkin's disease have been maintained in culture since 1978. These tumor cells have been shown to have the cytologic features, cytochemical staining, and cell surface markers of Reed-Sternberg cells. In this study we demonstrate that the cell line termed L428 is a potent stimulator of the primary human mixed lymphocyte reaction. Significant proliferation occurred when mononuclear leukocytes obtained from normal donors were stimulated with radiated L428 cells at responder:stimulator ratios varying from 200:1 to 20:1. Proliferative responses occurred between days 3 and 6 of the cultures with maximal proliferation on day 5. Under optimal culture conditions, mean net proliferative response of 14 normal donors was 51,000 +/- 10,600 dpm. The mixed lymphocyte response was totally blocked by concentrations of monoclonal anti-Ia antibody that had no effect on concanavalin A-induced proliferation. However, the mixed lymphocyte response was not blocked by an anti-K562 cell monoclonal antibody of the same immunoglobulin subclass that binds to the L428 cells. Antigen processing by responder monocytes or Ia-positive cells was not required for the MLC. When responder T cells from two normals were depleted of Ia-bearing cells and monocytes, the mixed lymphocyte reaction between the two normals was eliminated, yet the stimulation of each normal by the L428 cells was not reduced. The cells that proliferated in response to stimulation by the L428 cells were T cells, primarily of the helper subset. No IL 1 activity could be detected in concentrated supernatants of L428 cultures after stimulation of L428 cells by mitogens, phorbol esters, or muramyl dipeptide, or in the MLC. All of these cultures contain fetal calf serum. However, the L428 cells are capable of producing IL 1, because IL 1 was detected when the L428 cells were stimulated with LPS in the absence of fetal calf serum. These neoplastic cells, obtained from Hodgkin's disease, have many similarities to the murine as well as human dendritic cells.

Animals↗
PubMed1982

Immune modulation by epidermal cell products: possible role of ETAF in inflammatory and neoplastic skin diseases.

Recent studies have indicated that the epidermis plays an important role in the modulation of immunologic reactions. The factors involved in these processes include not only Langerhans cells but also keratinocyte products. One of these products, ETAF (Epidermal cell derived Thymocyte Activating Factor), which is similar to the macrophage derived product interleukin 1 (IL-1), is reviewed. Speculations as to its possible role in skin diseases are presented.

Antigens↗
PubMed1981

Lymphocyte kinetics in pustular psoriasis.

Generalized pustular psoriasis is a potentially lethal variant of psoriasis vulgaris characterized by the appearance of sterile pustules on inflamed psoriatic skin. We now report the finding of an absolute lymphopenia at the onset of pustular psoriasis. While the white blood cell count rises to a level of 25,000 to 40,000 in the initial stages of a pustular flare, the lymphocyte count drops from a normal level to an absolute lymphopenia. This "lymphocyte eclipse," as we have called it, appears to be a reliable sign of impending pustular activity and has now been documented in ten patients with pustular psoriasis. Immediate institution of therapy may abort a potentially lethal complication of psoriasis.

Adrenal Cortex Hormones↗
PubMed1981

Abnormalities of immunoregulation in progressive systemic sclerosis. Evidence for excess helper-cell function and altered B-cell function.

We investigated immunoregulatory function in patients with progressive systemic sclerosis (PSS) in terms of in vitro IgM synthesis. Suppressor-cell function seems normal in regard to the ability of concanavalin A-treated cells to inhibit IgM synthesis by normal cells. At 4 x 10(5) T cells to 3 x 10(5) allogeneic normal B cells per milliliter, T cells from patients with PSS induce significantly more IgM synthesis by normal B cells than do normal T cells. This increased helper T-cell function might be involved in the pathogenesis of the disease.

Adult↗
PubMed1980

Suppressor cell defect in SLE: relationship to native DNA binding.

Recent evidence suggests the presence of a suppressor T cell defect in systemic lupus erythematosus. We confirm the presence of such a defect and find a strong quantitative correlation between the loss of suppressor T cell function and the activity of SLE as measured by the presence of antibodies to native DNA. In addition, the serum of patients with active SLE contains a soluble factor which when incubated with normal peripheral blood lymphocytes induces a suppressor T cell defect. These data are consistent with the suppressor cell defect being involved in the propagation and possible the pathogenesis of SLE, and suggests a positive feedback mechanism whereby a suppressor cell defect results in autoantibodies including antibody to suppressor cells.

