WorldWideScience

Sample records for alpha melanocyte stimulating

  1. alpha-Melanocyte-stimulating-hormone precursors in the pig pituitary

    DEFF Research Database (Denmark)

    Fenger, M

    1986-01-01

    The occurrence of intermediates from the processing of ACTH-(1-39) [adrenocorticotropic hormone-(1-39)] to alpha-melanocyte-stimulating hormone was investigated in normal pig pituitaries by the use of sensitive and specific radioimmunoassays for ACTH-(1-13), ACTH-(1-14), ACTH-(1-13)-NH2 and ACTH-...

  2. Nitric oxide enhances the sensitivity of alpaca melanocytes to respond to {alpha}-melanocyte-stimulating hormone by up-regulating melanocortin-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yanjun; Cao, Jing; Wang, Haidong; Zhang, Jie; Zhu, Zhiwei; Bai, Rui; Hao, HuanQing; He, Xiaoyan; Fan, Ruiwen [College of Animal Science and Technology, Shanxi Agricultural University, 030801 Taigu, Shanxi (China); Dong, Changsheng, E-mail: cs_dong@sxau.edu.cn [College of Animal Science and Technology, Shanxi Agricultural University, 030801 Taigu, Shanxi (China)

    2010-06-11

    Nitric oxide (NO) and {alpha}-melanocyte-stimulating hormone ({alpha}-MSH) have been correlated with the synthesis of melanin. The NO-dependent signaling of cellular response to activate the hypothalamopituitary proopiomelanocortin system, thereby enhances the hypophysial secretion of {alpha}-MSH to stimulate {alpha}-MSH-receptor responsive cells. In this study we investigated whether an NO-induced pathway can enhance the ability of the melanocyte to respond to {alpha}-MSH on melanogenesis in alpaca skin melanocytes in vitro. It is important for us to know how to enhance the coat color of alpaca. We set up three groups for experiments using the third passage number of alpaca melanocytes: the control cultures were allowed a total of 5 days growth; the UV group cultures like the control group but the melanocytes were then irradiated everyday (once) with 312 mJ/cm{sup 2} of UVB; the UV + L-NAME group is the same as group UV but has the addition of 300 {mu}M L-NAME (every 6 h). To determine the inhibited effect of NO produce, NO produces were measured. To determine the effect of the NO to the key protein and gene of {alpha}-MSH pathway on melanogenesis, the key gene and protein of the {alpha}-MSH pathway were measured by quantitative real-time PCR and Western immunoblotting. The results provide exciting new evidence that NO can enhance {alpha}-MSH pathway in alpaca skin melanocytes by elevated MC1R. And we suggest that the NO pathway may more rapidly cause the synthesis of melanin in alpaca skin under UV, which at that time elevates the expression of MC1R and stimulates the keratinocytes to secrete {alpha}-MSH to enhance the {alpha}-MSH pathway on melanogenesis. This process will be of considerable interest in future studies.

  3. The neuropeptide alpha-melanocyte-stimulating hormone is critically involved in the development of cytotoxic CD8+ T cells in mice and humans.

    Directory of Open Access Journals (Sweden)

    Karin Loser

    Full Text Available BACKGROUND: The neuropeptide alpha-melanocyte-stimulating hormone is well known as a mediator of skin pigmentation. More recently, it has been shown that alpha-melanocyte-stimulating hormone also plays pivotal roles in energy homeostasis, sexual function, and inflammation or immunomodulation. Alpha-melanocyte-stimulating hormone exerts its antiinflammatory and immunomodulatory effects by binding to the melanocortin-1 receptor, and since T cells are important effectors during immune responses, we investigated the effects of alpha-melanocyte-stimulating hormone on T cell function. METHODOLOGY/PRINCIPAL FINDINGS: T cells were treated with alpha-melanocyte-stimulating hormone, and subsequently, their phenotype and function was analyzed in a contact allergy as well as a melanoma model. Furthermore, the relevance of alpha-melanocyte-stimulating hormone-mediated signaling for the induction of cytotoxicity was assessed in CD8(+ T cells from melanoma patients with functional and nonfunctional melanocortin-1 receptors. Here we demonstrate that the melanocortin-1 receptor is expressed by murine as well as human CD8(+ T cells, and we furthermore show that alpha-melanocyte-stimulating hormone/melanocortin-1 receptor-mediated signaling is critical for the induction of cytotoxicity in human and murine CD8(+ T cells. Upon adoptive transfer, alpha-melanocyte-stimulating hormone-treated murine CD8(+ T cells significantly reduced contact allergy responses in recipient mice. Additionally, the presented data indicate that alpha-melanocyte-stimulating hormone via signaling through a functional melanocortin-1 receptor augmented antitumoral immunity by up-regulating the expression of cytotoxic genes and enhancing the cytolytic activity in tumor-specific CD8(+ T cells. CONCLUSIONS/SIGNIFICANCE: Together, these results point to an important role of alpha-melanocyte-stimulating hormone in MHC class I-restricted cytotoxicity. Therefore, treatment of contact allergies or

  4. The association between the melanocyte-stimulating hormone receptor and the alpha 2-adrenoceptor on the Anolis melanophore.

    OpenAIRE

    Carter, R J; Shuster, S.

    1982-01-01

    1 The primary effect of catecholamines was to lighten Anolis skin previously darkened by alpha-melanocyte-stimulating hormone (alpha-MSH). In concentrations above 10(-7) M noradrenaline, 10(-6) M adrenaline and 10(-5) dopamine, darkening of subpopulations of melanophores occurred. Subsequent experiments were concerned with the effect of low catecholamine concentrations on alpha-MSH action. 2 The relationship between MSH receptors and alpha-adrenoceptors on the Anolis melanophore was studied b...

  5. Alpha-Melanocyte-Stimulating Hormone Attenuates Behavioral Effects of Corticotropin-Releasing Factor in Isolated Guinea Pig Pups

    OpenAIRE

    Schiml-Webb, Patricia A.; Miller, Emily; Deak, Terrence; Hennessy, Michael B.

    2009-01-01

    During a 3-hr period of social isolation in a novel environment, guinea pig pups exhibit an initial active phase of behavioral responsiveness, characterized primarily by vocalizing, which is then followed by a stage of passive responsiveness in which pups display a distinctive crouch, eye-closing, and extensive piloerection. Prior treatment of pups with alpha-melanocyte-stimulating hormone (α-MSH) reduces each of the passive behaviors. The onset of passive responding during separation can be ...

  6. Oral Bifidobacterium longum expressing alpha-melanocyte-stimulating hormone to fight experimental colitis.

    Science.gov (United States)

    Wei, Pijin; Yang, Yan; Liu, Zhaobing; Huang, Junli; Gong, Yahui; Sun, Hanxiao

    2016-07-01

    The oral delivery of peptides is a highly attractive treatment approach. However, the harsh environment of the gastrointestinal tract limits its application. Here, we utilize Bifidobacterium as a delivery system to orally deliver a potent anti-inflammatory but short duration peptide alpha-melanocyte-stimulating hormone (α-MSH) against experimental colitis. The aim of our study was to facilitate the efficient oral delivery of α-MSH. We designed a vector of pBDMSH and used it to construct a Bifidobacterium longum expressing α-MSH. We then determined the bioactivity of recombinant Bifidobacterium in lipopolysaccharide-induced inflammatory models of HT-29 cells. Finally, we used Bifidobacterium expressing α-MSH against dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Results based on the myeloperoxidase activity, the levels of inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10 and the histological injury of colon tissue reveal recombinant Bifidobacterium was efficient in attenuating DSS-induced ulcerative colitis, suggesting an alternative way to use Bifidobacterium as a delivery system to deliver α-MSH for DSS-induced ulcerative colitis therapy. PMID:26673899

  7. The Alpha-Melanocyte Stimulating Hormone Induces Conversion of Effector T Cells into Treg Cells

    Directory of Open Access Journals (Sweden)

    Andrew W. Taylor

    2011-01-01

    Full Text Available The neuropeptide alpha-melanocyte stimulating hormone (α-MSH has an important role in modulating immunity and homeostasis. The production of IFN-γ by effector T cells is suppressed by α-MSH, while TGF-β production is promoted in the same cells. Such α-MSH-treated T cells have immune regulatory activity and suppress hypersensitivity, autoimmune diseases, and graft rejection. Previous characterizations of the α-MSH-induced Treg cells showed that the cells are CD4+ T cells expressing the same levels of CD25 as effector T cells. Therefore, we further analyzed the α-MSH-induced Treg cells for expression of effector and regulatory T-cell markers. Also, we examined the potential for α-MSH-induced Treg cells to be from the effector T-cell population. We found that the α-MSH-induced Treg cells are CD25+  CD4+ T cells that share similar surface markers as effector T cells, except that they express on their surface LAP. Also, the α-MSH treatment augments FoxP3 message in the effector T cells, and α-MSH induction of regulatory activity was limited to the effector CD25+ T-cell population. Therefore, α-MSH converts effector T cells into Treg cells, which suppress immunity targeting specific antigens and tissues.

  8. Gallium-67-Labeled Lactam Bridge-Cyclized Alpha-Melanocyte Stimulating Hormone Peptide for Primary and Metastatic Melanoma Imaging

    OpenAIRE

    Guo, Haixun; Yang,Jianquan; Shenoy, Nalini; Miao, Yubin

    2009-01-01

    The purpose of this study was to examine the melanoma imaging properties of a novel 67Ga-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptide. A lactam bridge-cyclized α-MSH peptide, DOTA-GlyGlu-CycMSH {DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]}, was synthesized and radiolabeled with 67Ga. The melanoma targeting and pharmacokinetic properties of 67Ga-DOTA-GlyGlu-CycMSH were determined in B16/F1 flank primary melanoma-bearing and B16/F10 pu...

  9. 64Cu-Labeled Alpha-Melanocyte-Stimulating Hormone Analog for MicroPET Imaging of Melanocortin 1 Receptor Expression

    OpenAIRE

    CHENG Zhen; Xiong, Zhengming; Subbarayan, Murugesan; Chen, Xiaoyuan; Gambhir, Sanjiv Sam

    2007-01-01

    The alpha-melanocyte-stimulating hormone (α-MSH) receptor (melanocortin type 1 receptor, or MC1R) plays an important role in the development and growth of melanoma cells. It was found that MC1R was overexpressed on most murine and human melanoma, making it a promising molecular target for melanoma imaging and therapy. Radiolabeled α-MSH peptide and its analogs that can specifically bind with MC1R have been extensively explored for developing novel agents for melanoma detection and radionuclid...

  10. Melanome Therapy with Rhenium Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs. Final report

    International Nuclear Information System (INIS)

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with 188Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, 188Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The 177Lu-DOTA-Re(Arg11)CCMSH and

  11. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Thomas P Quinn

    2005-11-22

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  12. The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients

    Directory of Open Access Journals (Sweden)

    Shishioh-Ikejima Nobue

    2010-08-01

    Full Text Available Abstract Background Despite extensive research, no reliable biological marker for chronic fatigue syndrome (CFS has yet been identified. However, hyperactivation of melanotrophs in the pituitary gland and increased levels of plasma alpha-melanocyte-stimulating hormone (α-MSH have recently been detected in an animal model of chronic stress. Because CFS is considered to be caused partly by chronic stress events, increased α-MSH plasma levels may also occur in CFS patients. We therefore examined α-MSH levels in CFS patients. Methods Fifty-five CFS patients, who were previously diagnosed within 10 years of with the disease, were enrolled in this study. Thirty healthy volunteers were studied as controls. Fasting bloods samples were collected in the morning and evaluated for their plasma levels of α-MSH, adrenocorticotropic hormone (ACTH, serum cortisol and dehydroepiandrosterone sulfate (DHEA-S. Mean levels of α-MSH were compared between the CFS and control groups using Welch's t test. Results The mean plasma α-MSH concentration in the CFS group (17.9 ± 1.0 pg/mL was significantly higher than that in healthy controls (14.5 ± 1.0 pg/mL, p = 0.02. However, there was a wide range of values in the CFS group. The factors correlated with the plasma α-MSH values were analyzed using Spearman's rank correlation. A negative correlation was found between the duration of the CFS and the plasma α-MSH values (p = 0.04, rs = -0.28, but no correlations with ACTH, cortisol or DHEA-S levels were identified (p = 0.55, 0.26, 0.33, respectively. The CFS patients were divided into two groups: patients diagnosed for ≤ 5 years' duration, and those diagnosed for 5-10 years' duration. They were compared with the healthy controls using one-way ANOVA and Tukey-Kramer multiple comparison tests. The mean α-MSH concentration in the ≤ 5 years group was 20.8 ± 1.2 pg/mL, which was significantly higher than that in the healthy controls (p Conclusions CFS patients with

  13. In vivo multiplex quantitative analysis of 3 forms of alpha melanocyte stimulating hormone in pituitary of prolyl endopeptidase deficient mice

    Directory of Open Access Journals (Sweden)

    Perroud Bertrand

    2009-06-01

    Full Text Available Abstract Background In vitro reactions are useful to identify putative enzyme substrates, but in vivo validation is required to identify actual enzyme substrates that have biological meaning. To investigate in vivo effects of prolyl endopeptidase (PREP, a serine protease, on alpha melanocyte stimulating hormone (α-MSH, we developed a new mass spectrometry based technique to quantitate, in multiplex, the various forms of α-MSH. Methods Using Multiple Reaction Monitoring (MRM, we analyzed peptide transitions to quantify three different forms of α-MSH. Transitions were first confirmed using standard peptides. Samples were then analyzed by mass spectrometry using a triple quadrupole mass spectrometer, after elution from a reverse phase C18 column by a gradient of acetonitrile. Results We first demonstrate in vitro that PREP digests biological active alpha melanocyte stimulating hormone (α-MSH1–13, by cleaving the terminal amidated valine and releasing a truncated alpha melanocyte stimulating hormone (α-MSH1–12 product – the 12 residues α-MSH form. We then use the technique in vivo to analyze the MRM transitions of the three different forms of α-MSH: the deacetylated α-MSH1–13, the acetylated α-MSH1–13 and the truncated form α-MSH1–12. For this experiment, we used a mouse model (PREP-GT in which the serine protease, prolyl endopeptidase, is deficient due to a genetrap insertion. Here we report that the ratio between acetylated α-MSH1–13 and α-MSH1–12 is significantly increased (P-value = 0.015, N = 6 in the pituitaries of PREP-GT mice when compared to wild type littermates. In addition no significant changes were revealed in the relative level of α-MSH1–13 versus the deacetylated α-MSH1–13. These results combined with the demonstration that PREP digests α-MSH1–13 in vitro, strongly suggest that α-MSH1–13 is an in vivo substrate of PREP. Conclusion The multiplex targeted quantitative peptidomics technique we

  14. Effect of DOTA Position on Melanoma Targeting and Pharmacokinetic Properties of 111In-labeled Lactam Bridge-Cyclized Alpha-Melanocyte Stimulating Hormone Peptide

    OpenAIRE

    Guo, Haixun; Yang,Jianquan; Gallazzi, Fabio; Prossnitz, Eric R.; Sklar, Larry A.; Miao, Yubin

    2009-01-01

    The purpose of this study was to examine the effect of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) position on melanoma targeting and pharmacokinetics of radiolabeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptide.

  15. Plasma neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (a-MSH) levels in patients with or without hypertension and/or obesity: a pilot study

    OpenAIRE

    Baltazi, Maria; Katsiki, Niki; Savopoulos, Christos; Iliadis, Fotios; Koliakos, George; Hatzitolios, Apostolos I.

    2011-01-01

    Aim: Obesity frequently co-exists with hypertension (HTN). Hypothalamus neuropeptides such as neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (a-MSH) interact with leptin, an anorexic peptide produced mainly by adipose tissue and are involved in the regulation of appetite, energy balance and sympathetic nervous system (SNS) activity, possibly contributing to blood pressure (BP) elevation. We compared plasma NPY and a-MSH levels between patients with or without hypertension and/o...

  16. 64Cu-labeled alpha-melanocyte-stimulating hormone analog for microPET imaging of melanocortin 1 receptor expression.

    Science.gov (United States)

    Cheng, Zhen; Xiong, Zhengming; Subbarayan, Murugesan; Chen, Xiaoyuan; Gambhir, Sanjiv Sam

    2007-01-01

    The alpha-melanocyte-stimulating hormone (alpha-MSH) receptor (melanocortin type 1 receptor, or MC1R) plays an important role in the development and growth of melanoma cells. It was found that MC1R was overexpressed on most murine and human melanoma, making it a promising molecular target for melanoma imaging and therapy. Radiolabeled alpha-MSH peptide and its analogs that can specifically bind with MC1R have been extensively explored for developing novel agents for melanoma detection and radionuclide therapy. The goal of this study was to evaluate a 64Cu-labeled alpha-MSH analog, Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys(DOTA)-NH2 (DOTA-NAPamide), as a potential molecular probe for microPET imaging of melanoma and MC1R expression in melanoma xenografted mouse models. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated NAPamide was synthesized and radiolabeled with 64Cu (t1/2=12 h) in NH4OAc (0.1 M; pH 5.5) buffered solution for 60 min at 50 degrees C. Cell culture studies reveal rapid and high uptake and internalization of 64Cu-DOTA-NAPamide in B16F10 cells. Over 90% of receptor-bound tracer is internalized at 3 h incubation. A cellular retention study demonstrates that the receptor-bound 64Cu-DOTA-NAPamide is slowly released from the B16F10 cells into the medium; 66% of the radioactivity is still associated with the cells even after 3 h incubation. The biodistribution of 64Cu-DOTA-NAPamide was then investigated in C57BL/6 mice bearing subcutaneous murine B16F10 melanoma tumors with high capacity of MC1R and Fox Chase Scid mice bearing human A375M melanoma with a relatively low number of MC1R receptors. Tumor uptake values of 64Cu-DOTA-NAPamide are found to be 4.63 +/- 0.45% and 2.49 +/- 0.31% ID/g in B16F10 and A375M xenografted melanoma at 2 h postinjection (pi), respectively. The B16F10 tumor uptake at 2 h pi is further inhibited to 2.29 +/- 0.24% ID/g, while A375M tumor uptake at 2 h pi remains 2.20 +/- 0.41% ID/g with a coinjection of excess

  17. Alpha-melanocyte-stimulating hormone modulates activation of NF-kappa B and AP-1 and secretion of interleukin-8 in human dermal fibroblasts.

    Science.gov (United States)

    Böhm, M; Schulte, U; Kalden, H; Luger, T A

    1999-10-20

    Alpha-melanocyte-stimulating hormone (alpha-MSH) has evolved as a mediator of diverse biological activities in an ever-growing number of non-melanocytic cell types. One mechanism by which alpha-MSH exerts its effects is modulation of AP-1 and NF-kappa B. These two transcription factors also play an important role in fibroblasts, in extracellular matrix composition, and in cytokine expression. By use of electric mobility shift assays, we demonstrate that alpha-MSH (10(-6) to 10(-14) M) activates AP-1 in human dermal fibroblasts, whereas coincubation with interleukin-1 beta (IL-1 beta) results in suppression of its activation. alpha-MSH also induces activation of NF-kappa B but does not modulate DNA binding on costimulation with IL-1 beta. Since AP-1 and NF-kappa B are key elements in controlling interleukin-8 (IL-8) transcription, human fibroblasts were treated with alpha-MSH and IL-1 beta for 24 hours, and cytokine levels in the supernatants were measured by ELISA. alpha-MSH alone had little effect, whereas coincubation with IL-1 beta led to marked downregulation of IL-8 secretion (at most 288 +/- 152 ng/mL) when compared to treatment with IL-1 beta alone (919 +/- 157 ng/mL). Our results indicate that alpha-MSH exerts modulatory effects on the activation of NF-kappa B and AP-1, and that it can regulate chemokine secretion in human dermal fibroblasts. These effects of alpha-MSH may have important regulatory functions in extracellular matrix composition, wound healing, or angiogenesis. PMID:10816661

  18. 203Pb-Labeled Alpha-Melanocyte-Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

    Energy Technology Data Exchange (ETDEWEB)

    Yubin, Miao; Figueroa, Said D.; Fisher, Darrell R.; Moore, Herbert A.; Testa, Richard F.; Hoffman, Timothy J.; Quinn, Thomas P.

    2008-05-01

    Abbreviations: a-MSH; alpha melanocyte stimulating hormone, DOTA; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, Re(Arg11)CCMSH; DOTA-[Cys3,4,10, D-Phe7, Arg11]a-MSH3-13, NDP; [Nle4,d-Phe7] a-MSH3-13. Abstract Peptide-targeted alpha therapy with 200 mCi of 212Pb-DOTA-Re(Arg11)CCMSH cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-day study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient specific dosimetry and to monitor the tumor response to 212Pb-DOTA-Re(Arg11)CCMSH therapy. The purpose of this study was to evaluate the potential of 203Pb-DOTA-Re(Arg11)CCMSH as a matched-pair SPECT imaging agent for 212Pb-DOTA-Re(Arg11)CCMSH. Method: DOTA-Re(Arg11)CCMSH was labeled with 203Pb in 0.5 M NH4OAc buffer at pH 5.4. The internalization and efflux of 203Pb-DOTA-Re(Arg11)CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of 203Pb-DOTA-Re(Arg11)CCMSH were examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT imaging study was performed with 203Pb-DOTA-Re(Arg11)CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h post-injection. Results: 203Pb-DOTA-Re(Arg11)CCMSH was easily prepared in NH4OAc buffer and completely separated from the excess non-radiolabeled peptide by RP-HPLC. 203Pb-DOTA-Re(Arg11)CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of 203Pb-DOTA-Re(Arg11)CCMSH activity internalized after a 20-min incubation at 25C. After incubating the cells in culture media for 20 min, 78% of internalized activity remained in the cells. 203Pb-DOTA-Re(Arg11)CCMSH exhibited similar biodistribution pattern with 212Pb-DOTA-Re(Arg11)CCMSH in B16/F1 melanoma-bearing mice. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor uptake of 12.00 +/- 3.20 %ID/g at 1 h post-injection. The tumor uptake gradually decreased to 3.43 +/- 1.12 %ID/g at 48 h post-injection. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor to kidney

  19. Profiles of alpha-melanocyte-stimulating hormone in the Japanese flounder as revealed by a newly developed time-resolved fluoroimmunoassay and immunohistochemistry.

    Science.gov (United States)

    Amiya, Noriko; Amano, Masafumi; Takahashi, Akiyoshi; Yamanome, Takeshi; Yamamori, Kunio

    2007-03-01

    Profiles of alpha-melanocyte-stimulating hormone (alpha-MSH) in the Japanese flounder were examined by a newly developed time-resolved fluoroimmunoassay (TR-FIA) and immunohistochemistry. A TR-FIA for alpha-MSH was newly developed, and its levels in the pituitary gland and plasma of Japanese flounder reared in a white or black tank for 5 months were compared. A competitive assay using two antibodies was performed among secondary antibodies in the solid phase, alpha-MSH antibodies, samples, and europium-labeled Des-Ac-alpha-MSH. The sensitivity of the assay, defined as twice the standard deviation at a zero dose, was 0.98 ng/ml (49 pg/well). The intra- and interassay coefficients of variation of the assay were 8.8% (n=8) and 17.3% (n=5), respectively, at about 50% binding. Cross-reactivities of Des-Ac-alpha-MSH and Di-Ac-alpha-MSH were about 100%. Cross-reactivities of adrenocorticotropic hormone, salmon gonadotropin-releasing hormone (sGnRH), and chicken GnRH-II were less than 0.2%, and that of melanin-concentrating hormone was less than 2.0% at 50% binding. Displacement curves of serially twofold-diluted hypothalamus extract, pituitary gland extract, and plasma extract of Japanese flounder with the assay buffer were parallel to the alpha-MSH standard curve. Moreover, displacement curves of serially twofold-diluted hypothalamus and/or pituitary gland extract of masu salmon, goldfish, red seabream, Japanese eel, tiger puffer, and barfin flounder with the assay buffer were also parallel to the alpha-MSH standard. In Japanese flounder, total immunoreactive (ir)-alpha-MSH levels in the pituitary gland were lower in the black tank, whereas those in the plasma tended to be higher in the black tank, suggesting that the synthesis and release of alpha-MSH are higher in the black tank. alpha-MSH-ir cells were detected in the pars intermedia and a small part of the pars distalis of the pituitary gland. alpha-MSH-ir cell bodies were located in the basal hypothalamus and alpha

  20. Reducing renal uptake of 9Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    International Nuclear Information System (INIS)

    Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of 9Y- and 177Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys3,4,1, D-Phe7, Arg11]α-melanocyte stimulating hormone3-13 {DOTA-Re(Arg11)CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu2, Arg11)CCMSH was designed, synthesized and labeled with 9Y and 177Lu. Pharmacokinetics of 9Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: 9Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH exhibited significantly (P9Y- and 177Lu-DOTA-Re(Arg11)CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 9Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH were 28.16% and 28.81% of those of 9Y- and 177Lu-DOTA-Re(Arg11)CCMSH, respectively, at 4 h postinjection. 9Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH displayed higher tumor-to-kidney uptake ratios than 9Y- and 177Lu-DOTA-Re(Arg11)CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 9Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH was 2.28 and 1.69 times of 9Y- and 177Lu-DOTA-Re(Arg11)CCMSH, respectively, at 4 h postinjection. The 9Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH activity accumulation was low in normal organs except for kidney. Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 9Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma

  1. De novo design, synthesis, and pharmacology of alpha-melanocyte stimulating hormone analogues derived from somatostatin by a hybrid approach.

    Science.gov (United States)

    Han, Guoxia; Haskell-Luevano, Carrie; Kendall, Laura; Bonner, Gregg; Hadley, Mac E; Cone, Roger D; Hruby, Victor J

    2004-03-11

    A number of alpha-melanotropin (alpha-MSH) analogues have been designed de novo, synthesized, and bioassayed at different melanocortin receptors from frog skin (fMC1R) and mouse/rat (mMC1R, rMC3R, mMC4R, and mMC5R). These ligands were designed from somatostatin by a hybrid approach, which utilizes a modified cyclic structure (H-d-Phe-c[Cys---Cys]-Thr-NH(2)) related to somatostatin analogues (e.g. sandostatin) acting at somatostatin receptors, CTAP which binds specifically to micro opioid receptors, and the core pharmacophore of alpha-MSH (His-Phe-Arg-Trp). Ligands designed were H-d-Phe-c[XXX-YYY-ZZZ-Arg-Trp-AAA]-Thr-NH(2) [XXX and AAA = Cys, d-Cys, Hcy, Pen, d-Pen; YYY = His, His(1'-Me), His(3'-Me); ZZZ = Phe and side chain halogen substituted Phe, d-Phe, d-Nal(1'), and d-Nal(2')]. The compounds showed a wide range of bioactivities at the frog skin MC1R; e.g. H-d-Phe-c[Hcy-His-d-Phe-Arg-Trp-Cys]-Thr-NH(2) (6, EC(50) = 0.30 nM) and H-d-Phe-c[Cys-His-d-Phe-Arg-Trp-d-Cys]-Thr-NH(2) (8, EC(50) = 0.10 nM). In addition, when a lactam bridge was used as in H-d-Phe-c[Asp-His-d-Phe-Arg-Trp-Lys]-Thr-NH(2) (7, EC(50) = 0.10 nM), the analogue obtained is as potent as alpha-MSH in the frog skin MC1R assay. Interestingly, switching the bridge of 6 to give H-d-Phe-c[Cys-His-d-Phe-Arg-Trp-Hcy]-Thr-NH(2) (5, EC(50) = 1000 nM) led to a 3000-fold decrease in agonist activity. An increase in steric size in the side chain of d-Phe(7) reduced the bioactivity significantly. For example, H-d-Phe-c[Cys-His-d-Nal(1')-Arg-Trp-d-Cys]-Thr-NH(2) (24) is 2000-fold less active than 9. On the other hand, H-d-Phe-c[Cys-His-d-Phe(p-I)-Arg-Trp-d-Cys]-Thr-NH(2) (23) lost all agonist activity and became a weak antagonist (IC(50) = 1 x 10(-5) M). Furthermore, the modified CTAP analogues with a d-Trp at position 7 all showed weak antagonist activities (EC(50) = 10(-6) to 10(-7) M). Compounds bioassayed at mouse/rat MCRs displayed intriguing results. Most of them are potent at all four receptors tested (m

  2. Replacement of Lys Linker with Arg Linker Resulting in Improved Melanoma Uptake and Reduced Renal Uptake of Tc-99m-Labeled Arg-Gly-Asp-Conjugated Alpha-Melanocyte Stimulating Hormone Hybrid Peptide

    OpenAIRE

    Yang, Jianquan; Guo, Haixun; Padilla, R. Steve; Berwick, Marianne; Miao, Yubin

    2010-01-01

    The purpose of this study was to reduce the non-specific renal uptake of Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide through structural modification or L-lysine co-injection. The RGD motif {cyclic(Arg-Gly-Asp-dTyr-Asp)} was coupled to [Cys3,4,10, d-Phe7, Arg11]α-MSH3-13 {(Arg11)CCMSH} through the Arg linker (substituting the Lys linker) to generate a novel RGD-Arg-(Arg11)CCMSH hybrid peptide. The melanoma targeting and pharmacokinetic properties of...

  3. Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging

    International Nuclear Information System (INIS)

    Introduction: The purpose of this study was to examine whether 99mTc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and αvβ3 integrin receptors was superior in melanoma targeting to 99mTc-labeled α-MSH or RGD peptide targeting only the MC1 or αvβ3 integrin receptor. Methods: RGD-Lys-(Arg11)CCMSH, RAD-Lys-(Arg11)CCMSH and RGD-Lys-(Arg11)CCMSHscramble were designed to target both MC1 and αvβ3 integrin receptors, MC1 receptor only and αvβ3 integrin receptor only, respectively. The MC1 or αvβ3 integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of 99mTc-labeled RGD-Lys-(Arg11)CCMSH, RAD-Lys-(Arg11)CCMSH and RGD-Lys-(Arg11)CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of 99mTc-RGD-Lys-(Arg11)CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts. Results: RGD-Lys-(Arg11)CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and αvβ3 integrin receptors, whereas RAD-Lys-(Arg11)CCMSH or RGD-Lys-(Arg11)CCMSHscramble lost their αvβ3 integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of 99mTc-RGD-Lys-(Arg11)CCMSH was 2.49 and 2.24 times (P 99mTc-RAD-Lys-(Arg11)CCMSH and 99mTc-RGD-Lys-(Arg11)CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg11)CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of 99mTc-RGD-Lys-(Arg11)CCMSH, whereas the coinjection of RGD+(Arg11)CCMSH peptide mixture could block 66% of the tumor uptake of 99mTc-RGD-Lys-(Arg11)CCMSH. Conclusions: Targeting both MC1 and αvβ3 integrin receptors enhanced the melanoma uptake of 99mTc-RGD-Lys-(Arg11)CCMSH in M21 human melanoma xenografts. Flank M21 human melanoma tumors were clearly visualized by single

  4. The Natriuretic Mechanism of γ-Melanocyte-Stimulating Hormone

    OpenAIRE

    Kathpalia, Paru P.; Charlton, Carol; Rajagopal, Madhumitha; Pao, Alan C.

    2011-01-01

    γ-Melanocyte Stimulating Hormone (γ-MSH) regulates sodium (Na+) balance and blood pressure through activation of the melanocortin receptor 3 (MC3-R). The mechanism of the natriuretic effect is proposed to involve binding of MC3-R either in the kidney to directly inhibit tubular Na+ transport or in the brain to inhibit central neural pathways that control renal tubular Na+ absorption. This study aimed to clarify the mechanism involved in the natriuretic effect of γ-MSH on MC3-R in kidney cells...

  5. Gamma-melanocyte-stimulating hormone-like immunoreactivity in blood cells of human eosinophilic patients.

    Science.gov (United States)

    Johansson, O; Virtanen, M; Hilliges, M; Hansson, L O

    1991-01-01

    The immunohistochemical localization of the peptide gamma-melanocyte-stimulating hormone (gamma-MSH) within human polymorphonuclear leucocytes of blood from eosinophilic patients is described. The gamma-MSH immunoreactivity was observed only in neutrophilic granulocytes leaving all other cell types immuno-negative. PMID:1805488

  6. Nitric oxide enhances the sensitivity of alpaca melanocytes to respond to α-melanocyte-stimulating hormone by up-regulating melanocortin-1 receptor

    International Nuclear Information System (INIS)

    Nitric oxide (NO) and α-melanocyte-stimulating hormone (α-MSH) have been correlated with the synthesis of melanin. The NO-dependent signaling of cellular response to activate the hypothalamopituitary proopiomelanocortin system, thereby enhances the hypophysial secretion of α-MSH to stimulate α-MSH-receptor responsive cells. In this study we investigated whether an NO-induced pathway can enhance the ability of the melanocyte to respond to α-MSH on melanogenesis in alpaca skin melanocytes in vitro. It is important for us to know how to enhance the coat color of alpaca. We set up three groups for experiments using the third passage number of alpaca melanocytes: the control cultures were allowed a total of 5 days growth; the UV group cultures like the control group but the melanocytes were then irradiated everyday (once) with 312 mJ/cm2 of UVB; the UV + L-NAME group is the same as group UV but has the addition of 300 μM L-NAME (every 6 h). To determine the inhibited effect of NO produce, NO produces were measured. To determine the effect of the NO to the key protein and gene of α-MSH pathway on melanogenesis, the key gene and protein of the α-MSH pathway were measured by quantitative real-time PCR and Western immunoblotting. The results provide exciting new evidence that NO can enhance α-MSH pathway in alpaca skin melanocytes by elevated MC1R. And we suggest that the NO pathway may more rapidly cause the synthesis of melanin in alpaca skin under UV, which at that time elevates the expression of MC1R and stimulates the keratinocytes to secrete α-MSH to enhance the α-MSH pathway on melanogenesis. This process will be of considerable interest in future studies.

