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A Slominski

Publications and source records attributed to A Slominski.

At least 73 records · Page 4Linked to original sources
PubMed1995

Choriocarcinoma presenting as a cutaneous metastasis.

The rare presentation of choriocarcinoma as a cutaneous metastasis in a 23-year-old male is reported. Histological and immunohistochemical analysis of the biopsy material demonstrated two distinct cell populations, syncytiotrophoblasts and cytotrophoblasts, with syncytiotrophoblasts strongly positive for human chorionic gonadotropin antigen. Subsequent clinical evaluation revealed a testicular tumor with metastases to lungs, brain, liver and kidney and increased serum levels of human chorionic gonadotropin. The patient died shortly after diagnosis due to complications of metastatic disease despite chemotherapy.

Adult↗
PubMed1994

Mast cell involvement in murine hair growth.

We have examined the possibility that an involvement in hair growth regulation is one of the still obscure physiological roles of mast cells (MC) in normal skin. Using the murine hair cycle as a model, we first studied the number, localization and granulation status of skin MC during the hair cycle of C57 BL-6 mice. Shortly after the induction of hair growth (anagen) in the back skin of mice with resting (telogen) follicles, a sharp decline in the number of Giemsa-stainable MC was detected by morphometry. This was evident in depilation-induced, pharmacologically induced, and spontaneous anagen. By light and electron microscopy, the anagen-associated decline was correlated with the occurrence of substantial MC degranulation. In vivo, the IgE-independent MC secretagogues, compound 48/80 and ACTH, induced anagen in mouse telogen follicles after intracutaneous administration, while inhibitors of mast cell degranulation (cromoglycate, tiacrilast) and antagonists of selected MC products (clemastin, ranitidine, ketanserin) significantly retarded the induced development of anagen follicles in these mice. It is suggested that MC act via their secretory products as stimulators of anagen development in mice and that the murine hair cycle is an excellent model for studying growth regulatory functions of MC in developmentally regulated systems.

Animals↗
PubMed1994

Towards defining receptors for L-tyrosine and L-dopa.

We postulate that in mammalian systems neurotransmitter and hormone-like functions of L-tyrosine (LT) and L-DOPA (LD) are mediated via specific membrane-bound and/or nuclear receptors. The structure and function of these receptors may represent an evolutionary continuum of regulatory proteins binding LT or LD in unicellular and lower multicellular organisms.

Animals↗
PubMed1994

Melanogenesis during the anagen-catagen-telogen transformation of the murine hair cycle.

Melanin synthesis of follicular melanocytes is strictly coupled to the growth stage of the hair cycle (anagen), ceases during follicle regression (catagen), and is absent throughout the resting stage (telogen). Having previously characterized the expression and activity of melanogenesis-related proteins during the telogen-anagen transition of the murine hair cycle (JID 96:172, 1991), we here report a biophysical and biochemical analysis of follicular melanogenesis during the anagen-catagen-telogen transformation of the C57 BL-6 mouse hair cycle. Tyrosinase activity and concentration as well as dopachrome tautomerase activity were compared with melanin synthesis, as measured by electron paramagnetic resonance spectroscopy (EPR). The visible changes in skin color and the histologically appreciable switch-off of melanin formation during the anagen-catagen transformation were accompanied by a steep decline in 1) the melanin-associated EPR signal of full-thickness mouse skin, 2) tyrosinase and dopachrome tautomerase activities, and 3) the skin concentration of 80-85-kD melanogenesis related protein and 66-68-kD tyrosinase protein. Telogen skin displayed a minimum of the EPR amplitude as well as of tyrosinase and dopachrome tautomerase activity detected. By EPR, only eumelanin was identified during all hair cycle stages. The gradual switch-off of melanogenesis during anagen VI started with an unexpectedly early decline of the EPR melanin signal, followed by dopachrome tautomerase activity and the concentration of 80-85-kD melanogenesis related protein. The initiation of catagen was characterized by a significant and rapid decrease in activity and concentration of tyrosinase, and was accompanied by a second drop in dopachrome tautomerase activity. Together, these biochemical and biophysical parameters of follicular melanogenesis serve as novel and differential markers for the imminent termination of anagen and the development of catagen. They also show that the switch-off of melanogenesis during the anagen-catagen-telogen transition is a stochastic process commencing already in mid anagen VI.

