Carcinoembryonic antigen and related glycoproteins in psoriasis.

Psoriasis is a benign but hyperproliferative skin disease. Psoriatic basal cells show a phenotype similar to that of normal skin, while psoriatic suprabasal cells exhibit a qualitatively altered keratinization pathway, resulting in the absence of the granular layer. These cells further show an abnormal expression of cellular differentiation antigens, which does not lead to tumor development. This immunohistological study demonstrates the appearance of carcinoembryonic antigen (CEA) in psoriatic suprabasal cells below the parakeratotic layer, while other markers such as CEA-related antigens, the nonspecific cross-reacting antigens and alpha-fetoprotein are not expressed. CEA is absent in normal skin, lichen planus, ichthyosis vulgaris and allergic dermatitis. Our data support the notion that dedifferentiation of psoriatic suprabasal keratinocytes is due to the reactivation of early developmental patterns of differentiation in this disease.

Monoclonal antibody H3/5-47 recognizes an inducible cell surface antigen expressed differently in endothelium of normal and diseased tissues and in vitro.

Monoclonal antibody H3/5-47 was raised against a human melanoma metastasis and recognizes an antigen expressed in the endothelial cells of all normal human organs as assessed by immunohistochemistry. Antigen expression is higher in venous than in capillary or arterial endothelia; capillary endothelia of different microvascular beds, such as skin, lung, gut or liver, may express varying amounts of this antigen. H3/5-47 antigen expression in the endothelia of diseased tissues (inflammatory diseases, neoplasias) largely reflects its expression pattern in normal tissues. As might be anticipated, the highest expression of H3/5-47 antigen is found in resting adult cutaneous and hepatic cavernous venous hemangiomas. In contrast, psoriatic vessels, characterized by hypertrophy and fenestrations, tend to express H3/5-47 antigen at a much lower density. In human umbilical vein endothelial cells, half the single donor cases show no expression of H3/5-47 antigen, while the rest express the antigen at relatively low densities in about half the cells. Treatment with interferon-gamma or thrombin, but not interleukin-1, lipopolysaccharide, endothelial cell growth factor or phorbolester, either enhances or induces de novo expression in cultured human umbilical vein endothelial cells within 24h; maximum expression of H3/5-47 antigen is induced by interferon-gamma within 72 h. H3/5-47 antigen is not similar to other antigens inducible in human umbilical vein endothelial cells such as HLA-DR, ICAM-1, HECA-452, Leu13, MCP-1 or gamma-IP-10. It is not specifically expressed in the endothelium as it may also recognize certain epithelia, peripheral nervous tissue and bone marrow-derived cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization and differential expression of an endothelial cell-specific surface antigen in continuous and sinusoidal endothelial, in skin vascular lesions and in vitro.

Continuous and sinusoidal endothelial cells display marked morphological and functional heterogeneity as to their plasmalemmal vesicle content, to the kind of intercellular junctional complexes, to the existence and kind of fenestrae and gaps, to the existence and character of their basement membrane, to their ability for phagocytosis and to other functional parameters. Monoclonal antibody 1F10, raised against human umbilical vein endothelial cells (HUVE cells), reflects these differences in recognizing--without any nonendothelial side reactions--an endothelial cell surface antigen, abundantly expressed in continuous endothelia, low and inconsistently expressed in liver sinusoidal and dermal lymphatic endothelia and absent from splenic sinusoidal endothelial cells. In differentiated skin vascular tumors, 1F10 antigen is expressed in normal amounts while it is only low and inconsistently expressed in the dedifferentiated endothelial cells of Kaposi's sarcoma and hemangiosarcoma. HUVE cells in culture, in contrast to their in situ ancestors, express variable amounts of 1F10 antigen. When endothelial cell-conditioned medium (ECC medium) is supplied to HUVE cells in culture, no 1F10 antigen is expressed, while supplementation with fresh serum-containing medium (FSC medium) or cytokines, such as bFGF, suffices to maintain 1F10 expression in 10-70% of the cells. From this we conclude that developmental regulation, environmental influences and cytokine supply contribute to the differentiation and maintenance of the 1F10+ and 1F10-endothelial cell phenotypes, both in vivo and in vitro.

