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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antigen expression was studied by immunohistochemistry in 133 human melanocytic skin lesions to gain insight into the initial steps of tumor development, i.e. in particular the change from melanocytes to benign nevi. We refer to the proposed progression model of Clark and co-workers. The following types of antigens were investigated: (i) intermediate filament antigens (vimentin), (ii) melanoma-associated antigens (HMB-45, NKI/C3, MA-930, LS59), (iii) proliferation-associated antigens (S-100, Ki67, Ro/SSA, calmodulin), (iv) progression-associated antigens (HLA-DR, ICAM-1), and (v) basal membrane antigens (bullous pemphigoid antigen, laminin, fibronectin, collagen type IV). The intensity of expression and the topography of immunoreactive pigment cells were compared with the stage of tumor progression. Special attention was paid to the early steps of this process, i.e. the disturbance of the epidermal melanin unit and the development of melanocytic ("nevocellular")nevi. A dramatic shift of antigen expression (antigen types [i] to [v]) was noted in benign nevi compared with melanocytes. Nevi with cellular atypia disclosed a tendency towards an increased percentage of tumor cells reactive for melanoma- and progression-related antigens (types [ii] and [iv]). However, there was no clear cut level of distinction of antigen expression (types [i] to [v]) between benign and primary malignant melanocytic tumors. So-called dysplastic nevi resembled benign tumors or melanocytes rather than malignant melanoma. Metastatic melanoma of skin showed a relatively high number of Ki67-positive, cycling melanoma cells. The results have a bearing on the concepts of melanocytic nevus ontogenesis and "maturation". It appears that melanocytes lose maturity on their way down to the dermis in contrast to traditional concepts (Abtropfung); this might be of importance for our understanding of melanoma development in association with melanocytic nevi. Our findings are discussed with regard to Clark's model of tumor progression.
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PMID:The initial steps of tumor progression in melanocytic lineage: a histochemical approach. 174 97

Solubilized interstitial collagens will form a fibrillar, gel-like lattice when brought to physiologic conditions. In the presence of human dermal fibroblasts the collagen lattice will contract. The rate of contraction can be determined by computer-assisted planemetry. The mechanisms involved in contraction are as yet unknown. Using this system it was found that the rate of contraction was markedly decreased when collagen lacking telopeptides was substituted for native collagen. Histidinohydroxylysinonorleucine (HHL) is a major stable trifunctional collagen cross-link in mature skin that involves a carboxyl terminal, telopeptide site 16c, the sixteenth amino acid residue from the carboxy terminal of the telopeptide region of alpha 1 (I) in type I collagen. Little, if any, HHL was present in native, purified, reconstituted, soluble collagen fibrils from 1% acetic acid-extracted 2-year-old bovine skin. In contrast, HHL cross-links were present (0.22 moles of cross-link per mole of collagen) in lattices of the same collagen contracted by fibroblasts. However, rat tail tendon does not contain HHL cross-links, and collagen lattices made of rat tail tendon collagen are capable of contraction. This suggests that telopeptide sites, and not mature HHL cross-links per se, are essential for fibroblasts to contract collagen lattices. Beta-aminopropionitrile fumarate (BAPN), a potent lathyrogen that perturbs collagen cross-linking by inhibition of lysyl oxidase, also inhibited the rate of lattice cell contraction in lattices composed of native collagen. However, the concentrations of BAPN that were necessary to inhibit the contraction of collagen lattices also inhibited fibroblast growth suggestive of cellular toxicity. In accordance with other studies, we found no inhibition of the rate of lattice contraction when fibronectin-depleted serum was used. Electron microscopy of contracted gels revealed typical collagen fibers with a characteristic axial periodicity. The data provide evidence that collagen telopeptide sites play a role in collagen gel lattice contraction.
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PMID:Collagen telopeptides (cross-linking sites) play a role in collagen gel lattice contraction. 187 57