Adult↗
PubMed1979

Sézary syndrome.

A case of Sézary syndrome is presented and the clinical, histologic, and laboratory findings are reviewed.

Aged↗
PubMedDate not supplied

Modulation of the contact hypersensitivity response by AE-941 (Neovastat), a novel antiangiogenic agent.

BACKGROUND: AE-941 (Neovastat) is an angiogenesis inhibitor noted to have antiinflammatory properties. OBJECTIVE: We tested Neovastat in a contact hypersensitivity (CHS) model to determine the mechanism of action of its antiinflammatory effects. METHODS: Neovastat was orally administered (200 mg/kg/day) during the sensitization and challenge phases of a murine CHS assay and inflammatory responses were measured. Subsequent assays were performed on mice treated with Neovastat or Cortisone (120 mg/kg/day, IP) and differential mRNA expression of several pro- and antiinflammatory cytokines was quantified using RT-PCR. RESULTS: Neovastat decreased inflammation by 39% when administered during sensitization but did not alter the CHS response when given during the challenge phase. Neovastat significantly induced IL-10 expression in skin and skin-draining lymph nodes (49% and 45%, respectively) and decreased IFNgamma expression in the lymph nodes (35%). CONCLUSION: Antiinflammatory effects of Neovastat observed in CHS could be linked to modulation of cytokines early in the sensitization phase.

Administration, Oral↗
PubMedDate not supplied

Augmentation of interleukin-6 (IL-6) expression in squamous carcinoma cells and normal human keratinocytes treated with recombinant anti-neoplastic protein (ACP).

A protein purified from Eschericheri coli has previously been shown to have cytotoxic effects on neoplastic cells of several lineages both in vitro and in vivo. Accordingly, this protein has been named anti-neoplastic protein (ACP). Although ACP kills neoplastic cells by inducing apoptosis, it has negligible effects on various normal cells. In addition to the direct cytotoxic effects of ACP on tumour cells, previous studies have shown that in vivo ACP increases tumouricidal activity of cytotoxic lymphocytes. We investigated whether cytokines from host or tumour cells play a part in the enhanced cellular immunity seen in ACP-treated tumour-bearing mice. Growth of normal human keratinocytres (KC) was not significantly affected by subnanogram amounts of ACP, however ACP dose-dependently killed KHT cells, a murine fibrosarcoma cell line (LD50 = 8 x 10(4) ng/cell). as well as the human squamous carcinoma cell line COLO-16 (LD50 = 2.5 x 10(-4) ng/cell). Testing purified ACP on cultures of normal keratinocytes and squamous carcinoma cell lines revealed that ACP could induce both mRNA and protein for interleukin-6 (IL-6). Messenger RNA for IL-6 increased dose-dependently 4h after treatment of COLO-16 squamous carcinoma cells with 10(-4) to 10(-2) ng/cell ACP. Maximal increment was 50-fold. Interleukin-6 message remained elevated up to 24h later in both normal keratinocytes and squamous carcinoma cultures treated with ACP. Conditioned supernates from these cultures were analysed by ELISA and found to have 4-fold higher levels of IL-6 protein than untreated cells after 4h. After 24h, IL-6 did not increase above the 4h level. Boiling of the ACP preparation showed that the cytokine induction was not due to contaminating lipopolysaccharide. The cytoxic effect of ACP on tumour cells in vitro was not due to IL-6 protein induction since neither recombinant IL-6, nor the other proinflammatory cytokines, IL-1 alpha or Tumour necrosis factor-alpha (TNF-alpha) (0.1-10ng/ml) were able to kill malignant cells. We demonstrated IL-6 gene induction by ACP in the squamous carcinoma lines as well as in normal KC. This suggests that the in vivo effectiveness of ACP against tumours may be due to stimulatory effects of IL-6 on host immunity.

Antineoplastic Agents↗