  7. Effects of UVB and 7, 12, dimethylbenz(alpha)anthracene (DMBA) on epidermal melanocytes of the tail in C57BL mice

    Energy Technology Data Exchange (ETDEWEB)

    Blog, F.B.; Szabo, G.

    1979-12-01

    The morphological and numerical changes in the epidermal melanocyte system of the tail of C57BL mice were studied after exposure to 7, 12, dimethylbenz(alpha)anthracene(DMBA) followed by UVB irradiation. Biopsies were studied by the combined skin-splitting DOPA and electron microscopic techniques. After 10 weeks of DMBA treatment the following changes were observed: the original brick-like arrangement of melanocytes became confluent, melanocytes were irregularly shaped, dendrites shortened and clumped together, and the outer root sheaths of the hair follicles became covered with melanocytes. Damage of melanocytes by the DMBA treatment was seen, but no inflammation or tumor formation was observed.

  8. Oral delivery of Bifidobacterium longum expressing α-melanocyte-stimulating hormone to combat ulcerative colitis.

    Science.gov (United States)

    Wei, Pijin; Yang, Yan; Ding, Qing; Li, Xiuying; Sun, Hanxiao; Liu, Zhaobing; Huang, Junli; Gong, Yahui

    2016-02-01

    α-Melanocyte-stimulating hormone (α-MSH) is a tridecapeptide derived from pro-opiomelanocortin that exhibits potent anti-inflammatory properties by regulating the production of inflammatory mediators. This peptide has been well established in several inflammatory models, including inflammatory bowel disease (IBD). However, its extremely short duration in vivo limits its clinical application. To address this limitation, Bifidobacterium was used here as a carrier to deliver α-MSH. We utilized α-MSH-engineered Bifidobacterium against IBD, which is closely linked to immune and intestinal microbiota dysfunction. First, we constructed a Bifidobacterium longum secreting α-MSH (B. longum-α-MSH). We then tested the recombinant α-MSH expression and determined its bioactivity in HT-29 cells. To assess its effectiveness, B. longum-α-MSH was used against an ulcerative colitis (UC) model in rats induced by dextran sulfate sodium. The data showed that α-MSH expression in B. longum-α-MSH was effective, and its biological activity was similar to the synthesized one. This UC model experiment indicated that B. longum-α-MSH successfully colonized the intestinal gut, expressed bioactive α-MSH and had a significant anti-inflammatory effect. The results demonstrate the feasibility of preventing IBD by using B. longum-α-MSH. PMID:26567174

  9. Stimulated human melanocytes express and release interleukin-8, which is inhibited by luteolin: relevance to early vitiligo.

    Science.gov (United States)

    Miniati, A; Weng, Z; Zhang, B; Therianou, A; Vasiadi, M; Nicolaidou, E; Stratigos, A J; Antoniou, C; Theoharides, T C

    2014-01-01

    Vitiligo is a disorder of depigmentation, for which the pathogenesis is as yet unclear. Interleukin (IL)-8 (CXCL8) is a key inflammatory chemokine. We investigated the regulation of IL-8 production in human melanocytes, and the IL-8 serum levels and skin gene expression in patients with vitiligo and in controls. Cultured melanocytes were stimulated for 24 h with tumour necrosis factor (TNF) 100 ng/mL and IL-1β 10 ng/mL, with or without pretreatment with luteolin 50 μmol/L for 30 min, and IL-8 release was measured by ELISA. Serum cytokines were measured by a microbead array. Skin biopsies were taken from healthy subjects (n = 14) as well as from marginal lesional and nonlesional skin from patients with vitiligo (n = 15). IL-8 gene expression was evaluated by quantitative real time PCR. Both TNF and IL-1β stimulated significant IL-8 release (P < 0.01) from melanocytes, whereas pretreatment with luteolin significantly inhibited this effect (P < 0.01). IL-8 gene expression was significantly increased in vitiligo compared with control skin (P < 0.05). IL-8 may be involved in vitiligo inflammation. Inhibition by luteolin of IL-8 release could be useful for vitiligo therapy. PMID:23782102

  10. Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA

    International Nuclear Information System (INIS)

    Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C

  11. UVB-Stimulated TNFα Release from Human Melanocyte and Melanoma Cells Is Mediated by p38 MAPK

    Directory of Open Access Journals (Sweden)

    Visalini Muthusamy

    2013-08-01

    Full Text Available Ultraviolet (UV radiation activates cell signaling pathways in melanocytes. As a result of altered signaling pathways and UV-induced cellular damage, melanocytes can undergo oncogenesis and develop into melanomas. In this study, we investigated the effect of UV-radiation on p38 MAPK (mitogen-activated protein kinase, JNK and NFκB pathways to determine which plays a major role in stimulating TNFα secretion in human HEM (melanocytes and MM96L (melanoma cells. MM96L cells exhibited 3.5-fold higher p38 activity than HEM cells at 5 min following UVA + B radiation and 1.6-fold higher JNK activity at 15–30 min following UVB+A radiation, while NFκB was minimally activated in both cells. Irradiated HEM cells had the greatest fold of TNFα secretion (UVB: 109-fold, UVA + B: 103-fold & UVB+A: 130-fold when co-exposed to IL1α. The p38 inhibitor, SB202190, inhibited TNFα release by 93% from UVB-irradiated HEM cells. In the UVB-irradiated MM96L cells, both SB202190 and sulfasalazine (NFκB inhibitor inhibited TNFα release by 52%. Although, anisomycin was a p38 MAPK activator, it inhibited TNFα release in UV-irradiated cells. This suggests that UV-mediated TNFα release may occur via different p38 pathway intermediates compared to those stimulated by anisomycin. As such, further studies into the functional role p38 MAPK plays in regulating TNFα release in UV-irradiated melanocyte-derived cells are warranted.

  12. Hypergravity differentially modulates cGMP efflux in human melanocytic cells stimulated by nitric oxide and natriuretic peptides

    Science.gov (United States)

    Ivanova, K.; Stieber, C.; Lambers, B.; Block, I.; Krieg, R.; Wellmann, A.; Gerzer, R.

    Nitric oxide NO plays a key role in many patho physiologic processes including inflammation and skin cancer The diverse cellular effects of NO are mainly mediated by activation of the soluble guanylyl cyclase sGC isoform that leads to increases in intracellular cGMP levels whereas the membrane-bound isoforms serve as receptors for natriuretic peptides e g ANP In human skin epidermal melanocytes represent the principal cells for skin pigmentation by synthesizing the pigment melanin Melanin acts as a scavenger for free radicals that may arise during metabolic stress as a result of potentially harmful effects of the environment In previous studies we found that long-term exposure to hypergravity stimulated cGMP efflux in normal human melanocytes NHMs and non-metastatic melanoma cells at least partly by an enhanced expression of the multidrug resistance proteins MRP and cGMP transporters MRP4 5 The present study investigated whether hypergravity generated by centrifugal acceleration may modulate the cGMP efflux in NO-stimulated NHMs and melanoma cells MCs with different metastatic potential The NONOates PAPA-NO and DETA-NO were used as direct NO donors for cell stimulation In the presence of 0 1 mM DETA-NO t 1 2 sim 20 h long-term application of hypergravity up to 5 g for 24 h reduced intracellular cGMP levels by stimulating cGMP efflux in NHMs and non-metastatic MCs in comparison to 1 g whereas exposure to 5 g for 6 h in the presence of 0 1 mM PAPA-NO t 1 2 sim 30 min was not effective The hypergravity-stimulated

  13. Small-Animal PET of Melanocortin 1 Receptor Expression Using a 18F-Labeled α-Melanocyte-Stimulating Hormone Analog

    OpenAIRE

    CHENG Zhen; Zhang, Lan; Graves, Edward; Xiong, Zhengming; Dandekar, Mangal; Chen, Xiaoyuan; Gambhir, Sanjiv Sam

    2007-01-01

    18F-Labeled small synthetic peptides have emerged as attractive probes for imaging various molecular targets with PET. The α-melanocyte-stimulating hormone (α-MSH) receptor (melano-cortin type 1 receptor [MC1R]) is overexpressed in most murine and human melanomas. It is a promising molecular target for diagnosis and therapy of melanomas. However, 18F compounds have not been successfully developed for imaging the MC1R.

  14. Fluorine-18-labeled [Nle4,D-Phe7]-α-MSH, an α-melanocyte stimulating hormone analogue

    International Nuclear Information System (INIS)

    The α-melanocyte stimulating hormone (α-MSH) analogue [N1e4,D-Phe7]-α-MSH was labeled with 18F using N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) in >80% radiochemical yield. The IC50 values of [N1e4,D-Phe7]-α-MSH and para-fluorobenzoyl-[N1e4,D-Phe7]-α-MSH ([N1e4,D-Phe7,Lys11-(18F)PFB]-α-MSH) for inhibiting the binding of meta-[131I]iodobenzoyl-[N1e4,D-Phe7]-α-MSH ([N1e4,D-Phe7,Lys11-(131I)MIB]-α-MSH) to B16-F1 murine melanoma cells were 89 ± 9 pM and 112 ± 22 pM, respectively, suggesting that addition of 4-fluorobenzoate did not compromise α-MSH receptor binding affinity. Binding of [N1e4,D-Phe7,Lys11-(18F)PFB]-α-MSH was influenced by the specific activity of the preparation (400-1000 Ci/mmol). The normal tissue clearance of [N1e4,D-Phe7,Lys11-(18F)PFB]-α-MSH in mice was quite rapid, with little evidence for defluorination

  15. A 99mTc(CO)3-labeled pyrazolyl-α-melanocyte-stimulating hormone analog conjugate for melanoma targeting

    International Nuclear Information System (INIS)

    Melanoma primary tumors can be, in most cases, removed surgically, whereas there is no satisfactory treatment for metastatic melanoma, being almost always lethal at this stage. Therefore, early detection of primary melanoma tumors is essential. The finding that melanocortin-1 receptor (MC1R) is overexpressed in isolated melanoma cells and melanoma tissues led to the radiolabeling of several α-melanocyte-stimulating hormone (α-MSH) analogs for early detection and treatment of melanoma. We have coupled the α-MSH analog Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2, through the ε-amino group of Lys11, to a pyrazolyl-containing chelator (pz). The resulting pz-α-MSH analog reacted with the fac-[99mTc(CO)3]+ moiety, giving [Ac-Nle4,Asp5,D-Phe7,Lys11(pz-99mTc(CO)3)]α-MSH4-11 in high yield, high specific activity and high radiochemical purity. This radioconjugate, which presents remarkable stability in vitro, exhibited time- and temperature-dependent internalization (4 h at 37oC; 56.7% maximum internalization) and high cellular retention (only 38% was released from the cell after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake [4.2±0.9%ID/g, at 4 h postinjection (p.i.)] was also obtained in melanoma-bearing C57BL6 mice. The in vivo affinity and specificity of the radioconjugate to MC1R were demonstrated by receptor-blocking studies with the potent NDP-MSH agonist (63.5% reduction in tumor uptake at 4 h p.i.)

  16. Tyrosol and Its Analogues Inhibit Alpha-Melanocyte-Stimulating Hormone Induced Melanogenesis

    Directory of Open Access Journals (Sweden)

    Kuo-Ching Wen

    2013-11-01

    Full Text Available Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, 2-hydroxyphenylacetic acid (7, or salidroside (11 resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1, 4-hydroxyphenylacetic acid (5 and 2-hydroxyphenylacetic acid (7 suppressed MC1R expression. Tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, and 2-hydroxyphenylacetic acid (7 inhibited α-MSH induced TRP-1 expression, but salidroside (11 did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, and 2-hydroxyphenylacetic acid (7 at concentrations below 4 mM and salidroside (11 at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.

  17. Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats: Roles of Neuropeptide Y and α-Melanocyte-Stimulating Hormone.

    Science.gov (United States)

    Shi, Zhigang; Cassaglia, Priscila A; Gotthardt, Laura C; Brooks, Virginia L

    2015-12-01

    Pregnancy increases sympathetic nerve activity (SNA), but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose-anesthetized pregnant and nonpregnant rats. Baseline arterial pressure (AP) was lower, and heart rate (HR), lumbar sympathetic activity, and splanchnic SNA were higher in pregnant rats compared with nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased AP and HR more in pregnant rats than in nonpregnant rats and decreased lumbar SNA only in pregnant rats. Similarly, after arcuate muscimol nanoninjections, the decreases in AP, HR, and lumbar, renal, and splanchnic sympathetic nerve activities were greater in pregnant rats than in nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory neuropeptide Y (NPY) and excitatory α-melanocyte-stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased AP, HR, and lumbar SNA in pregnant rats but not in nonpregnant rats. Conversely, paraventricular nucleus NPY expression was reduced in pregnant animals, and although blockade of paraventricular NPY Y1 receptors increased AP, HR, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor, and bradycardic effects of paraventricular NPY nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal SNA during pregnancy, likely due in part to decreased tonic NPY inhibition and increased tonic α-melanocyte-stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus. PMID:26483343

  18. Ultraviolet radiation directly induces pigment production by cultured human melanocytes

    International Nuclear Information System (INIS)

    In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of 14C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus, it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms

  19. Withaferin A abolishes the stem cell factor-stimulated pigmentation of human epidermal equivalents by interrupting the auto-phosphorylation of c-KIT in human melanocytes.

    Science.gov (United States)

    Terazawa, Shuko; Nakajima, Hiroaki; Fukasawa, Katsunori; Imokawa, Genji

    2015-01-01

    We characterized the mechanism(s) underlying the abrogating effect of withaferin A (WFA) on the stem cell factor (SCF)-stimulated pigmentation of human epidermal equivalents (HEEs). Increased gene and protein expression levels of tyrosinase, tyrosinase-related protein1, dopachrome tautomerase, PMEL17, c-KIT and their targeted transcription factor, microphthalmia-associated transcription factor (MITF) were significantly reversed at days 7 and 10, respectively, by treatment with WFA. In WFA-treated normal human melanocytes (NHMs), there was a marked deficiency in the SCF-stimulated series of phosphorylations of c-KIT, Shc, Raf-1, MEK, ERK, MITF and CREB. Treatment with dithiothreitol (DTT) distinctly abolished the suppressive effect of WFA on the SCF-stimulated phosphorylation of c-KIT in NHMs. On the other hand, even after incubation at 4 °C for 2 h with 5 nM SCF, followed by the removal of unbound SCF by washing and then raising the temperature to 37 °C to start the signaling reaction, c-KIT was distinctly phosphorylated to a similar extent by incubation for 15 min with SCF only or with SCF + WFA. These findings indicate that WFA attenuates the SCF-induced activation of c-KIT in NHMs by interrupting the auto-phosphorylation of c-KIT through DTT-suppressible Michael addition thioalkylation reactions without interrupting the binding of SCF to the c-KIT receptor. PMID:25376854

  20. Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in α-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells.

    Science.gov (United States)

    Yoon, Hoon-Seok; Hyun, Chang-Gu; Lee, Nam-Ho; Park, Sung-Soo; Shin, Dong-Bum

    2016-06-01

    Previous research showed that resveratrol (trans-3,4',5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4',5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. Firstly, pterostilbene showed the inhibitory effects on α-melanocyte stimulating hormone (MSH)-induced melanin synthesis stronger than RTE, resveratrol, and arbutin. Pterostilbene inhibited melanin biosynthesis in a dose-dependent manner in α-MSH-stimulated B16/F10 murine melanoma cells. Specifically, melanin content and intracellular tyrosinase activity were inhibited by 63% and 58%, respectively, in response to treatment with 10 μM of pterostilbene. The results of western blot analysis indicated that pterostilbene induced downregulation of tyrosinase protein expression and suppression of α-MSH-stimulated melan-A protein expression stronger than RTE or resveratrol. Based on these results, our study suggests that pterostilbene can induce hypopigmentation effects more effectively than resveratrol and RTE, and it functions via downregulation of protein expression associated with hyperpigmentation in α-MSH-triggered B16/F10 murine melanoma cells. PMID:27390733

  1. Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in α-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells

    Science.gov (United States)

    Yoon, Hoon-Seok; Hyun, Chang-Gu; Lee, Nam-Ho; Park, Sung-Soo; Shin, Dong-Bum

    2016-01-01

    Previous research showed that resveratrol (trans-3,4′,5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4′,5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. Firstly, pterostilbene showed the inhibitory effects on α-melanocyte stimulating hormone (MSH)-induced melanin synthesis stronger than RTE, resveratrol, and arbutin. Pterostilbene inhibited melanin biosynthesis in a dose-dependent manner in α-MSH-stimulated B16/F10 murine melanoma cells. Specifically, melanin content and intracellular tyrosinase activity were inhibited by 63% and 58%, respectively, in response to treatment with 10 μM of pterostilbene. The results of western blot analysis indicated that pterostilbene induced downregulation of tyrosinase protein expression and suppression of α-MSH-stimulated melan-A protein expression stronger than RTE or resveratrol. Based on these results, our study suggests that pterostilbene can induce hypopigmentation effects more effectively than resveratrol and RTE, and it functions via downregulation of protein expression associated with hyperpigmentation in α-MSH-triggered B16/F10 murine melanoma cells. PMID:27390733

  2. Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary

    DEFF Research Database (Denmark)

    Fenger, M; Johnsen, A H

    1988-01-01

    Normal human pituitaries were extracted in boiling water and acetic acid, and the alpha-amidated peptide products of pro-opiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulating hormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well as their...... glycine-extended precursors, were characterized by sequence-specific radioimmunoassays, gel-chromatography, h.p.l.c. and amino acid sequencing. alpha MSH and gamma 1MSH constituted 0.27-1.32% and 0.10-5.10%, respectively, of the POMC-derived products [calculated as the sum of adrenocorticotropic hormone...

  3. Biological characteristics of mouse skin melanocytes.

    Science.gov (United States)

    Shi, Zhanquan; Ji, Kaiyuan; Yang, Shanshan; Zhang, Junzhen; Yao, Jianbo; Dong, Changsheng; Fan, Ruiwen

    2016-04-01

    The objective of this research was to evaluate the optimal passage number according to the biological characteristics of mouse skin melanocytes from different passages. Skin punch biopsies harvested from the dorsal region of 2-day old mice were used to establish melanocyte cultures. The cells from passage 4, 7, 10 and 13 were collected and evaluated for their melanogenic activity. Histochemical staining for tyrosinase (TYR) activity and immunostaining for the melanocyte specific markers including S-100 antigen, TYR, tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2) and micropthalmia associated transcription factor (MITF) confirmed purity and melanogenic capacity of melanocytes from different passages, with better melanogenic activity of passage 10 and 13 cells being observed. Treatment of passage 13 melanocytes with α-melanocyte stimulating hormone (α-MSH) showed increased expression of MITF, TYR and TYRP2 mRNA. However, considering the TYR mRNA dramatically high expression which is the characteristics of melanoma cells, melanocytes from passage 10 was the optimal passage number for the further research. Our results demonstrate culture of pure populations of mouse melanocytes to at least 10 passages and illustrate the potential utility of passage 10 cells for studies of intrinsic and extrinsic regulation of genes controlling pigmentation and coat color in mouse. PMID:26905193

  4. Solid-Phase Peptide Head-to-Side Chain Cyclodimerization: Discovery of C2-Symmetric Cyclic Lactam Hybrid α-Melanocyte-Stimulating Hormone (MSH)/Agouti-Signaling Protein (ASIP) Analogues with Potent Activities at the Human Melanocortin Receptors

    OpenAIRE

    Mayorov, Alexander V.; Cai, Minying; Palmer, Erin S.; Liu, Zhihua; Cain, James P.; Vagner, Josef; Trivedi, Dev; Victor J. Hruby

    2010-01-01

    A novel hybrid melanocortin pharmacophore was designed based on the pharmacophores of the Agouti signaling protein (ASIP), an endogenous melanocortin antagonist, and α-melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin agonist. The designed hybrid ASIP/MSH pharmacophore was explored in monomeric cyclic, and cyclodimeric templates. The monomeric cyclic disulfide series yielded peptides with hMC3R-selective non-competitive binding affinities. The direct on-resin peptide lactam c...

  5. α-Melanocyte stimulating hormone attenuates dexamethasone-induced osteoblast damages through activating melanocortin receptor 4-SphK1 signaling.

    Science.gov (United States)

    Guo, Shiguang; Xie, Yue; Fan, Jian-bo; Ji, Feng; Wang, Shouguo; Fei, Haodong

    2016-01-01

    Long-term glucocorticoid (GC) usage may cause non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) is shown to exert potent cytotoxic effect to osteoblasts. Here, we investigated the potential activity of α-melanocyte stimulating hormone (α-MSH) against the process. Our data revealed that pretreatment of α-MSH significantly inhibited Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Melanocortin receptor 4 (MC4R) acts as the receptor of α-MSH in mediating its actions in osteoblasts. The MC4R antagonist SHU9119, or shRNA-mediated knockdown of MC4R, almost abolished α-MSH-induced activation of downstream signalings (Akt and Erk1/2) and its pro-survival effect in osteoblasts. Further studies showed that α-MSH activated MC4R downstream sphingosine kinase 1 (SphK1) and increased cellular sphingosine-1-phosphate (S1P) content in MC3T3-E1 cells and primary murine osteoblasts, which were blocked by SHU9119 or MC4R shRNAs. SphK1 inhibition by the its inhibitor N,N-dimethylsphingosine (DMS), or SphK1 knockdown by targeted-shRNAs, largely attenuated α-MSH-mediated osteoblast protection against Dex. Together, these results suggest that α-MSH alleviates Dex-induced damages to cultured osteoblasts through activating MC4R-SphK1 signaling. PMID:26631960

  6. Single injection of naked plasmid encoding α-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice

    International Nuclear Information System (INIS)

    Oxidative stress has been implicated in the propagation of acute liver injury. The aim of our study was to investigate whether gene transfer of α-melanocyte-stimulating hormone (α-MSH), a potent anti-inflammatory peptide, could prevent fulminant hepatic failure in mice. Acute liver damage was induced by intraperitoneal administration of thioacetamide. Hydrodynamics-based gene transfection with α-MSH expression plasmid via rapid tail vein injection was initiated 1 day prior to intoxication. The mortality in the α-MSH-treated mice was significantly lower compared to the vehicle group 3 days after injury. Liver histology significantly improved and TUNEL-positive hepatocytes decreased in the treated mice. The degradation of IκBα, endogenous inhibitor of nuclear factor κB, and upregulation of inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels were prevented in the α-MSH-treated group, indicating decreased oxidative stress and inflammation. These results suggest α-MSH gene therapy might protect against acute hepatic necroinflammatory damage with further potential applications

  7. α-Melanocyte stimulating hormone treatment in pigs does not improve early graft function in kidney transplants from brain dead donors.

    Directory of Open Access Journals (Sweden)

    Willem G van Rijt

    Full Text Available Delayed graft function and primary non-function are serious complications following transplantation of kidneys derived from deceased brain dead (DBD donors. α-melanocyte stimulating hormone (α-MSH is a pleiotropic neuropeptide and its renoprotective effects have been demonstrated in models of acute kidney injury. We hypothesized that α-MSH treatment of the recipient improves early graft function and reduces inflammation following DBD kidney transplantation. Eight Danish landrace pigs served as DBD donors. After four hours of brain death both kidneys were removed and stored for 18 hours at 4°C in Custodiol preservation solution. Sixteen recipients were randomized in a paired design into two treatment groups, transplanted simultaneously. α-MSH or a vehicle was administered at start of surgery, during reperfusion and two hours post-reperfusion. The recipients were observed for ten hours following reperfusion. Blood, urine and kidney tissue samples were collected during and at the end of follow-up. α-MSH treatment reduced urine flow and impaired recovery of glomerular filtration rate (GFR compared to controls. After each dose of α-MSH, a trend towards reduced mean arterial blood pressure and increased heart rate was observed. α-MSH did not affect expression of inflammatory markers. Surprisingly, α-MSH impaired recovery of renal function in the first ten hours following DBD kidney transplantation possibly due to hemodynamic changes. Thus, in a porcine experimental model α-MSH did not reduce renal inflammation and did not improve short-term graft function following DBD kidney transplantation.

  8. Mode of action and functional significance of 7alpha-hydroxypregnenolone stimulating locomotor activity

    Directory of Open Access Journals (Sweden)

    Shogo eHaraguchi

    2011-08-01

    Full Text Available Previous studies over the past two decades have demonstrated that the brain and other nervous systems possess key steroidogenic enzymes and produces pregnenolone and other various neurosteroids in vertebrates in general. Recently, 7alpha-hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain of newts and quail. Importantly, this novel neurosteroid is produced from pregnenolone through the enzymatic activity of cytochrome P4507alpha and acts on brain tissue as a neuronal modulator to stimulate locomotor activity in these vertebrates. Subsequently, the mode of action of 7alpha-hydroxypregnenolone was demonstrated. 7alpha-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7alpha-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis were further characterized. Melatonin derived from the pineal gland and eyes regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7alpha-hydroxypregnenolone mediates corticosterone action to modulate locomotor activity under stress. This review summarizes the current knowledge regarding the mode of action and functional significance of 7alpha-hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating locomotor activity.

  9. 111In-labeled Lactam Bridge-cyclized Alpha-Melanocyte Stimulating Hormone Peptide Analogues for Melanoma Imaging

    OpenAIRE

    Miao, Yubin; Gallazzi, Fabio; Guo, Haixun; Quinn, Thomas P.

    2008-01-01

    The purpose of this study was to examine the influence of the lactam bridge cyclization on melanoma targeting and biodistribution properties of the radiolabeled conjugates. Two novel lactam bridge-cyclized α-MSH peptide analogues, DOTA-CycMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]) and DOTA-GlyGlu-CycMSH (DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]), were synthesized and radiolabeled with 111In. The in...

  10. Metastatic melanoma imaging with an {sup 111}In-labeled lactam bridge-cyclized {alpha}-melanocyte-stimulating hormone peptide

    Energy Technology Data Exchange (ETDEWEB)

    Guo Haixun; Shenoy, Nalini; Gershman, Benjamin M.; Yang, Jianquan [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Sklar, Larry A. [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Pathology, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)], E-mail: ymiao@salud.unm.edu

    2009-04-15

    Introduction: The purpose of this study was to examine whether a novel lactam bridge-cyclized {sup 111}In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Gly-Glu-c[Lys-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-Asp] {l_brace}DOTA-GlyGlu-CycMSH{r_brace} could be an effective imaging probe for metastatic melanoma detection. Methods: {sup 111}In-DOTA-GlyGlu-CycMSH was prepared and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of {sup 111}In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of {sup 111}In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission computed tomography (SPECT)/CT (Nano-SPECT/CT) using {sup 111}In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) positron emission tomography (PET) imaging. Results: {sup 111}In-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. {sup 111}In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. {sup 111}In-DOTA-GlyGlu-CycMSH exhibited significantly (P<.05) higher uptakes (2.00{+-}0.74%ID/g at 2 h post-injection and 1.83{+-}0.12%ID/g at 4 h post-injection) in metastatic melanoma-bearing lung than that in normal lung (0.08{+-}0.08%ID/g and 0.05{+-}0.05%ID/g at 2 and 4 h post-injection, respectively). The activity accumulation in normal organs was low (<0.5%ID/g) except for the kidneys 2 and 4 h post-injection. B16/F10 pulmonary melanoma metastases were clearly visualized with {sup 111}In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [{sup 18}F]FDG 1 h post-injection. Conclusions: {sup 111}In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting and -imaging properties, highlighting its potential as an effective imaging probe for metastatic melanoma detection.

  11. INOSITOL PHOSPHATES FORMED IN RAT AORTA AFTER ALPHA-1-ADRENOCEPTOR STIMULATION ARE INHIBITED BY FORSKOLIN

    NARCIS (Netherlands)

    MANOLOPOULOS, VG; PIPILISYNETOS, E; DENHERTOG, A; NELEMANS, A

    1991-01-01

    Rat aortic smooth muscle rings without endothelial cells were subjected to alpha-1-adrenoceptor stimulation. We measured the contractile state of the smooth muscle cells and the formation of inositol phosphates (InsPs) on receptor stimulation. Using different extracellular calcium-containing solutio

  12. Radiation response of melanocytes

    International Nuclear Information System (INIS)

    Radiation response of melanocytes in resting and growing hair follicles is being studied using black C57B1/6J mice. The mid-dorsum of the posterior one-third of the body was exposed to 60Co gamma-rays, shielding the remainder of the body. Hair from the second growth cycle after irradiation was plucked and scored individually for the greying effect. The percentage of black hairs in a sample reflects the fraction of melanocytes surviving. Single and fractionated dose survival curves are being determined over a dose range of 300-1200 rad. The results are not affected by hair loss. The radiosensitivity of melanocytes in resting and growing phase follicles is being determined. Fractionated regimens using time intervals from 45 minutes to 12 hours are also being given to study the repair kinetics of melanocytes

  13. Dynamics of the Alpha Peak Frequency During Flicker Stimulation

    OpenAIRE

    Garcia Molina, G.; Milanowski ,P.

    2012-01-01

    Repetitive visual stimulation elicits specific brain responses knownas steady state visual evoked potentials (SSVEP). The SSVEP manifests as oscillatory components at the stimulation frequency or harmonics in brain signals such as the electroencephalogram (EEG) or magnetoencephalogram. Analysis of the dynamics of the SSVEP permits to characterize the neurophysiological basis of visual processing. Classical SSVEP analysis is restricted to the study of the EEG power at thestimulation frequency....

  14. Treating Vitiligo in Progression Stage With Traditional Chinese Medicine Anti-vitiligo Capsule Joint Stimulation Melanocyte Granules%中药克白抑扩胶囊联合促黑冲剂治疗进展期白癜风

    Institute of Scientific and Technical Information of China (English)

    薛长连; 张克凌; 路建伟

    2011-01-01

    Objective: To observed the clinical curative effect of treating vitiligo with traditional Chinese medicine " Anti-vitiligo Capsule" joint "Stimulation Melanocyte Granules" . Methods: The 80 cases of vitiligo in progression stage were divided randomly into two groups. The treating group had 40 cases treated by traditional Chinese medicine "Anti-vitiligo Capsule" joint "Stimulation Melanocyte Granules", and treated by the "Anti-vitiligo Tincture" for external application. The control group had also 40 cases treated by "Anti-vitiligo Capsule", and treated by the "Anti-vitiligo Tincture" for external application. Result: The total effective rate of treating group and control group were 97.1% and 96.2%. There are no significant Different between the two group therapeutic effect ( P>0.001 ). The total recovery rate of treating group and control group were 48.6% and 36.4%. There are significantly different between the two group therapeutic effect ( P<0.001 ). Conclusion: The result suggested that traditional Chinese medicine "Anti-vitiligo Capsule" joint "Stimulation Melanocyte Granules" is better for treating vitiligo.%目的:观察中药克白抑扩胶囊联合促黑冲剂治疗白癜风的进展期疗效.方法:对80例进展期白癜风患者进行随机分组,治疗组40例口服中药克白抑扩胶囊联合促黑冲剂,克白酊外涂;对照组40例口服中药克白抑扩胶囊,克白酊外涂.结果:治疗组与对照组总有效率97.1%和96.2%,两组比较P>0.001,表明两组总有效率无明显差异.痊愈率分别为48.6%和36.4%,两组比较P<0.001,表明治疗组的痊愈率明显优于对照组.结论:中药克白抑扩胶囊联合促黑冲剂能够提高白癜风的痊愈率,治疗白癜风进展期疗效确切.

  15. Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity.

    Science.gov (United States)

    Bin, Bum-Ho; Kim, Dae-Kyum; Kim, Nan-Hyung; Choi, Eun-Jeong; Bhin, Jinhyuk; Kim, Sung Tae; Gho, Yong Song; Lee, Ai-Young; Lee, Tae Ryong; Cho, Eun-Gyung

    2016-05-01

    Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin-containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma. PMID:26854492

  16. MC1R and the response of melanocytes to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rouzaud, Francois [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States); Kadekaro, Ana Luisa [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Abdel-Malek, Zalfa A. [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Hearing, Vincent J. [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States)]. E-mail: hearingv@nih.gov

    2005-04-01

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists {alpha}-melanocyte-stimulating hormone ({alpha}MSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of {alpha}MSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is

  17. Narrow Band Ultraviolet B Treatment for Human Vitiligo Is Associated with Proliferation, Migration, and Differentiation of Melanocyte Precursors

    OpenAIRE

    Nathaniel B. Goldstein; Koster, Maranke I.; Hoaglin, Laura G.; Spoelstra, Nicole S.; Kechris, Katerina J.; Robinson, Steven E; Robinson, William A.; Roop, Dennis R.; Norris, David A; Birlea, Stanca A

    2015-01-01

    In vitiligo, the autoimmune destruction of epidermal melanocytes produces white spots that can be repigmented by melanocyte precursors from the hair follicles, following stimulation with UV light. We examined by immunofluorescence the distribution of melanocyte markers (C-KIT, DCT, PAX3, and TYR) coupled with markers of proliferation (KI-67) and migration (MCAM) in precursors and mature melanocytes from the hair follicle and the epidermis of untreated and narrow band UVB (NBUVB)-treated human...

