Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat monoclonal antibody MS-44B was raised against the dendritic human melanoma cell line SK-Mel 25 and detects highly dendritic cells and endothelial cells in various human organs. Among the cells recognized are dendritic cells in lymphoid organs, such as lymph node, tonsil and spleen, dendritic cells in skin, lung and lamina propria, (astro-)glial cells in the central nervous system and mesangial cells in the kidney. In peripheral lymph nodes (and less consistently in visceral lymph nodes), MS-44B reactive cells are found predominantly in the paracortical area and in the region of the marginal sinus; in tonsils these dendritic cells are concentrated at the outer rim of the follicle, while their distribution in the white pulp of the spleen is less well defined. In skin, both dermal and epidermal dendritic cells are stained. In the dermis just beneath the dermal-epidermal border, dendritic cells may be found with their processes protruding into the epidermal basal layer. MS-44B reactive epidermal dendritic cells send their processes in a horizontal direction or into the upper epidermal cell layers. MS-44B reactive epidermal dendritic cells are neither Langerhans cells, since they lack HLA-DR antigens and CD1, nor Merkel cells, since they lack cytokeratin expression. They rather seem to constitute a subpopulation of epidermal melanocytes that are low in tyrosinase expression and do not populate the melanocyte area of the hair bulb. With regard to the endothelium, monoclonal antibody MS-44B reveals marked heterogeneity in that it preferentially stains the endothelium of large and medium-sized arterial vessels, while capillary and venous endothelia are less well stained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoclonal antibody MS-44B reacts with human dendritic, glial and endothelial cells: differential expression of MS-44B antigen by epidermal dendritic cells and by MS-1+ splenic sinusoidal endothelial cells. An immunohistological study. 821 21

We established a retinal pigment epithelium-derived cell line from transgenic mouse harboring temperature-sensitive simian virus 40 T-antigen gene (tsSV40T) and examined its characteristics. We enucleated both eyes from a 2-month-old transgenic mouse and removed the retinal pigment epithelial (RPE) cells and neuroretinal cells. After cloning the RPE cells, we obtained a cell line (RPET). RPET cells grew well at 33 degrees C but not at 37 degrees C, expressing on the temperature-sensitive character of tsSV40T, and maintained characters of RPE cells such as T1-tyrosinase production, phagocytosis of rod outer segments, and presence of cytokeratin, microvilli on the cell surface and lysosome-like granules around the Golgi apparatus in the cytoplasm. Conditioned medium (CM) from a culture of neuroretinal cells harboring tsSV40T was essentially required for growth. The factor(s) in CM was heat-and acid labile, but was resistant to trypsin digestion. In the presence of 3% CM, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) and strong effects on RPET cells, whereas insulin, insulin-like growth factor I (IGF-I), and IGF-II had moderate growth effects. Interestingly, none of these growth factors stimulated the RPET cells in the absence of CM. EHS-Matrix had growth effect, whereas laminin, collagen types I and IV, and fibronectin had no marked growth effects on RPET cells. RPET cells were morphologically changed on a laminin-coated dish. They could not spread on the coated dish, and the majority of the cells floated. But when the floating cells were transferred to non-coated dishes, they immediately attached themselves. These results suggest that RPET cells are a good model for for finding novel growth factor(s) and for investigating the mechanism of cell-laminin attachment.
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PMID:A retinal pigment epithelium-derived cell line from transgenic mouse harboring temperature-sensitive simian virus 40 large T-antigen gene. 907 3

The pigment epithelium of the retina (RPE) is derived from the optic cup and is essential for function and development of the eye. We produced a transgenic mouse line that expresses simian virus (SV40) transforming sequences under control of the 1.4 kb tyrosinase-related protein 1 (TRP-1) promoter, targeting expression of T antigen (Tag) to the RPE. In transgenic embryos, RPE cells proliferated in the anterior part of the eye and near the optic nerve. This resulted in formation of tumors, which were pigmented and of epithelial origin. In 3 months-old mice, pigmented cells were detected in spleen and inguinal lymph nodes. In spleen, tyrosinase, TRP-1 and SV40 Tag were expressed and tyrosinase was enzymatically active. Pigmented regions were positive for an epithelial marker, cytokeratin. Cell lines were established from tumor and metastases and kept in culture for more than 2 months. These were pigmented, and maintained expression of tyrosinase, TRP-1, cytokeratin and SV40 Tag. This demonstrates that RPE tumor cells metastasize to lymph node and spleen. In conclusion, the metastasis from TRP-1/Tag RPE tumors towards spleen and lymph nodes serves as potential tool to investigate biology and metastasis of tumors derived from the pigment epithelium.
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PMID:Tumors of the retinal pigment epithelium metastasize to inguinal lymph nodes and spleen in tyrosinase-related protein 1/SV40 T antigen transgenic mice. 984 Sep 23

Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent. In an effort to characterize the roles of melanosomal proteins in human skin pigmentation, and to understand the underlying mechanism(s) of abnormal skin pigmentation, we have now generated polyclonal antibodies against the human melanocyte-specific markers, tyrosinase, tyrosinase-related protein (TYRP1), Dopachrome tautomerase (DCT) and Pmel17 (SILV, also known as GP100). We used these antibodies to determine the distribution and function of melanosomal proteins in normal human skin (adult and newborn) and in various cutaneous pigmented lesions, such as intradermal nevi, lentigo simplex, solar lentigines and malignant melanomas. We also examined cytokeratin expression in these same samples to assess keratinocyte distribution and function. Immunohistochemical staining reveals distinct patterns of melanocyte distribution and function in normal skin and in various types of cutaneous pigmented lesions. Those differences in the expression patterns of melanocyte markers provide important clues to the roles of melanocytes in normal and in disrupted skin pigmentation.
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PMID:Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions. 1154 13

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.
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PMID:Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature. 1516 28

Melanogenesis and melanosome transfer from the melanocytes to the neighboring keratinocytes are induced by ultraviolet radiation and modulated by autocrine and paracrine factors. Keratinocyte growth factor (KGF/fibroblast growth factor (FGF)7) is a paracrine mediator of human keratinocyte growth and differentiation. We evaluated the influence of KGF on melanosome transfer in co-cultures of keratinocytes and melanocytes. Immunofluorescence analysis using anti-tyrosinase and anti-human cytokeratin antibodies, phagocytic assays using fluorescent latex beads, and ultrastructural analysis indicated that KGF is able to induce melanosome transfer acting only on the recipient keratinocytes and as a consequence of a general role of KGF in the promotion of the phagocytic process. Inhibition of proteinase-activated receptor-2, to block the Rho-dependent phagocytic pathway, or of the Src family tyrosine kinases, to inhibit the Rac-dependent pathway, showed that KGF promotes phagocytosis through both mechanisms. Increased expression of the KGF receptor (KGFR) on the keratinocytes by transfection led to increased phagocytosis of latex beads following KGF treatment, suggesting that the KGF effect is directly mediated by KGFR expression and activation. Moreover, confocal microscopic analysis revealed that KGFR localize in phagosomes during KGF-induced phagocytosis, suggesting a direct role of the receptor in regulating both the early steps of uptake and the intracellular traffic of the phagosomes.
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PMID:Keratinocyte growth factor promotes melanosome transfer to keratinocytes. 1635 89

The authors describe 2 tumors that, to the best of their knowledge, are hitherto undescribed. The predominant cell type was small round to fusiform dark blue cells. The dark blue cells formed distinct epithelial cords with gland-like formations with mucicarmine-positive mucus. Another distinctive component of the tumors was a mesenchymal one. The mesenchymal areas appeared benign and could be likened to a fibroma having a densely collagenous stroma, or they had spindle cells set in the myxoid background, rendering a myxoma-like appearance. Another distinctive feature was ganglion cell differentiation. Mitotic figures, including atypical forms, were found only in the small cell component. All cells were immunohistochemically negative for actin, calponin, desmin, HMB45, neurofilament protein, CD99/MIC2, Melan A, tyrosinase, serotonin, CD56, Melan A, GFAP, and S-100 protein. Cytokeratin, synaptophysin, FLI1 protein, and chromogranin antibodies reacted only in the primitive small round cells, while all the other components were cytokeratin negative. Fluorescence in situ hybridization showed that the tumors are without the EWSR1 gene translocation and gain 12p. Ultrastructurally, the cells were endowed with well-formed intercellular desmosomes membrane-bound secretory in the cytoplasm. Granules were found in the cytoplasm. We suggest the name "primitive small cell tumor with epithelial, gangliocytic, neuroendocrine, and mesenchymal differentiation" for this neoplasm.
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PMID:Primitive small cell tumor with epithelial, gangliocytic, neuroendocrine, and mesenchymal differentiation: report of 2 cases. 1791 55

