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J C Simon

Publications and source records attributed to J C Simon.

At least 91 records · Page 5Linked to original sources
PubMed1996

Immunoscintigraphy for ocular melanoma: a reliable diagnostic technique?

BACKGROUND: Immunoscintigraphy (IS) has recently been used as a diagnostic tool for ocular melanoma. We wanted to reevaluate published data in our own patients and to correlate immunoscintigraphic results with histologic findings and immunohistochemical characteristics of the tumour tissue. METHODS: During a 4-year period, IS was performed on 35 patients (average age 64 years) with suspected ocular melanoma by i.v. injection of 225.28S, a monoclonal antibody against high-molecular-weight melanoma-associated antigen. Histology was available in 22 cases. Tumour tissue was evaluated for cell type, vascularization, necrosis, pigmentation, and lymphocytic infiltration, and immunohistochemistry was performed with 225.28S and antibodies against HMB-45, S-100 and vimentin. One hundred and two patients with metastasizing cutaneous melanoma served as controls. In these patients the identical immunoscintigraphic technique was applied. RESULTS: IS yielded a positive result in about 50% of our patients with ocular melanoma, while in patients with cutaneous melanoma sensitivity was 89%. In five patients who turned out not to have melanoma, two false-positive results were obtained (one subretinal hemorrhage and one Wegener's granulomatosis). No correlation was found between any of the histological features or the immunoreactivity pattern and the immunoscintigraphic outcome. However, antigenic differences between ocular and cutaneous melanoma were evident. CONCLUSION: We conclude that IS, using the antibody applied in this study, is of only limited value in patients with ocular melanoma. Our results suggest that antigenic differences, rather than histological characteristics or technical problems, are responsible for the low sensitivity in ocular melanoma compared to cutaneous melanoma.

Antibodies, Monoclonal↗
PubMed1996

[Dermatitis bullosa striata pratensis caused by Dictamnus albus L. (burning bush)].

We report two patients with bullous phototoxic contact dermatitis caused by Dictamnus albus L. (gas plant) which belongs to the Rutaceae family. In both cases long lasting postinflammatory hyper-pigmentations were observed as a result of the phototoxic contact dermatitis. The phototoxic components of Dictamnus albus L. are the furocoumarins 5-methoxypsoralen (bergapten) and 8-methoxypsoralen, and the alkaloid dictamnin whose phototoxic properties were recently discovered. Even though reactions to the gas plant have been infrequently reported, it is becoming more popular with gardenus and should be considered in the differential diagnosis of phototoxic contact dermatitis.

5-Methoxypsoralen↗
PubMed1996

[Bath additives in dermatologic balneotherapy. Indications and approaches in current research].

Progress in dermatological research during the last years has provided new insights into the mode of action of additives to dermatological baths. The present paper reviews the pharmacokinetics of dermatological bath therapy additives such as sulfur, salts and trace elements, tars and ichthyol, lipids, antiseptics, astringents, plant extracts, surface-active agents and proteins.

Balneology↗
PubMed1996

Expression of CD44 isoforms in human skin cancer.

In animal models, isoforms of CD44 (CD44v) containing sequences encoded by one or several of ten different exons (v1-v10) contribute to tumour metastasis. In certain human cancers, CD44v6 expression is associated with poor prognosis. This paper examines CD44v expression in skin carcinogenesis and skin cancer metastasis. CD44v expression was studied in basal cell carcinoma (BCC), squamous cell carcinoma (SCC), primary malignant melanoma (PMM), metastases of MM (MMM), benign melanocytic naevi (BMN) and normal skin (NS) by immunohistochemistry and reverse transcript polymerase chain reaction (RT-PCR). BCC, SCC and NS expressed several CD44v, including v6, albeit in different distributions and intensities. PMM, MMM and BMN expressed isoforms containing v7/8 and v10, but failed to express epitopes encoded by v5 or v6. Thus, different CD44 isoforms are found in human skin cancers and are modulated during carcinogenesis. However, we did not observe a correlation of CD44v6 expression with metastatic potential.

Antigens, Neoplasm↗
PubMed1996

Phototesting in bath-PUVA: marked reduction of 8-methoxypsoralen (8-MOP) activity within one hour after an 8-MOP bath.