  18. Eyes wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state dependent manner

    OpenAIRE

    Philipp Ruhnau; Toralf Neuling; Marco Fuscá; Herrmann, Christoph S.; Gianpaolo Demarchi; Nathan Weisz

    2016-01-01

    Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz...

  19. Open trial of topical tacalcitol [1 alpha 24(OH)2D3] and solar irradiation for vitiligo vulgaris: upregulation of c-Kit mRNA by cultured melanocytes.

    Science.gov (United States)

    Katayama, Ichiro; Ashida, Miwa; Maeda, Aki; Eishi, Kumiko; Murota, Hiroyuki; Bae, Sang Jae

    2003-01-01

    Vitiligo vulgaris is a common skin disease, however some cases show poor clinical responses to topical steroid ointment or PUVA therapy. Such regimens are generally avoided in the treatment of facial lesions or in pediatric cases because of the undesirable side effects. To confirm the excellent response to combination therapy with topical vitamin D3 ointment and solar irradiation for vitiligo achieved in the initial patients, we conducted an open trial on other patients, most of whom had poor clinical responses to the prior therapies. Fifteen patients (9 men and 6 women) with vitiligo vulgaris were enrolled in this study. Each patient was instructed to sunbathe for 30 minutes within 1 hour after topical application of the tacalcitol [1 alpha 24(OH)(2)D(3)] ointment or cream to the skin lesions every day. Six of 15 patients showed a fair and excellent clinical response to the combination therapy (more than 30% clearance of the vitiligo). The clinical effect was more apparent in patients with a history of less than 5 years of vitiligo (4 of 6 cases) in contrast to those with a history of more than 5 years (2 of 9 cases). In vitro experiments revealed that tacalcitol upregulated the expression of c-Kit mRNA by melanocytes irradiated with linear polarized infrared, UVA or short period solar irradiation. These results suggest that combination therapy with topical vitamin D(3) ointment and solar irradiation can be used as an alternate therapy for vitiligo vulgaris. PMID:12948918

  20. Narrow Band Ultraviolet B Treatment for Human Vitiligo Is Associated with Proliferation, Migration, and Differentiation of Melanocyte Precursors

    Science.gov (United States)

    Goldstein, Nathaniel B.; Koster, Maranke I.; Hoaglin, Laura G.; Spoelstra, Nicole S.; Kechris, Katerina J.; Robinson, Steven E.; Robinson, William A.; Roop, Dennis R.; Norris, David A.; Birlea, Stanca A.

    2015-01-01

    In vitiligo, the autoimmune destruction of epidermal melanocytes produces white spots that can be repigmented by melanocyte precursors from the hair follicles, following stimulation with UV light. We examined by immunofluorescence the distribution of melanocyte markers (C-KIT, DCT, PAX3, and TYR) coupled with markers of proliferation (KI-67) and migration (MCAM) in precursors and mature melanocytes from the hair follicle and the epidermis of untreated and narrow band UVB (NBUVB)-treated human vitiligo skin. NBUVB was associated with a significant increase in the number of melanocytes in the infundibulum and with restoration of the normal melanocyte population in the epidermis, which was lacking in the untreated vitiligo. We identified several precursor populations (melanocyte stem cells, melanoblasts, and other immature phenotypes), and progressively differentiating melanocytes, some with putative migratory and/or proliferative abilities. The primary melanocyte germ was present in the untreated and treated hair follicle bulge, whereas a possible secondary melanocyte germ composed of C-KIT+ melanocytes was found in the infundibulum and interfollicular epidermis of UV-treated vitiligo. This is an exceptional model for studying the mobilization of melanocyte stem cells in human skin. Improved understanding of this process is essential for designing better treatments for vitiligo, ultimately based on melanocyte stem cell activation and mobilization. PMID:25822579

  1. Narrow Band Ultraviolet B Treatment for Human Vitiligo Is Associated with Proliferation, Migration, and Differentiation of Melanocyte Precursors.

    Science.gov (United States)

    Goldstein, Nathaniel B; Koster, Maranke I; Hoaglin, Laura G; Spoelstra, Nicole S; Kechris, Katerina J; Robinson, Steven E; Robinson, William A; Roop, Dennis R; Norris, David A; Birlea, Stanca A

    2015-08-01

    In vitiligo, the autoimmune destruction of epidermal melanocytes produces white spots that can be repigmented by melanocyte precursors from the hair follicles, following stimulation with UV light. We examined by immunofluorescence the distribution of melanocyte markers (C-KIT, DCT, PAX3, and TYR) coupled with markers of proliferation (KI-67) and migration (MCAM) in precursors and mature melanocytes from the hair follicle and the epidermis of untreated and narrow band UVB (NBUVB)-treated human vitiligo skin. NBUVB was associated with a significant increase in the number of melanocytes in the infundibulum and with restoration of the normal melanocyte population in the epidermis, which was lacking in the untreated vitiligo. We identified several precursor populations (melanocyte stem cells, melanoblasts, and other immature phenotypes), and progressively differentiating melanocytes, some with putative migratory and/or proliferative abilities. The primary melanocyte germ was present in the untreated and treated hair follicle bulge, whereas a possible secondary melanocyte germ composed of C-KIT+ melanocytes was found in the infundibulum and interfollicular epidermis of UV-treated vitiligo. This is an exceptional model for studying the mobilization of melanocyte stem cells in human skin. Improved understanding of this process is essential for designing better treatments for vitiligo, ultimately based on melanocyte stem cell activation and mobilization. PMID:25822579

  2. Interdependence of the radioprotective effects of human recombinant interleukin 1 alpha, tumor necrosis factor alpha, granulocyte colony-stimulating factor, and murine recombinant granulocyte-macrophage colony-stimulating factor

    International Nuclear Information System (INIS)

    Interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), granulocyte-colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) are molecularly distinct cytokines acting on separate receptors. The release of these cytokines can be concomitantly induced by the same signal and from the same cellular source, suggesting that they may cooperate. Administered alone, human recombinant (hr)IL-1 alpha and hrTNF alpha protect lethally irradiated mice from death, whereas murine recombinant GM-CSF and hrG-CSF do not confer similar protection. On a dose basis, IL-1 alpha is a more efficient radioprotector than TNF alpha. At optimal doses, IL-1 alpha is a more radioprotective cytokine than TNF alpha in C57BL/6 and B6D2F1 mice and less effective than TNF alpha in C3H/HeN mice, suggesting that the relative effectiveness of TNF alpha and IL-1 alpha depends on the genetic makeup of the host. Administration of the two cytokines in combination results in additive radioprotection in all three strains. This suggests that the two cytokines act through different radioprotective pathways and argues against their apparent redundancy. Suboptimal, nonradioprotective doses of IL-1 alpha also synergize with GM-CSF or G-CSF to confer optimal radioprotection, suggesting that such an interaction may be necessary for radioprotection of hemopoietic progenitor cells

  3. Mitochondria are more numerous and smaller in pink-eyed dilution melanoblasts and melanocytes than in wild-type melanocytes in the neonatal mouse epidermis.

    Science.gov (United States)

    Hirobe, Tomohisa; Ishizuka, Kenji; Ogawa, Shigeru; Abe, Hiroyuki

    2008-11-01

    Abstract The mouse pink-eyed dilution (p) locus is known to control the melanin content in melanocytes. However, it was not known whether the p gene is involved in regulating the proliferation and differentation of melanocytes during development, especially the biogenesis of melanosomes and other organelles. Epidermal cell suspensions of neonatal dorsal skin derived from mice wild type for the p locus (black, C57BL/10JHir-P/P) and their congenic mutant phenotype (pink-eyed dilution, C57BL/10JHir-p/p) were cultured in serum-free melanocyte-proliferation medium (MDMD). The supplement of additional L-tyrosine (Tyr) into the MDMD stimulated the differentiation of p/p melanoblasts into melanocytes. Electron microscopy revealed that in p/p melanoblasts and melanocytes treated with L-Tyr, the number of stage II and III melanosomes dramatically increased. Moreover, p/p melanoblasts possessed smaller but more numerous mitochondria than P/P melanocytes. The treatment of p/p melanoblasts and melanocytes with L-Tyr decreased the number of mitochondria. The supplement of 2, 4-dinitrophenol (DNP), an inhibitor of mitochondrial function, into the MDMD stimulated both the proliferation and differentiation of p/p melanoblasts. Simultaneous treatment of DNP and L-Tyr dramatically stimulated the differetiation of p/p melanocytes. These results suggest that L-Tyr and some unknown factors related to mitochondrial function may influence the differentiation of melanoblasts in the epidermis of p/p mice. PMID:19267617

  4. TNF-{alpha} mediates the stimulation of sclerostin expression in an estrogen-deficient condition

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beom-Jun [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Bae, Sung Jin [Health Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Lee, Sun-Young; Lee, Young-Sun; Baek, Ji-Eun; Park, Sook-Young [Asan Institute for Life Sciences, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Lee, Seung Hun [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Koh, Jung-Min, E-mail: jmkoh@amc.seoul.kr [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Kim, Ghi Su [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Estrogen deprivation stimulates the bony sclerostin levels with reversal by estrogen. Black-Right-Pointing-Pointer TNF-{alpha} increases the activity and expression of MEF2 in UMR-106 cells. Black-Right-Pointing-Pointer TNF-{alpha} blocker prevents the stimulation of bony sclerostin expression by ovariectomy. Black-Right-Pointing-Pointer No difference in bony sclerostin expression between sham-operated and ovariectomized nude mice. -- Abstract: Although recent clinical studies have suggested a possible role for sclerostin, a secreted Wnt antagonist, in the pathogenesis of postmenopausal osteoporosis, the detailed mechanisms how estrogen deficiency regulates sclerostin expression have not been well-elucidated. Bilateral ovariectomy or a sham operation in female C57BL/6 mice and BALB/c nude mice was performed when they were seven weeks of age. The C57BL/6 mice were intraperitoneally injected with phosphate-buffered serum (PBS), 5 {mu}g/kg {beta}-estradiol five times per week for three weeks, or 10 mg/kg TNF-{alpha} blocker three times per week for three weeks. Bony sclerostin expression was assessed by immunohistochemistry staining in their femurs. The activity and expression of myocyte enhancer factors 2 (MEF2), which is essential for the transcriptional activation of sclerostin, in rat UMR-106 osteosarcoma cells were determined by luciferase reporter assay and western blot analysis, respectively. Bony sclerostin expression was stimulated by estrogen deficiency and it was reversed by estradiol supplementation. When the UMR-106 cells were treated with well-known, estrogen-regulated cytokines, only TNF-{alpha}, but not IL-1 and IL-6, increased the MEF2 activity. Consistently, TNF-{alpha} also increased the nuclear MEF2 expression. Furthermore, the TNF-{alpha} blocker prevented the stimulation of bony sclerostin expression by ovariectomy. We also found that there was no difference in sclerostin expression between ovariectomized

  5. Theta, alpha and beta burst transcranial magnetic stimulation: brain modulation in tinnitus

    OpenAIRE

    Dirk De Ridder, Elsa van der Loo, Karolien Van der Kelen, Tomas Menovsky, Paul van de Heyning, Aage Moller

    2007-01-01

    Introduction: Some forms of tinnitus are considered to be auditory phantom phenomena related to reorganization and hyperactivity of the auditory central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool capable of modulating human brain activity, using single pulse or burst stimuli. Burst rTMS has only been performed in the theta range, and has not been used clinically. The authors analyze whether burst TMS at theta (5 Hz), alpha (10 Hz) and beta (20 H...

  6. Theta, alpha and beta burst transcranial magnetic stimulation: brain modulation in tinnitus

    Directory of Open Access Journals (Sweden)

    Dirk De Ridder, Elsa van der Loo, Karolien Van der Kelen, Tomas Menovsky, Paul van de Heyning, Aage Moller

    2007-01-01

    Full Text Available Introduction: Some forms of tinnitus are considered to be auditory phantom phenomena related to reorganization and hyperactivity of the auditory central nervous system. Repetitive transcranial magnetic stimulation (rTMS is a non-invasive tool capable of modulating human brain activity, using single pulse or burst stimuli. Burst rTMS has only been performed in the theta range, and has not been used clinically. The authors analyze whether burst TMS at theta (5 Hz, alpha (10 Hz and beta (20 Hz frequencies can temporarily suppress narrow band noise/white noise tinnitus, which has been demonstrated to be intractable to tonic stimulation. Methods: rTMS is performed both in tonic and burst mode in 46 patients contralateral to the tinnitus side, at 5, 10 and 20 Hz. Fourteen placebo negative rTMS responders are further analyzed. Results: In 5 patients, maximal tinnitus suppression is obtained with theta, in 2 with alpha and in 7 with beta burst stimulation. Burst rTMS suppresses narrow band/white tinnitus much better than tonic rTMS t(13=6.4, p<.000. Women experience greater suppression of their tinnitus with burst stimulation than men, t(12=2.9, p<.05. Furthermore left sided tinnitus is perceived as more distressing on the TQ than right sided tinnitus, t(12=3.2, p<.01. The lower the tinnitus pitch the more effectively rTMS suppresses tinnitus(r=-0.65, p<0.05. Discussion: Burst rTMS can be used clinically, not only theta burst, but also alpha and beta burst. Burst rTMS is capable of suppressing narrow band/white noise tinnitus very much better than tonic rTMS. This could be due the simple fact that burst neuromodulation is more powerful than tonic neuromodulation or to a differential effect of burst and tonic stimulation on the lemniscal and extralemniscal auditory system. In some patients only alpha or beta burst rTMS is capable of suppressing tinnitus, and theta burst not. Therefore in future rTMS studies it could be worthwhile not to limit burst

  7. Secretion of albumin and alpha-foetoprotein by dimethylsulphoxide-stimulated hepatocellular carcinoma cells.

    OpenAIRE

    Higgins, P. J.; Darzynkiewicz, Z; Melamed, M R

    1983-01-01

    Exposure of BW77-1 and BW77-2 mouse hepatic tumour cells to the polar solvent dimethylsulphoxide (DMSO) altered extracellular accumulation of albumin and alpha-foetoprotein (AFP) and perturbed their cell cycle kinetics. The amount of albumin secreted into the culture growth medium was dependent on the concentration of DMSO used. Hepatic tumour cells cultured in 1 and 2% DMSO accumulated 50% and 111% more albumin, respectively, than non-DMSO-stimulated cells during the final 24 h of a 4-day ex...

  8. Giant Congenital Melanocytic Nevus

    DEFF Research Database (Denmark)

    Rasmussen, Bo Sonnich; Henriksen, Trine Foged; Kølle, Stig-Frederik Trojahn;

    2015-01-01

    , and 25% versus 44% required unplanned additional surgery, respectively. Complications were noted in 25% and 67% of the patients, respectively. Cosmetic result was satisfying in 76% of patients without difference between the groups. No malignant transformation was found during a mean follow-up of 11......Giant congenital melanocytic nevi (GCMN) occur in 1:20,000 livebirths and are associated with increased risk of malignant transformation. The treatment of GCMN from 1981 to 2010 in a tertiary referral center was reviewed evaluating the modalities used, cosmetic results, associated complications......, and malignant transformation. Of 35 patients, 25 underwent surgery. Curettage was most frequently used (64%) followed by excision and tissue expansion (20%). Six percent of the patients treated with curettage, and 78% of the patients who received excision surgery required more than 1 planned procedure...

  9. Eyes wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state dependent manner.

    Science.gov (United States)

    Ruhnau, Philipp; Neuling, Toralf; Fuscá, Marco; Herrmann, Christoph S; Demarchi, Gianpaolo; Weisz, Nathan

    2016-01-01

    Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz and Oz, which should affect parieto-occipital areas most strongly. Source space magnetoencephalography (MEG) data were used to estimate phase coherence between tACS and brain activity. Phase coherence was significantly increased in areas in the occipital pole in eyes open resting state only. The lag between tACS and brain responses showed considerable inter-individual variability. In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices. Interestingly, this effect is state dependent and is clearly observed with eyes open but only to a lesser extent with eyes closed. PMID:27252047

  10. UVB Stimulates the Expression of Endothelin B Receptor in Human Melanocytes via a Sequential Activation of the p38/MSK1/CREB/MITF Pathway Which Can Be Interrupted by a French Maritime Pine Bark Extract through a Direct Inactivation of MSK1.

    Directory of Open Access Journals (Sweden)

    Hideki Tagashira

    Full Text Available Melanogenesis is the physiological process by which melanin is synthesized to protect the skin from UV damage. While paracrine interactions between keratinocytes and melanocytes are crucial for regulating epidermal pigmentation, the endothelin (EDN-endothelin B-receptor (EDNRB interaction is one of the key linkages. In this study, we found that a single exposure of normal human melanocytes (NHMs with UVB stimulates the expression of EDNRB and its upstream transcription factor microphthalmia-associated transcription factor (MITF at the transcriptional and translational levels. That stimulation can be abrogated by post-irradiation treatment with a French maritime pine bark extract (PBE. UVB stimulated the phosphorylation of p38 and c-jun N-terminal kinase (JNK, but not ERK, followed by the increased phosphorylation of MSK1 and CREB. The post-irradiation treatment with PBE did not affect the increased phosphorylation of p38 and JNK, but distinctly abrogated the phosphorylation of MSK1 and CREB. Post-irradiation treatment with the MSK1 inhibitor H89 significantly down-regulated the increased gene expression of MITF and EDNRB in UVB-exposed NHMs. Our findings indicate for the first time that the increased expression of MITF that leads to the up-regulation of melanocyte-specific proteins in UVB-exposed NHMs is mediated via activation of the p38/MSK1/CREB pathway but not the ERK/RSK/CREB pathway. The mode of action by PBE demonstrates that interrupting MSK1 activation is a new target for antioxidants including PBE which can serve as anti-pigmenting agents in a reactive oxygen species-depletion-independent manner.

  11. Alpha-MSH decreases core and brain temperature during global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Spulber, S.; Moldovan, Mihai; Oprica, M.; Aronsson, A.F.; Post, C.; Winblad, B.; Schultzberg, M.

    2005-01-01

    A key pathological event during cerebral ischemia is the excitotoxic release of glutamate. We have shown previously that alpha-melanocyte-stimulating hormone (alpha-MSH) enhances the hypothermia induced by kainic acid. We have investigated the effects of systemic administration of alpha-MSH on four......-vessel occlusion forebrain ischemia on core temperature (CT) and brain temperature (BT), respectively. After 10 min cerebral ischemia, BT was lower in alpha-MSH- than in saline-injected animals. After 10 min reperfusion, both CT and BT were lower than the corresponding pre-ischemic levels after injection of alpha......-MSH. alpha-MSH did not influence CT or BT in sham-operated rats. The alpha-MSH-induced hypothermia and its potentiation of reduction in BT during global cerebral ischemia, may contribute to neuroprotective effects of alpha-MSH....

  12. Genetics Home Reference: giant congenital melanocytic nevus

    Science.gov (United States)

    ... mutation in large congenital melanocytic nevi. J Invest Dermatol. 2014 Apr;134(4):1067-74. doi: 10. ... applied to giant congenital melanocytic nevi. J Invest Dermatol. 2014 Apr;134(4):879-82. doi: 10. ...

  13. Interferon-alpha suppressed granulocyte colony stimulating factor production is reversed by CL097, a TLR7/8 agonist.

    LENUS (Irish Health Repository)

    Tajuddin, Tariq

    2012-02-01

    BACKGROUND AND AIM: Neutropenia, a major side-effect of interferon-alpha (IFN-alpha) therapy can be effectively treated by the recombinant form of granulocyte colony stimulating factor (G-CSF), an important growth factor for neutrophils. We hypothesized that IFN-alpha might suppress G-CSF production by peripheral blood mononuclear cells (PBMCs), contributing to the development of neutropenia, and that a toll-like receptor (TLR) agonist might overcome this suppression. METHODS: Fifty-five patients who were receiving IFN-alpha\\/ribavirin combination therapy for chronic hepatitis C virus (HCV) infection were recruited. Absolute neutrophil counts (ANC), monocyte counts and treatment outcome data were recorded. G-CSF levels in the supernatants of PBMCs isolated from the patients and healthy controls were assessed by enzyme-linked immunosorbent assay following 18 h of culture in the absence or presence of IFN- alpha or the TLR7\\/8 agonist, CL097. RESULTS: Therapeutic IFN-alpha caused a significant reduction in neutrophil counts in all patients, with 15 patients requiring therapeutic G-CSF. The reduction in ANC over the course of IFN-alpha treatment was paralleled by a decrease in the ability of PBMCs to produce G-CSF. In vitro G-CSF production by PBMCs was suppressed in the presence of IFN-alpha; however, co-incubation with a TLR7\\/8 agonist significantly enhanced G-CSF secretion by cells obtained both from HCV patients and healthy controls. CONCLUSIONS: Suppressed G-CSF production in the presence of IFN-alpha may contribute to IFN-alpha-induced neutropenia. However, a TLR7\\/8 agonist elicits G-CSF secretion even in the presence of IFN-alpha, suggesting a possible therapeutic role for TLR agonists in treatment of IFN-alpha-induced neutropenia.

  14. Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

    International Nuclear Information System (INIS)

    Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE2, a ligand for 4 related G-protein-coupled receptors (EP1, EP2, EP3 and EP4). Our previous work established that PGE2 stimulates melanocyte dendrite formation through activation of the EP1 and EP3 receptors. The purpose of the present report is to define the signaling intermediates involved in EP1- and EP3-dependent dendrite formation in human melanocytes. We recently showed that activation of the atypical PKCζ isoform stimulates melanocyte dendricity in response to treatment with lysophosphatidylcholine. We therefore examined the potential contribution of PKCζ activation on EP1- and EP3-dependent dendrite formation in melanocytes. Stimulation of the EP1 and EP3 receptors by selective agonists activated PKCζ, and inhibition of PKCζ activation abrogated EP1- and EP3-receptor-mediated melanocyte dendricity. Because of the importance of Rho-GTP binding proteins in the regulation of melanocyte dendricity, we also examined the effect of EP1 and EP3 receptor activation on Rac and Rho activity. Neither Rac nor Rho was activated upon treatment with EP1,3-receptor agonists. We show that melanocytes express only the EP3A1 isoform, but not the EP3B receptor isoform, previously associated with Rho activation, consistent with a lack of Rho stimulation by EP3 agonists. Our data suggest that PKCζ activation plays a predominant role in regulation of PGE2-dependent melanocyte dendricity

  15. Effects of PGF2α on human melanocytes and regulation of the FP receptor by ultraviolet radiation

    International Nuclear Information System (INIS)

    Prostaglandins are potent lipid hormones that activate multiple signaling pathways resulting in regulation of cellular growth, differentiation, and apoptosis. In the skin, prostaglandins are rapidly released by keratinocytes following ultraviolet radiation and are chronically present in inflammatory skin lesions. We have shown previously that melanocytes, which provide photoprotection to keratinocytes through the production of melanin, express several receptors for prostaglandins, including the PGE2 receptors EP1 and EP3 and the PGF2α receptor FP, and that PGF2α stimulates melanocyte dendricity. We now show that PGF2α stimulates the activity and expression of tyrosinase, the rate-limiting enzyme in melanin synthesis. Analysis of FP receptor regulation showed that the FP receptor is regulated by ultraviolet radiation in melanocytes in vitro and in human skin in vivo. We also show that ultraviolet irradiation stimulates production of PGF2α by melanocytes. These results show that PGF2α binding to the FP receptor activates signals that stimulate a differentiated phenotype (dendricity and pigmentation) in melanocytes. The regulation of the FP receptor and the stimulation of production of PGF2α in melanocytes in response to ultraviolet radiation suggest that PGF2α could act as an autocrine factor for melanocyte differentiation

  16. Histamine receptors on adult rat cardiomyocytes: antagonism of alpha1-receptor stimulation of cAMP degradation

    International Nuclear Information System (INIS)

    Incubation of intact cardiomyocytes with the histamine antagonist [3H]mepyramine results in rapid reversible binding to a single class of high affinity sites (K/sub D/ = 1.2nM; 50,000 sites/myocyte). In membranes from purified myocytes histamine competition of [3H]mepyramine binding (K/sub D/ = 300nM) is not altered by GTP (10μM). Competition of [3H]mepyramine binding by H-receptor subtype-selective antagonists suggests the presence of a single class of H1-receptors. Incubation of intact myocytes with histamine (luM, H1 receptor activation) plus norepinephrine (NE 1uM, alpha1 + beta1 receptor activation) for 3 min leads to significantly more cAMP accumulation (36.5 pmol/106 myocytes) than NE alone (30 pmol/106 myocytes). Histamine alone does not alter basal cAMP = 10.4 pmol/106 myocytes, or beta1 stimulation (isoproternol, 1uM) = 39.6 pmol/106 myocytes. Cyclic AMP accumulation with NE plus prazosin 10nM, (alpha1 + beta1 + alpha1 blockade) is indistinguishable from NE + histamine, (alpha1 + beta1 + H1) stimulation. Histamine competition for [3H]prazosin binding suggests that histamine does not block alpha1 receptors on the myocyte. These data suggest that H1 receptor activation leads to antagonism of the alpha1 receptor mediated activation of cAMP phosphodiesterase the authors have recently described

  17. Rhythmical Photic Stimulation at Alpha Frequencies Produces Antidepressant-Like Effects in a Mouse Model of Depression.

    Directory of Open Access Journals (Sweden)

    Shinheun Kim

    Full Text Available Current therapies for depression consist primarily of pharmacological agents, including antidepressants, and/or psychiatric counseling, such as psychotherapy. However, light therapy has recently begun to be considered as an effective tool for the treatment of the neuropsychiatric behaviors and symptoms of a variety of brain disorders or diseases, including depression. One methodology employed in light therapy involves flickering photic stimulation within a specific frequency range. The present study investigated whether flickering and flashing photic stimulation with light emitting diodes (LEDs could improve depression-like behaviors in a corticosterone (CORT-induced mouse model of depression. Additionally, the effects of the flickering and flashing lights on depressive behavior were compared with those of fluoxetine. Rhythmical flickering photic stimulation at alpha frequencies from 9-11 Hz clearly improved performance on behavioral tasks assessing anxiety, locomotor activity, social interaction, and despair. In contrast, fluoxetine treatment did not strongly improve behavioral performance during the same period compared with flickering photic stimulation. The present findings demonstrated that LED-derived flickering photic stimulation more rapidly improved behavioral outcomes in a CORT-induced mouse model of depression compared with fluoxetine. Thus, the present study suggests that rhythmical photic stimulation at alpha frequencies may aid in the improvement of the quality of life of patients with depression.

  18. Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans

    DEFF Research Database (Denmark)

    Rask-Madsen, Christian; Domínguez, Helena; Ihlemann, Nikolaj;

    2003-01-01

    -stimulated endothelial function in humans. METHODS AND RESULTS: Healthy, lean male volunteers were studied. On each study day, 3 acetylcholine (ACh) or sodium nitroprusside (SNP) dose-response studies were performed by infusion into the brachial artery. Before and during the last 2 dose-response studies, insulin and...... smaller (P<0.001); TNF-alpha had no effect on the SNP response without insulin infusion. Thus, TNF-alpha inhibition of the combined response to insulin and ACh was likely mediated through inhibition of NO production. CONCLUSIONS: These results support the concept that TNF-alpha could play a role in the...... development of insulin resistance in humans, both in muscle and in vascular tissue....

  19. Tumor necrosis factor alpha stimulates NMDA receptor activity in mouse cortical neurons resulting in ERK-dependent death

    OpenAIRE

    Jara, Javier H.; Singh, Brij B.; Floden, Angela M.; Combs, Colin K.

    2007-01-01

    Multiple cytokines are secreted in the brain during pro-inflammatory conditions and likely affect neuron survival. Previously, we demonstrated that glutamate and tumor necrosis factor alpha (TNFα) kill neurons via activation of the N-methyl-d-aspartate (NMDA) and TNFα receptors, respectively. This report continues characterizing the signaling cross-talk pathway initiated during this inflammation-related mechanism of death. Stimulation of mouse cortical neuron cultures with TNFα results in a t...

  20. Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Cheng, Jung-Chien [Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Huang, He-Feng, E-mail: huanghefg@hotmail.com [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Leung, Peter C.K., E-mail: peter.leung@ubc.ca [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada)

    2013-11-01

    Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.

  1. Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

    International Nuclear Information System (INIS)

    Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells

  2. GIANT MELANOCYTIC NEVUS IN GARMENT

    Directory of Open Access Journals (Sweden)

    González-Coquel Suanny del Carmen

    2015-01-01

    Full Text Available Introduction: the Giant Congenital Melanocytic Nevus (GCMN is a pigmented lesion of great size, usually presented since the birth, although some lesions could appear in the first months of life. It is an atypical benign proliferation of melanocytes in the skin that could have curious morphologies. It is associated in some cases to extracutaneous manifestations and melanoma development. It is characterized by a hyperpigmented lesion in different tones of brown and could affect since the brain until the lower limbs. The most frequent location is the posterior trunk, the face, scalp and extremities. Case report: the case of a young female patient with GCMN «in garment» with several satellite lesions is presented in order to carry out a thematic review and to indicate the importance of the control period and following. Conclusion: the GCMN is a benign cutaneous alteration that implies serious esthetic disorders when it increases its size. The treatment difficulties and the medico-social implications must be kept in mind. Rev.cienc.biomed. 2015;6(1:155-159 KEYWORDS Nevus, Pigmented nevus; Melanoma; Melanocytes.

  3. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    Directory of Open Access Journals (Sweden)

    Rinaldi L

    2016-05-01

    Full Text Available Leonardo Rinaldi, Helmy Selman One Day Medical Center, IVF Unit, Rome, Italy Abstract: A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH and luteinizing hormone (LH to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH and recombinant LH (rLH has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I. In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. Keywords: follicular growth, gonadotropins, implantation, ovarian stimulation, pregnancy

  4. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    Science.gov (United States)

    Rinaldi, Leonardo; Selman, Helmy

    2016-01-01

    A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

  5. Transient exposure of human myoblasts to tumor necrosis factor-alpha inhibits serum and insulin-like growth factor-I stimulated protein synthesis.

    Science.gov (United States)

    Frost, R A; Lang, C H; Gelato, M C

    1997-10-01

    Tumor necrosis factor-alpha (TNF-alpha) induces cachexia and is postulated to be responsible for muscle wasting in several pathophysiological conditions. The purpose of the present study was to investigate whether exposure of human myoblasts to TNF-alpha could directly inhibit the ability of serum or insulin-like growth factor I (IGF-I) to stimulate protein synthesis as assessed by the incorporation of [3H]phenylalanine into protein. Serum and IGF-I stimulated protein synthesis dose dependently. Half-maximal stimulation of protein synthesis occurred at 05% serum and 8 ng/ml of IGF-I, respectively. TNF-alpha inhibited IGF-I-stimulated protein synthesis in a dose-dependent manner. Additionally, as little as 2 ng/ml of TNF-alpha impaired the ability of IGF-I to stimulate protein synthesis by 33% and, at a dose of 100 ng/ml, TNF-alpha completely prevented the increase in protein synthesis induced by either serum or a maximally stimulating dose of IGF-I. Inhibition of protein synthesis was independent of whether TNF-alpha and growth factors were added to cells simultaneously or if the cells were pretreated with growth factors. Exposure ofmyoblasts to TNF-alpha for 10 min completely inhibited serum-induced stimulation of protein synthesis. TNF-alpha inhibited protein synthesis up to 48 h after addition of the cytokine. TNF-alpha also inhibited serum-stimulated protein synthesis in human myoblasts that were differentiated into myotubes. In contrast, exposure of myoblasts to TNF-alpha had no effect on IGF-I binding and failed to alter the ability of either IGF-I or serum to stimulate [3H]thymidine uptake. These data indicate that transient exposure of myoblasts or myotubes to TNF-alpha inhibits protein synthesis. Thus, the anabolic actions of IGF-I on muscle protein synthesis may be impaired during catabolic conditions in which TNF-alpha is over expressed. PMID:9322924

  6. TNF-alpha stimulates Akt by a distinct aPKC-dependent pathway in premalignant keratinocytes

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.

    2008-01-01

    renders keratinocytes less susceptible to proapoptotic stimuli and enhances cell growth. We have recently shown that TNF-alpha-induced Akt activation may promote the early stages of skin cancer. In this work, we demonstrate that in the premalignant keratinocyte cell line HaCaT, TNF-alpha activates Akt...

  7. Stimulated dopamine overflow and alpha-synuclein expression in the nucleus accumbens core distinguish rats bred for differential ethanol preference.

