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S J Orlow

Publications and source records attributed to S J Orlow.

At least 91 records · Page 5Linked to original sources
PubMed1992

Cutaneous findings in craniofacial malformation syndromes.

BACKGROUND: A number of craniofacial malformation syndromes are characterized by prominent abnormalities of the skin, hair, nails, and mucous membranes. Many of these findings have been discussed little or not at all in the dermatologic literature. The goal of this review is to present some of the more prominent and distinctive syndromes to increase their recognition by dermatologists and to stimulate further investigation. OBSERVATIONS: The literature regarding syndromes in which major craniofacial anomalies, eg, craniosynostosis or clefting, were present was reviewed and those syndromes with prominent mucocutaneous findings were identified. Although some are well described in the literature, the findings in others are insufficiently detailed from a dermatologic point of view. Little has been written regarding therapeutic intervention. CONCLUSIONS: More accurate descriptions of many craniofacial malformation syndromes are needed by dermatologists. Alerting the dermatologic community to their existence should stimulate attempts at therapeutic intervention on behalf of affected persons.

Cleft Lip↗
PubMed1991

Interactions between ultraviolet light and interleukin-1 on MSH binding in both mouse melanoma and human squamous carcinoma cells.

Interactions between beta-melanotropin (MSH), interleukin 1-a (IL-1), and ultraviolet light (UV) were examined in Cloudman S91 mouse melanoma and RHEK human squamous carcinoma cell lines. The following points were established: 1) both cell lines produced IL-1 and their production was stimulated by exposure of the cells to UV; 2) both cell lines possessed high affinity binding sites for MSH, and their ability to bind MSH was modulated by IL-1; 3) IL-1 exhibited both stimulatory and inhibitory effects on MSH binding to Cloudman cells; and 4) the stimulatory effect of IL-1 on MSH binding to melanoma cells was reflected in enhanced cellular responsiveness to MSH regarding tyrosinase activity (E.C. 1.14.18.1) and melanin content. The findings raise the possibility that interactions between keratinocytes and melanocytes may be regulated by IL-1 and MSH, and suggest a possible mechanism for stimulation of cutaneous melanogenesis by solar radiation: enhancement of MSH receptor activity by induction of IL-1.

Animals↗
PubMed1991

Structural/functional relationships between internal and external MSH receptors: modulation of expression in Cloudman melanoma cells by UVB radiation.

Expression of internal receptors for MSH is an important criterion for responsiveness to MSH by Cloudman melanoma cells (Orlow et al: J. Cell. Physiol., 142:129-136, 1990). Here, we show that internal and external receptors for MSH are of identical molecular weights (50-53 kDa) and share common antigenic determinants, indicating a structural relationship between the 2 populations of molecules. The internal receptors co-purified with a sub-cellular fraction highly enriched for small vesicles, many of which were coated. Ultraviolet B light (UVB) acted synergistically with MSH to increase tyrosinase activity and melanin content of cultured Cloudman melanoma cells, consistent with previous findings in the skin of mice and guinea pigs (Bolognia et al: J. Invest. Derm., 92:651-656, 1989). Preceding the rise in tyrosinase activity in cultured cells, UVB elicited a decrease in internal MSH binding sites and a concomitant increase in external sites. The time frame for the UVB effects on MSH receptors and melanogenesis, 48 hours, was similar to that for a response to solar radiation in humans. Together, the results indicate a key role for MSH receptors in the induction of melanogenesis by UVB and suggest a potential mechanism of action for UVB: redistribution of MSH receptors with a resultant increase in cellular responsiveness to MSH.

Animals↗
PubMed1991

Skin and bones. I.

Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. Part I of our review discusses the first two categories.

Abnormalities, Multiple↗
PubMed1991

Skin and bones. II.

Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II discusses categories 3 through 8.

Bone Diseases↗
PubMed1990

Stimulation of the receptor for melanocyte-stimulating hormone by retinoic acid.

Treatment of Cloudman S91 melanoma cells with retinoic acid (RA) inhibits MSH-induced tyrosinase activity and melanin formation [(1990) J. Invest. Dermatol. 94, 461-464]. We report here, however, that in spite of inhibiting MSH-induced pigmentation, RA treatment caused a marked increase in MSH binding capacity for both cell surface and internal MSH binding sites. The stimulation was dose- and time-dependent and reversible, with half-maximal effects seen at 2 microM RA. Stimulation of MSH binding was seen as early as 3 h after exposure of cells to RA. Cell surface and internal binding activity increased in concert. Scatchard analysis indicated that increased MSH binding resulted from a 3-4-fold increase in the number of sites with no significant difference in their affinity for MSH. It appears that in suppressing MSH-induced melanogenesis, RA elicited a compensatory up-regulation of the MSH receptor system.

Animals↗
PubMed1990

Internal binding sites for MSH: analyses in wild-type and variant Cloudman melanoma cells.