Melanoma can show a broad spectrum of immunoreactivity and exhibit aberrant expression of antigens or changes in immunophenotype, particularly at metastatic sites. We studied 70 primary melanomas and their metastases with a broad panel of immunohistochemical markers using a tissue microarray technique to determine possible antigenic shift between the primary lesions and their metastases. Representative tissue cores were taken and processed from each case, and the tissue microarrays were stained by standard methods using antibodies to vimentin, bcl-2, CD117, carcinoembryonic antigen, epithelial membrane antigen, S-100 protein, HMB-45, cytokeratin AE1/AE3, Melan-A, TTF-1, CD99, and tyrosinase. Histologically, all the melanomas were of the classic epithelioid type. A slight increase in the expression of Melan-A was noted in metastatic lesions as opposed to the primary tumors (63% vs. 48.4%). Expression of other melanoma-associated markers, including S-100 protein and tyrosinase was only slightly decreased at metastatic sites as opposed to the primary tumor. Increased aberrant expression of epithelial-associated markers, including epithelial membrane antigen and cytokeratin AE1/AE3 was also noted in the metastases. bcl-2, CD117, and TTF-1 also showed a modest increase in antigenic expression at metastatic sites over the primary lesions. The results of this study demonstrated minimal antigenic shift between primary and metastatic melanoma for some of the more conventional melanocytic markers, it showed increased expression of aberrant markers and oncogene expression at metastatic sites.
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PMID:Expression of immunohistochemical markers in primary and metastatic malignant melanoma: a comparative study in 70 patients using a tissue microarray technique. 1809 85

Epithelioid angiomyolipoma (eAMLoma) is an uncommon renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis (TSC). It is composed of polygonal large-sized tumor cells arranged in an epithelioid manner. Differential diagnosis from renal cell carcinoma (RCC) is often challenging because of its epithelioid morphology. Herein is reported three cases of eAMLoma, involving one in a 28-year-old man with TSC and two in women without TSC (34 and 62 years of age, respectively). The male TSC patient had microscopic conventional AMLomas in the same kidney. All patients were positive for melanoma (reactive with HMB45 antibody, and positive for melan A, tyrosinase and microphthalmia transcription factor) and smooth muscle markers (positive for alpha-smooth muscle-specific actin), but not for epithelial markers (cytokeratin, epithelial membrane antigen). In particular, the translocation RCC is an important differential diagnostic candidate, in terms of the positive reaction with HMB45 and morphological similarity. The present tumor samples did not show any reactivity for transcription factor binding to IGHM enhancer 3 or transcription factor EB, which excluded the possibility of translocation RCC. The possibility of eAMLoma should be evaluated as a diagnostic candidate, especially in cases of renal tumors (i) in young patients; (ii) associated with TSC; or (iii) with an epithelioid morphology and a high nuclear grade.
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PMID:Epithelioid angiomyolipoma of the kidney. 1912 Oct 90

Traditionally, immunology has considered a meaningful antibody response to be marked by large amounts of high-affinity antibodies reactive with the specific inciting antigen; the detection of small amounts of low-affinity antibodies binding to seemingly unrelated antigens has been considered to be beneath the threshold of immunological meaning. A systems-biology approach to immunology, however, suggests that large-scale patterns in the antibody repertoire might also reflect the functional state of the immune system. To investigate such global patterns of antibodies, we have used an antigen-microarray device combined with informatic analysis. Here we asked whether antibody-repertoire patterns might reflect the state of an implanted tumor. We studied the serum antibodies of inbred C57BL/6 mice before and after implantation of syngeneic 3LL tumor cells of either metastatic or non-metastatic clones. We analyzed patterns of IgG and IgM autoantibodies binding to over 300 self-antigens arrayed on slides using support vector machines and genetic algorithm techniques. We now report that antibody patterns, but not single antibodies, were informative: 1) mice, even before tumor implantation, manifest both individual and common patterns of low-titer natural autoantibodies; 2) the patterns of these autoantibodies respond to the growth of the tumor cells, and can distinguish between metastatic and non-metastatic tumor clones; and 3) curative tumor resection induces dynamic changes in these low-titer autoantibody patterns. The informative patterns included autoantibodies binding to self-molecules not known to be tumor-associated antigens (including insulin, DNA, myosin, fibrinogen) as well as to known tumor-associated antigens (including p53, cytokeratin, carbonic anhydrases, tyrosinase). Thus, low-titer autoantibodies that are not the direct products of tumor-specific immunization can still generate an immune biomarker of the body-tumor interaction. System-wide profiling of autoantibody repertoires can be informative.
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PMID:A systems immunology approach to the host-tumor interaction: large-scale patterns of natural autoantibodies distinguish healthy and tumor-bearing mice. 1955 35


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