Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HMB-45 is a monoclonal antibody directed against human melanoma cells and which stains epidermal and dermal melanoma cells, the junctional components of common and dysplastic melanocytic nevi, and melanocytes in fetal skin. In addition, melanocytes in a variety of reactive conditions have been shown to label with HMB-45, as have dermal melanocytes within Spitz and dysplastic nevi. No melanocytes in normal adult epidermis or in the dermis of common nevi have stained with HMB-45. In order to better understand the properties of this antibody, and of the melanocytes that react with it, we stained cultured human melanocytes grown in a variety of conditions. Melanocytes from human foreskins were grown for 2-3 weeks in MCDB 153 medium supplemented with insulin, epidermal growth factor, and bovine pituitary extract as a mixed population of keratinocytes and melanocytes. Some cells were transferred to basal medium MCDB 153 (unsupplemented) for periods ranging from 3-5 days, and a subset of these were returned to growth-factor supplemented medium. In all cases, S100 staining was used to confirm the presence of melanocytes. Melanocytes grown in complete medium showed strong granular cytoplasmic staining with HMB-45. Cells transferred to basal medium showed a markedly diminished staining intensity which was reversible within 3 days upon return of the cells to complete medium. The findings suggest that expression of the protein recognized by HMB-45 may be related to a growth factor present in complete medium, but missing from basal MCDB 153.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HMB-45 monoclonal antibody recognizes an inducible and reversible melanocyte cytoplasmic protein. 176 83

Proteus syndrome is a rare hamartomatous disorder characterized by multifocal overgrowths that can involve any structure of the body. Clinical manifestations include macrodactyly, hemihypertrophy, subcutaneous masses, exostosis, cerebroid thickening of palms and soles, and linear skin lesions. About 50 cases have been described, but the ultrastructural features of the linear skin lesions have not been characterized. We describe the clinical, histologic, and ultrastructural findings for a 30-year-old patient who had a mild form of Proteus syndrome with linear lesions characterized by a mixed pattern of hyperkeratosis and depigmentation. Light microscopy of the linear nevus showed acanthosis and hyperorthokeratosis. Electron microscopy revealed extensive vacuolation at the interface between melanocytes and keratinocytes, with large aggregations of densely packed granules in the intercellular space. Melanocytes showed only slight degenerative changes. An immunohistochemical study of the expression of epidermal growth factor receptors revealed no significant abnormalities.
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PMID:Proteus syndrome. Ultrastructural study of linear verrucous and depigmented nevi. 189 76

Regulation of urea transport by vasopressin in inner medullary collecting duct (IMCD) cells is thought to be important for the urinary concentrating mechanism. Isolated tubule perfusion studies suggest the existence of a saturable urea carrier. We have measured 14C-urea efflux in IMCD cells which were freshly isolated and grown in primary culture. Cells were isolated from rat papilla by collagenase digestion and hypotonic shock. In suspended cells, 14C-urea efflux (Jurea) from loaded cells was exponential with time constant 59 +/- 3 sec (SEM, n = 6, 23 degrees C). Jurea had an activation energy of 4.1 kcal/mole and was inhibited 42 +/- 7% by 0.25 mM phloretin and 30-40% by the high affinity urea analogues dimethylurea and phenylurea. Jurea was increased 40-60% by addition of vasopressin (10(-8) M) or 8-bromo-cAMP (1 mM); stimulated Jurea was inhibited 55 +/- 8% by the kinase A inhibitor H-8. Phorbol esters and epidermal growth factor did not alter Jurea. IMCD cells grown in primary culture were homogeneous in appearance with greater than fivefold stimulation of cAMP by vasopressin. The exponential time constant for urea efflux was 610 +/- 20 sec (n = 3). Jurea was not altered by vasopressin, cAMP or phloretin. Another function of in vivo IMCD cells, vasopressin-dependent formation of endosomes containing water channels, was absent in the cultured cells. These results demonstrate presence of a urea transporter on suspended IMCD cells which is activated by cAMP and inhibited by phloretin and urea analogues. The urea transporter and its regulation by cAMP, and cAMP-dependent apical membrane endocytosis, are lost after growth in primary culture.
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PMID:Urea transport in freshly isolated and cultured cells from rat inner medullary collecting duct. 217 46