    Science.gov (United States)

    Pelkonen, Anssi; Hiltunen, Mikko; Kiianmaa, Kalervo; Yavich, Leonid

    2010-08-01

    The key neurochemical systems and structures involved in the predisposition to substance abuse and preference to ethanol (EtOH) are not known in detail but clearly dopamine (DA) is an important modulator of addiction. Recent data indicate that alpha-synuclein (alpha-syn), a pre-synaptic protein, plays a role in regulation of DA release from the pre-synaptic terminals in striatum and the expression of this protein is different after drug abuse or following abstinence. In the present work, we analysed stimulated DA overflow in the dorsal and ventral striatum in EtOH naïve alko alchohol (AA) and alko non-alchohol (ANA) rats selected for more than 100 generations for their differential EtOH preference. In the same structures, we studied the expression of alpha-syn using western blotting. AA rats, in comparison with ANA rats, showed a marked reduction of stimulated peak DA overflow and higher levels of alpha-syn in the nucleus accumbens core. In the same structure, DA re-uptake was increased in AA rats in comparison with ANA rats. The effects of EtOH at low (0.1 g/kg) and higher (3 mg/kg) doses on DA overflow measured in the nucleus accumbens shell were similar in both lines. These results indicate that high expression of alpha-syn may contribute to the reduced DA overflow and the possible activation of re-uptake in the nucleus accumbens core of AA rats in comparison with ANA rats. PMID:20533994

  8. [alpha]2A-Adrenoceptor Stimulation Improves Prefrontal Cortical Regulation of Behavior through Inhibition of cAMP Signaling in Aging Animals

    Science.gov (United States)

    Verduzco, Luis; van Dyck, Christopher H.; Arnsten, Amy F. T.; Ramos, Brian P.; Stark, David

    2006-01-01

    The working-memory functions of the prefrontal cortex (PFC) are improved by stimulation of postsynaptic, [alpha]2A-adrenoceptors, especially in aged animals with PFC cognitive deficits. Thus, the [alpha]2A-adrenoceptor agonist, guanfacine, greatly improves working-memory performance in monkeys and rats following systemic administration or…

  9. Effect of aging on alpha-1 adrenergic stimulation of phosphoinositide hydrolysis in various regions of rat brain

    International Nuclear Information System (INIS)

    The effects of aging were examined on the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis in three brain regions. Tissue minces of thalamus, cerebral cortex and hippocampus from 3-, 18- and 28-month-old male Fischer 344 rats were prelabeled with [3H]myoinositol. Exposure of these prelabeled minces to phenylephrine and (-)-norepinephrine revealed that accumulation of [3H]inositol phosphates was selectively reduced by 20 to 30% in the thalamus and cerebral cortex of the oldest age group. Analysis of concentration-response and competition binding curves indicated that this decrease was due to diminished agonist efficacy rather than diminished receptor affinity. The reduction in responsiveness to phenylephrine and (-)-norepinephrine in the cerebral cortex and the lack of any changes in the hippocampus parallel previously reported changes in the density of alpha-1 adrenergic receptors with aging. These data indicate that the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis is reduced in some, but not all, brain regions of aged Fischer 344 rats

  10. Melanocytic naevi clustered on normal background skin.

    Science.gov (United States)

    Torchia, D

    2015-04-01

    Several types of maculopapular melanocytic naevi can occur in a multiple form, and be arranged in a nonrandom fashion on the skin. The most frequently reported segmentally grouped naevi are lentigines. Two types of segmentally arranged lentigines probably exist. The first is associated with neurofibromatosis (NF)1 or NF1 signs, features scattered light-brown lesions and can be considered a type of mosaic NF1. By contrast, non-NF1 associated lesions are characterized by densely packed, dark lesions, and can be defined as 'non-NF1 checkerboard-arranged lentigines'. Blue naevi, Spitz naevi and common acquired melanocytic naevi can occur, clustered in an agminated (or cannonball) shape. However, if large enough, they always follow a checkerboard pattern. Hence, such mosaic conditions should be termed 'checkerboard-arranged blue naevi', 'checkerboard-arranged Spitz naevi' and 'checkerboard-arranged common acquired melanocytic naevi'. Segmentally arranged dysplastic melanocytic naevi probably represent a mosaic form of dysplastic naevus syndrome. Dysplastic melanocytic naevi confined to a cutaneous segment could be defined as 'isolated segmental dysplastic naevus syndrome', while segmentally arranged dysplastic melanocytic naevi co-occurring with widespread, nonsegmental dysplastic melanocytic naevi might configure a 'superimposed segmental dysplastic naevus syndrome'. Small congenital melanocytic naevi are always grouped along Blaschko lines. The only other instances following Blaschko lines are the so-called 'linear lentiginous naevus' and a unique case of multiple deep penetrating naevi. PMID:25703021

  11. Melanocytic glaucoma in a cairn terrier.

    Science.gov (United States)

    Hanselman, Beth A

    2002-04-01

    Melanocytic glaucoma, previously known as pigmentary glaucoma, is characterized by diffuse intraocular infiltration of heavily pigmented melanocytes. This unusual ocular disorder has been documented only in the cairn terrier and is considered familial. Treatment strategies are based on evidence that the condition is slowly progressive but not neoplastic. PMID:11963666

  12. Melanocyte colonization and pigmentation of breast carcinoma

    DEFF Research Database (Denmark)

    Mele, Marco; Laurberg, Tinne; Engberg Damsgaard, Tine;

    2012-01-01

    Introduction. Melanocyte colonization of breast carcinoma by nonneoplastic melanocytes of epidermal origin is a rare and serious condition first described in 1977. We report on the exceptional clinical and pathological features of this migration phenomenon in a 74-year-old patient. Discussion. The...

  13. Stimulation of prostaglandin E2-synthesis by noradrenaline in primary cell cultures from rabbit splenic pulpa is mediated by atypical alpha-adrenoceptors.

    Science.gov (United States)

    Brückner-Schmidt, R; Jackisch, R; Hertting, G

    1981-02-01

    In primary cell cultures originating from rabbit splenic pulpa the effects of various adrenoceptor agonists on prostaglandin (PG)-synthesis were studied. The cells - microscopically identified as fibroblasts - released PGs into the medium: especially PGE2 besides small amounts of PGF2alpha and PGD2. Noradrenaline increased dose-dependently the amount of PGs released into the medium. Besides noradrenaline, only the catecholamines adrenaline and alpha-methylnoradrenaline strongly activated PG-synthesis. Other alpha-adrenoceptor agonists like the phenylethylamine and imidazoline derivatives were only weak agonists or completely ineffective. All adrenoceptor agonists without intrinsic activity in these cells antagonized the noradrenaline effect on PG-synthesis, the imidazolines being more potent antagonists than the phenylethylamines. The beta-adrenoceptor agonist isoprenaline stimulated PG-synthesis at high concentration only. The effects of both noradrenaline and isoprenaline were inhibited by low concentrations of phentolamine phenoxybenzamine, but not by propranolol. The preferential alpha2-adrenoceptor antagonists yohimbine and rauwolscine were about 50 times more potent in blocking the noradrenaline effect on PG-synthesis than the more alpha1-specific antagonist corynanthine. However, prazosin, another alpha1-adrenoceptor antagonist, was about equipotent with yohimbine. It is concluded that noradrenaline elicits PG-synthesis in rabbit splenic fibroblasts via alpha-adrenoceptor stimulation. The alpha-adrenoceptor involved has properties which are different from those reported so far for alpha1- or alpha2-adrenoceptors. PMID:6268994

  14. Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes.

    Science.gov (United States)

    Gelis, Lian; Jovancevic, Nikolina; Veitinger, Sophie; Mandal, Bhubaneswar; Arndt, Hans-Dieter; Neuhaus, Eva M; Hatt, Hanns

    2016-08-19

    Olfactory receptors, which belong to the family of G-protein-coupled receptors, are found to be ectopically expressed in non-sensory tissues mediating a variety of cellular functions. In this study we detected the olfactory receptor OR51E2 at the transcript and the protein level in human epidermal melanocytes. Stimulation of primary melanocytes with the OR51E2 ligand β-ionone significantly inhibited melanocyte proliferation. Our results further showed that β-ionone stimulates melanogenesis and dendritogenesis. Using RNA silencing and receptor antagonists, we demonstrated that OR51E2 activation elevated cytosolic Ca(2+) and cAMP, which could mediate the observed increase in melanin synthesis. Co-immunocytochemical stainings using a specific OR51E2 antibody revealed subcellular localization of the receptor in early endosomes associated with EEA-1 (early endosome antigen 1). Plasma membrane preparations showed that OR51E2 protein is present at the melanocyte cell surface. Our findings thus suggest that activation of olfactory receptor signaling by external compounds can influence melanocyte homeostasis. PMID:27226631

  15. Tyrosine dephosphorylation of nuclear proteins mimics transforming growth factor beta 1 stimulation of alpha 2(I) collagen gene expression.

    OpenAIRE

    Greenwel, P; Hu, W.; Kohanski, R A; Ramirez, F.

    1995-01-01

    Transforming growth factor beta 1 (TGF-beta 1) exerts a positive effect on the transcription of genes coding for several extracellular matrix-related products, including collagen I. We have previously identified a strong TGF-beta 1-responsive element (TbRE) in the upstream promoter sequence of the alpha 2(I) collagen (COL1A2) gene. Our experiments have shown that TGF-beta 1 stimulates COL1A2 transcription by increasing binding of an Sp1-containing complex (TbRC) to the TbRE. They have also su...

  16. Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

    International Nuclear Information System (INIS)

    The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism

  17. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6

    International Nuclear Information System (INIS)

    Highlights: • Melanocytes showed low ST8SIA1 and high B3GALT4 levels in contrast with melanomas. • Direct UVB irradiation of melanocytes did not induce ganglioside synthase genes. • Culture supernatants of UVB-irradiated keratinocytes induced ST8SIA1 in melanocytes. • TNFα and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. • Inflammatory cytokines induced melanoma-related ST8SIA1 in melanocytes. - Abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes

  18. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Maiko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Sugiura, Kazumitsu [Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Koichi, E-mail: koichi@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Keiko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan)

    2014-03-07

    Highlights: • Melanocytes showed low ST8SIA1 and high B3GALT4 levels in contrast with melanomas. • Direct UVB irradiation of melanocytes did not induce ganglioside synthase genes. • Culture supernatants of UVB-irradiated keratinocytes induced ST8SIA1 in melanocytes. • TNFα and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. • Inflammatory cytokines induced melanoma-related ST8SIA1 in melanocytes. - Abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.

  19. Maintenance of distinct melanocyte populations in the interfollicular epidermis.

    Science.gov (United States)

    Glover, James D; Knolle, Stefan; Wells, Kirsty L; Liu, Dianbo; Jackson, Ian J; Mort, Richard L; Headon, Denis J

    2015-07-01

    Hair follicles and sweat glands are recognized as reservoirs of melanocyte stem cells (MSCs). Unlike differentiated melanocytes, undifferentiated MSCs do not produce melanin. They serve as a source of differentiated melanocytes for the hair follicle and contribute to the interfollicular epidermis upon wounding, exposure to ultraviolet irradiation or in remission from vitiligo, where repigmentation often spreads outwards from the hair follicles. It is unknown whether these observations reflect the normal homoeostatic mechanism of melanocyte renewal or whether unperturbed interfollicular epidermis can maintain a melanocyte population that is independent of the skin's appendages. Here, we show that mouse tail skin lacking appendages does maintain a stable melanocyte number, including a low frequency of amelanotic melanocytes, into adult life. Furthermore, we show that actively cycling differentiated melanocytes are present in postnatal skin, indicating that amelanotic melanocytes are not uniquely relied on for melanocyte homoeostasis. PMID:25847135

  20. Microscopic analysis of epidermal melanocytes in human abdominal skin

    International Nuclear Information System (INIS)

    Objective: Microscopic analysis of epidermal melanocytes in human abdominal skin with respect to age and sex. Results: The melanocytes count per unit area of skin was significantly higher in the younger than older age groups. No significant difference was noticed between males and females epidermal melanocytes counts. Conclusion: Distribution of epidermal melanocytes was inversely proportional to the advancing age. However, there was no significant gender differences in the distribution of epidermal melanocytes. (author)

  1. Changes in the proliferation and differentiation of neonatal mouse pink-eyed dilution melanocytes in the presence of excess tyrosine.

    Science.gov (United States)

    Hirobe, Tomohisa; Wakamatsu, Kazumasa; Ito, Shosuke

    2003-12-01

    Changes in the proliferation and differentiation of epidermal melanocytes derived from newborn mice wild-type at the pink-eyed dilution (p) locus (P/P) and from congenic mice mutant at that locus (p/p) were investigated in serum-free primary culture, with or without the addition of L-Tyr. Incubation with added L-Tyr inhibited the proliferation of P/P melanocytes in a concentration-dependent manner and inhibition was gradually augmented as the donor mice aged. In contrast, L-Tyr stimulated the proliferation of p/p melanoblasts-melanocytes derived from 0.5-day-old mice, but inhibited their proliferation when derived from 3.5- or 7.5-day-old mice. L-Tyr stimulated the differentiation of P/P melanocytes. However, almost all cells were undifferentiated melanoblasts in control cultures derived from 0.5-, 3.5- and 7.5-day-old p/p mice, but L-Tyr induced their differentiation as the age of the donor mice advanced. The content of the eumelanin marker, pyrrole-2,3,5-tricarboxylic acid as well as the pheomelanin marker, 4-amino-3-hydroxyphenylalanine in p/p melanocytes was greatly reduced compared with P/P melanocytes. However, the contents of eumelanin and its precursor, 5,6-dihydroxyindole-2-carboxylic acid, as well as the contents of pheomelanin and its precursor, 5-S-cysteinyldopa in culture media from p/p melanocytes were similar to those of P/P melanocytes at all ages tested. L-Tyr increased the content of eumelanin and pheomelanin two- to threefold in cultured cells and media derived from 0.5-, 3.5- and 7.5-day-old mice. These results suggest that the proliferation of p/p melanoblasts-melanocytes is stimulated by L-Tyr, and that the differentiation of melanocytes is induced by L-Tyr as the age of the donor mice advanced, although eumelanin and pheomelanin fail to accumulate in p/p melanocytes and are released from them at all ages of skin development. PMID:14629719

  2. NEURODYNAMIC AND PREDICTABILITY OF ALPHA-STIMULATING BIOFEEDBACK COURSE IN SPORTSMEN AND PERSONS OCCUPYING PHYSICAL CULTURE

    OpenAIRE

    Cherapkina, L. P.; V. G. Tristan; S. P. Styopochkina

    2013-01-01

    The 15-days neurofeedback course was conducted with the purpose of neurodynamic and predictability assessment of mastering of arbitrary regulation skill of electroencephalographic (EEG) spectral power in alpha-band in sportsmen (n=260) and persons (n=69) occupying physical culture. The electroencephalographic parameters being predictors of neurofeedback course were defined in result of research. It was showed that different neurodynamical changes in examined groups supported training successf...

  3. NEURODYNAMIC AND PREDICTABILITY OF ALPHA-STIMULATING BIOFEEDBACK COURSE IN SPORTSMEN AND PERSONS OCCUPYING PHYSICAL CULTURE

    Directory of Open Access Journals (Sweden)

    L. P. Cherapkina

    2013-01-01

    Full Text Available The 15-days neurofeedback course was conducted with the purpose of neurodynamic and predictability assessment of mastering of arbitrary regulation skill of electroencephalographic (EEG spectral power in alpha-band in sportsmen (n=260 and persons (n=69 occupying physical culture. The electroencephalographic parameters being predictors of neurofeedback course were defined in result of research. It was showed that different neurodynamical changes in examined groups supported training successfulness.

  4. Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice

    Czech Academy of Sciences Publication Activity Database

    Bohuslavová, Romana; Kolář, František; Sedmera, David; Škvorová, Lada; Papoušek, František; Neckář, Jan; Pavlínková, Gabriela

    2014-01-01

    Roč. 14, Feb 6 (2014). ISSN 1472-6823 R&D Projects: GA ČR GA301/09/0117; GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:68378271 Keywords : Echocardiographic parameters * Hypoxia inducible factor 1 alpha * Diabetic cardiomyopathy Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.710, year: 2014

  5. Melanocytic nevi in children: A clinical study

    Directory of Open Access Journals (Sweden)

    Senthilkumar M

    2006-01-01

    Full Text Available BACKGROUND: Melanocytic nevi show different presentations in children which have not much studied in India. PURPOSES: To document the incidence and pattern of melanocytic nevi in children. METHODS: A total of 4,256 paediatric cases attending the dermatology OPD, JIPMER during the study period from August 2002 to August 2004 were screened for melanocytic nevi. FINDINGS: Out of these, 41 (0.96% cases were found to have melanocytic nevi. The mean age of these cases was 1.4 years (range of 3 days to 14 years. Fourteen (34.1% of them were males and 27 (65.9% were females with male to female ratio of 1:1.9. Majority of these cases (32 cases, 78% were in the age group of 0-1 year. Thirty-seven (90.2% cases had single lesion and 4 (9.8% cases had multiple lesions. The size of the nevi varied from 1.5 cm to 20 cm in 40 (97.6% cases and more than 20 cm in 1 (2.4% case. The most common site of involvement was the back (32 cases, 78% followed by head and neck (6 cases, 14.6%. Out of the total of 41 cases, 30 (73.2% were Mongolian spots, 8 (19.5% were congenital melanocytic nevi, one case (2.4% each had giant congenital melanocytic nevus, nevus spilus and nevus of Ota. Four cases had other associated cutaneous disorders. These included ashleaf macules in 2 cases, epidermolysis bullosa simplex in 1 case and a solitary case had both cafι-au-lait macule and mixed hemangioma. The systemic associations included seizures (suspected neurocutaneous melanosis in a solitary case of congenital melanocytic nevi. CONCLUSIONS: The spectrum of melanocytic nevi seen in children in this study partially differs from this of abroad studies. LIMITATION: Unicentre hospital-based study which cannot be generalized.

  6. Human keratinocytes are a source for tumor necrosis factor alpha: Evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light

    International Nuclear Information System (INIS)

    Tumor necrosis factor alpha (TNF-alpha), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-alpha. Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-alpha-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF-alpha activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-alpha revealed a molecular mass of 17 kD for keratinocyte-derived TNF-alpha. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF-alpha in LPS- or ultraviolet B (UVB)-treated HNK and KB cells. In addition, increased TNF-alpha levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-alpha, which may gain access to the circulation. Thus, TNF-alpha in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation

  7. Tumor necrosis factor alpha and interleukin-1 stimulate bone resorption in vivo as measured by urinary [3H]tetracycline excretion from prelabeled mice

    International Nuclear Information System (INIS)

    Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to stimulate bone resorption in vitro. We have now investigated whether these cytokines also cause a similar action when administered in vivo. This was made possible by the adaptation of a newly developed technique that enables the continual assessment of bone resorption in vivo in mice by measuring urinary excretion of 3H from [3H]tetracycline-prelabeled animals. Experiments using maneuvers known to influence bone resorption, such as a change in dietary calcium or administration of parathyroid hormone or dichloromethylenebisphosphonate, indicate that the technique is reliable and sensitive in mice. Daily intravenous administration of either recombinant human or recombinant murine TNF-alpha, as well as subcutaneous administration of recombinant human IL-1 alpha, were found to stimulate bone resorption in a dose-dependent manner. The effect was maximal within 2 days. Thus, exogenous TNF-alpha and IL-1 alpha can stimulate bone resorption in vivo, suggesting that these cytokines may also exert a systemic effect on bone

  8. Affinity purification of human granulocyte macrophage colony-stimulating factor receptor alpha-chain. Demonstration of binding by photoaffinity labeling

    International Nuclear Information System (INIS)

    The human granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain, a low affinity component of the receptor, was solubilized and affinity-purified from human placenta using biotinylated GM-CSF. Scatchard analysis of 125I-GM-CSF binding to the placental membrane extract disclosed that the GM-CSF receptor had a dissociation constant (Kd) of 0.5-0.8 nM, corresponding to the Kd value of the GM-CSF receptor alpha-chain on the intact placental membrane. Affinity labeling of the solubilized protein using a photoreactive cross-linking agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), demonstrated a single specific band of 70-95 kDa representing a ligand-receptor complex. Approximately 2 g of the placental membrane extract was subjected to a biotinylated GM-CSF-fixed streptavidin-agarose column, resulting in a single major band at 70 kDa on a silver-stained sodium dodecyl sulfate gel. The radioiodination for the purified material disclosed that the purified protein had an approximate molecular mass of 70 kDa and a pI of 6.6. Binding activity of the purified material was demonstrated by photoaffinity labeling using HSAB-125I-GM-CSF, producing a similar specific band at 70-95 kDa as was demonstrated for the crude protein

  9. Affinity purification of human granulocyte macrophage colony-stimulating factor receptor alpha-chain. Demonstration of binding by photoaffinity labeling

    Energy Technology Data Exchange (ETDEWEB)

    Chiba, S.; Shibuya, K.; Miyazono, K.; Tojo, A.; Oka, Y.; Miyagawa, K.; Takaku, F. (Univ. of Tokyo (Japan))

    1990-11-15

    The human granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain, a low affinity component of the receptor, was solubilized and affinity-purified from human placenta using biotinylated GM-CSF. Scatchard analysis of {sup 125}I-GM-CSF binding to the placental membrane extract disclosed that the GM-CSF receptor had a dissociation constant (Kd) of 0.5-0.8 nM, corresponding to the Kd value of the GM-CSF receptor alpha-chain on the intact placental membrane. Affinity labeling of the solubilized protein using a photoreactive cross-linking agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), demonstrated a single specific band of 70-95 kDa representing a ligand-receptor complex. Approximately 2 g of the placental membrane extract was subjected to a biotinylated GM-CSF-fixed streptavidin-agarose column, resulting in a single major band at 70 kDa on a silver-stained sodium dodecyl sulfate gel. The radioiodination for the purified material disclosed that the purified protein had an approximate molecular mass of 70 kDa and a pI of 6.6. Binding activity of the purified material was demonstrated by photoaffinity labeling using HSAB-{sup 125}I-GM-CSF, producing a similar specific band at 70-95 kDa as was demonstrated for the crude protein.

  10. The thermoluminescence and optically stimulated luminescence properties of Cr-doped alpha alumina transparent ceramics

    International Nuclear Information System (INIS)

    Highlights: •Polycrystalline Cr:α-Al2O3 transparent ceramics were obtained with vacuum sintering method. •The influence of different concentration of Cr2O3 on the thermoluminescence and optical stimulated luminescence properties of Cr:α-Al2O3 transparent ceramics was studied. •It had a main peak at 503 K of very high intensity and linear concentration dependence up to high concentration. •It showed so interesting results with high TL sensitivity and high stability of OSL signal that Cr:α-Al2O3 transparent ceramics might be a promising material in TL dosimetry and replace Cr:α-Al2O3 crystals. -- Abstract: Polycrystalline Cr:α-Al2O3 transparent ceramics were fabricated by conventional solid-state processing under vacuum condition. The SEM microstructure photographs of Cr:α-Al2O3 transparent ceramics doped with different content of Cr2O3 were investigated. The absorption, emission spectra, thermoluminescence and optical stimulated luminescence of Cr:α-Al2O3 transparent ceramics were comparable to those of Cr:α-Al2O3 crystals. The influence of different concentration of Cr2O3 on the thermoluminescence and optical stimulated luminescence properties of Cr:α-Al2O3 transparent ceramics was discussed. It showed so interesting results with high TL sensitivity and high stability of OSL signal that Cr:α-Al2O3 transparent ceramics might be a promising material in TL dosimetry and replace Cr:α-Al2O3 crystals

  11. Salivary alpha-amylase and cortisol responsiveness following electrically stimulated physical stress in bipolar disorder patients

    Directory of Open Access Journals (Sweden)

    Tanaka Y

    2013-12-01

    Full Text Available Yoshihiro Tanaka, Yoshihiro Maruyama, Yoshinobu Ishitobi, Aimi Kawano, Tomoko Ando, Rie Ikeda, Ayako Inoue, Junko Imanaga, Shizuko Okamoto, Masayuki Kanehisa, Taiga Ninomiya, Jusen Tsuru, Jotaro Akiyoshi Department of Neuropsychiatry, Faculty of Medicine, Oita University, Hasama-Machi, Oita, Japan Background: Bipolar disorder (BP is often associated with a change in hypothalamus–pituitary–adrenal axis function change due to chronic stress. Salivary α-amylase (sAA levels increase in response to psychosocial stress and thus function as a marker of sympathoadrenal medullary system activity. However, sAA has been studied less often than salivary cortisol in BP patients. Method: We measured Profile of Mood States and State-Trait Anxiety Inventory scores, heart rate variability, and salivary cortisol levels during electrical stimulation stress in 25 BP patients and 22 healthy volunteers. Results: Tension–anxiety, depression–dejection, anger–hostility, fatigue, and confusion scores in BP patients significantly increased compared with those of the healthy controls. In contrast, the vigor scores of BP patients significantly decreased compared with those of the healthy controls. Significant difference in the sAA levels was observed between BP patients and healthy controls. sAA of female patients was significantly higher than that of female healthy controls, and sAA in male patients tended to be higher than that of male healthy controls. No difference in salivary cortisol was observed between BP patients and the healthy controls. Only three time points were measured before and after the electrical stimulation stress. Furthermore, sAA secretion by BP patients increased before and after electrical stimulation. Conclusion: These preliminary results suggest that sAA may be a useful biological marker for BP patients. Keywords: HPA axis, bipolar disorder, α-amylase, cortisol, SAM activity

  12. Uniform decrease of alpha-global field power induced by intermittent photic stimulation of healthy subjects

    OpenAIRE

    2010-01-01

    Nineteen-channel EEGs were recorded from the scalp surface of 30 healthy subjects (16 males and 14 females, mean age: 34 years, SD: 11.7 years) at rest and under trains of intermittent photic stimulation (IPS) at rates of 5, 10 and 20 Hz. Digitalized data were submitted to spectral analysis with fast fourier transformation providing the basis for the computation of global field power (GFP). For quantification, GFP values in the frequency ranges of 5, 10 and 20 Hz at rest were divided by the c...

  13. Garlic (Allium sativum) stimulates lipopolysaccharide-induced tumor necrosis factor-alpha production from J774A.1 murine macrophages.

    Science.gov (United States)

    Sung, Jessica; Harfouche, Youssef; De La Cruz, Melissa; Zamora, Martha P; Liu, Yan; Rego, James A; Buckley, Nancy E

    2015-02-01

    Garlic (Allium sativum) is known to have many beneficial attributes such as antimicrobial, antiatherosclerotic, antitumorigenetic, and immunomodulatory properties. In the present study, we investigated the effects of an aqueous garlic extract on macrophage cytokine production by challenging the macrophage J774A.1 cell line with the garlic extract in the absence or presence of lipopolysaccharide (LPS) under different conditions. The effect of allicin, the major component of crushed garlic, was also investigated. Using enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction, it was found that garlic and synthetic allicin greatly stimulated tumor necrosis factor-alpha (TNF-α) production in macrophages treated with LPS. The TNF-α secretion levels peaked earlier and were sustained for a longer time in cells treated with garlic and LPS compared with cells treated with LPS alone. Garlic acted in a time-dependent manner. We suggest that garlic, at least partially via its allicin component, acts downstream from LPS to stimulate macrophage TNF-α secretion. PMID:25366263

  14. Biologically active monoiodinated alpha-MSH derivatives for receptor binding studies using human melanoma cells

    International Nuclear Information System (INIS)

    Three different monoiodinated radioligands of alpha-MSH (alpha-melanocyte-stimulating hormone) were compared in a binding assay with human D10 melanoma cells: [Tyr(125I)2]-alpha-MSH, [Tyr(125I)2,NIe4]-alpha-MSH, and [Tyr(125I)2,NIe4,D-Phe7]-alpha-MSH. They were prepared either by the classical chloramine T method or by the Enzymobead method. A simple and rapid purification scheme was developed consisting of a primary separation on reversed-phase C18 silica cartridges immediately after the iodination, followed by HPLC purification before each binding experiment. Biological testing of the three radioligands showed that they all retained high melanotropic activity in the B16 melanin assay and the Anolis melanophore assay. However, in human D10 melanoma cells, [Tyr(125I)2,NIe4]-alpha-MSH led to a high degree of non-specific binding to the cells which could not be displaced by excess alpha-MSH and only partially by [NIe4]-alpha-MSH. The [Tyr(125I)2,NIe4,D-Phe7]-alpha-MSH tracer gave similar results but with a much lower proportion of non-specific binding. On the other hand, [Tyr(125I)2]-alpha-MSH proved to be an excellent radioligand whose non-specific binding to the D10 cells was not higher than 20% of the total binding

  15. Cytolytic antibodies to melanocytes in vitiligo.

    Science.gov (United States)

    Cui, J; Arita, Y; Bystryn, J C

    1993-06-01

    Patients with vitiligo have been found to have circulating antibodies to pigment cells. To evaluate the functional activity of these antibodies, a highly sensitive europium release assay was used to compare complement-mediated cytolysis of human melanocytes by sera of 56 patients with vitiligo (20 with active disease, 25 with inactive disease, 11 with unidentified disease activity) and 47 control individuals. Significant melanocyte lysis was mediated by 32 (57%) of the patients with vitiligo but by only three (6%) of the control sera (p < 0.001), and by 17 (85%) of 20 patients with active vitiligo versus 11 (44%) of 25 patients with inactive disease (p < 0.025). Mean melanocyte lysis by vitiligo sera was 24% versus 6% by control sera (p < 0.0001). A subset of 12 vitiligo sera with high titers of cytolytic antibodies to melanocytes (34% mean cytolysis) reacted minimally (< 2% mean cytolysis) to a panel of control cells that included human and murine melanomas, human fibroblasts, lung carcinoma, and rhabdomyosarcoma. These findings indicate that antibodies present in patients with vitiligo have the functional ability to selectively kill melanocytes and are more common in active disease. These observations support, but do not prove, the hypothesis that vitiligo is an autoimmune disease and that anti-pigment cell antibodies have a role in inducing the disease. PMID:8496621

  16. Paraganglioma-like dermal melanocytic tumor

    Directory of Open Access Journals (Sweden)

    Anoop Thyvalappil

    2015-01-01

    Full Text Available Paraganglioma-like dermal melanocytic tumor (PDMT is a rare subtype of benign dermal melanocytic tumor, first described in 2004. Its histopathologic features resemble those of paraganglioma, showing presence of a distinctive partitioning of the tumor into small and large packets, nests, or short cords by delicate fibrous septa (zellballen pattern. But the immunostaining characteristics are those of melanocytic lesions, as PDMT express S-100, melan A, HMB 45 and lack pancytokeratin markers. It has a benign course, although a lesion of low malignant potential cannot be excluded. We describe a case of 60-year-old female who presented with three PDMT lesions on her right leg. To the best of our knowledge this is the first case reported from India.

  17. Dorsolateral prefrontal transcranial magnetic stimulation in patients with major depression locally affects alpha power of REM sleep

    Directory of Open Access Journals (Sweden)

    Maria Concetta Pellicciari

    2013-08-01

    Full Text Available Sleep alterations are among the most important disabling manifestation symptoms of Major Depression Disorder (MDD. A critical role of sleep importance is also underlined by the fact that its adjustment has been proposed as an objective marker of clinical remission in MDD. Repetitive transcranial magnetic stimulation (rTMS represents a relatively novel therapeutic tool for the treatment of drug-resistant depression. Nevertheless besides clinical evaluation of the mood improvement after rTMS, we have no clear understanding of what are the neurophysiological correlates of such treatment. One possible marker underlying the clinical outcome of rTMS in MDD could be cortical changes on wakefulness and sleep activity.The aim of this open-label study was to evaluate the efficacy of a sequential bilateral rTMS treatment over the dorsolateral prefrontal cortex (DLPFC to improve the mood in MDD patients, and to determine if rTMS can induce changes on the sleep structure, and if those changes can be used as a surrogate marker of the clinical state of the patient. Ten drug-resistant depressed patients participated to ten daily sessions of sequential bilateral rTMS with a low-frequency TMS (1 Hz over right-DLPFC and a subsequent high-frequency (10 Hz TMS over left-DLPFC. The clinical and neurophysiological effects induced by rTMS were evaluated respectively by means of the Hamilton Depression Rating Scale (HDRS, and by comparing the sleep pattern modulations and the spatial changes of EEG frequency bands during both NREM and REM sleep, before and after the real rTMS treatment. The sequential bilateral rTMS treatment over the DLPFC induced topographical-specific decrease of the alpha activity during REM sleep over left-DLPFC, which is significantly associated to the clinical outcome. In line with the notion of a left frontal hypoactivation in MDD patients, the observed local decrease of alpha activity after rTMS treatment during the REM sleep suggests that

  18. Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-{alpha} with BCAR1 and Traf6

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Lisa J., E-mail: robinsonlj@msx.upmc.edu [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Yaroslavskiy, Beatrice B.; Griswold, Reed D.; Zadorozny, Eva V.; Guo, Lida; Tourkova, Irina L. [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Blair, Harry C. [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Veteran' s Affairs Medical Center, Pittsburgh, PA 15243 (United States)

    2009-04-15

    The effects of estrogen on osteoclast survival and differentiation were studied using CD14-selected mononuclear osteoclast precursors from peripheral blood. Estradiol at {approx} 1 nM reduced RANKL-dependent osteoclast differentiation by 40-50%. Osteoclast differentiation was suppressed 14 days after addition of RANKL even when estradiol was withdrawn after 18 h. In CD14+ cells apoptosis was rare and was not augmented by RANKL or by 17-{beta}-estradiol. Estrogen receptor-{alpha} (ER{alpha}) expression was strongly down-regulated by RANKL, whether or not estradiol was present. Mature human osteoclasts thus cannot respond to estrogen via ER{alpha}. However, ER{alpha} was present in CD14+ osteoclast progenitors, and a scaffolding protein, BCAR1, which binds ER{alpha} in the presence of estrogen, was abundant. Immunoprecipitation showed rapid ({approx} 5 min) estrogen-dependent formation of ER{alpha}-BCAR1 complexes, which were increased by RANKL co-treatment. The RANKL-signaling intermediate Traf6, which regulates NF-{kappa}B activity, precipitated with this complex. Reduction of NF-{kappa}B nuclear localization occurred within 30 min of RANKL stimulation, and estradiol inhibited the phosphorylation of I{kappa}B in response to RANKL. Inhibition by estradiol was abolished by siRNA knockdown of BCAR1. We conclude that estrogen directly, but only partially, curtails human osteoclast formation. This effect requires BCAR1 and involves a non-genomic interaction with ER{alpha}.

