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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although mast cells have been implicated in mediating antitumor activity, the kinetics, mechanism(s), and suspectibility of different tumors to mast cell-mediated cytotoxicity have not been defined. Rat connective tissue mast cells (CTMC) of greater than or equal to 99% purity were investigated in vitro and found to express maximal spontaneous cytotoxicity against the mouse fibrosarcoma cell line WEHI-164 (56.0% +/- 2.1 SEM), the ultraviolet B (UVB)-induced, cutaneous fibrosarcoma 5C25 (34.7% +/- 3.4 SEM), and the human renal cell tumor Currie (26.8% +/- 2.0 SEM) at an effector to target (E:T) ratio of 80:1. Kinetic studies of CTMC-mediated cytotoxicity demonstrated significant detectable lysis against these tumors within 8 h, which was maximal by 16 h. Binding experiments showed that CTMC formed conjugates with all three lytic-sensitive targets; however, CTMC also attached to the lytic-resistant target YAC-1, indicating that conjugate formation alone is not sufficient for mast cell-mediated cytotoxicity. At two different concentrations, mast cell granules (MCG) lysed WEHI-164 (36.5% +/- 6.8 SEM) and 5C25 (34.4% +/- 6.9 SEM), but were only slightly cytotoxic (5.7% +/- 2.9 SEM) against Currie. A potential role for tumor necrosis factor-alpha (TNF-alpha) in CTMC-mediated cytotoxicity also was investigated. Polyclonal antibodies to TNF-alpha greatly reduced CTMC and TNF-mediated lysis of WEHI-164, but only partially inhibited CTMC killing of the slightly TNF-sensitive 5C25 tumors, and had no effect on CTMC cytolysis of Currie. Thus, this study demonstrates that CTMC mediate cytotoxicity in vitro by both TNF-associated and TNF-independent mechanisms. We conclude that CTMC are capable of mediating antitumor activity and that this effect may be important for tumor surveillance in the skin and other sites.
J Invest Dermatol 1989 Sep
PMID:Studies of connective tissue mast cell-mediated cytotoxicity. 276 40

The mechanism of irritant dermatitis and the immunologic consequences of such reactions are unclear. We evaluated the number and function of epidermal antigen-presenting cells contained in epidermal cell suspensions obtained from normal and irritant patch test reaction sites. Application of sodium lauryl sulfate or croton oil to human skin in vivo resulted in a progressive depletion in the number of epidermal OKT6+HLA-DR+ (T6+DR+) Langerhans cells (LC) from 3.1 +/- 0.2% of total epidermal cells (EC) to 1.2 +/- 0.1% after 8 d (mean values +/- SEM, N = 9). Between 1-4 d irritant patch test sites demonstrated an influx of non-Langerhans cell T6-DR+ cells. These cells were not DR+ keratinocytes but appeared to be of bone marrow derivation because they expressed the marker, HLe1. Among bone marrow derived cells, the T6-DR+EC appeared to be of monocyte, macrophage lineage, because they expressed the determinant recognized by the OKM5 (M5) antibody. Despite the induction of M5+DR+EC the total number of DR+EC showed progressively decreasing percentages over an 8-d period. Partial recovery to 73 +/- 12% of control value was observed at 2 weeks, with full recovery by 4 weeks after challenge. Concomitantly with the depletion of DR+EC, the capacity of EC to present alloantigens to T cells decreased. This reduction in antigen-presenting cell activity was strongly correlated to the reduction in total DR+ EC (r = 0.94, p less than 0.05). Thus, the capacity of irritants such as croton oil to abrogate the function of epidermal antigen-presenting cells may be related to the tumor promoting potential of these agents.
J Invest Dermatol 1989 Jun
PMID:Decreased number and function of antigen-presenting cells in the skin following application of irritant agents: relevance for skin cancer? 278 39

Thirty women who were seen at our institution between 1984 and 1988 for pruritic urticarial papules and plaques of pregnancy (PUPPP) were retrospectively evaluated and interviewed. We found a significantly increased maternal weight gain and newborn birth weight in patients with PUPPP, compared with age and parity-matched controls. The average weight gain during pregnancy was 18.1 +/- 0.9 (SEM) kg for the patients with PUPPP (excluding twin gestations) and 14.6 +/- 1.0 kg for the controls. The mean newborn birth weight was 3.6 +/- 0.09 kg for the PUPPP group and 3.3 +/- 0.08 kg for the control group. There were three twin pregnancies (10%), compared with the twin gestation rate at our institution of 1.6%. Therefore, based on our findings of an increased maternal weight gain and neonatal birth weight, an increased twin rate, and an abdominal eruption that occurs in primigravidas in their third trimester of pregnancy, we suggest that abdominal distention or a reaction to it may play a role in the development of PUPPP.
Arch Dermatol 1989 Nov
PMID:Pruritic urticarial papules and plaques of pregnancy and its relationship to maternal-fetal weight gain and twin pregnancy. 800 57