Immunolocalization of an angiogenic factor (HAF) in normal, inflammatory and tumor tissues.

The distribution of a novel human angiogenic factor (HAF) (Schulze Osthoff et al., 1987) has been investigated on various human cell lines, isolated blood cells as well as in normal, inflammatory and tumor tissues. Localization was performed by using the monoclonal antibody (MAb) 5F4 directed against HAF. It was found that 30% of freshly isolated human monocytes expressed the 5F4 antigen. The number of positive cells increased to 75-90% on day 4 to 7 upon culture and then decreased. Twenty percent of freshly isolated human lymphocytes also stained positively, whereas granulocytes and platelets were negative. In cryostat sections of normal human tissue (skin, lung, liver, spleen, placenta) 5F4 is positive with capillary endothelial cells and few macrophages. In inflammatory tissue derived from gingivitis and rheumatoid arthritis, more macrophages than in normal tissues and less endothelial cells were positive. In tumor tissues some endothelial cells and a subset of tumor-infiltrating macrophages expressed the antigen. Tumor cells were positive in advanced melanomas, but only occasionally in stomach carcinomas. We conclude that the angiogenic factor is produced mainly by a subset of inflammatory macrophages which appear to be the principal source of HAF in regenerating or growing tissues.

Architectural features in melanocytic lesions with cellular atypia.

According to the quantity of single atypical melanocytes at the dermoepidermal junction 334 nevi were assigned to 3 groups: (1) with pronounced nuclear and cellular atypia (n = 73); (2) with moderate atypia (n = 127), and (3) without atypical melanocytes (n = 134). Three architectural features were almost exclusively observed in groups 1 and 2 with cellular and nuclear atypia: atypical localization of melanocytes in the epidermis, irregular distribution of melanocytes in the junctional zone and atypical nests of melanocytes. A combination of 2 or 3 of these features was seen in 76% of the nevi with pronounced cellular and nuclear atypia, in 28% of those with moderate atypia and in none of those without atypical melanocytes. Regarding 4 other criteria only minor but still statistically significant differences were found between the 3 groups of nevi. We conclude that these 4 other criteria, i.e. inflammatory infiltrate, lamellar and/or concentric fibroplasia, persisting lentiginous hyperplasia and dust-like pigment in melanocytes and nevus cells are not helpful for the diagnosis of a dysplastic nevus because of their low specificity. Minimal requirements for the diagnosis of a dysplastic nevus are suggested.

Biologic characterization of human bone tumors. VI. The aneurysmal bone cyst: an enzyme histochemical, electron microscopical, and immunohistological study.

The etiology of aneurysmal bone cyst is still unknown. Most theories of the histogenesis of this lesion assume a vascular origin and speculation has focused on the characteristic pseudoendothelial lining of the cyst walls. In the present study, this structure has been subjected to enzyme histochemical, electron microscopical, and immunohistochemical investigation. Of the enzymes tested only alkaline phosphatase was present in the cyst lining. Electron microscopy revealed fibroblast-like cells covering the walls of cystic cavities, but no genuine endothelium, basement membranes or pericytes were identified. For the immunohistochemical studies a panel of poly- and monoclonal antibodies against HLA-DR antigens, mature and immature macrophages/histiocytes, smooth muscle fibers and endothelial cells, as well as the lectin Ulex europaeus I agglutinin were used. None of these markers demonstrated the presupposed vascular characteristics in the cells constituting the pseudoendothelial lining of the cyst walls. Despite current theories to the contrary, it was concluded that aneurysmal bone cyst is unlikely to originate from the vascular system, and that a new concept of its pathogenesis must be sought.

Characterization and expression kinetics of an endothelial cell activation antigen present in vivo only in acute inflammatory tissues.