  19. Interleukin 1 alpha stimulates hemopoiesis but not tumor cell proliferation and protects mice from lethal total body irradiation

    International Nuclear Information System (INIS)

    Interleukin 1 alpha (IL-1) is a polypeptide/glycoprotein growth factor with multiple functions including the modulation of hematopoietic cell proliferation and differentiation. In vivo studies were performed with C57BL/6J mice injected with 0, 0.2, or 2.0 micrograms of IL-1 24 hr before or after lethal total body irradiation (TBI) (9.5 Gy). More mice in the groups administered IL-1 before TBI survived (90% of the 2.0 micrograms group) than those treated 2 or 24 hr after TBI, which was still slightly superior to the uninjected group, which all died within 15 days (p = .0001). Proliferation of bone marrow granulocyte/macrophage colonies following split dose TBI was also greatest for mouse groups treated with IL-1 prior to TBI. These experiments support data from other investigators that IL-1 stimulation of BM is related to IL-1 timing with respect to TBI. Stimulation of hemopoiesis was also assessed in terms of changes in peripheral blood and BM cell numbers and cell cycle kinetics using an electronic particle counter and flow cytometric techniques. Mice injected with 2 micrograms of IL-1 showed an initial decline (at 3-6 hr) and then a selective proliferation (24-48 hr) of early and more committed progenitor cells to 125% and 200% of control values, respectively. Peripheral blood counts rose accordingly. Cells in S and G2/M phases increased over 10 hr and then declined in number. It thus appeared that some synchronization of cell cycling occurred, which might place cells in a more radioresistant phase of the cell cycle. The glutathione (GSH) content and synthesis in BM cells were measured by isocratic paired-ion high performance liquid chromatography and 35S-labelled cysteine incorporation into the GSH tripeptide. An increase in cellular GSH content and synthesis was demonstrated following IL-1 which lasted 24 hr

  20. Extrafollicular Dermal Melanocyte Stem Cells and Melanoma

    Directory of Open Access Journals (Sweden)

    James D. Hoerter

    2012-01-01

    Full Text Available Recent studies suggest that extrafollicular dermal melanocyte stem cells (MSCs persist after birth in the superficial nerve sheath of peripheral nerves and give rise to migratory melanocyte precursors when replacements for epidermal melanocytes are needed on the basal epidermal layer of the skin. If a damaged MSC or melanocyte precursor can be shown to be the primary origin of melanoma, targeted identification and eradication of it by antibody-based therapies will be the best method to treat melanoma and a very effective way to prevent its recurrence. Transcription factors and signaling pathways involved in MSC self-renewal, expansion and differentiation are reviewed. A model is presented to show how the detrimental effects of long-term UVA/UVB radiation on DNA and repair mechanisms in MSCs convert them to melanoma stem cells. Zebrafish have many advantages for investigating the role of MSCs in the development of melanoma. The signaling pathways regulating the development of MSCs in zebrafish are very similar to those found in humans and mice. The ability to easily manipulate the MSC population makes zebrafish an excellent model for studying how damage to MSCs may lead to melanoma.

  1. Stimulation of phospholipase A2 activity in bovine rod outer segments by the beta gamma subunits of transducin and its inhibition by the alpha subunit.

    OpenAIRE

    Jelsema, C L; Axelrod, J

    1987-01-01

    In the rod outer segments (ROS) of bovine retina, light activation of phospholipase A2 has been shown to occur by a transducin-dependent mechanism. In this report, the transducin-mediated stimulation of phospholipase A2 is shown to require dissociation of the alpha beta gamma heterotrimer. Addition of transducin to dark-adapted transducin-poor ROS stimulated phospholipase A2 activity only with coincident exposure to white light or, in the dark, with addition of the hydrolysis-resistant GTP an...

  2. Expression and localization of estrogen receptor-alpha protein in normal and abnormal term placentae and stimulation of trophoblast differentiation by estradiol

    Directory of Open Access Journals (Sweden)

    Henley Donald C

    2003-02-01

    compared to cultures in PhR+ medium. These data indicate that the considerable increase in estrogen production during pregnancy may play a role, via the ER-alpha, in the stimulation of CT differentiation and promote function in normal placentae. This mechanism, however, may not operate in abnormal placentae, which show a lack of ER-alpha expression.

  3. Overexpression of cellular repressor of E1A-stimulated genes inhibits TNF-{alpha}-induced apoptosis via NF-{kappa}B in mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Cheng-Fei [Xijing Hospital, Fourth Military Medical University, Xi' an (China); Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang (China); Han, Ya-Ling, E-mail: hanyaling53@gmail.com [Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang (China); Jie-Deng,; Yan, Cheng-Hui; Jian-Kang,; Bo-Luan,; Jie-Li [Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang (China)

    2011-03-25

    Research highlights: {yields} CREG protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis. {yields} CREG inhibits the phosphorylation of I{kappa}B{alpha} and prevents the activation of NF-{kappa}B. {yields} CREG inhibits NF-{kappa}B nuclear translocation and pro-apoptosis protein transcription. {yields} CREG anti-apoptotic effect involves inhibition of the death receptor pathway. {yields} p53 is downregulated by CREG via NF-{kappa}B pathway under TNF-{alpha} stimulation. -- Abstract: Bone marrow-derived mesenchymal stem cells (MSCs) show great potential for therapeutic repair after myocardial infarction. However, poor viability of transplanted MSCs in the ischemic heart has limited their use. Cellular repressor of E1A-stimulated genes (CREG) has been identified as a potent inhibitor of apoptosis. This study therefore aimed to determine if rat bone marrow MSCs transfected with CREG-were able to effectively resist apoptosis induced by inflammatory mediators, and to demonstrate the mechanism of CREG action. Apoptosis was determined by flow cytometric and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays. The pathways mediating these apoptotic effects were investigated by Western blotting. Overexpression of CREG markedly protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis by 50% after 10 h, through inhibition of the death-receptor-mediated apoptotic pathway, leading to attenuation of caspase-8 and caspase-3. Moreover, CREG resisted the serine phosphorylation of I{kappa}B{alpha} and prevented the nuclear translocation of the transcription factor nuclear factor-{kappa}B (NF-{kappa}B) under TNF-{alpha} stimulation. Treatment of cells with the NF-{kappa}B inhibitor pyrrolidine dithiocarbamate (PDTC) significantly increased the transcription of pro-apoptosis proteins (p53 and Fas) by NF-{kappa}B, and attenuated the anti-apoptotic effects of CREG on MSCs. The results of this study

  4. A distinct population of nonphagocytic and low level CD4+ null lymphocytes produce IFN-alpha after stimulation by herpes simplex virus-infected cells

    International Nuclear Information System (INIS)

    Human PBMC were stimulated for 6 h in vitro by HSV or Sendai virus (SV) and analyzed by flow cytometry. IFN-alpha producing cells (IPC) were identified through their content of IFN-alpha mRNA by in situ hybridization using a 35S-labeled IFN-alpha 2 cRNA probe. The IPC induced by HSV-infected WISH cells lacked capacity to adhere to and phagocytose latex particles. The induction of IFN-alpha by free infectious SV occurring in monocytes was abolished by phagocytosis of latex particles present in the cultures during the induction period. Such latex particles actually enhanced the IFN-alpha response induced by glutaraldehyde-fixed HSV- or SV-infected WISH cells or by free intact HSV. The HSV-induced IPC did not express the CD14 Ag expressed on monocytes. Cell sorting was performed on HSV-induced PBMC labeled with phycoerythrin-conjugated anti-CD3 and FITC-conjugated anti-CD4 mAb. A small population consisting of 1.4% of all PBMC, which was CD3- but expressed low but significant levels of CD4, contained the majority of the IPC with a 50-fold increase of their frequency. This cell population had a forward- and right-angle light scatter different from typical monocytes/macrophages. The results therefore further delineate IPC among PBMC into monocytes, being stimulated by viruses such as SV. Another distinct population of infrequent but highly efficient IPC, tentatively designated natural IFN-alpha producing cells, is activated by stimuli such as HSV

  5. Concentration-response relationship of {alpha}{sub 1}-adrenoceptor-stimulated increase of {sup 86}Rb{sup +} efflux in rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, G.Oe.; Enger, M.; Skomedal, T.; Osnes, J.B. [Univ. of Oslo, Dept. of Pharmacology (Norway)

    1996-10-01

    The aim of the present study was to establish a concentration-response relationship for the {alpha}{sub 1}-adrenoceptor mediated increase of{sup 86}Rb{sup +} efflux, and to characterize the sensitivity of this response to the selective {alpha}{sub 1}-adrenoceptor antagonist prazosin. Isolated rat hearts were perfused retrogradely at constant flow and at 31 deg. Timolol (10{sup -}26 mol/l) was used to block {beta}-adrenoceptors. After a loading period with {sup 86}Rb{sup +} and 55 min. washout, the hearts were exposed to phenylephrine in a concentration range from 3x10{sup -8} mol/l to 10{sup -4} mol/l. Control experiments comparing the effects of {alpha}{sub 1}-adrenoceptor stimulation on {sup 86}Rb{sup +} efflux and {sup 42}K{sup +} efflux were performed. {alpha}{sub 1}-Adrenoceptor stimulation increased the {sup 86}Rb{sup +} efflux with a pD{sub 2}=6.35{+-}0.20 (mean{+-}S.E.M.) The maximal response to phenylephrine was 22.5{+-}2.0% (mean{+-}S.E.M.) of the control values. The concentration-response curve was shifted to higher concentration of agonist in the presence of the {alpha}{sub 1}-adrenoceptor antagonist prazosin (3x10{sup -10} mol/l). The calculated inhibition constant for prazosin was 6.1x10{sup -11} mol/l. {sup 86}Rb{sup +} was found to be a suitable K{sup +} analogue in the study of relative changes in K{sup +} efflux concentration-dependently. A high sensitivity to prazosin confirmed the involvement of the {alpha}{sub 1}-adrenoceptor population. (au) 37 refs.

  6. Proton pump inhibitors decrease melanogenesis in melanocytes

    OpenAIRE

    Baek, Seung-Hwa; Lee, Sang-Han

    2015-01-01

    Proton pump inhibitors (PPIs) are widely used as inhibitors of gastric juice secretion for treatment of gastroesophageal reflux disease. However, there are no previous studies of the effects on melanogenesis resulting from PPI treatments. Therefore, the aim of the present study was to investigate the effects of PPIs on melanogenesis in melan-a cells derived from immortalized mouse melanocytes. Tyrosinase activity and copper-chelating activity were measured spectrophotometrically. In addition,...

  7. Oncogene-induced senescence in melanocytes

    OpenAIRE

    Leikam, Claudia

    2013-01-01

    Melanoma is the most aggressive skin cancer with very limited treatment options. Upon appearance of metastases chemotherapeutics are used to either kill or slow down the growth of cancer cells by inducing apoptosis or senescence, respectively. With melanomas originating from melanocytes, it is vital to elucidate the mechanisms that distinguish senescence induction from proliferation and tumourigenicity. Xmrk (Xiphophorus melanoma receptor kinase), the fish orthologue of the human epidermal gr...

  8. Melanocytes as Instigators and Victims of Oxidative Stress

    OpenAIRE

    Denat, L.; Kadekaro, A.L.; Marrot, L; Leachman, S; Abdel-Malek, Z.A.

    2014-01-01

    Epidermal melanocytes are particularly vulnerable to oxidative stress due to the pro-oxidant state generated during melanin synthesis, and to intrinsic antioxidant defences that are compromised in pathologic conditions. Melanoma is thought to be oxidative stress-driven, and melanocyte death in vitiligo is thought to be instigated by a highly pro-oxidant state in the epidermis. We review the current knowledge about melanin and the redox state of melanocytes, how paracrine factors help countera...

  9. Design and Evaluation of New Tc-99m-Labeled Lactam Bridge-Cyclized Alpha-MSH Peptides for Melanoma Imaging

    OpenAIRE

    Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

    2013-01-01

    The purpose of this study was to examine the melanoma targeting and imaging properties of new 99mTc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of 99mTc-MAG3-GGNle-CycMSHhex, 99mTc-AcCG3-GGNle-CycMSHhex...

  10. 6-Gingerol inhibits ROS and iNOS through the suppression of PKC-{alpha} and NF-{kappa}B pathways in lipopolysaccharide-stimulated mouse macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Tzung-Yan, E-mail: joyamen@mail.cgu.edu.tw [Graduate Institute of Traditional Chinese Medicine, Chang Gung University, No. 259, Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan 333, Taiwan (China); Lee, Ko-Chen [School of Traditional Chinese Medicine, Chang Gung University, Taiwan (China); Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chen, Shih-Yuan [Graduate Institute of Traditional Chinese Medicine, Chang Gung University, No. 259, Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan 333, Taiwan (China); Chang, Hen-Hong [Graduate Institute of Traditional Chinese Medicine, Chang Gung University, No. 259, Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan 333, Taiwan (China); Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China)

    2009-04-24

    Inflammation is involved in numerous diseases, including chronic inflammatory diseases and the development of cancer. Many plants possess a variety of biological activities, including antifungal, antibacterial and anti-inflammatory activities. However, our understanding of the anti-inflammatory effects of 6-gingerol is very limited. We used lipopolysaccharide (LPS)-stimulated macrophages as a model of inflammation to investigate the anti-inflammatory effects of 6-gingerol, which contains phenolic structure. We found that 6-gingerol exhibited an anti-inflammatory effect. 6-Gingerol could decrease inducible nitric oxide synthase and TNF-{alpha} expression through suppression of I-{kappa}B{alpha} phosphorylation, NF-{kappa}B nuclear activation and PKC-{alpha} translocation, which in turn inhibits Ca{sup 2+} mobilization and disruption of mitochondrial membrane potential in LPS-stimulated macrophages. Here, we demonstrate that 6-gingerol acts as an anti-inflammatory agent by blocking NF-{kappa}B and PKC signaling, and may be developed as a useful agent for the chemoprevention of cancer or inflammatory diseases.

  11. Agonist-promoted desensitization and phosphorylation of. cap alpha. /sub 1/-adrenergic receptors coupled to stimulation of phosphatidylinositol metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Leeb-Lundberg, L.M.F.; Cotecchia, S.; Caron, M.G.; Lefkowitz, R.J.

    1986-03-05

    In the DDT/sub 1/ MF-2 hamster vas deferens smooth muscle cell line the ..cap alpha../sub 1/-adrenergic receptor (..cap alpha../sub 1/-AR) agonist norepinephrine (NE) promotes rapid attenuation of ..cap alpha../sub 1/-AR-mediated phosphatidylinositol (PI) metabolism which is paralleled by rapid phosphorylation of the ..cap alpha../sub 1/-AR. Cells were labeled by incubation with /sup 32/P/sub i/. Coincubation with NE (100 ..mu..M) significantly increases the rate of /sup 32/P-labeling of both PI and phosphatidic acid. Pretreatment of cells with 100 ..mu..M NE (in the presence of 1 ..mu..M propranolol to prevent ..beta..-AR interactions) results in a drastic attenuation of the NE response on PI metabolism. ..cap alpha../sub 1/-AR from labeled cells can be solubilized and purified by affinity chromatography on Affigel-A55414 and wheat germ agglutinin agarose chromatography. SDS-PAGE of purified ..cap alpha../sub 1/-AR shows a NE-promoted increase in phosphorylation of the M/sub r/ 80K ligand binding peptide. Stoichiometry of phosphorylation increases from approx. 1 mol phosphate/mol ..cap alpha../sub 1/-AR in the basal condition to approx. 2.5 after NE treatment. Both desensitization and phosphorylation are rapid being maximal within 10-20 min of agonist exposure. These results together with previous findings that phorbol esters promote rapid ..cap alpha../sub 1/-AR uncoupling and phosphorylation suggest that receptor phosphorylation is an important mechanism of regulation of ..cap alpha../sub 1/-AR receptor responsiveness.

  12. Coordinate increase in major transcripts from the high pI alpha-amylase multigene family in barley aleurone cells stimulated with gibberellic acid.

    Science.gov (United States)

    Rogers, J C; Milliman, C

    1984-10-10

    The purpose of this study was to identify specifically genes and transcripts for the high pI isozyme of barley alpha-amylase. From hybridization of coding sequence probes to blots of genomic DNA digested with restriction enzymes that do not cut within our cloned high pI alpha-amylase cDNA, it is estimated that about 7 alpha-amylase genes or pseudogenes exist. No difference could be detected between barley aleurone cell and sprout DNAs. Experiments using probes from the 5' and 3' untranslated sequences of the high pI alpha-amylase cDNA clone identified three HindIII fragments that probably carry high pI sequences. Primer extension experiments used as a primer the terminal 5' coding sequence from our cDNA clone; this primer would not cross-hybridize to low pI alpha-amylase transcripts. Two major transcripts were identified. These shared a conserved 23-base sequence immediately 5' to the ATG start codon, although a C----G transversion and a 3-base deletion were present within this sequence. An unusual 8-base pair GC palindrome was present in the conserved region immediately preceding the ATG start codon. Distal to the conserved sequence there was no apparent homology. One transcript carrying a 97-base untranslated region was identical to our high pI cDNA clone E. The gene for the other was recovered from a lambda phage genomic library. The 5' coding sequence was very similar, but not identical to clone E, demonstrating that these transcripts arise from separate genes. The two transcripts increased coordinately in aleurone cells stimulated with gibberellic acid. These data indicate that there is a high pI alpha-amylase multigene family with at least two active members, both of which are regulated in some manner by the plant hormone gibberellic acid. PMID:6090459

  13. Tumor necrosis factor. alpha. and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor. kappa. B

    Energy Technology Data Exchange (ETDEWEB)

    Osborn, L.; Kunkel, S.; Nabel, G.J. (Howard Hughes Medical Institute, Ann Arbor, MI (USA))

    1989-04-01

    Binding of peptide hormones to surface membrane receptors leads to the transcription of specific genes within relevant target cells. How these signals are transduced to alter gene expression is largely unknown, but this mechanism probably involves a sequence of enzymatic steps that activate factors in the nucleus that modulate transcription. The authors demonstrate that two different peptide hormones, or cytokines, stimulate the human immunodeficiency virus enhancer, and this effect is mediated by nuclear factor (NF) {kappa}B. These cytokines, tumor necrosis factor {alpha} and interleukin 1, act on multiple cell types and represent the only naturally occurring activators of this transcription factor among eight cytokines examined. Although NF-{kappa}B binding can be stimulated by phorbol 12-myristate 13-acetate, tumor necrosis factor {alpha} acts through an independent mechanism, inducing NF-{kappa}B binding in HT-2 cells, which did not show increased binding in response to phorbol 12-myristate 13-acetate, and causing superinduction in Jurkat T-lymphoma cells. These findings suggest that human immunodeficiency virus gene expression can be induced in T cells without activating lymphokine secretion and that the role of these cytokines in the activation of latent human immunodeficiency virus infection deserves further clinical evaluation. Finally, this link between binding at the surface membrane and stimulation of a specific transcription factor should help define intermediates for these cytokine activation pathways.

  14. Melanocyte response to gravitational stress: an overview with a focus on the role of cyclic nucleotides

    Science.gov (United States)

    Ivanova, Krassimira; Tsiockas, Wasiliki; Eiermann, Peter; Hauslage, Jens; Hemmersbach, Ruth; Block, Ingrid; Gerzer, Rupert

    Human melanocytes are responsible for skin pigmentation by synthesizing the pigment melanin. A well known modulator of melanogenesis is the second messenger adenosine 3',5'-cyclic monophos-phate (cAMP). It has also been reported that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/guanosine 3',5'-cyclic monophosphate (cGMP) pathway is involved in UVB-induced melanogenesis. Melanin acts as a scavenger for free radicals during oxidative stress, but it may additionally act as a photosensitizer that generates active oxygen species upon UV radiation, which may initiate hypopigmentary disorders (e.g., vitiligo) as well as UV-induced oncogene cell transformation. Melanoma, a deadly skin cancer which arises from transformed melanocytes, is characterized by a resistance to chemotherapy. In our studies we were able to show that hu-man melanocytic cells differentially respond to gravitational stress. Hypergravity (up to 5 g for 24 h) stimulated cGMP efflux in cultured human melanocytes and non-metastatic melanoma cells, but not in metastatic phenotypes under the conditions of limited degradation [e.g., in the presence of phosphodiesterase (PDE) inhibitors] or stimulated synthesis of cGMP [e.g., by NO donors, but not natriuretic peptides], whereas cellular proliferation and morphology were not altered. Interestingly, long-term exposure to hypergravity stimulated an increase in both intra-cellular as well as extracellular cAMP levels as well as melanogenesis in pigmented melanocytes and non-metastatic melanoma cells. As some cAMP-PDEs are regulated by cGMP, it seems that the hypergravity-induced alteration of melanocyte pigmentation could be a result of a cross-talk between these two cyclic nucleotides. Hypergravity induced further an increase in the mRNA and protein levels of the selective cGMP and cAMP exporters, the multidrug resistance proteins (MRP) 4 and 5 -but not 8 -, whereas simulated microgravity (up to 1.21x10-2 g for 24 h) -provided by a fast-rotating clinostat

  15. ITER Plasma at Ion Cyclotron Frequency Domain: The Fusion Alpha Particles Diagnostics Based on the Stimulated Raman Scattering of Fast Magnetosonic Wave off High Harmonic Ion Bernstein Modes

    Science.gov (United States)

    Stefan, V. Alexander

    2014-10-01

    A novel method for alpha particle diagnostics is proposed. The theory of stimulated Raman scattering, SRS, of the fast wave and ion Bernstein mode, IBM, turbulence in multi-ion species plasmas, (Stefan University Press, La Jolla, CA, 2008). is utilized for the diagnostics of fast ions, (4)He (+2), in ITER plasmas. Nonlinear Landau damping of the IBM on fast ions near the plasma edge leads to the space-time changes in the turbulence level, (inverse alpha particle channeling). The space-time monitoring of the IBM turbulence via the SRS techniques may prove efficient for the real time study of the fast ion velocity distribution function, spatial distribution, and transport. Supported by Nikola Tesla Labs., La Jolla, CA 92037.

  16. Stimulation of complement production in mice by N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutamine)-N epsilon-stearoyl-L-lysine.

    OpenAIRE

    Endo, N.; Okuda, T; Osada, Y; Zen-Yoji, H

    1983-01-01

    N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutamine)-N epsilon-stearoyl-L-lysine, a synthetic muramyl dipeptide analog, stimulated the production of the third component of complement (C3) in mice. The serum concentration of C3 was elevated significantly by subcutaneous treatment with a single dose (10 to 100 micrograms per mouse) of the adjuvant 24 h before assay of the serum. Thereafter, the concentration decreased gradually with time and returned to the normal level on day 4 to 5. Immunoelectr...

  17. Role of nitric oxide and cyclic GMP signaling in melanocyte response to hypergravity

    Science.gov (United States)

    Ivanova, Krassimira; Lambers, Britta; Tsiockas, Wasiliki; Block, Ingrid; Gerzer, Rupert

    , respond to hyper-g (up to 5xg for 24 h) with an increase in cGMP efflux and pigmentation in comparison to 1-g controls under conditions of reduced cGMP hydrolysis or accelerated cGMP synthesis (e.g., by NO but not natriuretic peptides). The elevated cGMP extrusion was related to a hyper-g-induced increase in the expression of the multidrug resistance proteins 4/5 as selective cGMP exporters as shown on mRNA and protein levels using real-time polymerase chain reaction and flow cytometric analysis. These results suggest that an environment modified by centrifugal acceleration represents a new factor for regulating cGMP levels in unstimulated and NO-stimulated human melanocytes that involves multidrug resistance proteins, which could be important for malignant transformation. Future studies on these aspects in real microgravity will be important for residents on the International Space Station and astronauts involved in long space flights.

  18. Cytotoxic T lymphocyte responses against melanocytes and melanoma

    Directory of Open Access Journals (Sweden)

    Schwartz Erich J

    2011-07-01

    Full Text Available Abstract Background Vitiligo is a common toxicity associated with immunotherapy for melanoma. Cytotoxic T lymphocytes (CTLs against melanoma commonly target melanoma-associated antigens (MAAs which are also expressed by melanocytes. To uncouple vitiligo from melanoma destruction, it is important to understand if CTLs can respond against melanoma and melanocytes at different levels. Methods To understand the dichotomous role of MAA-specific CTL, we characterized the functional reactivities of established CTL clones directed to MAAs against melanoma and melanocyte cell lines. Results CTL clones generated from melanoma patients were capable of eliciting MHC-restricted, MAA-specific lysis against melanocyte cell lines as well as melanoma cells. Among the tested HLA-A*0201-restricted CTL clones, melanocytes evoked equal to slightly higher degranulation and cytolytic responses as compared to melanoma cells. Moreover, MAA-specific T cells from vaccinated patients responded directly ex vivo to melanoma and melanocytes. Melanoma cells express slightly higher levels of MART-1 and gp100 than melanocytes as measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR and immunohistochemistry. Conclusions Our data suggest that CTLs respond to melanoma and melanocytes equally in vitro and directly ex vivo.

  19. Spontaneous regression of a congenital melanocytic nevus

    Directory of Open Access Journals (Sweden)

    Amiya Kumar Nath

    2011-01-01

    Full Text Available Congenital melanocytic nevus (CMN may rarely regress which may also be associated with a halo or vitiligo. We describe a 10-year-old girl who presented with CMN on the left leg since birth, which recently started to regress spontaneously with associated depigmentation in the lesion and at a distant site. Dermoscopy performed at different sites of the regressing lesion demonstrated loss of epidermal pigments first followed by loss of dermal pigments. Histopathology and Masson-Fontana stain demonstrated lymphocytic infiltration and loss of pigment production in the regressing area. Immunohistochemistry staining (S100 and HMB-45, however, showed that nevus cells were present in the regressing areas.

  20. Oncostatin M, but not interleukin-6 or leukemia inhibitory factor, stimulates expression of alpha1-proteinase inhibitor in A549 human alveolar epithelial cells.

    Science.gov (United States)

    Sallenave, J M; Tremblay, G M; Gauldie, J; Richards, C D

    1997-06-01

    Alpha-1 proteinase inhibitor (A1-Pi) is the main serine proteinase inhibitor found in human plasma and is a potent elastase inhibitor in various tissues, including lung. A1-Pi is expressed and induced in liver during inflammatory responses but can also be produced by epithelial cells. Since hepatocyte A1-Pi production is stimulated by interleukin-6 (IL-6) and other gp130-cytokines, such as leukemia inhibitory factor (LIF) and oncostatin M (OM), we investigated the role of these cytokines in regulating A1-Pi in lung epithelial cells. We show that OM, a monocyte and T cell product, can specifically and potently induce A1-Pi production in lung-derived A549 alveolar (epithelial) cells, as well as in liver-derived HepG2 cells. Both A1-Pi protein (as detected by ELISA and Western blots) and mRNA levels were enhanced 20-fold to 30-fold in A549 cells. OM was also able to stimulate the expression of tissue inhibitor of metalloproteinase-1 in these cells. Interestingly, other members of the IL-6 family (IL-6 and LIF) had little or no effect on A549 cells, and proinflammatory cytokines, such as IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) also had no stimulatory effect on A1-Pi synthesis in A549 cells. Costimulation with IL-1 beta resulted in a decrease in A1-Pi production from OM-stimulated A549 cells. However, IL-6 production was synergistically enhanced. OM was also able to stimulate A1-Pi production from a bronchial epithelial primary cell line, whereas an intestinal epithelial cell line HT29 responded to IL-6 but not OM. These results suggest that lung levels A1-Pi could be derived not only from liver and inflammatory cells but also from epithelial cells, which can be upregulated on stimulation by OM. This may have implications for regulation of local activity of human neutrophil elastase (HNE) in such diseases as emphysema and cystic fibrosis. PMID:9198001

  1. The Production of Nitric Oxide, IL-6, and TNF-Alpha in Palmitate-Stimulated PBMNCs Is Enhanced through Hyperglycemia in Diabetes

    Directory of Open Access Journals (Sweden)

    Caroline Maria Oliveira Volpe

    2014-01-01

    Full Text Available We examined nitric oxide (NO, IL-6, and TNF-α secretion from cultured palmitate-stimulated PBMNCs or in the plasma from type 2 diabetes mellitus (T2MD patients or nondiabetic (ND controls. Free fatty acids (FFA have been suggested to induce chronic low-grade inflammation, activate the innate immune system, and cause deleterious effects on vascular cells and other tissues through inflammatory processes. The levels of NO, IL-6, TNF-α, and MDA were higher in supernatant of palmitate stimulated blood cells (PBMNC or from plasma from patients. The results obtained in the present study demonstrated that hyperglycemia in diabetes exacerbates in vitro inflammatory responses in PBMNCs stimulated with high levels of SFA (palmitate. These results suggest that hyperglycemia primes PBMNCs for NO, IL-6, and TNF-alpha secretion under in vitro FFA stimulation are associated with the secretion of inflammatory biomarkers in diabetes. A combined therapy targeting signaling pathways activated by hyperglycemia in conjunction with simultaneous control of hyperglycemia and hypertriglyceridemia would be suggested for controlling the progress of diabetic complications.

  2. Melanocyte Transformation Associated with Substrate Adhesion Impediment

    Directory of Open Access Journals (Sweden)

    Sueli M. Oba-Shinjo

    2006-03-01

    Full Text Available Exclude experimental models of malignant transformation employ chemical and physical carcinogens or genetic manipulations to study tumor progression. In this work, different melanoma cell lines were established after submitting a nontumorigenic melanocyte lineage (melan-a to sequential cycles of forced anchorage impediment. The great majority of these cells underwent anoikis when maintained in suspension. After one deadhesion cycle, phenotypic alterations were noticeable in the few surviving cells, which became more numerous and showed progressive alterations after each adhesion impediment step. No significant differences in cell surface expression of integrins were detected, but a clear electrophoretic migration shift, compatible with an altered glycosylation pattern, was observed for β1 chain in transformed cell lines. In parallel, a progressive enrichment of tri- and tetra-antennary N-glycans was apparent, suggesting increased N-acetylglucosaminyl-transferase V activity. Alterations both in proteoglycan glycosylation pattern and core protein expression were detected during the transformation process. In conclusion, this model corroborates the role of adhesion state as a promoting agent in transformation process and demonstrates that cell adhesion disturbances may act as carcinogenic stimuli, at least for a nontumorigenic immortalized melanocyte lineage. These findings have intriguing implications for in vivo carcinogenesis, suggesting that anchorage independence may precede, and contribute to, neoplastic conversion.

  3. Lactobacillus casei secreting alpha-MSH induces the therapeutic effect on DSS-induced acute colitis in Balb/c Mice.

    Science.gov (United States)

    Yoon, Sun-Woo; Lee, Chul-Ho; Kim, Jeong-Yoon; Kim, Jie-Youn; Sung, Moon-Hee; Poo, Haryoung

    2008-12-01

    The neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-alpha-MSH on the colitis, L. casei or L. casei-alpha-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-alpha-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45+/-0. 2 g; L. casei-alpha- MSH: 18.2+/-0.12 g), colitis score (DSS alone: 3.6+/-0.4; L. casei-alpha-MSH: 1.4+/-0.6), MPO activity (DSS alone: 42.7+/-4.5 U/g; L. casei-alpha-MSH: 10.25+/-0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappaB activation. The alpha-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases. PMID:19131702

  4. MC1R and the response of melanocytes to ultraviolet radiation

    International Nuclear Information System (INIS)

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists α-melanocyte-stimulating hormone (αMSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of αMSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is considered a

  5. Isoflurane anesthesia is a valuable alternative for alpha-chloralose anesthesia in the forepaw stimulation model in rats.

    NARCIS (Netherlands)

    Sommers, M.G.J.; Egmond, J. van; Booij, L.H.D.J.; Heerschap, A.

    2009-01-01

    Isoflurane (ISO) can be a valuable alternative for alpha-chloralose (ACL) anesthesia in functional MRI (fMRI) studies. Therefore, we compared the efficacy of the blood oxygen level dependent (BOLD) effect in fMRI studies during ISO and ACL anesthesia sequentially in the same animals. After non-invas

  6. New sesquiterpene dimers from Inula britannica inhibit NF-kappaB activation and NO and TNF-alpha production in LPS-stimulated RAW264.7 cells.

    Science.gov (United States)

    Jin, Hui Zi; Lee, Dongho; Lee, Jeong Hyung; Lee, Kyeong; Hong, Young-Soo; Choung, Dong-Ho; Kim, Young Ho; Lee, Jung Joon

    2006-01-01

    A bioassay-guided isolation of an ethyl acetate-soluble extract of the aerial parts of Inula britannica var. chinensis (Rupr.) Regel, using an in vitro NF-kappaB reporter gene assay, led to the isolation of four new sesquiterpene dimers bearing a norbornene moiety, inulanolides A-D, and three known sesquiterpenes, 1,6alpha-dihydroxyeriolanolide, 1-acetoxy-6alpha-hydroxyeriolanolide, and eupatolide. The structures of the new compounds were elucidated by spectroscopic methods. Among these compounds, inulanolides B and D and eupatolide, exhibited potent inhibitory activity on the LPS-induced NF-kappaB activation with IC50 values of 0.49 microM, 0.48 microM, and 1.54 microM, respectively. Consistent with their inhibitory effect on NF-kappaB activation, compounds and also strongly inhibited the production of NO and TNF-alpha in the LPS-stimulated RAW264.7 cells with IC50 values in the range of 2 microM. PMID:16450294

  7. Defects in ErbB-dependent establishment of adult melanocyte stem cells reveal independent origins for embryonic and regeneration melanocytes.