The functional properties of the melanoma-associated antigens detected by monoclonal antibodies (MAbs) AMF-6 and AMF-7 were investigated. These MAbs were selected previously because of their capacity to block the anti-melanoma reactivity of cytotoxic T-lymphocyte clones AMF-6 and AMF-7 detect a melanoma-associated proteoglycan (MW greater than 450-250 kDa) and a molecular complex, which under reducing conditions consists of 4 compounds of 120, 95, 29 and 25 kDa respectively. AMF-6 reacted strongly with all 30 cultured melanomas and all 41 melanomas in frozen tissue sections. Significant cross-reactivity was only observed with nevi and perineurium, whereas normal skin melanocytes were negative. AMF-7 reacted with all 25 cultured melanomas and all 34 melanomas in frozen sections. AMF-7 cross-reacted with a proportion of nevi and endothelial cells from small vessels. The antigen detected by AMF-6 and AMF-7 could not be modulated by retinoic acid or recombinant gamma-IFN, which induced or enhanced the expression of HLA-DR, HLA-DQ and Class-I MHC antigens. In addition, the antigens were not readily modulated when cells were incubated in excess amounts of AMF-6 and AMF-7. Interestingly, the antigen detected by AMF-7 was strongly associated with the adhesion and cytoplasmic spreading of melanoma cells to plastic surfaces and monolayers of vascular endothelial cells. AMF-6 did not block the adhesion of melanoma cells but delayed cytoplasmic spreading. Both AMF-6 and AMF-7 blocked fibronectin-induced chemotaxic motility and chemokinesis of melanoma cells. In addition to their membrane localization, the antigens detected by AMF-6 and AMF-7 were also abundant in extracellular adhesion plaques deposited by cultured melanoma cells. Our results indicate that the high-MW melanoma-associated proteoglycan and the antigen detected by AMF-7 are associated with adhesion and/or cytoplasmic spreading and motility of human melanoma cells, suggesting that these antigens are associated with the (hematogenic) dissemination of human melanoma. This is supported by the finding that AMF-7 stained primary tumors heterogeneously, whereas metastases were homogeneously stained.
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PMID:Characterization of melanoma-associated surface antigens involved in the adhesion and motility of human melanoma cells. 242 58

The arrays of proteins adsorbed from plasma onto a series of polystyrene copolymeric latexes were analyzed by enzyme-linked immunosorbent assay (ELISA) of washed beads and immunoblotting of proteins desorbed from the beads and separated by polyacrylamide gel electrophoresis (PAGE). Beads were prepared by continuous emulsion polymerization in the absence of surfactant. Coomassie brilliant blue staining of gel electropherograms of desorbed proteins indicated that the presence of small amounts of comonomers (1 to 10 mole %) significantly influenced the composition of the adsorbed protein layer. Immunoblotting revealed that fibrinogen, fibronectin, and vitronectin were adsorbed by all surfaces investigated. C3 and Clq adsorption varied significantly with copolymer composition. The ELISAs revealed that although the concentrations of vitronectin and fibronectin in plasma are similar, the extent of vitronectin adsorption from 70% to 85% plasma was greater by two orders of magnitude than fibronectin adsorption. Vitronectin adsorbed on carboxylic acid-containing copolymers reacted more strongly with a conformationally sensitive antivitronectin monoclonal antibody (MoAb) than vitronectin adsorbed to polystyrene and was more susceptible to cleavage by plasma proteases(s). The results show that vitronectin is a major protein adsorbed from concentrated plasma and that small changes in the chemical composition of a copolymer profoundly affects the extent and nature of protein adsorption from complex mixtures such as plasma.
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PMID:Identification of vitronectin as a major plasma protein adsorbed on polymer surfaces of different copolymer composition. 247 28