It is not known how long after 8-MOP bath-PUVA administration erythema can be induced. Therefore, after determination of dose-dependence and kinetics of bath-PUVA erythema, we investigated the development of erythema using an erythematogenic UVA-dose (3 J/cm2) in time course experiments. Our results show that there is a loss of biological 8-MOP activity already 1 h after 8-MOP bath. This has important consequences for clinical practice with bath-PUVA, concerning the optimum time interval between the 8-MOP bath and irradiation as well as the persistence of photosensitivity in normal skin after bath-PUVA.

Baths↗
PubMed1995

[Malignant melanoma of the skin].

The incidence of malignant melanoma (MM) of the skin is on the increase. If the mortality of this disease is to be reduced, the identification of persons at risk, and early clinical diagnosis are of decisive importance. The prognosis depends on the stage of the disease and has improved over the last few decades. The present article provides an overview of the risk factors and discusses the latest guidelines for the diagnosis, treatment and follow-up, the aim of which is to make possible a uniform approach to the management of malignant melanoma.

Combined Modality Therapy↗
PubMed1995

In situ expression of B7 and CD28 receptor families in human malignant melanoma: relevance for T-cell-mediated anti-tumor immunity.

Work in animal models has suggested that interactions of members of the B7 receptor family (e.g., B7-1, B7-2) on tumor cells with their ligands CD28 and CTLA-4 on cytotoxic T cells (CTL) are important for the induction of anti-tumor immunity against malignant melanoma (MM). To determine whether these molecules are of relevance for CTL responses against human MM, we studied the expression of B7-1, B7-2, CD28 and CTLA-4 in primary tumors of MM (PMM), MM metastases (MMM) and benign melanocytic nevi (BMN) by immunohistochemistry (IH) and by reverse transcription polymerase chain reaction (RT-PCR). By RT-PCR, B7-1 and B7-2-specific mRNAs were detected in most PMM, MMM and BMN. These PCR-signals were derived from CD45(+)-infiltrating leukocytes and not from tumor cells since (I) MMM depleted of CD45+ cells contained no B7-1 or B7-2 mRNA; and (2) by IH, B7-1 and B7-2 were found on infiltrating dendritic cells, macrophages and a variable proportion of tumor-infiltrating lymphocytes (TIL) but not on melanoma cells or nevus cells. The important exceptions were 5/5 spontaneously regressing PMM, in which B7-1 and B7-2 were expressed by melanoma cells, that were surrounded by TIL expressing CD28 but not CTLA-4. We conclude that, in PMM, MMM and BMN, the majority of TIL are CD28+ and that B7-1 and B7-2 are expressed by CD45(+)-infiltrating antigen-presenting cells (APC) and TIL, but not by the tumor cells. However, in spontaneously regressing PMM, melanoma cells express B7-1, B7-2 and MHC class-I and -II antigens, particularly in areas with clinical and histological signs of an ongoing anti-tumor response. These data suggest that the absence of B7-1 and B7-2 favors the escape of MM from immunosurveillance, while B7-1, B7-2 expression enhances T-cell-mediated anti-tumor immunity.

Abatacept↗
PubMed1995

Expression of functional CD40 by vascular endothelial cells.

The interaction between activated vascular endothelium and T cells has been shown to play an important role in the recruitment and activation of T cells at sites of inflammation. Here we report the expression of CD40 by vascular endothelial cells and its regulation by inflammatory agents. Using the soluble recombinant CD40 ligand, sgp39, we show that the interaction of CD40 with its ligand can lead to endothelial cell activation, which in turn leads to leukocyte adhesion. This adhesion is partly mediated by the expression of E-selectin. In addition to E-selectin expression, sgp39 induces the expression of intercellular adhesion molecule 1 and augments the tumor necrosis factor alpha-induced expression of vascular cell adhesion molecule 1. The effects of sgp39 on endothelial cells can be blocked with anti-gp39 monoclonal antibody (mAb), anti-CD40 mAb, or soluble CD40. Staining of tissues from healthy human skin using anti-CD40 mAb showed very weak expression of CD40 by the endothelium, while skin involved in inflammatory disease showed marked upregulation of CD40 expression. These studies suggest that interactions between cell surface proteins expressed by activated T cells with their receptors on vascular endothelium can stimulate the vasculature at sites of inflammation and may be involved in normal inflammatory responses and in inflammatory disease.