Animals↗
PubMed1994

Murine skin as a target for melatonin bioregulation.

Specific binding sites for 3H-melatonin were detected in membrane fractions prepared from C57 BL-6 mouse skin, and were localized to the epidermis and the epithelial bulb of the hair follicle by in situ autoradiography. In skin organ culture, melatonin stimulated DNA synthesis by the epidermal keratinocytes at concentration 0.1-10 nM, while at > or = 1 microM it inhibited tyrosinase activity. We concluded that murine skin is a target for melatonin bioregulation.

Animals↗
PubMed1993

Melanocytes as "sensory" and regulatory cells in the epidermis.

Epidermal melanocytes (MC) are pigment-producing and secretorily active cells of neural crest origin that communicate directly with multiple targets. Here, we propose that normal epidermal MC also are "sensory" and regulatory cells operating in the context of a regulatory network for the maintenance of human epidermal homeostasis. Altered regulatory MC functions may play a role in selected skin diseases, and racial pigmentation may affect cutaneous functions.

Cell Communication↗
PubMed1993

Melatonin inhibits proliferation and melanogenesis in rodent melanoma cells.

The effects of melatonin on proliferation and on the induction of melanogenesis in rodent melanoma cells were investigated. It was found that melatonin at low concentrations (0.1-10 nM) inhibited cell growth but had no effect on melanogenesis, while at high concentrations (> or = 0.1 microM) it inhibited the induction of melanogenesis but not cell growth. These effects were specific since corresponding concentrations of the direct precursor and product of melatonin degradation N-acetylserotonin (N-Ac-5HT) and 5-methoxytryptamine (5MT), respectively, did not have any effect on cell proliferation or melanogenesis. At very high concentration (100 microM) both N-Ac-5HT and melatonin could stimulate melanoma proliferation while 5MT inhibited it. The demonstration of differential and unparalleled effects of melatonin on cell proliferation and melanogenesis suggests that melatonin can regulate or modify both processes via different mechanisms.

5-Methoxytryptamine↗
PubMed1993

On the potential role of proopiomelanocortin in skin physiology and pathology.

Pro-opiomelanocortin (POMC) is the precursor of ACTH, alpha-MSH and beta-endorphin, neuropeptides with multiple regulatory functions. Both the pituitary gland and peripheral tissues such as mammalian skin are capable of generating POMC-derived neuropeptides. Mammalian skin is also a target for POMC products; their possible roles in skin physiology and pathology are discussed in this communication.

Amino Acid Sequence↗
PubMed1993

Melanogenesis is coupled to murine anagen: toward new concepts for the role of melanocytes and the regulation of melanogenesis in hair growth.

Hair is actively pigmented only when it grows: the melanogenic activity of follicular melanocytes (MC) is strictly coupled to the anagen stage of the hair cycle. In catagen, melanin formation is switched off and is absent throughout telogen. The appearance of pigmentation is preceded, and further accompanied by, a time-frame - restricted, differential pattern of tyrosinase transcription, translation, and enzyme activities during the development of anagen follicles. In this speculative review, we argue that signals required for melanin synthesis and pigment transfer to bulb keratinocytes (KC) are intrinsic to the skin, rather than coming from the serum. First, the proopiomelanocortin (POMC) gene is expressed and translated during anagen, but is below the level of detectability in telogen; POMC is a precursor protein for adrenocorticotropin and melanotropins, which are potent regulators of MC proliferation and differentiation. Second, fibroblasts and KC produce factors that affect MC proliferation and differentiation. We suggest that signals regulating follicular MC activity partially derive from cutaneous cells expressing POMC. Vice versa, MC transfer to surrounding KC pigment granules with potent bioregulatory properties. MC also produce and secrete various signal molecules that can regulate mesenchymal and epithelial cell functions. Anagen-associated melanogenesis and the cyclic production of a pigmented hair shaft result from programmed and tightly coordinated epithelial-mesenchymal-neuroectodermal interactions, in which MC may act not only as pigmentary, but also as hair growth-regulatory cells.

