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)

Conley et al., in 1971, described a special type of melanoma characterized by a superficial melanic lesion at the onset; repeated local relapses as subcutaneous tumorations with an histological picture closely resembling an atypical fibroxantoma or fibrosarcoma. After a review of all the published material the autors presents a personal case with the clinical, histological and evolutive characteristics of this disease. The most interesting findings of the published case are the following: The special stains for the melanocytes (silver stain, Dopa, tyrosinase and cholinesterase) were all negative. There was an intense positivity for the lisosomal enzymes (non specific sterases, and acid phosphatases). The ultrastructural study of the tumoral tissues as well as the cells of cultures showed abundant cells with tumoral aspects, with prominent nucleoli somewhat dilated granular endoplasmic reticulum, myelin-like figures, lipidic vacuoles and abundant lisosomes. No melanosomes or premelanosomes were observed. Beside these tumoral cells abundant typical fibroblastic elements were found. There was a great amount of collagen fibers with periodicity superior to the normal. The conclusion is that the desmoplastic melanoma must be considered as a tumor of mesenchimatous origin intervening in its development multiple local and general factors.
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PMID:[Desmoplastic melanoma]. 34 19

To elucidate the interaction between melanoma and its matrix, we cultured B16 murine melanoma cells on and in type I collagen gel and evaluated specified functions of melanoma cells; tyrosinase activity and melanin-synthesizing capacity. Proliferation of cells cultured in these environments was markedly suppressed compared with that of cells cultured conventionally on plastic. On the other hand, the tyrosinase activity of cells cultured in or on collagen gel was two to three times higher than that of cells cultured on the plastics, while their melanin production was approximately double that achieved during conventional culture of cells. In conclusion, collagen gel influenced the growth and cell-specific functions of the melanoma cell. The culture system using collagen gel as substrate may be useful for the investigation of the interaction between melanoma and its matrix.
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PMID:Enhanced melanogenesis of murine melanoma cells cultured on or in collagen gel. 211 20

1. Melanophores and xanthophores are pigment cell derivatives of the NC. In amphibian embryos they migrate from their original position on the neural tube dorsally (into the dorsal fin) as well as laterally (between somites and epidermis) and arrange themselves into typical pigment patterns of the skin. We investigated pigment pattern formation in two species of tailed amphibians, Triturus alpestris (alpine newt) and Ambystoma mexicanum (Mexican axolotl). In larvae of T. alpestris alternating longitudinal stripes or bands of melanophores and xanthophores develop, whereas in larvae of A. mexicanum a barred pattern with alternating transverse bands of melanophores and xanthophores is formed. Iridophores, a third type of pigment cell, are present later in both species and therefore play no role during early larval pigment pattern development. Visibly differentiated melanophores and xanthophores can be distinguished from each other under the light microscope by their contents of black melanins and yellow pterins respectively. With the dopa reaction (indicates tyrosinase in melanophores), and ammonia treatment (stimulates pterin fluorescence in xanthophores), the pigment cell phenotypes can be visualized even before their normal visible differentiation. In the TEM, melanophores and xanthophores can be distinguished from each other by their morphologically distinct pigment organelles and in the SEM by their different surface structure. 2. Because of the NC origin of melanophores and xanthophores and the ease with which these cells can be demonstrated even before they are visible from outside, their different arrangements in Triturus and axolotl embryos offer suitable model systems for studying the migration, interaction and localization of NC derivatives in relation to specific environmental influences. The environment of NC cells are the neural tube, epidermis, somites and lateral plate mesoderm, and the subepidermal ECM, a network of collagen fibrils associated with glycosaminoglycans, proteoglycans and glycoproteins. 3. Development of the pigment pattern in T. alpestris: Melanophores and xanthophores start to leave the NC at stage 28, melanophores slightly earlier than xanthophores. Both cell types become scattered in the dorsolateral trunk. In contrast to melanophores in the axolotl, melanophores in T. alpestris cannot be demonstrated with the dopa reaction before they become visibly black. From stage 29+ onwards, melanophores start to accumulate in zones alongside the dorsal and lateral somite edges, where they form compact stripes later. Xanthophores can be demonstrated from stage 28+ onwards only with the SEM (by means of their specific surface structures) or with the fluorescence microscope (by means of their fluorescing pterins). At state 34, xanthophores become visible externally as yellow cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The development of the larval pigment patterns in Triturus alpestris and Ambystoma mexicanum. 236 40