Antibodies, Monoclonal↗
PubMed1995

Low-dose UVB radiation perturbs the functional expression of B7.1 and B7.2 co-stimulatory molecules on human Langerhans cells.

In previous studies, we have shown that ultraviolet (UV) B radiation perturbs the APC function of Langerhans cells (LC) by interfering with as-yet unidentified co-stimulatory signals. Recently, B7.1 and B7.2 on APC were shown to deliver important co-stimulatory signals through interaction with their counter receptors CD28 and CTLA-4 on T cells. To determine whether UVB affects the functional expression of B7.1 or B7.2 on LC, B7.1 and B7.2 expression was studied on human LC by multiparameter flow cytometry. Little, if any, B7.1 or B7.2 was detected on LC freshly isolated from skin. However, following 48 h of tissue culture, expression of both B7.1 and B7.2 were markedly up-regulated. To test whether these molecules were functional, primary mixed epidermal cell leukocyte reactions (MECLR) were performed. Blocking monoclonal antibody (mAb) to B7.1 or B7.2 both inhibited the MECLR, with anti-B7.2 being much more effective than anti-B7.1. UVB radiation dose-dependently (100-200 J/m2) suppressed the culture-induced up-regulation of B7.1 and B7.2 on LC. Since LC exposed to the same UVB flux (UVB-LC) failed to stimulate alloreactive T cells in a MECLR, we questioned whether this was related to their inability to provide B7 co-stimulation. Indeed, when effective B7-CD28 signaling was ascertained by adding submitogenic doses of exogenous anti-CD28 mAb to UVB-LC, the proliferative response of alloreactive T cells was restored. We conclude that the suppressive effects of low-dose UVB radiation on the APC function of LC are, at least in part, due to an inhibition of functional B7.1 and B7.2 expression.

Antibodies, Monoclonal↗
PubMed1995

[Chronic bullous dermatosis in childhood. Association with salmonella enteritis].

We report on a 2-year-old girl with chronic bullous disease of childhood (CBDC). Concomitantly with a feverish gastrointestinal infection caused by Salmonella enteritidis, the child presented with lesions resembling impetigo contagiosa on the legs and face. Following antibiotic treatment with cephalosporins p.o. and flucloxacillin i.v. she developed typical symptoms of CBDC, i.e. tense blisters on erythematous skin in the perineal area, on the flexor aspects of the thighs and upper arms and on the face. Direct immunofluorescence revealed a linear IgA deposition along the basement membrane zone, confirming the diagnosis of CBDC. These lesions cleared rapidly after treatment with dapsone p.o. This case prompted us to consider new aspects of the pathogenesis, clinical entity and treatment of this rare bullous disease of childhood.

Anti-Bacterial Agents↗
PubMed1995

CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor.

Glycosaminoglycan-modified isoforms of CD44 have been implicated in growth factor presentation at sites of inflammation. In the present study we show that COS cell transfectants expressing CD44 isoforms containing the alternatively spliced exon V3 are modified with heparan sulfate (HS). Binding studies with three HS-binding growth factors, basic-fibroblast growth factor (b-FGF), heparin binding-epidermal growth factor (HB-EGF), and amphiregulin, showed that the HS-modified CD44 isoforms are able to bind to b-FGF and HB-EGF, but not AR. b-FGF and HB-EGF binding to HS-modified CD44 was eliminated by pretreating the protein with heparitinase or by blocking with free heparin. HS-modified CD44 immunoprecipitated from keratinocytes, which express a CD44 isoform containing V3, also bound to b-FGF. We examined whether HS-modified CD44 isoforms were expressed by activated endothelial cells where they might present HS-binding growth factors to leukocytes during an inflammatory response. PCR and antibody-binding studies showed that activated cultured endothelial cells only express the CD44H isoform which does not contain any of the variably spliced exons including V3. Immunohistological studies with antibodies directed to CD44 extracellular domains encoded by the variably spliced exons showed that vascular endothelial cells in inflamed skin tissue sections do not express CD44 spliced variants. Keratinocytes, monocytes, and dendritic cells in the same specimens were found to express variably spliced CD44. 35SO4(-2)-labeling experiments demonstrated that activated cultured endothelial cells do not express detectable levels of chondroitin sulfate or HS-modified CD44. Our results suggest that one of the functions of CD44 isoforms expressing V3 is to bind and present a subset of HS-binding proteins. Furthermore, it is probable that HS-modified CD44 is involved in the presentation of HS-binding proteins by keratinocytes in inflamed skin. However, our data suggests that CD44 is not likely to be the proteoglycan principally involved in presenting HS-binding growth factors to leukocytes on the vascular cell wall.