Hyaline globular inclusions were found in a case of malignant melanoma. The globules were both intracellular and extracellular in the primary neoplasm and in metastases to lymph nodes, liver, and lung. They were studied immunohistochemically and were found to contain fibronectin, a glycoprotein of high molecular weight. Ultrastructurally, the globules were composed of electron-dense, finely fibrillar aggregates. It is suggested that the neoplastic cells produced the fibronectin, which accumulated in globular form. Ten additional cases of malignant melanoma were studied; none of these had hyaline globules or intracellular globular fibronectin. The globules were compared to similar structures described in Spitz's nevi and other neoplasms. Immunohistochemical analysis was most useful in distinguishing the globules found in the malignant melanoma from those found in other conditions.
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PMID:Fibronectin-containing hyaline globules in malignant melanoma. 248 47

Fibrinogen and plasma fibronectin were shown to interact in the presence of factor XIIIa. The reaction was enhanced by dithiothreitol and was accompanied by an increase in the turbidity of the solution and the formation of particulate matter and gel structures. At a constant concentration of fibrinogen the turbidity increase was dependent on the fibronectin concentration and at a constant concentration of fibronectin, on the fibrinogen concentration. Kinetic experiments showed that an initial step in the reaction between fibrinogen and fibronectin was the formation of a transient intermediate containing 1 mole of fibrinogen and 1 mole of fibronectin. Transient intermediates of larger molecular weight and containing both fibrinogen and fibronectin were also formed. These heterooligomers eventually reached huge molecular sizes and at early times formed particulate matter that sedimented on centrifugation. The predominant molecular species formed in an equimolar mixture of fibrinogen and fibronectin were heteropolymers. Small amounts of homopolymers composed of fibrinogen and possibly also homopolymers of fibronectin were detected. The results are discussed in terms of reaction mechanism and potential importance of this novel oligomerization pathway in haemostasis, thrombosis and tissue repair.
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PMID:Factor XIII catalyzed formation of fibrinogen-fibronectin oligomers--a thiol enhanced process. 286 45

Dermal nevus cells in the skin are surrounded by electron-dense deposits resembling a basement membrane (BM), and epidermal melanocytes rest on the epidermal BM. Using antibodies directed against various BM components, we have determined that the BM-like structure surrounding nevus cells in vivo contains type IV collagen, laminin, and BM-1 proteoglycan, analogous to BM throughout the body, but not bullous pemphigoid antigen or epidermolysis bullosa acquisita antigen that are keratinocyte-associated proteins present in the epidermal BM. Moreover, in vitro, both nevus cells and melanocytes derived from adult donors display intracellular and extracellular fibronectin, BM-1 proteoglycan, type IV collagen, and laminin. In contrast, newborn melanocytes maintained under identical culture conditions display none of these BM components, emphasizing the influence of donor age on cell behavior. The data suggest that dermal nevus cells manufacture a BM in vivo, as do certain other neural crest-derived cells. The apparent shared ability of cultured nevus cells and melanocytes to synthesize BM components, coupled with other previously noted behavioral and morphologic similarities in vitro, suggests that these cell types are very closely related; and that morphologic or histochemical differences present in vivo are the result of environmental influences rather than intrinsic differences.
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PMID:Human nevocellular nevus cells are surrounded by basement membrane components. Immunohistologic studies of human nevus cells and melanocytes in vivo and in vitro. 327 59