We have tested the hypothesis that the mechanism of platelet-derived growth factor (PDGF) and phorbol diester action to decrease the apparent affinity of the epidermal growth factor (EGF) receptor is the phosphorylation of the EGF receptor at the Ca2+/phospholipid-dependent protein kinase (protein kinase C) phosphorylation site, threonine 654. Protein kinase C-deficient cells were prepared by prolonged incubation of human fibroblasts with phorbol diester. Addition of phorbol diesters to these cells fails to regulate EGF receptor affinity or threonine 654 phosphorylation. In contrast, PDGF treatment of both control and protein kinase C-deficient fibroblasts causes a decrease in the apparent affinity of the EGF receptor and an increase in threonine 654 phosphorylation. Thus, the ability of PDGF or phorbol diester to modulate EGF receptor affinity occurs only when threonine 654 phosphorylation is increased. The stoichiometry of threonine 654 phosphorylation associated with a 50% decrease in the binding of 125I-EGF to high affinity sites was 0.15 versus 0.3 mol of phosphate per mole of EGF receptor when 32P-labeled fibroblasts are treated with PDGF or phorbol diester, respectively. It is concluded that EGF receptor phosphorylation at threonine 654 can be regulated by PDGF independently of protein kinase C, substoichiometric phosphorylation of the total EGF receptor pool at threonine 654 is caused by maximally effective concentrations of PDGF, and different extents of phosphorylation of EGF receptors at threonine 654 are observed for maximally effective concentrations of PDGF and phorbol diester, respectively. The data are consistent with the hypothesis that a specific subpopulation of EGF receptors that exhibit high affinity for EGF are regulated by threonine 654 phosphorylation.
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PMID:Stimulation of epidermal growth factor receptor threonine 654 phosphorylation by platelet-derived growth factor in protein kinase C-deficient human fibroblasts. 310 61

Melanoma growth stimulatory activity (MGSA) is an acid and heat stable, auto-stimulatory growth factor which was first isolated from culture medium conditioned by the Hs294T human melanoma cell line. In this report, we describe the purification of MGSA from acid ethanol extracts of Hs294T tumors grown in nude mice using a series of Bio-Gel P30, reverse phase-high performance liquid chromatography and heparin-sepharose steps. This modified procedure provides a 10-fold improved yield of MGSA over previously published procedures. Purified MGSA-stimulated melanoma cell growth in both 3H-thymidine and cell number assays over a concentration range of 0.06 to 6 ng/ml. The MGSA bioactivity was primarily associated with fractions which exhibited molecular weights of 16 and 13-14 Kd based upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Purified platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-1), transforming growth factor-beta (TGF beta), and epidermal growth factor (EGF) in combination with TGF beta did not stimulate 3H-thymidine incorporation in Hs294T cells under the conditions used for MGSA bioassay. Monoclonal antibody to MGSA was used to screen melanoma and benign nevus cultures as well as fixed sectioned tissue for MGSA. The majority of the melanoma cultures were MGSA positive, while most nevus cultures were MGSA negative. However, when fixed sectioned tissue was screened for MGSA immunoreactivity, melanoma tissue was MGSA positive and three-fourths of the benign nevi were MGSA positive. In addition, epidermal keratinocytes and several tissues exhibiting proliferative disorders contained immunoreactive MGSA. These data suggest that MGSA may be a normal regulator of growth and that the microenvironment of the cell may regulate both production of MGSA and response to MGSA.
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PMID:Melanoma growth stimulatory activity: isolation from human melanoma tumors and characterization of tissue distribution. 335 54

Transient ATP synthesized by preparations enriched with plasmatic membranes of particles from the human placenta in the presence of insulin (4 micrograms/ml) and epidermal growth factor (1 microgram/ml) within 1 min after the addition of hormones at 30 degrees C, was isolated by means of chromatography on Dowex 1 X 8. ATP was synthesized in a medium containing Tris-HCl buffer, pH 7.5, ADP, Mg2+, and Pi during NADH-dependent oxidation in the presence of cytochrome C and oxygen. The amount of ATP was 10(-9) mole/mg protein/min. Quantitative assessment of ATP in lyophilized product was carried out by means of fluorimetry (excitation wavelength--360 nm; emission wavelength--460 nm) of NADH formed during coupled enzymatic reactions involving hexokinase and glucose-6-phosphate dehydrogenase. A possible biological role of peptide growth factor-stimulated formation of transient ATP in plasmatic membranes is discussed.
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PMID:[ATP generation by the plasma membranes of human placental cells as affected by insulin and epidermal growth factor]. 354 74

A single exposure to a low concentration (10(-9) mole/l) of exogenous arachidonic acid or of prostaglandins of A, E, and F series significantly stimulated primary neonatal rat hepatocytes to enter S phase irrespective of whether the extracellular calcium concentration was high (i.e., 1.8 mmole/l) or markedly reduced (i.e., 0.01 mmole/l). Similarly, a single treatment with an even smaller (10(-10) mole/l) dose of the known tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital, and nafenopin enhanced hepatocytic DNA synthesis when the environmental calcium level was both high and low. By contrast, a single application of a small concentration (10(-11)-10(-10) mole/l) of hormones such as epidermal growth factor (EGF), glucagon, and insulin, and of drugs such as imidazole and indomethacin only increased the hepatocytic flow into DNA synthesis when the extracellular calcium was high. These findings reveal that the mechanisms of physiological or pharmacological, calcium-dependent stimulation of hepatocellular growth are likely to be different from those of pathological, calcium-independent stimulation, as the latter, but not the former, would involve prostaglandin-mediated metabolic processes.
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PMID:The tumor promoters TPA, phenobarbital, and nafenopin and the prostaglandins of A, E, and F series overcome the G1/S block imposed by extracellular calcium deprivation on neonatal rat hepatocytes. 658 44