    Directory of Open Access Journals (Sweden)

    Keith A Hultman

    2009-07-01

    Full Text Available Adult stem cells are responsible for maintaining and repairing tissues during the life of an organism. Tissue repair in humans, however, is limited compared to the regenerative capabilities of other vertebrates, such as the zebrafish (Danio rerio. An understanding of stem cell mechanisms, such as how they are established, their self-renewal properties, and their recruitment to produce new cells is therefore important for the application of regenerative medicine. We use larval melanocyte regeneration following treatment with the melanocytotoxic drug MoTP to investigate these mechanisms in Melanocyte Stem Cell (MSC regulation. In this paper, we show that the receptor tyrosine kinase, erbb3b, is required for establishing the adult MSC responsible for regenerating the larval melanocyte population. Both the erbb3b mutant and wild-type fish treated with the ErbB inhibitor, AG1478, develop normal embryonic melanocytes but fail to regenerate melanocytes after MoTP-induced melanocyte ablation. By administering AG1478 at different time points, we show that ErbB signaling is only required for regeneration prior to MoTP treatment and before 48 hours of development, consistent with a role in establishing MSCs. We then show that overexpression of kitla, the Kit ligand, in transgenic larvae leads to recruitment of MSCs, resulting in overproliferation of melanocytes. Furthermore, kitla overexpression can rescue AG1478-blocked regeneration, suggesting that ErbB signaling is required to promote the progression and specification of the MSC from a pre-MSC state. This study provides evidence that ErbB signaling is required for the establishment of adult MSCs during embryonic development. That this requirement is not shared with the embryonic melanocytes suggests that embryonic melanocytes develop directly, without proceeding through the ErbB-dependent MSC. Moreover, the shared requirement of larval melanocyte regeneration and metamorphic melanocytes that develops at

  8. Differences in Salivary Alpha-Amylase and Cortisol Responsiveness following Exposure to Electrical Stimulation versus the Trier Social Stress Tests

    OpenAIRE

    Yoshihiro Maruyama; Aimi Kawano; Shizuko Okamoto; Tomoko Ando; Yoshinobu Ishitobi; Yoshihiro Tanaka; Ayako Inoue; Junko Imanaga; Masayuki Kanehisa; Haruka Higuma; Taiga Ninomiya; Jusen Tsuru; Hiroaki Hanada; Jotaro Akiyoshi

    2012-01-01

    BACKGROUND: Cortisol is an essential hormone in the regulation of the stress response along the HPA axis, and salivary cortisol has been used as a measure of free circulating cortisol levels. Recently, salivary alpha-amylase (sAA) has also emerged as a novel biomarker for psychosocial stress responsiveness within the sympathetic adrenomedullary (SAM) system. PRINCIPAL FINDINGS: We measured sAA and salivary cortisol in healthy volunteers after exposure to the Trier Social Stress Test (TSST) an...

  9. Differences in Salivary Alpha-Amylase and Cortisol Responsiveness following Exposure to Electrical Stimulation versus the Trier Social Stress Tests

    OpenAIRE

    Maruyama, Yoshihiro; Kawano, Aimi; Okamoto, Shizuko; Ando, Tomoko; Ishitobi, Yoshinobu; Tanaka, Yoshihiro; Inoue, Ayako; Imanaga, Junko; Kanehisa, Masayuki; Higuma, Haruka; Ninomiya, Taiga; Tsuru, Jusen; Hanada, Hiroaki; Akiyoshi, Jotaro

    2012-01-01

    Background Cortisol is an essential hormone in the regulation of the stress response along the HPA axis, and salivary cortisol has been used as a measure of free circulating cortisol levels. Recently, salivary alpha-amylase (sAA) has also emerged as a novel biomarker for psychosocial stress responsiveness within the sympathetic adrenomedullary (SAM) system. Principal Findings We measured sAA and salivary cortisol in healthy volunteers after exposure to the Trier Social Stress Test (TSST) and ...

  10. Primary transpupillary thermotherapy of choroidal melanocytic lesions

    Directory of Open Access Journals (Sweden)

    Kaan Gündüz

    2011-01-01

    Full Text Available Purpose : To evaluate the role of primary transpupillary thermotherapy (TTT in the treatment of choroidal melanocytic lesions. Materials and Methods : Retrospective chart review of 24 patients (24 eyes with choroidal melanocytic lesions, including 20 choroidal melanoma and four choroidal nevus treated with primary TTT. Choroidal nevus cases treated with primary TTT either demonstrated risk factors for growth into an early melanoma or had overlying choroidal neovascularization. Results : The mean initial tumor basal diameter was 6.6 (3.0-10.0 mm and the mean initial tumor thickness was 3.0 (1.0-5.0 mm. The mean number of TTT sessions was 2.5 (1-6. The mean decrease in tumor thickness was 1.2 mm (from 3.0 to 1.8 mm at a mean follow-up of 22.7 (range 3-90 months. On the LogMar scale, visual acuity was stable at 1.0. Complications occurred in 50% of eyes. The most frequent complications were vitreous hemorrhage [5 patients (20.8%], focal cataract [5 patients (20.8%], iris atrophy [4 patients (16.6%] and posterior synechia [4 patients (16.6%]. There was no significant difference in the complication rate with respect to tumor thickness >3 mm versus tumor thickness ≤3 mm and juxtapapillary versus nonjuxtapapillary location (Fisher′s exact test, P>0.05. Kaplan-Meier curves showed that 9% of eyes develop recurrence by 1 year and 27% develop recurrence by 5 years after primary TTT. Two eyes (8.3% were enucleated because of neovascular glaucoma and one eye (4.1% was exenterated because of extraocular tumor recurrence. Globe salvage was achieved in 21 patients (87.5%. One patient (4.1% with extraocular tumor recurrence developed liver metastasis and expired. Conclusions : Although TTT may be useful in the treatment of small choroidal melanocytic lesions, the high complication and recurrence rates warrant close monitoring of patients after primary TTT even when a flat chorioretinal scar has been achieved.

  11. Clonal and Lineage Analysis of Melanocyte Stem Cells and Their Progeny in the Zebrafish

    OpenAIRE

    Tryon, Robert C.; Johnson, Stephen L

    2012-01-01

    The study of melanocyte biology in the zebrafish presents a highly tractable system for understanding fundamental principles of developmental biology. Melanocytes are visible in the transparent embryo and in the mature fish following metamorphosis, a physical transformation from the larval to adult form. While early developing larval melanocytes are direct derivatives of the neural crest, the remainder of melanocytes develop from unpigmented precursors, or melanocyte stem cells (MSCs). The To...

  12. Adipose-Derived Stem Cells Improve Efficacy of Melanocyte Transplantation in Animal Skin

    OpenAIRE

    Lim, Won-Suk; Kim, Chang-Hyun; Kim, Ji-Young; Do, Byung-Rok; Kim, Eo Jin; Lee, Ai-Young

    2014-01-01

    Vitiligo is a pigmentary disorder induced by a loss of melanocytes. In addition to replacement of pure melanocytes, cocultures of melanocytes with keratinocytes have been used to improve the repigmentation outcome in vitiligo treatment. We previously identified by in vitro studies, that adipose-derived stem cells (ADSCs) could be a potential substitute for keratinocytes in cocultures with melanocytes. In this study, the efficacy of pigmentation including durability of grafted melanocytes and ...

  13. Melanocyte regeneration in vitiligo requires WNT beneath their wings

    Science.gov (United States)

    Harris, John E.

    2015-01-01

    Melanocytes in patients with vitiligo possess intrinsic abnormalities that contribute to its pathogenesis. In this issue, Regazzetti, et al. report that CXCL10 expression reflects subtle inflammation in normal-appearing skin but not in stable depigmented lesions, supporting the hypothesis that melanocytes themselves initiate autoimmune inflammation prior to clinically evident disease. In addition, they find that oxidative stress in melanocytes impairs WNT signaling and that targeting this pathway induces melanoblast differentiation. Thus, activating the WNT pathway may serve as an adjunctive strategy to support repigmentation in patients with vitiligo. PMID:26569586

  14. Giant congenital melanocytic nevus in a bulgarian newborn.

    Science.gov (United States)

    Chokoeva, A A; Fioranelli, M; Roccia, M G; Lotti, T; Wollina, U; Tchernev, G

    2016-01-01

    Giant congenital melanocytic nevus (GCMN) is a rare disorder affecting 1 in 200,000–500,000 live births. Central nervous system defects such as spina bifida, meningocele, Dandy Walker malformation may accompany it and thus cause significant morbidity. Despite the related risk for malignant transformation, GCMNs may be associated with neurocutaneous melanosis, a rare syndrome in which a giant CMN or multiple smaller CMNs are accompanied by melanocytic deposition in the brain and the spinal cord. We present a case of a 5-day-old newborn with giant congenital melanocytic nevus on his back, as we discuss the diagnostic and treatment approach. PMID:27373137

  15. Dorsolateral prefrontal transcranial magnetic stimulation in patients with major depression locally affects alpha power of REM sleep

    OpenAIRE

    Pellicciari, Maria Concetta; Cordone, Susanna; Marzano, Cristina; Bignotti, Stefano; Gazzoli, Anna; Miniussi, Carlo; De Gennaro, Luigi

    2013-01-01

    Sleep alterations are among the most important disabling manifestation symptoms of Major Depression Disorder (MDD). A critical role of sleep importance is also underlined by the fact that its adjustment has been proposed as an objective marker of clinical remission in MDD. Repetitive transcranial magnetic stimulation (rTMS) represents a relatively novel therapeutic tool for the treatment of drug-resistant depression. Nevertheless, besides clinical evaluation of the mood improvement after rTMS...

  16. Retrospective study of canine epithelial and melanocytic tumors

    Directory of Open Access Journals (Sweden)

    Aleksić-Kovačević Sanja

    2005-01-01

    Full Text Available Out of the total number of canine tumors examined at the Department of pathology based on biopsy and section materials over the last five years skin tumors and mammary gland tumors were proved to be the two largest groups diagnosed in 33.4% and 36% of cases, respectively. Cutaneous tumors were diagnosed in 211 cases, i.e., in 123 (58.3% male dogs and 88 (41.7% bitches, of different breeds, on average 7 years old. Among the total number of 211 skin tumors, 32 types of cutaneous neoplasms were diagnosed, with epithelial and melanocytic tumors being the most predominant, followed by hematopoietic tumors and mesenchymal tumors of the skin and soft tissues. In our bioptic and section materials, epithelial and melanocytic skin tumors were the most frequent -123 cases (58.75% with four subgroups within the group tumors with adnexal differentiation - 66 cases (53.23% of all epithelial and melanocytic skin tumors, epidermal tumors - 25 cases (20.16% of all epithelial and melanocytic skin tumors, tumors without squamous or adnexal differentiation -16 cases (12.90% of all epithelial and melanocytic skin tumors and finally melanocytic tumors -14 cases (11.29% of all epithelial and melanocytic skin tumors. The age of dogs with epithelial and melanocytic cutaneous tumors ranged between 5 months to 15 years. The fact that the number of skin tumors diagnosed in 1999 was doubled in 2002 is of particular importance, which may be, the result of increasingly high interest of clinicians for biopsy-based diagnosis.

  17. Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

    OpenAIRE

    Jenkins, Noah C.; Douglas Grossman

    2013-01-01

    We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS) than these other epidermal cell types. Given the role of ...

  18. Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes.

    Science.gov (United States)

    Sun, Xiaoyun; Kim, Arianna; Nakatani, Masashi; Shen, Yao; Liu, Liang

    2016-09-01

    Solar ultraviolet radiation (UVR) is the major risk factor for skin carcinogenesis. To gain new insights into the molecular pathways mediating UVR effects in the skin, we performed comprehensive transcriptomic analyses to identify shared and distinctive molecular responses to UVR between human keratinocytes and melanocytes. Keratinocytes and melanocytes were irradiated with varying doses of UVB (10, 20 and 30 mJ/cm(2) ) then analysed by RNA-Seq at different time points post-UVB radiation (4, 24 and 72 h). Under basal conditions, keratinocytes and melanocytes expressed similar number of genes, although they each expressed a distinctive subset of genes pertaining to their specific cellular identity. Upon UVB radiation, keratinocytes displayed a clear pattern of time- and dose-dependent changes in gene expression that was different from melanocytes. The early UVB-responsive gene set (4 h post-UVR) differed significantly from delayed UVB-responsive gene sets (24 and 72 h). We also identified multiple novel UVB signature genes including PRSS23, SERPINH1, LCE3D and CNFN, which were conserved between melanocyte and keratinocyte lines from different individuals. Taken together, our findings elucidated both common and distinctive molecular features between melanocytes and keratinocytes and uncovered novel UVB signature genes that might be utilized to predict UVB photobiological effects on the skin. PMID:27119462

  19. Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Noah C. Jenkins

    2013-01-01

    Full Text Available We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

  20. Features of immunohistochemical diagnostic of melanocytic tumours

    Directory of Open Access Journals (Sweden)

    Shpon’ka I.S.

    2013-12-01

    Full Text Available Background. The malignant melanomas are the most important group of skin cancers. Although less common than the familiar basal and squamous cell tumours of the skin, they are much more frequently fatal, due to their intrinsic tendency to lymphatic and haematogenic metastasis. Objective. The article is devoted to parsing cases melanocytic tumours that were established through immunohistochemical study. Methods. In the study analyzed 236 patient material (150 women and 86 men aged 28 to 77 years during 2010-2013 turned out to clarify the histological diagnosis of skin tumors or metastases to lymph nodes (rare at other sites. The primary monoclonal antibodies used Сytokeratin, Рan Ab1 (clone AE1/AE3, S100 (clone 4C4.9, Ki-67 (clone SP6, Vimentin (clone V9, Melanoma gp100 (clone HMB-45. Results. Naevus proliferation rate showed a statistically significant difference with respect to proliferation rate of malignant melanomas (p<0,05. All samples (100% showed positive expression of high-intensity staining (+++ or moderate (++ intensity on the marker S100; 98,30% of samples (232 of 236 showed positive expression of marker HMB-45 at least in terms of tumor cells with intensity color from the high (+++ to weak (+ and 83.89% of the samples (198 of 236 were negative (– Сytokeratin, Рan Ab1 (other 38 cases showed weakly positive expression (+/– of tumor cells. Conclusions. 1. In the differential diagnosis of melanoma and naevus, we must bear in mind the uniformity immunophenotype of these tumors and consider only the cytological features of the tumor, changes in the structure of the epidermis and dermis (contour, symmetry, depth, inflammatory infiltration and proliferation rate. 2. Patients whose lymph nodes were the first clinical signs of cancer are always in need for additional immunohistochemical studies to avoid diagnostic errors. 3. The most common phenotype of melanocytic tumours responsible Сytokeratin, Рan–, Vimintin+, S100+, HMB-45

  1. Ex-vivo in-vitro inhibition of lipopolysaccharide stimulated tumor necrosis factor-alpha and interleukin-1 beta secretion in human whole blood by extractum urticae dioicae foliorum.

    Science.gov (United States)

    Obertreis, B; Ruttkowski, T; Teucher, T; Behnke, B; Schmitz, H

    1996-04-01

    An extract of Urtica dioica folium (IDS 23, Rheuma-Hek), monographed positively for adjuvant therapy of rheumatic diseases and with known effects in partial inhibition of prostaglandin and leukotriene synthesis in vitro, was investigated with respect to effects of the extract on the lipopolysaccharide (LPS) stimulated secretion of proinflammatory cytokines in human whole blood of healthy volunteers. In the assay system used, LPS stimulated human whole blood showed a straight increase of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion reaching maximum concentrations within 24 h following a plateau and slight decrease up to 65 h, respectively. The concentrations of these cytokines was strongly positively correlated with the number of monocytes/macrophages of each volunteer. TNF-alpha and IL-1 beta concentration after LPS stimulation was significantly reduced by simultaneously given IDS 23 in a strictly dose dependent manner. At time 24 h these cytokine concentrations were reduced by 50.8% and 99.7%, respectively, using the highest test IDS 23 assay concentration of 5 mg/ml (p flavonoides such as caffeic malic acid, caffeic acid, chlorogenic acid, quercetin and rutin did not influence LPS stimulated TNF-alpha, IL-1 beta and IL-6 secretion in tested concentrations up to 5 x 10(-5) mol/l. These further findings on the pharmacological mechanism of action of Urticae dioica folia may explain the positive effects of this extract in the treatment of rheumatic diseases. PMID:8740085

  2. Prediction of Dermoscopy Patterns for Recognition of both Melanocytic and Non-Melanocytic Skin Lesions

    Directory of Open Access Journals (Sweden)

    Qaisar Abbas

    2016-06-01

    Full Text Available A differentiation between all types of melanocytic and non-melanocytic skin lesions (MnM–SK is a challenging task for both computer-aided diagnosis (CAD and dermatologists due to the complex structure of patterns. The dermatologists are widely using pattern analysis as a first step with clinical attributes to recognize all categories of pigmented skin lesions (PSLs. To increase the diagnostic accuracy of CAD systems, a new pattern classification algorithm is proposed to predict skin lesions patterns by integrating the majority voting (MV–SVM scheme with multi-class support vector machine (SVM. The optimal color and texture features are also extracted from each region-of-interest (ROI dermoscopy image and then these normalized features are fed into an MV–SVM classifier to recognize seven classes. The overall system is evaluated using a dataset of 350 dermoscopy images (50 ROIs per class. On average, the sensitivity of 94%, specificity of 84%, 93% of accuracy and area under the receiver operating curve (AUC of 0.94 are achieved by the proposed MnM–SK system compared to state-of-the-art methods. The obtained result indicates that the MnM–SK system is successful for obtaining the high level of diagnostic accuracy. Thus, it can be used as an alternative pattern classification system to differentiate among all types of pigmented skin lesions (PSLs.

  3. Does Melanoma Begin in a Melanocyte Stem Cell?

    Directory of Open Access Journals (Sweden)

    James D. Hoerter

    2012-01-01

    Full Text Available What is the cellular origin of melanoma? What role do melanocyte stem cells (MSC and other melanocyte precursors play in the development of melanoma? Are MSCs and other latent melanocyte precursors more susceptible to solar radiation? These and many other questions can be very effectively addressed using the zebrafish model. Zebrafish have a robust regenerative capability, permitting the study of how MSCs are regulated and recruited at specific times and places to generate the pigment pattern following fin amputation or melanocyte ablation. They can be used to determine the effects of environmental radiation on the proliferation, survival, repair, and differentiation of MSCs. Our lab is using zebrafish to investigate how UVA- (320–400 nm and UVB- (290–320 nm induced damage to MSCs may contribute to the development of melanoma. A review is given of MSCs in zebrafish as well as experimental techniques and drugs for manipulating MSC populations. These techniques can be used to design experiments to help answer many questions regarding the role of MSCs or melanocyte precursors in the formation of melanoma stem cells and tumors following exposure to UVA/UVB radiation.

  4. Light stimulation of iris tyrosinase in vivo

    International Nuclear Information System (INIS)

    This paper presents evidence that light stimulates tyrosinase activity in iris melanocytes in rabbits. Levels of iris tyrosinase were found to be greater in eyes of rabbits exposed to light for 6 weeks than in eyes of rabbits maintained in darkness. Despite increasing tyrosinase levels, exposure to light produced no clinically observable change in iris color

  5. Wnt inhibitory factor (WIF)-1 promotes melanogenesis in normal human melanocytes.

    Science.gov (United States)

    Park, Tae Jun; Kim, Misun; Kim, Hyeran; Park, Sun Yi; Park, Kyoung-Chan; Ortonne, Jean-Paul; Kang, Hee Young

    2014-01-01

    Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Using a microarray analysis, hyperpigmentary skin of melasma expressed high levels of Wnt inhibitory factor-1 (WIF-1) compared with perilesional normal skin. In this study, the expression and functional roles of WIF-1 on melanocytes were investigated. WIF-1 was expressed both in the melanocytes of normal human skin and in cultured melanocytes. The upregulation of WIF-1 on cultured normal human melanocytes significantly induced expressions of MITF and tyrosinase, which were associated with increased melanin content and tyrosinase activity. Consistent with the stimulatory effect of WIF-1, WIF-1 siRNA reduced melanogenesis in the cells. Moreover, WIF-1 increases pigmentation in melanocytes co-cultured with WIF-1-overexpressed fibroblasts and of organ-cultured human skin. These findings suggest that melanocytes express WIF-1 constitutively in vivo and in vitro and that WIF-1 promotes melanogenesis in normal human melanocytes. PMID:24131586

  6. The epidermal melanocyte system in individuals of Scandinavian origin, determined by DOPA-staining and TEM

    DEFF Research Database (Denmark)

    Drzewiecki, K T; Piltz-Drzewiecka, J

    1979-01-01

    The quantitative evaluation of DOPA-positive epidermal melanocytes in 16 patients of Scandinavian origin showed both individual and regional differences in the melanocyte count. Our data is in agreement with other published studies. The distribution in the number of melanocytes varies significant...

  7. High-definition optical coherence tomography imaging of melanocytic lesions

    DEFF Research Database (Denmark)

    Boone, Marc A L M; Norrenberg, Sarah; Jemec, Gregor B E; Del Marmol, V

    2014-01-01

    cytologic features of melanocytic lesions. All lesions were examined by one observer clinically and using dermoscopy. Cross-sectional HD-OCT images were compared with histopathology. En face HD-OCT images were compared with reflectance confocal microscopy (RCM). Twenty-six melanocytic lesions of 26 patients...... sufficient resolution and penetration depth to discriminate architectural patterns and cytologic features of pigmented cells in epidermis and dermis. The method appears to offer the possibility of additional three-dimensional structural information complementary to that of RCM, albeit at a slightly lower...

  8. Design of potent linear alpha-melanotropin 4-10 analogues modified in positions 5 and 10.

    Science.gov (United States)

    Al-Obeidi, F; Hruby, V J; Castrucci, A M; Hadley, M E

    1989-01-01

    alpha-Melanocyte stimulating hormone (alpha-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) that has diverse physiological functions in addition to its reversible darkening of amphibian skins by stimulating melanosome dispersion within melanophores. On the basis of theoretical and experimental results from our laboratory and others, we have designed a group of 1-13, 4-13, and especially 4-10 analogues related to the superpotent analogue [Nle4,D-Phe7]alpha-MSH in which the Glu5 has been replaced with Asp5, and the Gly10 has been replaced with Lys10 and other basic amino acid residues in the 4-10 analogues, and in which Gly10 and Lys11 were interchanged in the longer peptide analogues. In the 1-13 and 4-13 series the Lys10, Gly11 analogues generally retained superpotency for the D-Phe7-containing analogues. Most interestingly, synthesis of Ac-[Nle4,Xxx5,Yyy7,Zzz10]alpha-MSH4-10-NH2 analogues where Xxx = Asp or Glu, Yyy = Phe or D-Phe, and Zzz = basic amino acids (Lys, Orn, alpha,gamma-diaminobutyric acid (Dab), and alpha,beta-diaminopropionic acid (Dpr] provided melanotropins with potencies up to 10 times that of the native hormone in stimulating frog (Rana pipiens) skin darkening and 8-50 times more potent than alpha-MSH in stimulating lizard (Anolis carolinensis) skin melanophores in vitro. To our knowledge, Ac-[Nle4,Asp5,D-Phe7,Dab10]alpha-MSH4-10-NH2, the most potent analogue, is the most potent melanotropin obtained thus far for the Anolis assay system. These results provide new insights into the structural and conformational requirements for biological potency of alpha-MSH and the differential structural and conformational requirements of alpha-MSH and its analogues at two different types of pigment cell receptors. PMID:2535874

  9. Differential stimulation by CCAAT/enhancer-binding protein alpha isoforms of the estrogen-activated promoter of the very-low-density apolipoprotein II gene

    NARCIS (Netherlands)

    Calkhoven, CF; Snippe, L; Ab, G

    1997-01-01

    The transcription factors CCAAT/enhancer-binding proteins alpha and beta (C/EBP alpha and C/EBP beta) are highly expressed in liver and are believed to function in maintaining the differentiated state of the hepatocytes, C/EBP alpha appears to be a critical regulator of genes involved in metabolic p

  10. Effects of Single Herbal Drugs on Adhesion and Migration of Melanocytes

    Institute of Scientific and Technical Information of China (English)

    Zhang Xianqi; Feng Jie; Mu Kuanhou; Ma Huiqun; Niu Xinwu; Liu Chao; Dang Qianli

    2005-01-01

    Objective: To find herbs with effects on adhesion and migration of melanocytes in vitro. Materials and Methods: Ethanol extracts from 14 herbs were tested. Normal human melanocytes were obtained from neonatal foreskin, and the 48-well culture dish covered with fibronectin was used for the melanocyte adhesion assay. Motility was assessed by using the micropore filter method. Results: The extracts of could promote both adhesion and migration of melanocytes. Conclusion: The above herbs may play a role through promoting adhesion and/or migration of melanocytes in the treatment of vitiligo.

  11. Regulation of eumelanin / pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor

    OpenAIRE

    Le Pape, Elodie; Wakamatsu, Kazumasa; Ito, Shosuke; Wolber, Rainer; Hearing, Vincent J.

    2008-01-01

    The production of melanin in the hair and skin is tightly regulated by the melanocortin 1 receptor (MC1R) whose activation is controlled by 2 secreted ligands, α-melanocyte stimulating hormone (αMSH) and agouti signal protein (ASP). Since melanin is extremely stable, lasting years in biological tissues, the mechanism underlying the relatively rapid decrease in visible pigmentation elicited by ASP is of obvious interest. In this study, the effects of ASP and αMSH on the regulation of melanin s...

  12. Effect of Xiaobailing Decoction on Melanocytes in Vitro

    Institute of Scientific and Technical Information of China (English)

    Xue Wenhui; Qu Xing; Chen Changbin; Li Minying

    2007-01-01

    Objective: To observe the effect of Xiaobailing Decoction ( 消白灵汤 ) on murine melanocytes in vitro and to explore the mechanism of Xiaobailing Decoction in the treatment of vitiligo. Methods: B-16F10murine melanoma cells were cultured in 1640 medium and treated respectively with different concentrations (1mg/ml, 2mg/ml, 3mg/ml) of the Chinese drug Xiaobailing Decoction and its main components, the drugs for replenishing the kidney-yang, and the drugs for nourishing blood and activating blood circulation, etc. For 7 days. MMT assay was used to determine the proliferation of B-16F10 murine melanoma cells. NaOH cleavage assay was adopted to measure the melanogenesis of melanocytes. Results:Xiaobailing Decoction, the drugs for replenishing the kidney-yang and the drugs for nourishing blood and activating blood circulation at different concentrations significantly improved the proliferation of B-16F10murine melanoma cells from the 3rd day to the 5th day (P<0.05), with Xiaobailing Decoction at the concentrations of 1mg/ml having the most distinct action on promoting the proliferation of melanocytes on the 3rd day (P<0.001); And the drugs for replenishing the kidney-yang at the concentrations of 2mg/ml and 3mg/ml and the drugs for nourishing blood and activating blood circulation at 3mg/ml significantly increased melanogenesis of melanocytes (P<0.05). Conclusion: Xiaobailing Decoction can promote melanocytic proliferation and melanogenesis in vitro, and it is indicated that the drugs for replenishing the kidney-yang and the drugs for nourishing blood and activating blood circulation play an important role in treating vitiligo.

  13. Endothelin-1 increases melanin synthesis in an established sheep skin melanocyte culture.

    Science.gov (United States)

    Pang, Yamiao; Geng, Jianjun; Qin, Yilong; Wang, Haidong; Fan, Ruiwen; Zhang, Ying; Li, Hongquan; Jiang, Shan; Dong, Changsheng

    2016-08-01

    The aims of the study were to establish a culture system for sheep skin melanocytes and uncover the effects of endothelin-1 on melanin synthesis in cultured melanocytes in order to provide an optimal cell system and a theoretical basis for studying the regulatory mechanism of coat color in sheep. In this study, skin punch biopsies were harvested from the dorsal region of 1-3-yr-old sheep, and skin melanocytes were then obtained by the two-step digestion using dispase II and trypsin/ethylene diamine tetraacetic acid (EDTA). The primary cultures of the melanocytes were established and characterized by dopa-staining, immunocytochemical localization of melanocyte markers, and RT-polymerase chain reaction (PCR) analysis of coat color genes. To determine the effect of endothelin-1 on proliferation and melanin synthesis of melanocytes, the cultured cells were treated with different doses of endothelin-1 (10(-7), 10(-8), 10(-9), 10(-10), and 0 mol/L), and the growth rate of melanocytes, production of melanin, expression of related genes, and location of related protein in cultured cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ultraviolet spectrophotometry, qRT-PCR, and immunocytochemical localization, respectively. The results showed that the established melanocyte culture functions properly. Endothelin-1 treatment increased markedly the number of melanocytes and melanin content. In responding to this treatment, expressions of microphthalmia-associated transcription factor (MITF), melanocortin 1 receptor (MC1R), tyrosinase (TYR), and endothelin receptor B (EDNRB) in the melanocytes were significantly up regulated (P < 0.05). Immunocytochemical localization revealed that TYR was mainly localized in the cytoplasm. Positive staining of TYR in the melanocytes was significant. The findings demonstrated that the culture system of sheep skin melanocytes was established successfully in vitro, and endothelin-1 promotes the

  14. Anti-tumor effects of paeonol in a HepA-hepatoma bearing mouse model via induction of tumor cell apoptosis and stimulation of IL-2 and TNF-alpha production.

    Science.gov (United States)

    Sun, Guo-Ping; Wang, Hua; Xu, Shu-Ping; Shen, Yu-Xian; Wu, Qiang; Chen, Zhen-Dong; Wei, Wei

    2008-04-28

    Paeonol, a phenolic component from the root bark of Paeonia moutan, is traditionally used as a Chinese herbal medicine to activate the blood flow and remove blood stasis. Evidence shows that paeonol have anti-tumor, anti-inflammatory, and analgesic effects; however, the underlying mechanisms remain unknown. In this study, we investigated the molecular mechanisms by which paeonol exerts the anti-tumor effects by using a murine model of hepatoma established by in vivo injection of mouse HepA-hepatoma cells. Treatment of mice with 100, 200, or 400 mg/kg/day of paeonol significantly inhibited the growth of the HepA tumor in mice, induced HepA cell apoptosis as demonstrated by light microscopy and electron microscopy analyses, decreased the expression of Bcl-2 and increased the expression of Bax in HepA tumor tissues in a dose-related manner. Administration of paeonol in vivo also elevated serum levels of IL-2 and TNF-alpha in tumor-bearing mice. Moreover, splenocytes and macrophages isolated from paeonol-treated HepA tumor-bearing mice produced higher levels of IL-2 and TNF-alpha in response to concanavalin A and lipopolysaccharide stimulation, respectively, compared to these isolated from non-treated HepA tumor-bearing mice. In vitro treatment with paeonol was able to directly stimulate IL-2 and TNF-alpha production in splenocytes and macrophages from tumor-bearing mice, respectively. In conclusion, paeonol has the anti-tumor effect against hepatoma cells, which are likely mediated via induction of tumor cell apoptosis and stimulation of IL-2 and TNF-alpha production. Paeonol could be a promising drug to treat hepatocellular carcinoma. PMID:18329639

  15. Giant Congenital Cerebriform Melanocytic Nevus of the Scalp in Adult

    Directory of Open Access Journals (Sweden)

    Shashikala Krishnamurthy

    2014-04-01

    Full Text Available Congenital melanocytic nevi are defined as benign nevomelanocytic proliferation present at birth. They are rare lesions and occur in approximately 1% of new-borns and are usually classified according to their size. We report a case of 32 year old female who presented with a giant cerebriform lesion of the scalp which was present since birth. Diagnosis of Giant congenital melanocytic nevi was made on the basis of definite histological criteria. Wide excision of the lesion was done with split skin graft. This case is unique due to the fact that this young female lived with this disfiguring lesion for 3 decades and never consulted any physician for cosmetic purpose and fortunately the lesion never turned malignant. [J Interdiscipl Histopathol 2014; 2(2.000: 108-111

  16. Giant congenital melanocytic nevus scalp: report of a rare case

    Directory of Open Access Journals (Sweden)

    A. Bhagyalakshmi

    2013-06-01

    Full Text Available Giant congenital melanocytic nevus (garment nevus is a kind of congenital malformation of neural crest cells with size greater than 20 cm. Malignant melanoma may develop in 2-31% of these lesions. The objective of this paper is to present a unique case of giant nevus which is rare. [Int J Res Med Sci 2013; 1(3.000: 317-319

  17. Bilateral diffuse uveal melanocytic proliferation: a management dilemma

    OpenAIRE

    Alrashidi, Salah; Aziz, Ayman A; Krema, Hatem

    2014-01-01

    A female patient suffered from gradual decline of vision for few months. She presented with bilateral multiple pigmented choroidal tumours, associated with overlying retinal changes. The clinical presentation suggested bilateral diffuse uveal melanocytic proliferation (BDUMP) syndrome, which is a paraneoplastic disease, although there was no evidence of any concurrent malignancy. The periodic systemic surveillance that was undertaken for the following 4 years failed to reveal any occult cance...