Cloudman S91 mouse melanoma cells express both external (plasma membrane) and internal binding sites for MSH. Using 125I-beta melanotropin (beta-MSH) as a probe, we report here an extensive series of studies on the biological relevance of these internal sites. Cells were swollen in a hypotonic buffer and lysed, and a particulate fraction was prepared by high-speed centrifugation. This fraction was incubated with 125I-beta-MSH with or without excess nonradioactive beta-MSH in the cold for 2 hours. The material was then layered onto a step-wise sucrose gradient (8-80%) and centrifuged (156,000g, 60 min); fractions were collected and counted in a gamma counter or assayed for various enzymatic activities. The following points were established: 1) Specific binding sites for MSH were observed sedimenting at an average density of 50% sucrose in amelanotic cells and at higher densities in melanotic cells. 2) These sites were similar in density to those observed when intact cells were labeled externally with 125I-beta-MSH and then warmed to promote internalization of the hormone. 3) Most of the internal binding sites were not as dense as fully melanized melanosomes. 4) In control experiments, the MSH binding sites were not found in cultured hepatoma cells. 5) Variant melanoma cells, which differed from the wild-type in their responses to MSH, had reduced expression of internal binding sites even though their ability to bind MSH to the outer cell surface appeared normal. (MSH-induced responses included changes in tyrosinase, dopa oxidase, and dopachrome conversion factor activities, melanization, proliferation, and morphology.) 6) Isobutylmethylxanthine, which enhanced cellular responsiveness to MSH, also enhanced expression of internal binding sites. The results indicate that expression of internal binding sites for MSH is an important criterion for cellular responsiveness to the hormone.

Animals↗
PubMed1990

Inhibition of induced melanogenesis in Cloudman melanoma cells by four phenotypic modifiers.

Retinoic acid, hexamethylene bisacetamide, sodium butyrate, and dimethylsulfoxide, four compounds which modulate phenotypic expression in a variety of neoplastic cell lines, all inhibited the induction of tyrosinase activity and melanogenesis by the combination of melanocyte-stimulating hormone and isobutylmethyxanthine in Cloudman S91 melanoma cells. Results were the same in assays of whole cells or in extracts made from them. Only retinoic acid, however, was effective at inhibiting the activation of dopachrome isomerase, another regulatory enzyme in melanogenesis. Despite inhibiting the effects of melanocyte-stimulating hormone (MSH) and isobutylmethylxanthine on tyrosinase activity, all of the agents tested increased the binding of MSH to intact cells. Ultrastructural analysis of treated cells following DOPA cytochemistry revealed that both retinoic acid and hexamethylene bisacetamide arrested melanosomal maturation at stage I-II. Retinoic acid resulted in a derangement of melanosomal structure. The specificity of these agents for preventing the induction of melanogenesis makes them powerful tools for the dissection of this complex cellular process.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Retinoic acid is a potent inhibitor of inducible pigmentation in murine and hamster melanoma cell lines.

Melanocyte-stimulating hormone (MSH) induces melanogenesis in Cloudman mouse melanoma cells. The activities of two enzymes in the melanogenesis pathway, tyrosinase and dopachrome conversion factor, are increased as part of the induction process. Trans retinoic acid (RA), at concentrations as low as 0.1 nM, inhibited the induction of tyrosinase, dopachrome conversion factor, and melanogenesis, but had no effect on the basal levels of either enzyme or of cellular melanin content. Half-maximal effects of RA occurred at a concentration of 10 nM; maximal effects were observed at 1 microM. The effects of RA on melanogenesis were independent of its effects on cellular growth since one Cloudman line tested was growth-inhibited by RA and another was growth-stimulated by RA, but the induction of melanogenesis by MSH in both lines was inhibited by RA. Mixing experiments with cell lysates failed to demonstrate the induction of a tyrosinase inhibitor by RA. The effects of RA were not limited to MSH or to Cloudman melanoma cells since RA blocked cholera toxin-inducible melanogenesis in Cloudman cells, as well as the induction of tyrosinase activity by L-tyrosine in Bomirski hamster melanoma cells. The effects of RA were specific to melanogenesis, however, since RA did not interfere with MSH-induced changes in cellular morphology and growth. Thus, RA appears to be a new and potent tool for understanding mechanisms regulating induction of the pigmentary system.

Animals↗
PubMed1990

Figurate and bullous eruption in association with breast carcinoma.

We describe a patient with two coexistent cutaneous eruptions: (1) trauma-induced bullae of the distal extremities and elbows and (2) multiple concentric gyrate lesions on the trunk and extremities, some of which became bullous. The gyrate lesions were stationary and nonpruritic. Biopsy of both types of lesions showed a subepidermal blister and a minimal inflammatory infiltrate. Direct immunofluorescence revealed linear deposition of IgG and C3 at the dermoepidermal junction and indirect immunofluorescence was negative. By immunoelectron microscopy, these immune deposits were localized to the lower lamina lucida. The eruption was not controlled despite high-dose (80 mg/d) oral administration of prednisone and required the addition of an oral administration of methotrexate (20 mg weekly). On further evaluation, an intraductal mammary carcinoma was detected. Following radiation therapy, the methotrexate and prednisone therapy were tapered without recurrence of the eruption during a follow-up period of 18 months.