Extracts of conditioned medium (CM) from Hs0294 human malignant melanoma cells stimulate [3H]thymidine incorporation and an increase in cell number in serum-depleted Hs0294 cells. This activity is acid and heat stable, nonproteolytic, protease sensitive, contains disulfide bonds and elutes broadly from a Bio-Gel P-30 column with an approximate molecular weight range of 6,000 to 25,000. Hs0294 CM also stimulates [3H]thymidine incorporation in nonmalignant human nevus cells and normal rat kidney fibroblast cells but not in human fibroblasts. There was only limited competition with 125I-epidermal growth factor in binding assays. Hs0294 CM extracts stimulate anchorage-independent growth in normal rat kidney fibroblast cells in soft agar but not in Hs0294 cells, nevus cells, or human fibroblasts. This second activity elutes from the Bio-Gel P-30 column in two positions with apparent molecular weights of 27,000 and 11,000.
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PMID:Extraction of a melanoma growth-stimulatory activity from culture medium conditioned by the Hs0294 human melanoma cell line. 660 Sep 64

Type beta transforming growth factor (TGF-beta) has been purified 200 000-fold from bovine kidneys. This peptide is characterized by its ability to induce anchorage-dependent normal rat kidney cells to grow in soft agar in the presence of epidermal growth factor (EGF); TGF-beta is not mitogenic for cells grown in monolayer culture. Purified TGF-beta does not compete with EGF for binding to membrane receptors. The concentration of TGF-beta required to elicit a half-maximal response for formation of colonies greater than 3100 micron2 in the soft agar assay is 2-3 pM (55 pg/mL) when assayed in the presence of 0.8 nM EGF (5 ng/mL). The four-step purification procedure which includes chromatography of acid--ethanol tissue extracts on polyacrylamide sizing gels, cation exchange, and two steps of high-pressure liquid chromatography results in a 10% overall yield of colony-forming activity with a recovery of 3-4 micrograms/kg. Amino acid analysis of purified TGF-beta shows 16 half-cystine residues per mole. Analysis of the purified polypeptide by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels indicates that TGF-beta is composed of two closely related polypeptide chains cross-linked by disulfide bonds. In the absence of beta-mercaptoethanol, the colony-forming activity is associated with a single silver-staining band of molecular weight 25 000; in the presence of beta-mercaptoethanol, the TGF-beta is converted to an inactive species that migrates as a single band of molecular weight 12 500-13 000. Sequence analysis indicates that at least the first 15 N-terminal amino acids of the two TGF-beta subunits are identical.
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PMID:Purification and properties of a type beta transforming growth factor from bovine kidney. 660 69

Cell aggregates of bovine parathyroid tissue were prepared by limited collagenase digestion and placed in culture in Weymouth's MB752/1 (calcium = 3.3 mg/100 ml) containing 5% fetal bovine serum and supplemented with insulin alone, or insulin, hydrocortisone, transferrin and epidermal growth factor. Only insulin was required for the maintenance of PTH secretion over a 9-day period. The cell aggregates spread to form monolayer in 3-5 days. The majority of the cells in monolayer were polygonal with well-defined borders. Nuclei were round and the cytoplasm was free of vacuoles. Cell cultures responded to secretory stimulation by low calcium or by isoproterenol with increases in the secretion of PTH and SP-1. At low calcium, about 18% of both the cellular PTH and SP-1 was secreted per hour, and up to 50% of the cell content of these proteins was released per hour upon stimulation by isoproterenol and low calcium combined. The responses to calcium and isoproterenol decreased as a function of time in culture, and calcium responses often disappeared completely by 10 days of culture. When cells were cultured in medium containing a higher (5 mg%) than standard concentration of calcium between days 3-6 of culture, the degree of secretory inhibition attainable with high calcium was greater than that of cells cultured in the standard medium. When secreted hormonal peptides were separated by SDS-gel electrophoresis prior to RIA, it was found that the secretion of intact hormone was sensitive to calcium. For every molecule of PTH secreted into the medium, 1.5-2 mole-equivalents of carboxyl fragments were also released. Calcium control of fragment release was not as stringent as that of PTH release.
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PMID:Primary monolayer cell culture of bovine parathyroids: effects of calcium, isoproterenol and growth factors. 686 97


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