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to modulate different granulocyte functions. In the present study we investigated the effect of purified and recombinant human GM-CSF, particularly on the oxidative metabolism of isolated human granulocytes. In addition, ultrastructural changes upon stimulation were evaluated. For detection of granulocyte activation the following assay systems were used: 1) lucigenin-dependent chemiluminescence (CL), 2) superoxide-dismutase (SOD) inhibitable cytochrome C-reduction (superoxide), 3) horseradish peroxidase-mediated oxidation of phenol red (hydrogen peroxide), 4) release of myeloperoxidase, 5) ultrastructural detection of hydrogen peroxide-production, and 6) scanning and transmission electron microscopy (SEM and TEM, respectively). A significant CL response was seen upon stimulation with recombinant human GM-CSF at concentrations ranging from 1 to 10(3) U/ml. The CL response started within 5-10 min with a maximum at 60-90 min and lasted more than 3 h. Thereafter granulocytes were completely deactivated to restimulation with the same mediator and with Tumor Necrosis Factor, but responded to other triggers of the oxidative burst, whereas the response to f-met-leu-phe was significantly increased. The CL signal was completely blocked by an antiserum to GM-CSF. Moreover, the response was significantly inhibited by SOD and D-Mannitol, suggesting the involvement of distinct reactive oxygen species (ROS) in generating the CL response. Significant amounts of superoxide were detected within 180 min after stimulation with GM-CSF, whereas release of hydrogen peroxide and peroxidase were only minimal as shown by functional and ultrastructural assays. Activation of granulocytes could be visualized by SEM and TEM. GM-CSF stimulated cells showed an increased adherence to the substratum developing polarized filopodia and an increased number of intracellular vesicles within 30 min after addition of the stimulus. The results clearly demonstrate that GM-CSF directly stimulates granulocytes and, particularly, their oxidative metabolism. Therefore, GM-CSF which is probably released by epidermal cells appears to be a candidate for neutrophil activation in the skin, and thereby may play a crucial role in inflammatory skin diseases.
J Invest Dermatol 1988 Jul
PMID:Human granulocyte-macrophage colony stimulating factor: an effective direct activator of human polymorphonuclear neutrophilic granulocytes. 283 54

As shown previously monocytes upon stimulation with bacterial lipopolysaccharides (LPS) release granulocyte-activating mediator(s) (M-GRAM) which induced a long-lasting chemiluminescence (CL) response in human granulocytes. M-GRAM could be separated from interleukin-1 alpha and beta, interleukin-2, interferon alpha and gamma, granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), since these cytokines are shown to be unable to induce a significant CL response. In contrast, granulocyte macrophage colony stimulating factor (GM-CSF) and particularly tumor necrosis factor (TNF) are important triggers of the oxidative burst and they are capable of inducing a CL response. TNF activity but not lymphotoxin (LT) activity could be demonstrated in M-GRAM samples. A polyclonal rabbit IgG as well as a monoclonal antibody to recombinant human TNF which neutralized the TNF activity in M-GRAM preparations did not substantially block the CL signal. Furthermore, M-GRAM-induced CL response was not significantly inhibited by a polyclonal calf antiserum to human recombinant GM-CSF. For further functional characterization of M-GRAM-induced granulocyte activation different assays were performed in order to compare GM-CSF and TNF: (a) SOD-inhibitable cytochrome C-reduction (.O2-); (b) horseradish peroxidase-mediated oxidation of phenol red (H2O2); (c) the release of peroxidase; (d) ultrastructural detection of hydrogen peroxide production; and (e) scanning and transmission electron microscopy (SEM and TEM). Significant release of .O2- was induced by M-GRAM, TNF, and GM-CSF, whereas H2O2 production was significantly stimulated only by M-GRAM and TNF, as shown by functional and ultrastructural assays.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Dermatol Res 1988
PMID:Granulocyte-activating mediators (GRAM): III. Further functional characterization of monocyte-derived GRAM. 284 61

A new approach studying the characteristics of the stratum corneum is presented: the electrophoretic mobility of corneocytes by laser Doppler spectroscopy. The detergent scrub technique was used for harvesting corneocytes from three body regions (forehead, palm, and sole) of normal persons (n = 20) under casual conditions and after thorough defattening of the skin with 70% isopropyl alcohol or petrol. Similarly, cells from the forehead, shoulder, and palm were obtained from 22 acne patients treated with isotretinoin (13-cis retinoic acid) 0.5-0.7 mg/kg body weight (b.wt.)/day for 12-16 weeks, and in patients receiving arotinoid (Ro 15-0778) 192 mg (n = 5) or 500 mg (n = 5) per kg/b.wt./day for 6 weeks (forehead and shoulder). In another experiment, cell suspensions with a pH ranging from 5.0-7.3 were evaluated. Measurements were performed by dynamic laser light scattering. This laser application allows exact electrophoretic mobility measurements in a short time (3 min). When cells pass the laser beam, the scattered light is frequency-shifted due to the optical Doppler effect. These frequency shifts are analyzed by the heterodyne light beating technique. The analog signal of the photodetector is converted into a power spectrum by Fourier analysis. This power spectrum represents the spectrum of electrophoretic cell mobility distribution. Results showed different electrophoretic mobility values for corneocytes dependent on the topographic region: forehead 1.18 +/- 0.16, palm 1.10 +/- 0.14, and sole 0.83 +/- 0.10 (means +/- SEM) micron cm/Vs. Defattening with isopropyl alcohol decreased the mobility values to 0.90 +/- 0.09 (p less than or equal to 0.01), 0.95 +/- 0.10, and 0.77 +/- 0.10 micron cm/Vs respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Dermatol Res 1987
PMID:Electrophoretic mobility of corneocytes measured by laser Doppler spectroscopy. 295 13