Alternative Splicing↗
PubMed1995

Pentoxifylline inhibits tumor necrosis factor-alpha (TNF alpha)-induced T-lymphoma cell adhesion to endothelioma cells.

Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell-mediated cutaneous immune response by yet ill-understood mechanisms. Because cell adhesion to endothelial cells is a critical step in the initiation of such immune responses, we analyzed whether pentoxifylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis factor-alpha (TNF alpha), was studied. Pentoxifylline reduced the ability of endothelioma cells stimulated with different concentrations of TNF alpha, but not of untreated endothelioma cells, to bind T-lymphoma cells in dose-dependent (10(-5)-10(-3) M) fashion. Selective incubation of either endothelioma cells or T-lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma cells, even when added after TNF alpha stimulation. We questioned whether pentoxifylline suppressed T-lymphoma cell/endothelioma cell interactions by interfering with adhesion molecules expressed by either cell. However, as determined by flow cytometry, pentoxifylline did not alter TNF alpha-induced upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or alpha 4-integrin expression on T-lymphoma cells, suggesting that rather than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. We conclude that pentoxifylline in therapeutically achievable concentrations is a potent inhibitor of TNF alpha-induced T-lymphoma cell adhesion to endothelioma cells. This finding may account, at least in part, for the recently discovered anti-inflammatory action of pentoxifylline.

Animals↗
PubMed1995

Prostaglandin E1 inhibits TNF alpha-induced T-cell adhesion to endothelial cells by selective down-modulation of ICAM-1 expression on endothelial cells.

Prostaglandins have been shown to be involved in the suppression of contact hypersensitivity (CHS) by so-far ill understood mechanisms. T-cell migration across the lining of cytokine-activated endothelial cells (EC) is thought to be a central step in the initiation of CHS. The aim of our investigation was therefore to examine whether prostaglandin E1 (PGE1) influences cytokine-induced TK-1 mouse T-cell lymphoma adhesion to eEnd.2 mouse endothelioma cells. Here, we report that PGE1 (10(-12)-10(-8) M) dose-dependently reduced TNF alpha-induced T-cell binding, while TNF alpha-unstimulated adhesion was not affected. To test whether PGE1 acted primarily on T-cells or on EC, they were separately pretreated with PGE1 prior to the adhesion assay. Selective PGE1 pretreatment of eEnd.2, but not of TK-1 dose-dependently inhibited TNF alpha, stimulated T-cell adhesion. Since binding of TK-1 to TNF alpha-treated eEnd.2 is mediated by the interaction of ICAM-1 and VCAM-1 (on EC) with their receptors LFA-1 and VLA-4 (on T-cells), we further investigated whether PGE1 would modulate the expression of these molecules. FACS-analysis revealed PGE1 to inhibit TNF alpha-induced upregulation of ICAM-1, but not of VCAM-1 on EC. Furthermore, constitutive LFA-1 and VLA-4 expression on T-cells was not affected by PGE1. We conclude that PGE1 supresses T-cell adhesion to EC by selectively inhibiting TNF alpha-induced upregulation of ICAM-1 on EC. This may be one mechanism by which prostaglandins suppress immune responses requiring T-cell EC interactions such as contact hypersensitivity in skin.