  18. UVA Phototransduction Drives Early Melanin Synthesis in Human Melanocytes

    OpenAIRE

    Nadine L Wicks; Chan, Jason W.; Najera, Julia A.; Ciriello, Jonathan M.; Oancea, Elena

    2011-01-01

    Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% UVA and ~5% UVB at the Earth’s surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (...

  19. Cellular origin and developmental mechanisms during the formation of skin melanocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ernfors, Patrik, E-mail: patrik.ernfors@ki.se [Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm (Sweden)

    2010-05-01

    Melanocytes are derived from the neural crest (NC), which are transient multipotent cells arising by delamination from the developing dorsal neural tube. During recent years, signaling systems and molecular mechanisms of melanocyte development have been studied in detail, but the exact diversification of the NC into melanocytes and how they migrate, expand and disperse in the skin have not been fully understood. The recent finding that Schwann cell precursors (SCPs) of the growing nerve represents a stem cell niche from which various cell types, including Schwann cells, endoneural fibroblasts and melanocytes arise has exposed new knowledge on the cellular basis for melanocyte development. This opens for the identification of new factors and reinterpretation of old data on cell fate instructive, proliferative, survival and cell homing factors participating in melanocyte development.

  20. Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K(+)-induced 45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose-dependently reduced mean arterial pressure after oral administration. Only at maximal anti-hypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the anti-hypertensive effect of verapamil and related calcium channel blockers

  1. EFFECT OF PARACETAMOL ON MELANIZATION PROCESS IN HUMAN EPIDERMAL MELANOCYTES.

    Science.gov (United States)

    Wrześniok, Dorota; Oprzondek, Martyna; Hechmann, Anna; Beberok, Artur; Otreba, Michał; Buszman, Ewa

    2016-01-01

    Paracetamol (acetaminophen) is commonly used as a drug of choice for treatment of pain and fever. Unlike non-steroidal anti-inflammatory drugs (NSAIDs) it does not cause gastrointestinal damage or untoward cardiorenal effects, however cutaneous adverse effects have been reported. It is known that paracetamol binds to melanin biopolymers, but the relation between the affinity of this drug to melanin and its toxicity is not documented. The aim of this work was to examine the impact of paracetamol on melanogenesis in cultured human normal epidermal melanocytes (HEMn-DP). The effect of paracetamol on cell viability was determined by WST-1 assay, melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that paracetamol induced concentration-dependent loss in melanocytes viability. The value of EC50 was found to be - 20.0 mM. The analyzed drug inhibited melanin biosynthesis in a concentration-dependent manner by decreasing the melanin content as well as the tyrosinase activity. The demonstrated inhibitory effect of paracetamol on melanization process in normal epidermal melanocytes in vitro may explain the potential role of melanin biopolymer in the mechanisms of undesirable side effects of this drug in vivo, as a result of its accumulation in pigmented tissues. PMID:27476283

  2. Expression profiling of human melanocytes in response to UV-B irradiation

    Directory of Open Access Journals (Sweden)

    Saioa López

    2015-12-01

    Full Text Available A comprehensive gene expression analysis of human melanocytes was performed assessing the transcriptional profile of dark melanocytes (DM and light melanocytes (LM at basal conditions and after UV-B irradiation at different time points (6, 12 and 24 h, and in culture with different keratinocyte-conditioned media (KCM+ and KCM−. The data, previously published in [1], have been deposited in NCBI's Gene Expression Omnibus (GEO accession number: GSE70280.

  3. UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes

    OpenAIRE

    Bellono, Nicholas W.; Kammel, Laura G.; Zimmerman, Anita L.; Oancea, Elena

    2013-01-01

    Human skin is constantly exposed to solar ultraviolet radiation (UVR), the most prevalent environmental carcinogen. Humans have the unique ability among mammals to respond to UVR by increasing their skin pigmentation, a protective process driven by melanin synthesis in epidermal melanocytes. The molecular mechanisms used by melanocytes to detect and respond to long-wavelength UVR (UVA) are not well understood. We recently identified a UVA phototransduction pathway in melanocytes that is media...

  4. Positive Emotional Experience: Induced by Vibroacoustic Stimulation Using a Body Monochord in Patients with Psychosomatic Disorders: Is Associated with an Increase in EEG-Theta and a Decrease in EEG-Alpha Power.

    Science.gov (United States)

    Sandler, H; Tamm, S; Fendel, U; Rose, M; Klapp, B F; Bösel, R

    2016-07-01

    Relaxation and meditation techniques are generally characterized by focusing attention, which is associated with an increase of frontal EEG Theta. Some studies on music perception suggest an activation of Frontal Midline Theta during emotionally positive attribution, others display a lateralization of electrocortical processes in the attribution of music induced emotion of different valence. The present study examined the effects of vibroacoustic stimulation using a Body Monochord and the conventional relaxation music from an audio CD on the spontaneous EEG of patients suffering from psychosomatic disorders (N = 60). Each treatment took about 20 min and was presented to the patients in random order. Subjective experience was recorded via self-rating scale. EEG power spectra of the Theta, Alpha-1 and Alpha-2 bands were analysed and compard between the two treatment conditions. There was no lateralization of electrocortical activity in terms of the emotional experience of the musical pieces. A reduction in Alpha-2 power occurred during both treatments. An emotionally positive attribution of the experience of the vibroacoustically induced relaxation state is characterized by a more pronounced release of control. In the context of focused attention this is interpreted as flow experience. The spontaneous EEG showed an increase in Theta power, particularly in the frontal medial and central medial area, and a greater reduction in Alpha-2 power. The intensity of positive emotional feelings during the CD music showed no significant effect on the increase in Theta power. PMID:26936595

  5. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    International Nuclear Information System (INIS)

    Highlights: → PAX3 retains embryonic roles in adult melanocytes and melanoma cells. → Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. → Regulates melanoma and melanocyte migration through MCAM and CSPG4. → PAX3 regulates melanoma but not melanocyte proliferation via TPD52. → Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.

  6. Giant congenital melanocytic nevus with developmental dysplasia of bilateral hip: A rare association

    OpenAIRE

    Sutsungkokla Imchen; Sangita Ghosh; Surabhi Dayal; Nisha Marwah; Nidhi Jindal; Shikha Sangal

    2013-01-01

    Giant congenital melanocytic nevi are rare congenital disfiguring benign neoplasms with a risk of transformation to malignant melanoma. They often present with various extra-cutaneous features. Here, we describe a case of giant melanocytic nevus with developmental dysplasia of bilateral hip, a novel association.

  7. Giant congenital melanocytic nevus with developmental dysplasia of bilateral hip: A rare association

    Directory of Open Access Journals (Sweden)

    Sutsungkokla Imchen

    2013-01-01

    Full Text Available Giant congenital melanocytic nevi are rare congenital disfiguring benign neoplasms with a risk of transformation to malignant melanoma. They often present with various extra-cutaneous features. Here, we describe a case of giant melanocytic nevus with developmental dysplasia of bilateral hip, a novel association.

  8. Effects of Narrowband UVB, UVA1 and PUVA Treatments on Dermoscopic Features of Melanocytic Nevi

    Directory of Open Access Journals (Sweden)

    Fulya Karaca

    2014-03-01

    Full Text Available Background and Design: Ultraviolet (UV radiation can effect dermoscopic features of melanocytic nevi by inducing melanin synthesis or melanocyte proliferation. Although UV radiation has widespread usage in the treatment of several skin diseases, only few studies of its effect on dermoscopic features of melanocytic nevi have been performed to date. The present study was designed to determine the effects of narrowband UVB, UVA1 and psoralen and UVA (PUVA treatments on dermoscopic features of melanocytic nevi. Material and Method: A total 55 patients who referred to our phototherapy unit for the treatment of miscellaneous skin disorders were enrolled in this prospective study. 21 patients underwent narrowband UVB, 18 patients underwent UVA1 and 16 patients underwent PUVA treatment. Dermoscopic images of 233 nevi in narrowband UVB group, 233 nevi in UVA1 group and 229 nevi in PUVA group were evaluated for the alterations in dermoscopic structures at the end of three months. Total dermoscopic scores (TDS of melanocytic nevi were calculated according to ABCD rule. Results: The size of melanocytic nevi in all therapy groups did not show any statistically significant increase. Narrowband UVB, UVA1, PUVA cause statistically significant changes in dermoscopic structures of melanocytic nevi. In narrowband UVB therapy group de novo dot formation was documented (p=0,002. The mean TDS of nevi did not show any significant change. Conclusion: Narrowband UVB, UVA1 and PUVA therapies have significant effects on dermoscopic features of melanocytic nevi. Only in narrowband UVB group de novo dot formation was observed.

  9. Deep penetrating nevus: A distinct variant of melanocytic nevus

    Directory of Open Access Journals (Sweden)

    Aparna Gupta

    2011-01-01

    Full Text Available Deep penetrating nevus (DPN is a variant of melanocytic nevus which goes unrecognized due to its relative rarity and may be misinterpreted as malignant melanoma. It commonly presents in young adults as a dark pigmented lesion on the face, neck, or shoulder. A 60-year-old lady presented with a mole over the left arm of 8 years duration. A biopsy of the lesion was performed under the clinical impression of a compound nevus with suspicion of malignancy. Based on the histologic features, a diagnosis of DPN was put forward.

  10. A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human Melanocytes

    Directory of Open Access Journals (Sweden)

    Gang Ren

    2012-01-01

    Full Text Available Recent high-throughput-sequencing of the cancer genome has identified oncogenic mutations in BRaf genetic locus as one of the critical events in melanomagenesis. In normal cells, the activity of BRaf is tightly regulated. Gain-of-function mutations like those identified in melanoma frequently lead to enhanced cell-survival and unrestrained growth. The activating mutation of BRaf will also induce the cells to senesce. However, the mechanism by which the oncogenic BRaf induces the senescent barrier remains poorly defined. microRNAs have regulatory functions toward the expression of genes that are important in carcinogenesis. Here we show that expression of several microRNAs is altered when the oncogenic version of BRaf is introduced in cultured primary melanocytes and these cells undergo premature cellular senescence. These include eight microRNAs whose expression rates are significantly stimulated and three that are repressed. While most of the induced microRNAs have documented negative effects on cell cycle progression, one of the repressed microRNAs has proven oncogenic functions. Ectopic expression of some of these induced microRNAs increased the expression of senescence markers and induced growth arrest and senescence in primary melanocytes. Taken together, our results suggest that the change in microRNA expression rates may play a vital role in senescence induced by the oncogenic BRaf.

  11. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.

    Science.gov (United States)

    Thompson, Benjamin C; Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2014-07-01

    Cutaneous melanoma is a significant cause of morbidity and mortality. Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. Here, we report the effect of nicotinamide on DNA damage and repair in primary human melanocytes. Nicotinamide significantly enhanced the repair of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine) and cyclobutane pyrimidine dimers induced by UV exposure. It also enhanced the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine induced by the culture conditions in unirradiated melanocytes. A significant increase in the percentage of melanocytes undergoing unscheduled but not scheduled DNA synthesis was observed, confirming that nicotinamide enhances DNA repair in human melanocytes. In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma. PMID:24798949

  12. Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review

    Directory of Open Access Journals (Sweden)

    Bernd Th Krause

    2009-06-01

    Full Text Available Bernd Th Krause1, Ralf Ohlinger2, Annette Haase31Center for Endocrinology and Reproductive Medicine, MVZ Uhlandstr, Berlin, Germany; 2Ernst-Moritz-Arndt-University, Department of Gynecology and Obstetrics, Greifswald, Germany; 3Uhlandstr. 162, 10719 BerlinAbstract: Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a

  13. YY1 regulates melanocyte development and function by cooperating with MITF.

    Directory of Open Access Journals (Sweden)

    Juying Li

    Full Text Available Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP-seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1 gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF-a general mechanism which may confer tissue-specific gene expression in multiple lineages.

  14. Protective Effect of HemoHIM on Epidermal Melanocytes in Ultraviolet-B irradiated Mice

    International Nuclear Information System (INIS)

    We induced the activation of melanocytes in the epidermis of C57BL/6 mice by ultraviolet-B (UV-B) irradiation, and observed the effect of an herbal preparation (HemoHIM, HH) on the formation, and decrease of UV-B-induced epidermal melanocytes. C57BL/6 mice were irradiated by UV-B 80 mJ:cm-2 (0.5 mW:sec-1) daily for 7 days, and HH was intraperitoneally, orally or topically applied pre- or post-irradiation. For the estimation of change of epidermal melanocytes, light microscopic observation with dihydroxyphenylalanine (DOPA) stain was performed. Split epidermal sheets prepared from the ear of untreated mice exhibited 13∼15 melanocytes:mm-2, and one week after UV irradiation, the applied areas showed an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal, oral or topical treatment with HH before each irradiation interrupted UV-B-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to the number found in UV-B-irradiated, untreated control skin. The number and size of DOPA-positive epidermal melanocytes were also significantly decreased in intraperitoneally injected or topically applicated group after irradiation with HH at 3rd and 6th weeks after irradiation. The present study suggests the HH as inhibitor of UV-B-induced pigmentation, and depigmenting agent

  15. Protective Effect of HemoHIM on Epidermal Melanocytes in Ultraviolet-B irradiated Mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae June [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of); Kim, Jong Choon; Moon, Chang Jong; Kim, Sung Ho [Chonnam National University, Gwangju (Korea, Republic of); Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Jeongeup Campus of Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Jang, Jong Sik; Kim, Tae Hwan [Kyungpook National University, Daegu (Korea, Republic of)

    2011-06-15

    We induced the activation of melanocytes in the epidermis of C57BL/6 mice by ultraviolet-B (UV-B) irradiation, and observed the effect of an herbal preparation (HemoHIM, HH) on the formation, and decrease of UV-B-induced epidermal melanocytes. C57BL/6 mice were irradiated by UV-B 80 mJ:cm{sup -2} (0.5 mW:sec{sup -1}) daily for 7 days, and HH was intraperitoneally, orally or topically applied pre- or post-irradiation. For the estimation of change of epidermal melanocytes, light microscopic observation with dihydroxyphenylalanine (DOPA) stain was performed. Split epidermal sheets prepared from the ear of untreated mice exhibited 13∼15 melanocytes:mm{sup -2}, and one week after UV irradiation, the applied areas showed an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal, oral or topical treatment with HH before each irradiation interrupted UV-B-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to the number found in UV-B-irradiated, untreated control skin. The number and size of DOPA-positive epidermal melanocytes were also significantly decreased in intraperitoneally injected or topically applicated group after irradiation with HH at 3rd and 6th weeks after irradiation. The present study suggests the HH as inhibitor of UV-B-induced pigmentation, and depigmenting agent.

  16. Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chantarawong, Wipa [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Inter Departmental Multidisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok (Thailand); Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Pradermwong, Kantimanee [Department of Zoology, Faculty of Science, Kasetsart University, Bangkok (Thailand); Shibahara, Shigeki, E-mail: shibahar@med.tohoku.ac.jp [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan)

    2014-11-28

    Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure.

  17. Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

    International Nuclear Information System (INIS)

    Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure

  18. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Medic, Sandra [School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA (Australia); Rizos, Helen [Westmead Institute for Cancer Research and Melanoma Institute of Australia, University of Sydney at Westmead Millennium Institute, Westmead, NSW (Australia); Ziman, Mel, E-mail: m.ziman@ecu.edu.au [School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA (Australia); School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA (Australia)

    2011-08-12

    Highlights: {yields} PAX3 retains embryonic roles in adult melanocytes and melanoma cells. {yields} Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. {yields} Regulates melanoma and melanocyte migration through MCAM and CSPG4. {yields} PAX3 regulates melanoma but not melanocyte proliferation via TPD52. {yields} Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.

  19. The relationship between Na+/H+ exchanger expression and tyrosinase activity in human melanocytes

    International Nuclear Information System (INIS)

    The activity of melanosome-associated tyrosinase in human melanocytes differs based on racial skin type. In melanocytes from Black skin, tyrosinase activity is high while in White melanocytes the activity of the enzyme is low. Recent studies suggest that low tyrosinase activity in White melanocytes may be due to an acidic pH environment within the melanosome. Because sodium/hydrogen (Na+/H+) exchangers (NHEs) are known to regulate intracellular pH, melanocytes were treated with NHE inhibitors to determine what effect this inhibition might have on tyrosinase activity. Treatment of Black melanocytes with ethyl-isopropyl amiloride (EIPA) caused a rapid dose-dependent inhibition of tyrosinase activity. This inhibition was not due to either direct enzyme inhibition or to a decrease in tyrosinase abundance. In contrast, treatment of White melanocytes with EIPA, cimetidine, or clonidine resulted in little inhibition of tyrosinase activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis showed that both Black and White melanocytes expressed mRNA and protein for NHE-1, NHE-3, NHE-5, NHE-6, and NHE-7. Immunohistochemical analysis showed that NHE-7 and NHE-3 co-localized with the melanosomal protein, Tyrosinase Related Protein-1 (TRP-1). In addition, the vesicular proton pump, vesicular ATPase (V-ATPase), was found to be present in both White and Black melanosomes, indicating that organelles from both racial skin types are capable of being acidified. The results suggest that one or more NHEs may help regulate melanosome pH and tyrosinase activity in human melanocytes

  20. In ovo gene manipulation of melanocytes and their adjacent keratinocytes during skin pigmentation of chicken embryos.

    Science.gov (United States)

    Murai, Hidetaka; Tadokoro, Ryosuke; Sakai, Ken-Ichiro; Takahashi, Yoshiko

    2015-04-01

    During skin pigmentation in avians and mammalians, melanin is synthesized in the melanocytes, and subsequently transferred to adjacently located keratinocytes, leading to a wide coverage of the body surface by melanin-containing cells. The behavior of melanocytes is influenced by keratinocytes shown mostly by in vitro studies. However, it has poorly been investigated how such intercellular cross-talk is regulated in vivo because of a lack of suitable experimental models. Using chicken embryos, we developed a method that enables in vivo gene manipulations of melanocytes and keratinocytes, where these cells are separately labeled by different genes. Two types of gene transfer techniques were combined: one was a retrovirus-mediated gene infection into the skin/keratinocytes, and the other was the in ovo DNA electroporation into neural crest cells, the origin of melanocytes. Since the Replication-Competent Avian sarcoma-leukosis virus long terminal repeat with Splice acceptor (RCAS) infection was available only for the White leghorn strain showing little pigmentation, melanocytes prepared from the Hypeco nera (pigmented) were back-transplanted into embryos of White leghorn. Prior to the transplantation, enhanced green fluorescent protein (EGFP)(+) Neo(r+) -electroporated melanocytes from Hypeco nera were selectively grown in G418-supplemented medium. In the skin of recipient White leghorn embryos infected with RCAS-mOrange, mOrange(+) keratinocytes and transplanted EGFP(+) melanocytes were frequently juxtaposed each other. High-resolution confocal microscopy also revealed that transplanted melanocytes exhibited normal behaviors regarding distribution patterns of melanocytes, dendrite morphology, and melanosome transfer. The method described in this study will serve as a useful tool to understand the mechanisms underlying intercellular regulations during skin pigmentation in vivo. PMID:25739909

  1. The eukaryotic translation initiation factor 3f (eIF3f) interacts physically with the alpha 1B-adrenergic receptor and stimulates adrenoceptor activity

    OpenAIRE

    Gutiérrez-Fernández, Mario Javier; Higareda-Mendoza, Ana Edith; Gómez-Correa, César Adrián; Pardo-Galván, Marco Aurelio

    2015-01-01

    Background eIF3f is a multifunctional protein capable of interacting with proteins involved in different cellular processes, such as protein synthesis, DNA repair, and viral mRNA edition. In human cells, eIF3f is related to cell cycle and proliferation, and its deregulation compromises cell viability. Results We here report that, in native conditions, eIF3f physically interacts with the alpha 1B-adrenergic receptor, a plasma membrane protein considered as a proto-oncogene, and involved in vas...

  2. Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha.

    OpenAIRE

    Takashiba, S; Takigawa, M; Takahashi, K; Myokai, F; Nishimura, F.; Chihara, T.; Kurihara, H.; Nomura, Y.; Murayama, Y.

    1992-01-01

    Inflammatory mediators produced by cells in the gingiva have been implicated in the initiation and progression of periodontal disease, a common infectious disease. In this study, we examined the biological activity of neutrophil chemotactic factors and the kinetics of expression of interleukin-8 (IL-8) mRNA derived from normal gingival fibroblasts in response to inflammatory mediators in an in vitro model. Gingival fibroblasts stimulated by either recombinant human interleukin-1 beta or recom...

  3. Granulocyte-Macrophage Colony-Stimulating Factor- and Tumor Necrosis Factor Alpha-Mediated Matrix Metalloproteinase Production by Human Osteoblasts and Monocytes after Infection with Brucella abortus ▿

    OpenAIRE

    Scian, Romina; Barrionuevo, Paula; Giambartolomei, Guillermo H.; Fossati, Carlos A.; Baldi, Pablo C.; Delpino, M. Victoria

    2010-01-01

    Osteoarticular complications are common in human brucellosis, but the pathogenic mechanisms involved are largely unknown. Since matrix metalloproteinases (MMPs) are involved in joint and bone damage in inflammatory and infectious diseases, we investigated the production of MMPs by human osteoblasts and monocytes, either upon Brucella abortus infection or upon reciprocal stimulation with factors produced by each infected cell type. B. abortus infection of the normal human osteoblastic cell lin...

  4. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Axel, Anne Marie Dixen; Mikkelsen, Jens D; Hansen, Henrik H

    2010-01-01

    Tesofensine is a novel monoamine reuptake inhibitor that inhibits both norepinephrine, 5-HT, and dopamine (DA) reuptake function. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong effect in obesity management is not cl......Tesofensine is a novel monoamine reuptake inhibitor that inhibits both norepinephrine, 5-HT, and dopamine (DA) reuptake function. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong effect in obesity management...... antagonist), or ritanserin (0.03 mg/kg, 5-HT(2A/C) receptor antagonist). Hence, the mechanism underlying the suppression of feeding by tesofensine in the obese rat is dependent on the drug's ability to indirectly stimulate alpha(1) adrenoceptor and DA D(1) receptor function....

  5. THE EFFECT OF Ge-132 ON ULTRASTRUCTURE OF CULTURED MELANOCYTES

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To elucidate the effect of Ge-132 on the growth of melanocytes. Mothods Melanocyes from epidermis were cultured and purified ;the second generation of the cell was used for study ;the cells were divided into two groups randomly,to group A, Ge-132 was added to the media at 0.04mg/L ;to group B ,common culturing method was used without Ge-132. After 5d, the cells were seperated by digestion for study by transmission electronic micro- scope. Results Compared to group B, the vacuioes of the cells were increased,mitochondria distended, endoplasmic reticulum dilated and the number of melanosome declined in the group A. Conclusion Ge-132 can inhibit the melanocyte's growth at a certain concentration and might be used for treating pigmented diseases.

  6. Increase in cytokine production (IL-1 beta, IL-6, TNF-alpha but not IFN-gamma, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis.

    Science.gov (United States)

    Zheng, S X; Vrindts, Y; Lopez, M; De Groote, D; Zangerle, P F; Collette, J; Franchimont, N; Geenen, V; Albert, A; Reginster, J Y

    1997-01-01

    Postmenopausal osteoporosis is a progressive disorder characterized by a decreased bone mass and increased susceptibility to fractures. Several investigations have suggested that one of the mechanisms through which estrogen prevents bone loss was a modulation on secretion or release of various cytokines that are known to influence bone remodeling, even if some recent data have challenged this hypothesis. However, in established osteoporosis, the possibility that enhanced cytokines activity may account for the progression of this disease remains unclear and controversial. We sought here to determine whether production of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, GM-CSF and LIF, after direct stimulation in whole blood, was different in healthy (n = 30) or osteoporotic postmenopausal women (n = 24) and whether lumbar bone density (1-BMD) correlated with the values of cytokine production observed in these conditions. A significant difference was observed between the osteoporotic and control subjects for IL-1 beta (p immune cells cultured in autologous whole blood suggests that in women more than 10 years past the menopause and presenting a decrease in lumbar bone density corresponding to the new WHO definition of "osteoporosis', production of IL-1 beta, IL-6 and TNF-alpha is still increased compared to controls matched for age and ovarian function, while no differences are reported for IFN-gamma, GM-CSF or LIF production. PMID:9032749

  7. Coefficient Alpha

    OpenAIRE

    Panayiotis Panayides

    2013-01-01

    Heavy reliance on Cronbach’s alpha has been standard practice in many validation studies. However, there seem to be two misconceptions about the interpretation of alpha. First, alpha is mistakenly considered as an indication of unidimensionality and second, that the higher the value of alpha the better. The aim of this study is to clarify these misconceptions with the use of real data from the educational setting. Results showed that high alpha values can be obtained in multidimensional scale...

  8. Insulin-like growth factors (IGFs) stimulate the release of alpha 1-antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast cancer cells.

    Science.gov (United States)

    Confort, C; Rochefort, H; Vignon, F

    1995-09-01

    The growth of hormone-responsive MCF7 human breast cancer cells is controlled by steroid hormones and growth factors. By metabolic labeling of cells grown in steroid- and growth factor-stripped serum conditions, we show that insulin-like growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260 kilodaltons) and one minor (approximately 85 kilodaltons) that probably represents a proteolytic fragment of the larger soluble molecule. IGFs increased receptor release in a dose-dependent fashion with 50-60% of newly synthesized receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated with the levels of secreted cathepsin D in different human breast cancer cells or in rats stable transfectants that are constitutively expressing variable levels of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release, whereas estradiol treatment preferentially enhanced the release of protease and antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not only act as strong mitogens but also regulate release of alpha 1-antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins that potentially regulate cell proliferation and/or invasion. PMID:7649082

  9. Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors

    Science.gov (United States)

    Yang, Ruifeng; Zheng, Ying; Li, Ling; Liu, Shujing; Burrows, Michelle; Wei, Zhi; Nace, Arben; Herlyn, Meenhard; Cui, Rutao; Guo, Wei; Cotsarelis, George; Xu, Xiaowei

    2015-01-01

    Direct reprogramming provides a fundamentally new approach for the generation of patient-specific cells. Here, by screening a pool of candidate transcription factors, we identify that a combination of three factors, MITF, SOX10 and PAX3, directly converts mouse and human fibroblasts to functional melanocytes. Induced melanocytes (iMels) activate melanocyte-specific networks, express components of pigment production and delivery system, and produce melanosomes. Human iMels properly integrate into the dermal-epidermal junction, and produce and deliver melanin pigment to surrounding keratinocytes in a 3D organotypic skin reconstruct. Human iMels generate pigmented epidermis and hair follicles in skin reconstitution assays in vivo. The generation of iMels has important implications for studies of melanocyte lineage commitment, pigmentation disorders and cell replacement therapies. PMID:25510211

  10. Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors.

    Science.gov (United States)

    Yang, Ruifeng; Zheng, Ying; Li, Ling; Liu, Shujing; Burrows, Michelle; Wei, Zhi; Nace, Arben; Herlyn, Meenhard; Cui, Rutao; Guo, Wei; Cotsarelis, George; Xu, Xiaowei

    2014-01-01

    Direct reprogramming provides a fundamentally new approach for the generation of patient-specific cells. Here, by screening a pool of candidate transcription factors, we identify that a combination of the three factors, MITF, SOX10 and PAX3, directly converts mouse and human fibroblasts to functional melanocytes. Induced melanocytes (iMels) activate melanocyte-specific networks, express components of pigment production and delivery system and produce melanosomes. Human iMels properly integrate into the dermal-epidermal junction and produce and deliver melanin pigment to surrounding keratinocytes in a 3D organotypic skin reconstruct. Human iMels generate pigmented epidermis and hair follicles in skin reconstitution assays in vivo. The generation of iMels has important implications for studies of melanocyte lineage commitment, pigmentation disorders and cell replacement therapies. PMID:25510211

  11. EdnrB Governs Regenerative Response of Melanocyte Stem Cells by Crosstalk with Wnt Signaling

    Directory of Open Access Journals (Sweden)

    Makoto Takeo

    2016-05-01

    Full Text Available Delineating the crosstalk between distinct signaling pathways is key to understanding the diverse and dynamic responses of adult stem cells during tissue regeneration. Here, we demonstrate that the Edn/EdnrB signaling pathway can interact with other signaling pathways to elicit distinct stem cell functions during tissue regeneration. EdnrB signaling promotes proliferation and differentiation of melanocyte stem cells (McSCs, dramatically enhancing the regeneration of hair and epidermal melanocytes. This effect is dependent upon active Wnt signaling that is initiated by Wnt ligand secretion from the hair follicle epithelial niche. Further, this Wnt-dependent EdnrB signaling can rescue the defects in melanocyte regeneration caused by Mc1R loss. This suggests that targeting Edn/EdnrB signaling in McSCs can be a therapeutic approach to promote photoprotective-melanocyte regeneration, which may be useful for those with increased risk of skin cancers due to Mc1R variants.

  12. Isolation and culture of melanocytes from the arctic fox (Alopex lagopus

    Directory of Open Access Journals (Sweden)

    Jiarong Bao

    2015-09-01

    Full Text Available Coat colour is a phenotypic marker of fur animal species, which was determined by the pigment generated from melanocytes. In this study, we developed and validated a method for isolation, purification and passage culture of melanocytes from the arctic fox (Alopex lagopus. Skin biopsies were harvested from the dorsal region of adult foxes and enzyme digestion by Dispase II. The primary culture of melanocytes from arctic fox skin was obtained by using keratinocyte serum-free medium supplemented with epidermal growth factor and bovine pituitary extract with/without phorbol- 12-myristate-13-acetate, and by carrying out a medium change strategy. After serial passages, it yielded pure population of melanocytes, which become efficient tools for investigating the function of colour genes and unraveling the process of melanin synthesis.

  13. EdnrB Governs Regenerative Response of Melanocyte Stem Cells by Crosstalk with Wnt Signaling.

    Science.gov (United States)

    Takeo, Makoto; Lee, Wendy; Rabbani, Piul; Sun, Qi; Hu, Hai; Lim, Chae Ho; Manga, Prashiela; Ito, Mayumi

    2016-05-10

    Delineating the crosstalk between distinct signaling pathways is key to understanding the diverse and dynamic responses of adult stem cells during tissue regeneration. Here, we demonstrate that the Edn/EdnrB signaling pathway can interact with other signaling pathways to elicit distinct stem cell functions during tissue regeneration. EdnrB signaling promotes proliferation and differentiation of melanocyte stem cells (McSCs), dramatically enhancing the regeneration of hair and epidermal melanocytes. This effect is dependent upon active Wnt signaling that is initiated by Wnt ligand secretion from the hair follicle epithelial niche. Further, this Wnt-dependent EdnrB signaling can rescue the defects in melanocyte regeneration caused by Mc1R loss. This suggests that targeting Edn/EdnrB signaling in McSCs can be a therapeutic approach to promote photoprotective-melanocyte regeneration, which may be useful for those with increased risk of skin cancers due to Mc1R variants. PMID:27134165

  14. Ecto-mesenchymal stem cells from dental pulp are committed to differentiate into active melanocytes

    Directory of Open Access Journals (Sweden)

    F Paino

    2010-10-01

    Full Text Available Dental pulp stem cells (DPSCs are multipotent stem cells derived from neural crest and mesenchyme and have the capacity to differentiate into multiple cell lineages. It has already been demonstrated that DPSCs differentiate into melanocyte-like cells but only when cultivated in a specific melanocyte differentiating medium. In this study we have shown, for the first time, that DPSCs are capable of spontaneously differentiating into mature melanocytes, which display molecular and ultrastructural features of full development, including the expression of melanocyte specific markers and the presence of melanosomes up to the terminal stage of maturation. We have also compared the differentiating features of DPSCs grown in different culture conditions, following the timing of differentiation at molecular and cytochemical levels and found that in all culture conditions full development of these cells was obtained, although at different times. The spontaneous differentiating potential of these cells strongly suggests their possible applications in regenerative medicine.

  15. Blood Supply--Susceptible Formation of Melanin Pigment in Hair Bulb Melanocytes of Mice

    Directory of Open Access Journals (Sweden)

    Shogo Maeda, MD

    2015-03-01

    Conclusions: Melanin pigment formation in the hair bulb melanocytes appeared to be susceptible to the blood supply, and melanocytosis was promoted in the follicles and in the epidermis of Kitl-Tg C57BL/6 mice.

  16. Improved discrimination of melanotic schwannoma from melanocytic lesions by combined morphological and GNAQ mutational analysis

    OpenAIRE

    Küsters-Vandevelde, Heidi V. N.; van Engen-van Grunsven, Ilse A. C. H.; Küsters, Benno; van Dijk, Marcory R. C. F.; Groenen, Patricia J. T. A.; Wesseling, Pieter; Blokx, Willeke A. M.

    2010-01-01

    The histological differential diagnosis between melanotic schwannoma, primary leptomeningeal melanocytic lesions and cellular blue nevus can be challenging. Correct diagnosis of melanotic schwannoma is important to select patients who need clinical evaluation for possible association with Carney complex. Recently, we described the presence of activating codon 209 mutations in the GNAQ gene in primary leptomeningeal melanocytic lesions. Identical codon 209 mutations have been described in blue...