Animals↗
PubMed1993

Identification and characterization of two isozymic forms of arylamine N-acetyltransferase in Syrian hamster skin.

Arylamine N-acetyltransferase (EC 2.3.1.5) activity was examined using skin from Syrian hamster. Two isozymes of arylamine N-acetyltransferase, designated NAT-1 and NAT-2, were detected on anion-exchange high-performance liquid chromatography analysis. Both enzyme activities had indistinguishable molecular masses (30 kDa), but differed significantly in their specificity toward the aromatic amines including serotonin, dopamine, methoxytryptamine, tryptamine, para-phenetidine, para-aminobenzoic acid, and sulphamethazine. Specifically, NAT-2 but not NAT-1 catalyzed acetylation of dopamine to N-acetyldopamine and acetylation of serotonin to form N-acetylserotonin, a direct precursor of melatonin. The two isozymes were also distinguishable based upon their sensitivity toward methotrexate inhibition (50% inhibiting dose for NAT-1 = 380 microM; NAT-2 > 2 mM). The presence of these two activities in the skin raises new questions about the physiologic role of this enzyme in general and in the skin-specific functions in particular.

Animals↗
PubMed1993

Characterization of a hamster melanoma-associated ganglioside antigen as 7-O-acetylated disialoganglioside GD3.

We previously reported a hamster animal model of melanoma in which the tumor tissue expresses gangliosides GM3, GD3, and O-acetyl GD3. This ganglioside pattern is similar to that in human melanomas (Ren, S., A. Slominski, and R. K. Yu. 1989 Cancer Res. 49: 7051). In this study, we isolated and purified these gangliosides using chloroform-methanol extraction, Folch partition, chromatographies on DEAE-Sephadex A-25, and Iatrobeads columns. The yields of gangliosides GM3, GD3, and O-acetyl GD3 were 44.1 mg, 19.6 mg, and 9 mg per 100 g of Ma melanotic melanoma tissues, respectively. The structures of these gangliosides were characterized by periodate oxidation, gas chromatographic (GC) analysis, fast-atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR) studies. The structure of hamster melanoma O-acetyl GD3 is different from the 9-O-acetyl GD3 previously reported in human melanoma. The major fatty acids of this ganglioside are C16:0, C18:0, C20:0, C22:0, and C24:0 and the long-chain base is C18-sphingosine.

Animals↗
PubMed1993

Detection of proopiomelanocortin-derived antigens in normal and pathologic human skin.

We investigated the presence of proopiomelanocortin (POMC) products in sections of skin from normal subjects and patients with neoplastic and non-neoplastic cutaneous disorders. Antibodies specific against adrenocorticotropin, beta-melanotropin, and beta-endorphin were used for detection and characterization of cell types bearing POMC peptides. POMC products were not observed in sections of normal skin from the corporal (non-scalp) areas (six cases), whereas the hair follicles of scalp skin exhibited positive immunostains that were readily apparent (four cases). POMC products were frequently detected in corporal skin affected by diseases (13 of 26 cases), for example, psoriatic keratinocytes, the inflammatory infiltrate in scarring alopecia, nevocytes, the epithelial cell nests of basal cell carcinoma, and melanoma cells. Further tests were performed in keloids, a primary reactive skin disorder, to evaluate whether POMC accumulation represented a disease-related phenomenon or an expression of normal cutaneous reactivity. POMC products were consistently detected (10 of 11 cases) in the keratinocytes and mononuclear cells at keloid lesions. Thus these observations indicate that POMC products may accumulate locally in lesional skin representing, presumably, a novel cutaneous response to injury. The broad spectrum of POMC products detected suggests that these arise from production in situ (expression of the POMC gene itself) by human skin.