Alprostadil↗
PubMed1995

Low N-acetylating capacity in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Low constitutive N-acetylating capacity has been implicated as a predisposing factor for the development of adverse reactions to certain drugs. This prompted us to investigate whether the N-acetylating capacity of patients with serious cutaneous adverse reactions, i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) differed from that of healthy control subjects. N-acetylating activity was measured in hair root cells by preparing a homogenate from freshly extracted hair roots and assessing acetyl-CoA-dependent N-acetylation by RP-HPLC using 2-aminofluorene as a substrate. Samples were obtained from hospitalized patients suffering from acute SJS and TEN or from healthy controls. All patients with SJS and TEN were found to have a low N-acetylating capacity (0.85 nmol/mg/min compared to 2.21 nmol/mg/min in controls, p < 0.05). Based on these findings, a low constitutive N-acetylating capacity may be one of the predisposing factors for the development of serious cutaneous adverse reactions to drugs that require N-acetylation in these patients.

Acetylation↗
PubMed1995

Rapid purification of human Langerhans cells using paramagnetic microbeads.

Detailed studies on the biology of Langerhans cells (LC), which account for only 1-3% of all epidermal cells, require isolation from their cutaneous symbionts. Several techniques of LC isolation have been reported, including positive enrichment with mAb coupled to immunomagnetic beads. The disadvantage of this technique is the size of the beads (approximately 2-5 microns), which can interfere with subsequent phenotypic and functional analyses. This limitation prompted us to test whether paramagnetic microbeads (15 nm) employed by the MACS system could be used to purify LC from human skin. To isolate fresh LC (fLC), epidermal cell suspensions (EC) were stained with anti-CD1a mAb and with appropriate secondary reagents conjugated to microbeads and to FITC. They were then passed over a separation column and exposed to a strong magnetic field. Thereafter both CD1a-depleted and CD1a-enriched cells were collected. Cultured LC (cLC) were isolated by staining 72-h cultured EC with anti-HLA-DR mAb followed by the same isolation procedure. Using this technique, we could routinely isolate viable EC that were 45-88% CD1a+ or HLA-DR+ as determined by FACS. Two-color FACS analysis demonstrated the majority of MACS-purified cells to be CD1a+/HLA-DR+, indicating that they were indeed LC. By transmission electron microscopy (TEM), the MACS-purified CD1a+/HLA-DR+ cells showed typical ultrastructural characteristics of LC. Furthermore, MACS-purified fLC or cLC were functionally intact, because they stimulated the proliferation of alloreactive T cells in a primary, one-way, mixed epidermal cell leukocyte reaction (MECLR). We conclude that MACS-separation is an efficient and rapid method to isolate human fLC and cLC of high purity and unimpaired function.

Bacterial Proteins↗
PubMed1995

[Antigen pattern in choroid melanoma in correlation with immunoscintigraphy].

We have reported that the sensitivity of immunoscintigraphy in ocular melanoma is fairly low in comparison with (metastasizing) cutaneous melanoma. No significant correlation was found between the histological data for ocular melanoma and the immunoscintigraphic results. We therefore wanted to see whether we could demonstrate an antigen pattern that was different from that of cutaneous melanoma, which might explain our previous results. Our study comprised tumor tissue from 20 patients with ocular melanoma who had undergone previous immunoscintigraphic examination. Using immunohistochemical techniques, tumor immunoreactivity was investigated against 225.28S, the antibody used for immunoscintigraphy, on cryosections in 12 cases, and against anti-HMB-45, and anti-S-100 and anti-vimentin on paraffin sections in all 20 patients. In summary, there was marked immunohistochemical heterogeneity, and none of the antibodies examined showed a significant correlation with immunoscintigraphy. Even 225.28S that was used for the immunoscintigraphic examination did not retrospectively allow a predictable immunoscintigraphic outcome. When comparing our results with the literature on cutaneous melanoma we were also able to confirm differences in immunoreactivity with regard to the other antibodies. We conclude that the comparatively poor results in ocular immunoscintigraphy obtained with 225.28S are due to antigenic differences between ocular and cutaneous melanoma.

Antigens, Neoplasm↗
PubMed1994

[The skin--an immunocompetent organ].

Not only is the skin a mechanical barrier vis-à-vis the external environment, it also forms part of the immunological defence system. This skin-related component of the immune system is made up of a multitude of cells, and structures such as the Langerhans cells, keratinocytes, T-lymphocytes, endothelial cells, tissue macrophages, dendritic cells and mast cells. The skin is also provided with a dense network of afferent lymphatic vessels. Taking allergic contact dermatitis as an example, an immune response in the skin is described.

Allergens↗