Endothelial cell activation by endotoxin (LPS), tumor necrosis factor (TNF), Interleukin-1-alpha, beta (IL-1-alpha, beta) and phorbolesters (TPA) results in increased monocyte adhesion. Examination of kinetics of monocyte adhesion shows that the onset of adherence enhancement (AE) is similar in all five agents (about 300% AE at 6 h), while its decrease is delayed in LPS/TNF versus IL-1-alpha, beta/TPA-induced activation (LPS versus IL-1-beta:260% versus 60% at 18 h). Monoclonal antibody (4D10), raised against 24 h LPS-stimulated endothelial cells detects an endothelial cell-specific activation antigen at Mr 81,000 that is induced by LPS, TNF, IL-1-alpha, beta and TPA (within 6 h about 100% positive cells). Decrease in antigen-positive cells is delayed in LPS/TNF versus IL-1-alpha, beta/TPA-induced antigen expression (LPS vs. IL-1-beta: 60% vs. 5% at 24 h). In situ the antigen is not expressed in normal and chronic inflammatory tissues. Acute inflammatory tissues, including contact and atopic dermatitis, psoriasis and periodontitis, however, show endothelial cells staining strongly positive. In contact eczemas at different times after elicitation (0, 6, 24, 72, 96 h), expression of the antigen is first seen after 24 h and is still strong at 96 h. These data indicate that LPS/TNF conduct an endothelial cell activation program in vitro, showing the same prolonged kinetics that is found for endothelial cell activation in the acute inflammatory process in vivo.

A monoclonal antibody reacting with endothelial cells of budding vessels in tumors and inflammatory tissues, and non-reactive with normal adult tissues.

This report describes a monoclonal antibody (MAb) generated by immunization of mice with cell suspensions of capillary-rich fragments of mammary carcinomas. The antibody (EN 7/44) belongs to the IgM class and detects a 30.5 kDa antigen which is found in the cytoplasm of human placental and umbilical vein-endothelial cells (HUVEC) and on the surface of tumor endothelium. Using indirect immunofluorescence and immunoperoxidase techniques, we did not find the MAb in peripheral blood cells or in any human cell lines tested, nor in endothelial cells from normal, nonproliferating adult tissues. Positively staining endothelium was found in the placenta, the umbilical vein and in proliferating normal tissues (intestine). Positive endothelial cells were found in acute inflammatory reactions and in tumors. In the latter, the strongest reactions were seen in newly formed budding capillaries, which were identified by their reactivity with Ulex europaeus I-lectin and antibodies against F VIII-RAG. In tumor tissues, large vessels could be positively stained with the EN 7/44 antigen, in contrast to inflammatory tissues. It is concluded that endothelial cells at the tip of a budding capillary express distinct phenotypic characteristics.

[Therapy of erythrosquamous dermatoses. Betamethasone dipropionate plus salicylic acid in comparison with betamethasone dipropionate solution]. / Therapie erythrosquamöser Dermatosen. Betamethason-Dipropionat plus Salizylsäure im Vergleich zu Betamethason-Dipropionat-Lösung.

Efficacy and tolerance of an alcoholic solution containing 0.64 mg betamethasone-dipropionate plus 20 mg salicylic acid (Diprosalic Solution) were compared with an alcoholic solution containing 0,64 mg betamethasone-dipropionate in a 3 week double blind study in 100 patients with psoriasis and other steroid-responsive dermatoses of dry nature, comprising scalp and other hairy and non-hairy areas of the body. This double blind study was followed by a 3 week open study in another 100 patients with similar diagnosis, using Diprosalic Solution only. Although the therapeutic results of the double blind study showed no significant differences between both treatment groups, distinct advantages of the drug containing salicylic acid could be clearly demonstrated, such as: 1. More rapid onset of action, 2. rapid clearing of scaling, pruritus and inflammation, 3. these advantages are in compliance with the fact that topically applied salicylic acid softens keratin, loosens cornified epithelium and desquamates the epidermis, making the underlying layers more accessible to the antiinflammatory steroid.