Cancer's random, reversible, unstable transitions to "normal" structures imply their functional relation. Similar random, continuous, reversible oncogene "mutational transformation" also lacks a consistent hybrid. Positing cancer's "mutationally altered genotype" leads to medically foreign causes, qualities, inducers, suppressors, immune proteins, and viruses. Its random variation, however, opposes the functionally discrete, ordered, stable, irreversible hybrid variation and single-valued transforms of molecular genetics. There, "causal mutational operators" remain unspecified; only consistent single-valued DNA base and amino acid change, as "transform operand", are made explicit. A mitotically "blocked" (normal) and "unblocked" (malignant) stem cell "phenotype", operationally constructed from microscopic data, is therefore viewed within the homeostatic context of open-system enzyme-regulatory equilibrium. This functional, stochastic field distribution between "structurally bound" and "freely dividing" stem cell number discloses their putative regulatory mitotic-blocking factor. A tyrosinase complex, interacting by Cu2+-Fe2+ chelation with a proline hydroxylase divisional enzyme near stem cell ribosomes, maintains steady-state mitotic equilibrium. Based upon familiar medical, biochemical, and energy principles this confronts cancer's pigmentary-depigmentary signs, glycolytic metabolism, elevated serum tyrosinase, defective collagen production, exposed membrane binding sites, and tyrosine's recent growth control role.
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PMID:A membrane-specific tyrosinase chelate: the mitotic regulator? 311 30

Choroidal melanocytes and the retinal pigmented epithelium (RPE) were studied morphologically and histochemically in the Smyth chicken, an avian model for human vitiligo. The sequence of cytological events occurring in the ocular tissue of minimally depigmented Smyth birds was determined. Abnormalities of melanocytes and the associated inflammation was least severe in peripheral areas of the choroid and most pronounced in the back of the eye at the base of the optic nerve head. In the peripheral choroid, morphologically normal melanocytes and an occasional mononuclear leukocyte were observed. However, some of these morphologically normal melanocytes histochemically demonstrated atypical tyrosinase activity at the trans area of the Golgi apparatus. Toward the back of the eye, the melanocytes first appeared swollen and had retracting dendrites. Ultrastructurally these melanocytes demonstrated an increase in extramelanosomal cytoplasm. Later, melanocytes became spherical and had membrane bound, autophagosome-like compartments of pigment granules. As the melanocyte injury progressed, macrophages invaded the tissue and phagocytized melanocytic dendrites. These were followed by numerous plasma cells. Eventually, the back of the eye contained no pigment and was infiltrated with numerous mononuclear inflammatory cells. The retinal pigment epithelium also demonstrated a gradient in the degree of destruction, related to its topography. These cytological features consisted of the retraction of apical RPE processes, the disappearance of the basal plasma membrane infoldings, and the replacement of Bruch's membrane by collagen-like fibrils. These results demonstrate that the uveitis which develops in vitiligo appears to be a consequence of an inherent choroidal melanocyte defect.
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PMID:Ocular pathology in the minimally depigmented subline of the vitiliginous Smyth chicken. 314 18

All-trans retinoic acid is used topically for treating a variety of dermatologic conditions ranging from acne to photoaged skin. Although the clinical effects of retinoic acid treatment are often considerable, relatively little is known about the basic mechanisms underlying such effects. With the development of an in vivo human assay we have investigated the pleiotypic effects of topical retinoids from the histologic to the molecular. Histologically, retinoic acid induces epidermal proliferation and differentiation coupled with dermal fibroblast production of collagen. Immunologic effects include stimulation of the antigen-presenting capacity of Langerhans cells and induction of keratinocyte ICAM-1 expression. At the biochemical level, retinoic acid regulates transglutaminase and tyrosinase activities and activates protein kinase C. Both polar metabolites and stereoisomers of all-trans retinoic acid are also biologically active. Molecular biologic techniques have revealed that elevation of mRNA for cellular retinoic acid binding protein II is a retinoid-related event and that nuclear receptors such as retinoic acid receptors and retinoid X-receptors may transduce the retinoid response.
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PMID:Human in vivo pharmacology of topical retinoids. 772 37

Photoaging is primarily composed of wrinkling, mottled hyperpigmentation and a tactile roughness of the skin, all three of these parameters improve following use of topical retinoids. It appears that smoothening of the skin results from a combination of epidermal changes including thickening, stratum corneum compaction and glycosaminoglycan deposition. Lightening of actinic lentigines and mottled hyperpigmentation correlates with a reduction in epidermal melanin content maybe resulting from inhibition of tyrosinase activity. Effacement of wrinkling in mice correlates with new collagen synthesis, and there is evidence that this is also the case in humans. An irritant dermatitis is a feature of retinoid-treated skin but this diminishes in severity during treatment despite continued improvement in photoaging. Thus it is unlikely that irritation per se is responsible for clinical improvement.
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PMID:Topical retinoic acid for photoaging: clinical response and underlying mechanisms. 814 14