Limited proteolysis of porcine plasma fibronectin by the 56 kDa proteinase (56K proteinase) (EC 3.4.24.4) from Serratia marcescens released six polypeptides: a 27 kDa peptide, the heparin-binding domain which comprises the NH2-terminal end; a 50 kDa peptide, a mid-molecule that mediates binding to gelatin or collagen; a 160 kDa peptide, that contained the heparin-binding domain with cell-spreading activity; and a 140 and a 20 kDa peptide which released from the 160 kDa peptide. Each fragment was purified and characterized by its chemical and biological properties, and it was found that they were respectively different domains. Both the 160 and the 140 kDa peptide contained one cysteine per mole of peptide. The 160 kDa peptides were connected by a 6 kDa peptide, which was present at the COOH-terminal end of the molecule and was biologically inactive. Only 6 kDa peptide contained a disulfide bond and produced 3 kDa peptide after reduction, whereas other fragments did not change with or without reduction on SDS-polyacrylamide gel electrophoresis. NH2-terminal sequence analyses of the released peptides showed that the 56K proteinase cleaved the fibronectin between the Arg-Thr (located at two different sites), Leu-Ser and Gln-Glu bonds. Out of 118 Arg residues, there are nine sequences containing Arg-Thr, and two of them near or at an interdomain location (at Arg 259 and 2239) were cleaved. Out of 124 Leu residues, there are 11 Leu-Ser sequences and only one, at 687, was cleaved. The above fragments with functional domain activity could be aligned according to the previously reported amino-acid sequence of human or bovine plasma fibronectin. The treatment of fibroblast cells by the 56K proteinase resulted in loss of morphological integrity and extracellular matrix.
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PMID:Interdomain cleavage of plasma fibronectin by zinc-metalloproteinase from Serratia marcescens. 328 20

Two thrombin independent reactions involving polymerization and gelation of fibrinogen (FBG) and of FBG and fibronectin (FN) are described. In the first reaction FXIII, in the presence of calcium ions, induces oligomerization and eventually complete gelation of FBG, i.e. formation of fibrinogenin. FBG dimers and probably also higher oligomers are formed by the crosslinking of gamma-chains prior to gelation. During gelation the A alpha-chains also become completely crosslinked. These reactions are enhanced by a variety of thiol compounds. With DTT, reduction of specific disulfides in the A alpha-chain of FBG appear to be responsible for the enhancement. In the second reaction, FXII catalyzes the formation of heteropolymers of FBG-FN. These complexes eventually form visible particulate matter called heteronectin. Dimers consisting of 1 mole FBG and 1 mole FN form first, followed by the appearance of higher order heteronectin intermediates. In heteronectin the A alpha-chain of FBG provides the linkage to FN. Thiols also enhance the heteronectin reaction. Formation of fibrinogen and/or heteronectin depends upon the initial relative concentrations of FBG and FN. At equimolar concentrations mainly heteronectin is formed. During clotting of normal whole blood, thrombin induced fibrin formation is the initial event followed by rapid fibrinogen formation. Addition of iodoacetamide (an inhibitor of FXIII) to whole blood prevents the formation of fibrinogenin. These findings suggest that the fibrinogen pathway is important in vivo.
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PMID:Alternative pathways in blood coagulation. 360 76

Nevus cells are of biologic interest because of their uncertain relationship to epidermal melanocytes and of clinical interest because of their statistical association with melanoma. We report a technique that allows reliable cultivation of nevus cells from small acquired and congenital nevi and permits in vitro characterization of this cell type. Morphologically, cultured nevus cells were found to closely resemble epidermal melanocytes from the same or comparably aged donors, manifesting marked dendricity and specific ultrastructural features characteristic of melanocytes; but could be distinguished by the presence of occasional large binucleate or trinucleate cells and by the frequent finding of grouped melanosomes in nevus cell cytoplasm. Growth kinetics were also similar for nevus cells and epidermal melanocytes, with population doubling times of 1-2 weeks in hormone-supplemented serum-free medium, and substantial growth enhancement by fetal bovine serum. As previously noted for epidermal melanocytes, nevus cells in serum-free culture demonstrated striking substrate responsiveness, with far greater attachment rates and degree of cytoplasmic spreading on fibronectin or type I/III collagen than on laminin, type IV collagen, or uncoated plastic. These strong similarities in vitro suggest that morphologic and behavioral differences observed between epidermal melanocytes and nevus cells in the skin may result from local environmental influences rather than from intrinsic cellular differences. The availability of a satisfactory culture system for nevus cells may facilitate future investigations into their malignant potential and other biologic features.
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PMID:Characteristics of cultivated adult human nevocellular nevus cells. 372 58


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