Adrenocorticotropic Hormone↗
PubMed1992

L-dopa binding sites in rodent melanoma cells.

Rapid, saturable, specific and stereoselective binding of L-dopa to crude membranes and purified nuclei from rodent amelanotic melanoma cells is reported. Cross-linking of [3H]dopa to melanoma cell surface emphasized proteins of approx. 55, 30, 25 and less than 20 kDa. It is suggested that these binding sites may regulate melanocyte activity.

Animals↗
PubMed1992

Proopiomelanocortin expression in the skin during induced hair growth in mice.

We demonstrate for the first time a hair cycle-dependent gene and protein expression of proopiomelanocortin in mouse skin in vivo. Northern blot detected POMC mRNA with an apparent size of 0.9 kb in anagen but not telogen skin. Western blot emphasized a specific protein of 30-33 kDa recognized by anti beta-endorphin in late but not early anagen or telogen skin. By immunocytochemistry, beta-endorphin antigen was localized in the sebaceous gland in a hair cycle dependent manner.

Animals↗
PubMed1992

Melanotropic activity of gamma MSH peptides in melanoma cells.

We studied the pigmentary activity of the peptides gamma 1, gamma 2 and gamma 3 melanocyte stimulating hormone (MSH), which differ in the structure of their C-termini, using hamster and mouse melanoma cell lines responsive to beta-MSH by increasing tyrosinase activity. Gamma 1-MSH alone or in combination with beta-MSH had no effect on either cell line. Gamma 2-MSH alone was biologically inactive but potentiated beta-MSH stimulation of tyrosinase activity. Gamma 3-MSH at high concentration (10 microM) induced tyrosinase activity and dendrite formation in the hamster melanoma line. When added together with beta-MSH, gamma 3-MSH partially inhibited the tyrosinase activity response to beta-MSH. Thus, gamma-MSH peptides have low intrinsic melanotropic activity in mammalian melanoma cells; the specific pigmentary responses appear to be affected by the structure of the C-terminal portion.

Amino Acid Sequence↗
PubMed1992

Defect of insulin receptor in insulin-resistant variants of Cloudman S91 mouse melanoma cells.

To study the mechanisms by which insulin regulates proliferation, we have compared wild-type Cloudman melanoma cells, whose growth in inhibited by insulin (insinh) to variant lines that were genetically selected for resistance to insulin (insres). Scatchard analysis of insulin binding to five insres) lines and six insres variants revealed a marked reduction in the number of high-affinity binding sites for insulin in the insres lines, and insres lines displayed an abnormal beta-subunit of the insulin receptor. During autophosphorylation of the wheat germ agglutinin-purified receptor, the beta-subunit apparently underwent proteolytic degradation. This proteolysis was ATP-dependent and was prevented by bovine pancreatic trypsin inhibitor, and phenylmethylsulphonyl fluoride, but not by aprotinin or leupeptin. Receptor proteolysis was not observed in wild-type lines. The results suggest that insulin resistance in the mutant Cloudman melanoma cells is apparently due to proteolysis of the beta-subunit of insulin receptor which, in turn, alters insulin binding capacity of the cells and blocks their anti-proliferative response to the hormone.

Animals↗
PubMed1992

L-dopa inhibits in vitro phosphorylation of melanoma glycoproteins.

L-DOPA had no effect on the endogenous phosphorylation of proteins after extraction with 1% Triton X-100 from hamster melanoma. When proteins were purified further by wheat germ-agglutinin chromatography, however, a dramatic and dose-dependent inhibitory effect of DOPA on glycoprotein phosphorylation was observed in the presence of Mn+2.

Animals↗