The effects of four retinoids, all-trans-retinoic acid (tretinoin), 13-cis-retinoic acid (isotretinoin), R0 10-1670 (etretin) and the arotinoid, R0 15-0778, on fibroblast proliferation and glycosaminoglycans (GAG) secretion in vitro were studied. Fibroblasts lines cultured from normal skin (HSF) were compared with those from lesional (PSA) and non-lesional (PSB) psoriatic skin. In general, the retinoids inhibited proliferation; the action was cytostatic, in rank order tretinoin greater than isotretinoin greater than etretin greater than arotinoid. The psoriatic cells tended to be more sensitive than the HSF lines, overall mean proliferation values (+/- SEM), as a percentage of untreated controls being: HSF 72 ++- 3, PSA 61 +/- 3 and PSB 54 +/- 3. Stimulation of GAG secretion at low concentrations (10(-7) M) of all four retinoids, declined as concentrations increased, and secretion was inhibited at 10(-4)M in PSB fibroblasts. Calculation of effects on GAG secretion due to changes in cell density confirmed the rank order for direct stimulation of secretion as arotinoid greater than etretin greater than isotretinoin greater than tretinoin. Electrophoresis of [3H]-labelled glycosaminoglycans secreted in the presence of 10(-7) M arotinoid showed that it was predominantly hyaluronic acid, as in untreated cells. These data confirm that different retinoids have contrasting levels of effects on mesenchymal cells and suggest a greater sensitivity to drugs in fibroblasts from psoriatic skin.
Br J Dermatol 1987 Nov
PMID:Proliferation and glycosaminoglycans secretion in fibroblasts from psoriatic skin: differential responses to retinoids. 296 63

Sixty patients with palmoplantar pustulosis were treated in a double-blind trial with either acitretin (etretin, Ro 10-1670) or with etretinate. The study consisted of 4 weeks of therapy with three 10 mg capsules/day followed by 8 weeks of therapy with a varying number of capsules given daily according to therapeutic response. At the end of the 12-week treatment period, the mean number of pustules (+/- SEM) had decreased from 57.8 (+/- 8.6) to 3.9 (+/- 1.6) in the acitretin group and from 57.1 (+/- 14.1) to 5.7 (+/- 2.7) in the etretinate group. With regard to influence on erythema, infiltration, scaling, and area involved, similar improvements were obtained in both treatment groups. Adverse reactions of the hypervitaminosis A type were observed with almost the same frequency and severity in both treatment groups. The mean number of 10 mg capsules used daily was comparable in the two groups: 2.82 (range 1.23-4.67) for acitretin and 2.77 (range 1.60-4.82) for etretinate. It can be concluded that acitretin and etretinate do not significantly differ with regard to efficacy and overall safety in the treatment of patients with palmoplantar pustulosis.
Br J Dermatol 1988 Dec
PMID:Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial. 297 6

Radiolabelled clobetasol 17-propionate in two different bases, propylene glycol (PG) and di-n-butyl adipate (BA), was applied to the backs of 10 normal male volunteers, and the application sites protected. After 8 h samples of stratum corneum (SC) were taken from the application site and an adjacent site, and the level of steroid measured. At the application site there were higher concentrations of the PG formulation at the deeper levels of the SC. At the adjacent sites there were higher concentrations of the BA formulation at the superficial levels. The mean radioactivity at the adjacent sites expressed as a percentage of that at the corresponding application sites (+/- SEM) was 7.8 +/- 5.3% for the BA formulation and 3.0 +/- 2.9% for the PG, (P = 0.0002). Total percentage of the applied dose in the skin adjacent to the application site was 11.7 +/- 6.3% for the BA formulation and 5.3 +/- 5.7% for the PG (P less than 0.0002). Clobetasol 17-propionate, therefore, moves laterally to a greater extent in BA than in PG.
Br J Dermatol 1988 Sep
PMID:The lateral spread of clobetasol 17-propionate in the stratum corneum in vivo. 317 8

We measured sister chromatid exchanges (SCEs) in lymphocytes of eight MF patients before, and 2 h, and 24 h after treatment with topical nitrogen mustard. The mean number of SCEs/cell (+/- SEM) were 8.15 (+/- 0.62), 8.34 (+0.55) and 8.26 (+/- 0.56), respectively. The 2 h and 24 h results do not differ significantly from pretreatment levels. Our results show that concentrations of nitrogen mustard used to control MF do not induce SCEs in peripheral blood lymphocytes.
Br J Dermatol 1988 Dec
PMID:No detectable increase in sister chromatid exchanges in lymphocytes from mycosis fungoides patients after topical treatment with nitrogen mustard. 320 68


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