Aged↗
PubMed1985

Purification and distribution of a novel macrophage-specific calmodulin-binding glycoprotein.

The murine macrophage-like cell line J774.16 and peritoneal exudate cells elicited with thioglycollate or starch contain a major calmodulin (CaM)-binding protein (CaMBP) which is absent in trifluoperazine-resistant variants of J774, resident peritoneal macrophages and peritoneal macrophages elicited with concanavalin A, lipopolysaccharide, proteose peptone, or Bacillus Calmette-Guerin. Resident murine peritoneal cells maintained in tissue culture for 3 days begin to accumulate this protein, as do human peripheral blood monocytes after 7 days of culture. A specific competitive displacement radioimmunoassay was developed with the use of a rabbit antiserum raised to the partially purified CaM-binding protein and [125I]CaM covalently cross-linked to the principal CaM-binding protein in the preparation. The radioimmunoassay confirmed the unique cellular distribution of this protein, suggesting that it may be a marker for certain stages of macrophage differentiation. Monoclonal antibodies were prepared, and one of these was used to further purify the protein by immunoaffinity chromatography. A protein of Mr 50,000 to 60,000 was isolated. The protein could be selectively adsorbed to wheat germ agglutinin agarose and subsequently eluted with N-acetyl glucosamine. This property, plus the sensitivity of the protein to endoglycosidase F, led to the conclusion that it is a glycoprotein. The cellular distribution, subcellular localization, and evidence for glycosylation suggest that this protein may be a macrophage-specific receptor with a high affinity for Ca2+-CaM.

Animals↗
PubMed1983

Characterization of a calmodulin-binding protein that is deficient in trifluoperazine-resistant variants of the macrophage-like cell line J774.

A calmodulin-binding protein is present in extracts of the macrophage-like mouse cell line J774 and in extracts of thioglycollate-stimulated mouse peritoneal macrophages; it is deficient in variants of J774 resistant to trifluoperazine and in resident peritoneal macrophages. The calmodulin-binding protein [CaMBP (J7)0.5] was purified from J774 and resolved from endogenous cyclic nucleotide phosphodiesterase and protein kinase activities. The protein has an apparent native Mr of 125,000-150,000 and binds calmodulin in a calcium-dependent manner with a Kd of 20 nM. It inhibits the ability of calmodulin to activate phosphodiesterase. Its sedimentation constant in glycerol gradients containing calmodulin was dependent upon the relative concentrations of calmodulin and the calmodulin-binding protein.

Animals↗
PubMed1981

The extracellular cyclic nucleotide phosphodiesterase of Dictyostelium discoideum. Purification and characterization.

Two forms of the extracellular cyclic nucleotide phosphodiesterase (EC 3.1.4.17) of Dictyostelium discoideum have been purified. One species has a molecular weight of about 55,000 measured by gel filtration and has been purified to apparent homogeneity. This monomeric form of the enzyme can be resolved by isoelectrofocusing into 4 bands with isoelectric points between 7.5 and 9. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two bands with molecular weights of 50,000 and 48,000. The second form of the enzyme has been partially purified and has a higher molecular weight (150,000-200,000) and an isoelectric point of about 5. The high molecular weight form of the enzyme is converted to the low molecular weight monomer by isoelectrofocusing in the presence of 6 M urea. Under these conditions the isoelectric point is shifted to that of the monomeric form of the enzyme. The two species are immunologically indistinguishable after urea treatment, and react identically with the cyclic nucleotide phosphodiesterase inhibitor (see the accompanying paper: Franke, J., and Kessin, R. H. (1981) J. Biol. Chem. 256, 7628-7637). The two forms have the same Km and show equal sensitivity to a number of ions, chelators, and low molecular weight cyclic nucleotide phosphodiesterase inhibitors. Tryptic maps of the purified monomeric enzyme and the urea dissociated high molecular weight form revealed no differences.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Binding of inhibitor alters kinetic and physical properties of extracellular cyclic AMP phosphodiesterase from Dictyostelium discoideum.

The extracellular adenosine 3',5'-cyclic monophosphate phosphodiesterase (3',5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) produced by Dictyostelium discoideum has two kinetic forms. The free enzyme has a Km of approximately 10 microM. The second form is the result of a complex formed with a heat-stable inhibitor and has a Km in the millimolar range. Treating the enzyme-inhibitor complex with dithiothreitol stimulated enzyme activity 20- to 100-fold and changed in Km from millimolar to micromolar. Dithiothreitol inactivated the inhibitor. Reconstituting purified enzyme with excess inhibitor returned the Km to the millimolar range. Under conditions known to inhibit the production of extracellular inhibitor or in mutants that lack it, extracellular phosphodiesterase activity was already high and could not be increased by dithiothreitol. The phosphodiesterase and inhibitor sedimented at 6 S and 3 S, respectively; the enzyme-inhibitor complex sedimented at 6.7 S.

3',5'-Cyclic-AMP Phosphodiesterases↗