Several studies have indicated that extracellular matrix (ECM) proteins can influence melanocyte behaviour in vitro. However, the choice of medium is known to have a profound effect on melanocyte behaviour and it is currently difficult to ascribe which reported effects are due to ECM proteins and those which are attributable to the medium used in these different studies. The purpose of this study was to learn more about the influence of ECM proteins on melanocyte function by examining a range of cell-derived and individual ECM proteins for their impact on melanocyte tyrosinase activity in cells cultured under conditions of varying mitogenic drive. We found that ECM derived from human dermal fibroblasts, bovine endothelial cells and a human endothelial cell line as well as collagen I, collagen IV, fibronectin, and to a lesser extent laminin, were all capable of increasing tyrosinase activity in cultures of normal melanocytes. Effects of these ECM were seen most consistently in media with relatively few mitogens, for example ECM proteins influenced melanocyte morphology and this was seen most readily in cells cultured in medium without any mitogens (which ordinarily fails to support melanocyte survival). This study illustrates that ECM proteins can influence melanocyte morphology, proliferation, and tyrosinase activity in vitro and supports a possible role of ECM proteins in the regulation of melanocyte function in vivo.
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PMID:Investigation of the influence of extracellular matrix proteins on normal human melanocyte morphology and melanogenic activity. 897 8

Age-related macular degeneration is one of the most serious diseases in elderly people because of its disasterous visual outcome and its prevalence. Even if the submacular and choroidal neovascular membranes could be surgically excised, severe damage or evacuation of retinal pigment epithelium is inevitable in the operated area. Pigmentary dystrophy is also a devastating hereditary eye disease with severe visual disturbance. Up to now, there have been no effective treatments for either of them. We conducted basic experiments on retinal pigment epithelium (RPE) culture, transplantation of the cells to the subretinal space of animals, especially, the Royal College of Surgeon's (RCS) rat, a model of hereditary retinal degeneration, and observed their effects in preventing photoreceptor cell death. 1) We reviewed recent reports of RPE function in relation to cytokine production and autocrine/paracrine function of these ligands. Some cytokines with strong mitogenic effects as nerve trophic/growth factors were able to rescue photoreceptor cell death in dystrophic, ischemic, and light-damaged retinas in the rats. We transplanted allograft pigmented RPE from Long Evans rats or xenograft, human and bovine RPE into the subretinal space of RCS rats, and could observe the retardation of the photoreceptor cell death. 2) As a source of human transplantable RPE in clinical practice, we could use patients' own RPE cells as autografts or those from aborted human fetus eyes as allografts. At present, we cannot use RPE cells from different species as xenografts. We tried to obtain enough RPE cells for culture in vitro from patients with large or giant retinal tears, but were unsuccessful. Cells were easily obtained from fetus eyes, and could be cultured and transplanted as fresh, primary, or multiple passage cells. We also tried cryopreservation of these cells for up to 3 months. Enzymatic expression of tyrosinase, tyrosinase related protein I and II and some other enzymes was examined by proliferating chain reaction to detect possible transformation during the procedure. The cell characteristics were well preserved. In the future, if these RPE cells could be safely kept and available in deep-frozen condition, we could use them clinically at the appropriate time and in appropriate numbers for patients as an "RPE bank" just like an "eye bank" for corneal transplantation. 3) Immunological reaction is very important if we consider this technique for clinical application. Up to now, in experimental animals, no immunological reaction has been reported even for xenograft human RPE in rats, in funduscope and histological examination, because the intraocular space is an immunologically privileged site. But transplantation of human RPE cells with a collagen sheet into the anterior chamber in rabbits caused a definite reaction detected by suppression of the electroretinogram and macrophage infiltration into the subretinal space, not only in the operated eye but also in the contralateral non-operated eye. These results suggest that we must be cautious in clinical use of heterogeneous RPE transplantation. The expression of MHC class II cells was observed in the course of photoreceptor cell degeneration in the RCS rats but it was suppressed if they were rescued by the transplantation of human cultured RPE in these animals. 4) For clinical application of this technique, autografts are naturally much better than the xeno grafts or allografts. We tried to use iris pigment epithelium (IPE) for transplantation because it consists of pigmented cells of neural origin and enough could be obtained with ease by peripheral iridectomy. We also tried transfection of a vector (pCNX2) or vector-inserted cDNA of rat bFGF into the rat IPE and transplanted into the subretinal space of RCS rats. These transfected cells expressed strong mRNA of bFGF. The photoreceptors were well preserved and immunological reaction could not be detected by funduscopical or histological examinat
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PMID:[Retinal pigment epithelial cell transplantation: perspective]. 902 10

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


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