  17. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche.

    Science.gov (United States)

    Chang, Chiung-Ying; Pasolli, H Amalia; Giannopoulou, Eugenia G; Guasch, Géraldine; Gronostajski, Richard M; Elemento, Olivier; Fuchs, Elaine

    2013-03-01

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in

  18. Effective tumor treatment targeting a melanoma/melanocyte-associated antigen triggers severe ocular autoimmunity

    OpenAIRE

    Douglas C Palmer; Chan, Chi-Chao; Gattinoni, Luca; Wrzesinski, Claudia; Paulos, Chrystal M.; Hinrichs, Christian S.; Powell, Daniel J.; Klebanoff, Christopher A.; Finkelstein, Steven E.; Fariss, Robert N.; Yu, Zhiya; Nussenblatt, Robert B.; Rosenberg, Steven A.; Restifo, Nicholas P

    2008-01-01

    Nonmutated tissue differentiation antigens expressed by tumors are attractive targets for cancer immunotherapy, but the consequences of a highly effective antitumor immune response on self-tissue have not been fully characterized. We found that the infusion of ex vivo expanded adoptively transferred melanoma/melanocyte-specific CD8+ T cells that mediated robust tumor killing also induced autoimmune destruction of melanocytes in the eye. This severe autoimmunity was associated with the up-regu...

  19. Cooperative response of keratinocytes and melanocytes to UV radiation during PUVA therapy

    Science.gov (United States)

    Stolnitz, Mikhail M.; Baskakov, Pavel V.; Peshkova, Anna Y.

    1999-03-01

    The mathematical model of processes in UV-irradiated furocoumarin-sensitized epidermis is presented taking into account the mutual influence of keratinocytes and melanocytes populations. The model describes epidermis as a hierarchical structure on tissue (keratinocytes-melanocytes cooperation, melanin screen formation), cellular (proliferation and differentiation, transitions between subpopulations), subcellular (cell movement on mitotic cycle, generation, maturing and migration of melanosomes), and molecular (melanin synthesis, processes of DNA damage and repair, molecular signal transduction) levels.

  20. Complete regression of a melanocytic nevus after epilation with diode laser therapy

    OpenAIRE

    Boleira, Manuela; de Almeida Balassiano, Laila Klotz; Jeunon, Thiago

    2015-01-01

    The use of lasers and intense pulsed light (IPL) technology has become an established practice in dermatology and aesthetic medicine. The use of laser therapy and IPL in the treatment of pigmented melanocytic lesions is a controversial issue. We report clinical, dermoscopic and histological changes of a completely regressed pigmented melanocytic nevus after hair removal treatment with the LightSheer™ Diode Laser (Lumenis Ltd, Yokneam, Israel).

  1. Melanoregulin regulates a shedding mechanism that drives melanosome transfer from melanocytes to keratinocytes

    OpenAIRE

    Wu, Xufeng S.; Masedunskas, Andreas; Weigert, Roberto; Copeland, Neal G.; Jenkins, Nancy A.; Hammer, John A.

    2012-01-01

    Mammalian pigmentation is driven by the intercellular transfer of pigment-containing melanosomes from the tips of melanocyte dendrites to surrounding keratinocytes. Tip accumulation of melanosomes requires myosin Va, because melanosomes concentrate in the center of melanocytes from myosin Va-null (dilute) mice. This distribution defect results in inefficient melanosome transfer and a dilution of coat color. Dilute mice that simultaneously lack melanoregulin, the product of the dilute suppress...

  2. Topology of feather melanocyte progenitor niche allows complex pigment patterns to emerge

    OpenAIRE

    Lin, S J; J. Foley; Jiang, T.X.; Yeh, C.Y.; Wu, P; Foley, A.; Yen, C.M.; Huang, Y. C.; H.C. Cheng; Chen, C.F.; Reeder, B.; Jee, S.H.; Widelitz, R. B.; Chuong, C. M.

    2013-01-01

    Color patterns of bird plumage affect animal behavior and speciation. Diverse patterns are present in different species and within the individual. Here we study the cellular and molecular basis of feather pigment pattern formation. Melanocyte progenitors are distributed as a horizontal ring in the proximal follicle, sending melanocytes vertically up into the epithelial cylinder which gradually emerges as feathers grow. Different pigment patterns form by modulating the presence, arrangement, o...

  3. Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes.

    Science.gov (United States)

    Chantarawong, Wipa; Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki; Pradermwong, Kantimanee; Shibahara, Shigeki

    2014-11-28

    Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure. PMID:25449283

  4. Effects of exposure to tritiated water on differentiation of melanocytes in hair follicles in mice

    International Nuclear Information System (INIS)

    The frequency of abnormal melanocytes in hair follicles in offsprings of mice exposed to tritiated water was described. Tritiated water with different concentrations of tritium was injected intraperitoneally into female C57BL/6J mice at the 12th and 15th days of pregnancy and abnormal melanocytes of hair follicles were observed on skin of back in the offsprings of first generation (F1) at 3.5 days of their postnatal life. The results show that the frequencies of abnormal melanocytes were found to be 1.0-5.1% when mice received cumulative absorbed doses of 0.11-0.67 Gy at the 15th day of their fetal life and these frequencies to be 3.4-6.0% when mice received cumulative absorbed doses of 0.116-0.463 Gy, which indicates an increase in frequency of abnormal melanocytes in hair follicles with increasing cumulative absorbed dose of beta radiation and a higher frequency of abnormal melanocytes hair follicles of skin in F1 offsprings which were exposed to tritium at the earlier period of their fetal life. For mice exposed to HTO at the 12th day of their fetal life, the frequency of abnormal melanocytes in hair follicles was found to be significantly higher than that for mice exposed to HTO at the 15th day of their fetal life

  5. Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

    International Nuclear Information System (INIS)

    Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress

  6. Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

    Energy Technology Data Exchange (ETDEWEB)

    Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa, E-mail: ebuszman@sum.edu.pl

    2014-10-15

    Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.

  7. The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas

    DEFF Research Database (Denmark)

    de Heer, J; Pedersen, J; Orskov, C; Holst, Jens Juul

    2007-01-01

    . MATERIALS AND METHODS: The expression of the GLP-2 receptor gene, Glpr2, and the localisation of the protein were evaluated by real-time PCR on cDNA from isolated rat islets and by immunohistochemistry in rat and human pancreas. The glucagon, insulin and somatostatin responses to 0.1, 1 and 10 nmol/l GLP-2......AIMS/HYPOTHESIS: Glucagon-like peptide-2 (GLP-2) is a gut hormone regulating intestinal growth and nutrient absorption. Recently, GLP-2 has been reported to stimulate glucagon secretion in healthy humans. We sought to clarify the mechanism and physiological significance of this endocrine effect...... and to GLP-1 and GLP-2 given simultaneously were studied in the isolated perfused rat pancreas. RESULTS: Expression of Glp2r transcript was confirmed by PCR. In both human and rat pancreas, GLP-2r immunoreactivity was colocalised with proglucagon. GLP-2 at 10 nmol/l increased glucagon secretion...

  8. Follicle and melanocyte stem cells, and their application in neuroscience: A Web of Science-based literature analysis

    OpenAIRE

    Wu, Weifu

    2012-01-01

    OBJECTIVE: To identify global research trends of follicle and melanocyte stem cells, and their application in neuroscience. DATA RETRIEVAL: We performed a bibliometric analysis of studies from 2002 to 2011 on follicle and melanocyte stem cells, and their application in neuroscience, which were retrieved from the Web of Science, using the key words follicle stem cell or melanocyte stem cell, and neural, neuro or nerve. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published article...

  9. Epoetin Alpha and Epoetin Zeta: A Comparative Study on Stimulation of Angiogenesis and Wound Repair in an Experimental Model of Burn Injury

    Directory of Open Access Journals (Sweden)

    Natasha Irrera

    2015-01-01

    Full Text Available Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-α and EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80°C water for 10 seconds. Mice were then randomized to receive EPO-α (400 units/kg/day/sc or EPO-Z (400 units/kg/day/sc or their vehicle (100 μL/day/sc 0.9% NaCl solution. After 12 days, both EPO-α and EPO-Z increased VEGF protein expression. EPO-α caused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001. Our study showed that EPO-α and EPO-Z accelerated wound closure and angiogenesis; however EPO-α resulted more effectively in achieving complete skin regeneration. Our data suggest that EPO-α and EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-α might be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling.

  10. Functional melanocytes are readily reprogrammable from multilineage-differentiating stress-enduring (muse) cells, distinct stem cells in human fibroblasts.

    Science.gov (United States)

    Tsuchiyama, Kenichiro; Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Nojima, Makoto; Sawaya, Natsue; Yamasaki, Kenshi; Aiba, Setsuya; Dezawa, Mari

    2013-10-01

    The induction of melanocytes from easily accessible stem cells has attracted attention for the treatment of melanocyte dysfunctions. We found that multilineage-differentiating stress-enduring (Muse) cells, a distinct stem cell type among human dermal fibroblasts, can be readily reprogrammed into functional melanocytes, whereas the remainder of the fibroblasts do not contribute to melanocyte differentiation. Muse cells can be isolated as cells positive for stage-specific embryonic antigen-3, a marker for undifferentiated human embryonic stem cells, and differentiate into cells representative of all three germ layers from a single cell, while also being nontumorigenic. The use of certain combinations of factors induces Muse cells to express melanocyte markers such as tyrosinase and microphthalmia-associated transcription factor and to show positivity for the 3,4-dihydroxy-L-phenylalanine reaction. When Muse cell-derived melanocytes were incorporated into three-dimensional (3D) cultured skin models, they localized themselves in the basal layer of the epidermis and produced melanin in the same manner as authentic melanocytes. They also maintained their melanin production even after the 3D cultured skin was transplanted to immunodeficient mice. This technique may be applicable to the efficient production of melanocytes from accessible human fibroblasts by using Muse cells, thereby contributing to autologous transplantation for melanocyte dysfunctions, such as vitiligo. PMID:23563197

  11. Dedifferentiation of human epidermal melanocytes into melanoblasts in vitro.

    Science.gov (United States)

    Zhao, Zhiguo; Jin, Cheng; Ding, Keyun; Ge, Xiaopeng; Dai, Lllan

    2012-07-01

    Melanoblasts (MB) are also called melanocyte (MC) precursor cells. In recent years, people have successfully cultivated human and mouse MB. Previous studies have shown that EDN3 induces cultivated bird MC to re-differentiate into double potential progenitor cells of MB. However, no study has reported whether in vitro cultivated human MC can be dedifferentiated. Our research on MC that were purified and cultivated in vitro found that adding 10 nm endothelin 1 (EDN1) (ET-1) to the MC medium without phorbol 12-myristate 13-acetate (PMA) induced a few MC to dedifferentiate and become a new type of cell. This new cell type was separated, purified, cloned and identified using multiple approaches. The results show that 88.7%, 8.69% and 2.5% of this new cell type were cells in the G(0) -G(1) , G(2) -M and S stages, respectively. The new cell type did not exhibit an apparent apoptotic peak, and its apoptotic rate was 0.09%. Stage I melanosomes were observed in the cytoplasm and were negative for the DOPA reaction. The cell surface antigen expression was positive for tyrosinase-related protein 2, negative or positive for c-kit and negative for S-100 and HMB45, showing that these cells were dedifferentiated MB of MC. Our findings provided evidence for atavism of mature human MC under certain conditions. PMID:22540983

  12. UVR induction of TGFα: a possible autocrine mechanism for the epidermal melanocytic response and for promotion of epidermal carcinogenesis

    International Nuclear Information System (INIS)

    The occurrence of the epidermal growth factor homologue, transforming growth factor α (TGFα), in embryonic and neoplastic tissues suggest that it may be an oncofetal version of epidermal growth factor. A strong case is developing for TGFα to have an autocrine mode of action in sustaining the autonomous growth of several types of tumour. We propose that TGFα normally has an autocrine role not only in stimulating the growth of some fetal tissues but also with postnatal epidermal cells in response to local stimuli-in particular ultraviolet radiation (UVR). We found that cultures of normal foreskin melanocytes do not produce detectable amounts of TGFα when grown under routine conditions, but, within 12 h of exposure to low doses of short-wavelength UVR, significant quantities of TGFα are produced. The UVR-induced TGFα is both cell associated and released into the medium of these cultures. Also, UVR has a promoting action on epidermal cells which have been initiated by carcinogenic activity. A significant part of the promoting activity may be due to autocrine stimulation of multiplication of partially transformed epidermal cells. In this regard we found that UVR induced TGFα in HeLa cells and all human melanoma lines so far tested. (author)

  13. Treatment of a giant congenital melanocytic nevus in the adult: review of the current management of giant congenital melanocytic nevus.

    Science.gov (United States)

    Su, Jeannie J; Chang, Daniel K; Mailey, Brian; Gosman, Amanda

    2015-05-01

    Giant congenital melanocytic nevi (GCMNs) create cosmetic disfigurements and pose risk for malignant transformation. Adult GCMN cases are uncommon because most families opt for surgical treatment during childhood. We review the current literature on GCMN and present an interesting case of an adult with a GCMN encompassing the entire back with painful nodules exhibiting gross involvement of his back musculature, without pathologic evidence of malignancy. Surgical management was deferred in childhood because of parental desires to allow the patient to make his own decision, and treatment in adulthood was pursued on the basis of the significant impairment of the patient's quality of life and self-esteem due to the massive size and deforming nature of the nevus. The treatment strategy used for this young adult male patient involved a massive en bloc excision of the GCMN with partial resection of the latissimus dorsi, followed by a 5-week staged reconstructive process using dermal regenerative matrices and split-thickness skin grafting. Because of the shift in GCMN management from early surgical management to more conservative management, we may see an increase in adult cases of GCMN. Thus, it is critical to better understand the controversy surrounding early versus delayed management of GCMN. PMID:25664413

  14. Defining the Contribution of MC1R Physiological Ligands to ATR Phosphorylation at Ser435, a Predictor of DNA Repair in Melanocytes.

    Science.gov (United States)

    Jarrett, Stuart G; Wolf Horrell, Erin M; Boulanger, Mary C; D'Orazio, John A

    2015-12-01

    The melanocortin 1 receptor (MC1R), a GS-coupled receptor that signals through cAMP and protein kinase A (PKA), regulates pigmentation, adaptive tanning, and melanoma resistance. MC1R-cAMP signaling promotes PKA-mediated phosphorylation of ataxia telangiectasia and rad3-related (ATR) at Ser435 (ATR-pS435), a modification that enhances nucleotide excision repair (NER) by facilitating recruitment of the XPA protein to sites of UV-induced DNA damage. High-throughput methods were developed to quantify ATR-pS435, measure XPA-photodamage interactions, and assess NER function. We report that melanocyte-stimulating hormone (α-MSH) or ACTH induce ATR-pS435, enhance XPA's association with UV-damaged DNA and optimize melanocytic NER. In contrast, MC1R antagonists agouti signaling protein (ASIP) or human β-defensin 3 (HBD3) interfere with ATR-pS435 generation, impair the XPA-DNA interaction, and reduce DNA repair. Although ASIP and HBD3 each blocked α-MSH-mediated induction of the signaling pathway, only ASIP depleted basal ATR-pS435. Our findings confirm that ASIP diminishes agonist-independent MC1R basal signaling whereas HBD3 is a neutral MC1R antagonist that blocks activation by melanocortins. Furthermore, our data suggest that ATR-pS435 may be a useful biomarker for the DNA repair-deficient MC1R phenotype. PMID:26168232

  15. Postnatal lineage mapping of follicular melanocytes with the Tyr∷CreERT2 transgene

    OpenAIRE

    Melissa L Harris; Pavan, William J.

    2012-01-01

    One of the main advantages of using inducible and conditional transgenes to study pigment cell biology is that they allow for genetic manipulation within melanocytes after roles in general neural crest or melanoblast development have been fulfilled. Specifically, we focus here on the ability of the Tyr∷CreERT2 transgenic line to alter genes within follicular melanocytes postnatally. Using the Gt(ROSA)26Sortm1sor reporter allele, we present in detail the expression and activity of Tyr∷CreERT2 ...

  16. A Comparison Between Phorbol 12 Myristate 13 Acetate and Phorbol 12, 13 Dibutyrate in Human Melanocyte Culture

    Science.gov (United States)

    Padma, Divya

    2016-01-01

    Introduction Melanocyte culture is an integral part of the studies of skin biology and cosmetic applications. After the introduction of selective medium for the culture of human melanocyte using Phorbol 12-myristate13-acetate (PMA) in 1982, a lot of methods of culturing were tried but till date PMA is a preferred mitogen because of its cost effectiveness compared to growth factors. We have tried to preliminarily evaluate the efficacy of another phorbol ester, Phorbol 12, 13-dibutyrate (PDBu) in melanocyte culture because of its less hydrophobic nature compared to PMA. This property minimizes the trace amount of mitogen in cell culture after washing off and hence does not interfere in other biological assays. Aim To evaluate the differences in the melanocyte survival rate, morphology and mitotic index when grown in media supplemented with PMA and PDBu. Materials and Methods Foreskins were collected from children undergoing circumcision. Epidermal cells were isolated from foreskin and cultured using PMA and PDBu. Melanocytes in culture were monitored for the better establishment and documented. In proliferative assay, melanocytes were treated with PMA and PDBu for 24, 48 and 72 hours and proliferation was measured using 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay method. Results When cultured, melanocytes acquired proliferative status and bipolar morphology quicker in PDBu medium than in PMA medium. Keratinocytes survived as contamination in PMA medium whereas PDBu medium had minimal keratinocytes. MTT assay showed that PDBu has higher proliferative induction capacity than PMA. In even lower concentration of PDBu in medium, melanocytes survived till 72 hours without significant cell loss in compared to PMA medium. Conclusion PDBu can be a valuable replacement for PMA in human melanocyte culture. Higher proliferation induction, unfavourable to keratinocyte survival and less hydrophobicity make PDBu a promising alternative for quicker

  17. Clinical and histological responses of congenital melanocytic nevi after single treatment with Q-switched lasers

    NARCIS (Netherlands)

    Grevelink, JM; vanLeeuwen, RL; Anderson, RR; Byers, HR

    1997-01-01

    Background: Laser irradiation of congenital melanocytic nevi is a controversial treatment. Recurrence of lesions after laser treatment appears to be the rule, and the effects of laser irradiation on cellular biological behavior and the possible mutagenic responses of nevomelanocytes that have receiv

  18. Progressive Increase in Telomerase Activity From Benign Melanocytic Conditions to Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Ruben D. Ramirez

    1999-04-01

    Full Text Available The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction—based assay (TRAP. High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastasess = 54.5, lymph node metastasess = 56.5. Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9. Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.

  19. Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation

    International Nuclear Information System (INIS)

    HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma. To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created. Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate in vitro whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF-/-/Ink4a+/- mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model. The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue

  20. Postnatal lineage mapping of follicular melanocytes with the Tyr::CreER(T) (2) transgene.

    Science.gov (United States)

    Harris, Melissa L; Pavan, William J

    2013-03-01

    One of the main advantages of using inducible and conditional transgenes to study pigment cell biology is that they allow for genetic manipulation within melanocytes after roles in general neural crest or melanoblast development have been fulfilled. Specifically, we focus here on the ability of the Tyr::CreER(T) (2) transgenic line to alter genes within follicular melanocytes postnatally. Using the Gt(ROSA)26Sor(tm1sor) reporter allele, we present in detail the expression and activity of Tyr::CreER(T) (2) when induced during hair morphogenesis and adult hair cycling. We find that despite similarities in expression pattern to endogenous TYR, Tyr::CreER(T) (2) is effective at targeting both undifferentiated and differentiated melanocytes within the hair follicle. We also find that Tyr::CreER(T) (2) provides the highest levels of recombination when induced during the early phases of hair growth. In conclusion, the descriptions provided here will guide future analyses of gene function within the melanocyte system of the hair follicle when using this Tyr::CreER(T) (2) transgene. PMID:23176440

  1. (Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes

    NARCIS (Netherlands)

    Wenczl, E.; Schans, G.P. van der; Roza, L.; Kolb, R.M.; Timmerman, A.J.; Smit, N.P.M.; Pavel, S.; Schothorst, A.A.

    1998-01-01

    The question of whether melanins are photoprotecting and/or photosensitizing in human skin cells continues to be debated. To evaluate the role of melanin upon UVA irradiation, DNA single-strand breaks (ssb) were measured in human melanocytes differing only in the amount of pigment produced by cultur

  2. Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects

    NARCIS (Netherlands)

    Kusters-vandevelde, H.V.; Kusters, B.; Grunsven, A.C.H. van; Groenen, P.J.T.A.; Wesseling, P.; Blokx, W.A.M.

    2015-01-01

    Primary melanocytic tumors of the central nervous system (CNS) represent a spectrum of rare tumors. They can be benign or malignant and occur in adults as well as in children, the latter often in the context of neurocutaneous melanosis. Until recently, the genetic alterations in these tumors were la

  3. The epidermal melanocyte system in individuals of Scandinavian origin, determined by DOPA-staining and TEM

    DEFF Research Database (Denmark)

    Drzewiecki, K T; Piltz-Drzewiecka, J

    1979-01-01

    in some specimens. This is due partly to the preparation procedure and partly to normal biological variations. We believe that we have demonstrated a cyclic function of the melanocyte in the epidermis. The varying density of cells in epidermal sheets as well as their varying morphology support the...

  4. Alpha fetoprotein

    Science.gov (United States)

    Fetal alpha globulin; AFP ... Greater than normal levels of AFP may be due to: Cancer in testes , ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer ...

  5. The effect of Bu-Zhong-Yi-Qi-Tang on epidermal melanocytes in ultraviolet B-irradiated mice

    International Nuclear Information System (INIS)

    We induced the activation of melanocytes in the epidermis of C57BL/6 mice by UltraViolet B (UVB) irradiation and observed the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) on the formation, and decrease of UVB-induced epidermal melanocytes. C57BL/6 mice were irradiated by UVB 80 mJ/cm2 (0.5 mW/sec) daily for 7 days, and BZYQT was intraperitoneally or topically applied pre- or post-irradiation. For the estimation of change of epidermal melanocytes, light microscopic observation with dihydroxyphenylalanine (DOPA) stain was performed. Split epidermal sheets prepared from the ear of untreated mice exhibited 11-16 melanocytes/mm2, and one week after UV irradiation, the applied areas show an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal or topical treatment with BZYQT before each irradiation interrupted UVB-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to radiation control skin. The number and size of DOPA-positive epidermal melanocytes were also significantly decreased in intraperitoneally injected or topically applicated group after irradiation with BZYQT at 3rd and 6th weeks after irradiation. The present study suggests the BZYQT as inhibitor of UVB-induced pigmentation and depigmenting agent

  6. The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

    Science.gov (United States)

    Pilloni, L.; Bianco, P.; Difelice, E.; Cabras, S.; Castellanos, M.E.; Atzori, L.; Ferreli, C.; Mulas, P.; Nemolato, S.; Faa, G.

    2011-01-01

    C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intra-dermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing

  7. The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

    Directory of Open Access Journals (Sweden)

    L. Pilloni

    2011-06-01

    Full Text Available C-Kit (CD117, the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intradermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus, 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007 in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014. The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008 compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi. Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for

  8. An enhanced and sensitive autocrine stimulation by transforming growth factor-alpha is acquired in the brain metastatic variant of a human non-small-cell lung cancer cell line.

    OpenAIRE

    Fang, K.

    1996-01-01

    Transforming growth factor-alpha (TGF-alpha)-mediated autocrine regulation in human non-small-cell lung cancer (NSCLC) cells NCI-H226 and its brain metastatic variant H226Br were compared. An enhanced TGF-alpha-induced dose-dependent mitogenic responsiveness in H226Br cells was observed. Neutralising antibody that binds TGF-alpha inhibits H226Br cell growth more effectively than NCI-H226 cell growth. Binding assay with 125I-labelled epidermal growth factor (EGF) revealed that H226Br has two t...

  9. Diagnosis and staging of female genital tract melanocytic lesions using pump-probe microscopy (Conference Presentation)

    Science.gov (United States)

    Robles, Francisco E.; Selim, Maria A.; Warren, Warren S.

    2016-02-01

    Melanoma of the vulva is the second most common type of malignancy afflicting that organ. This disease caries poor prognosis, and shows tendencies to recur locally and develop distant metastases through hematogenous dissemination. Further, there exists significant clinical overlap between early-stage melanomas and melanotic macules, benign lesions that are believed to develop in about 10% of the general female population. In this work we apply a novel nonlinear optical method, pump-probe microscopy, to quantitatively analyze female genitalia tract melanocytic lesions. Pump-probe microscopy provides chemical information of endogenous pigments by probing their electronic excited state dynamics, with subcellular resolution. Using unstained biopsy sections from 31 patients, we find significant differences between melanin type and structure in tissue regions with invasive melanoma, melanoma in-situ and non-malignant melanocytic proliferations (e.g., nevi, melanocytic macules). The molecular images of non-malignant lesion have a well-organized structure, with relatively homogenous pigment chemistry, most often consistent with that of eumelanin with large aggregate size or void of metals, such as iron. On the other hand, pigment type and structure observed in melanomas in-situ and invasive melanomas is typically much more heterogeneous, with larger contributions from pheomelanin, melanins with larger metal content, and/or melanins with smaller aggregate size. Of most significance, clear differences can be observed between melanocytic macules and vulvar melanoma in-situ, which, as discussed above, can be difficult to clinically distinguish. This initial study demonstrates pump-probe microscopy's potential as an adjuvant diagnostic tool by revealing systematic chemical and morphological differences in melanin pigmentation among invasive melanoma, melanoma in-situ and non-malignant melanocytic lesions.

  10. Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes

    OpenAIRE

    Devi, Sulochana; Markandeya, Yogananda; Maddodi, Nityanand; Dhingra, Anuradha; Vardi, Noga; Ravi C Balijepalli; Setaluri, Vijayasaradhi

    2013-01-01

    Mutations in TRPM1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM1 activity is negatively coupled to metabotropic glutamate receptor 6 (mGluR6) signaling through Gαo and TRPM1 mutations result in the loss of responsiveness of TRPM1 to mGluR6 signaling. Here, we show that human melanocytes express mGluR6 and treatment of melanocytes with L-AP4, a type I...

  11. NEW ASPECTS OF MELANOCORTIN SIGNALING: A ROLE FOR PRCP IN ALPHA-MSH DEGRADATION

    OpenAIRE

    Diano, Sabrina

    2010-01-01

    The role of the central melanocortin system in the regulation of energy metabolism has received much attention during the past decade since gene mutations of key components in melanocortin signaling cause monogenic forms of obesity in animals and humans. In the arcuate nucleus of the hypothalamus the prohormone proopiomelanocortin (POMC) is posttranslationally cleaved to produce α-melanocyte stimulating hormone (α-MSH), a peptide with anorexigenic effects upon activation of the melanocortin r...

  12. An enhanced and sensitive autocrine stimulation by transforming growth factor-alpha is acquired in the brain metastatic variant of a human non-small-cell lung cancer cell line.

    Science.gov (United States)

    Fang, K

    1996-12-01

    Transforming growth factor-alpha (TGF-alpha)-mediated autocrine regulation in human non-small-cell lung cancer (NSCLC) cells NCI-H226 and its brain metastatic variant H226Br were compared. An enhanced TGF-alpha-induced dose-dependent mitogenic responsiveness in H226Br cells was observed. Neutralising antibody that binds TGF-alpha inhibits H226Br cell growth more effectively than NCI-H226 cell growth. Binding assay with 125I-labelled epidermal growth factor (EGF) revealed that H226Br has two types of EGF receptors (EGFRs), whereas the parental cell line, NCI-H226, has only one. H226Br cells contain twice as many EGFRs as H226 cells, as proved by Scatchard analysis and immune kinase assay. Northern analysis indicated that there is more EGFR transcript in H226Br than in NCI-H226, indicating a transcriptional EGFR gene elevation during metastasis progression. The level of accumulated immunoactive TGF-alpha is lower in the conditioned medium of H226Br than in that of NCI-H226. demonstrating down-regulation of TGF-alpha transcript. The accumulated data suggest an elevated and sensitive autocrine modulation by TGF-alpha and EGFR in immortalising the brain metastatic variant cells that were derived from a human NSCLC squamous cell line. PMID:8956792

  13. Follicle and melanocyte stem cells, and their application in neuroscience A Web of Science-based literature analysis

    Institute of Scientific and Technical Information of China (English)

    Weifu Wu

    2012-01-01

    OBJECTIVE: To identify global research trends of follicle and melanocyte stem cells, and their application in neuroscience. DATA RETRIEVAL: We performed a bibliometric analysis of studies from 2002 to 2011 on follicle and melanocyte stem cells, and their application in neuroscience, which were retrieved from the Web of Science, using the key words follicle stem cell or melanocyte stem cell, and neural, neuro or nerve. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on follicle and melanocyte stem cells, and their application in neuroscience, which were indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) a number of corrected papers from the total number of articles. MAIN OUTCOME MEASURES: (1) Distribution of publications on follicle and melanocyte stem cells by years, journals, countries, institutions, institutions in China, and most cited papers. (2) Distribution of publications on the application of follicle and melanocyte stem cells in neuroscience by years, journals, countries, institutions, and most cited papers. RESULTS: Of the 348 publications from 2002 to 2011 on follicle and melanocyte stem cells, which were retrieved from the Web of Science, more than half were from American authors and institutes. The most prolific institutions in China for publication of papers on follicle and melanocyte stem cells were the Fourth Military Medical University and Third Military Medical University. The most prolific journals for publication of papers on follicle and melanocyte stem cells were the Journal of Investigative Dermatology, Pigment Cell & Melanoma Research. Of the 63 publications from 2002 to 2011 on the application of follicle and melanocyte stem cells in neuroscience, which

  14. $\\alpha_s$ review (2016)

    CERN Document Server

    d'Enterria, David

    2016-01-01

    The current world-average of the strong coupling at the Z pole mass, $\\alpha_s(m^2_{Z}) = 0.1181 \\pm 0.0013$, is obtained from a comparison of perturbative QCD calculations computed, at least, at next-to-next-to-leading-order accuracy, to a set of 6 groups of experimental observables: (i) lattice QCD "data", (ii) $\\tau$ hadronic decays, (iii) proton structure functions, (iv) event shapes and jet rates in $e^+e^-$ collisions, (v) Z boson hadronic decays, and (vi) top-quark cross sections in p-p collisions. In addition, at least 8 other $\\alpha_s$ extractions, usually with a lower level of theoretical and/or experimental precision today, have been proposed: pion, $\\Upsilon$, W hadronic decays; soft and hard fragmentation functions; jets cross sections in pp, e-p and $\\gamma$-p collisions; and photon F$_2$ structure function in $\\gamma\\,\\gamma$ collisions. These 14 $\\alpha_s$ determinations are reviewed, and the perspectives of reduction of their present uncertainties are discussed.

  15. Transplantation of Melanocytes Obtained from the Skin Ameliorates Apomorphine-Induced Abnormal Behavior in Rodent Hemi-Parkinsonian Models

    OpenAIRE

    Masato Asanuma; Ikuko Miyazaki; Diaz-Corrales, Francisco J.; Youichirou Higashi; Masayoshi Namba; Norio Ogawa

    2013-01-01

    Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-park...

  16. Transplantation of melanocytes obtained from the skin ameliorates apomorphine-induced abnormal behavior in rodent hemi-parkinsonian models

    OpenAIRE

    Asanuma, Masato; Miyazaki, Ikuko; Francisco J., Diaz-Corrales; Higashi, Youichirou; Namba, Masayoshi; Ogawa,Norio

    2013-01-01

    Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-park...

  17. Characterization and expression of soluble guanylate cyclase in skins and melanocytes of sheep.

    Science.gov (United States)

    Yang, Shanshan; Zhang, Junzhen; Ji, Kaiyuan; Jiao, Dingxing; Fan, Ruiwen; Dong, Changsheng

    2016-04-01

    The study reported the characterization of soluble guanylate cyclase (sGC) with the size of CDS of 1860bp, encoding a protein of 620 amino acids and containing several conserved functional domains including HNOB, HNOBA, and CHD. Quantitative real time PCR analysis of sGC showed that the expression of sGC mRNA is higher (∼5 fold) in white sheep skin relative to black sheep skin with significant difference (Ptyrosinase (TYR), tyrosinase related protein 1(TYRTP1), and tyrosinase related protein 2(TYRP2) both at mRNA and protein level. Moreover, the melanocytes was capable of producing cGMP and cAMP. The observed differential expression and localization of sGC in sheep skins and melanocytes and the capability of producing cGMP and cAMP, which suggested a potential role for this gene in hair color regulation. PMID:26805580

  18. Time-dependent effect of tamoxifen on melanogenesis in normal human melanocytes

    OpenAIRE

    Matamá, Maria Teresa; Guimarães, Diana; Costa, Cristiana; Paulo, Artur Cavaco; Gomes, A. C.

    2014-01-01

    In medical literature, occasional case reports describe gray hair re-pigmentation in patients after administration of certain drugs, such as tamoxifen, supporting the possibility of reversing pigmentation loss associated with ageing. This work aimed to study, in vitro, the effect on melanin production in primary human melanocytes of tamoxifen, an antagonist of the estrogen receptor in breast tissue, and of its most bioactive derivative, 4-hydroxy-tamoxifen. Adult normal human epidermal mel...

  19. New combined laser therapy for small mass of melanocytic nevi on the face

    OpenAIRE

    Ohmaru, Youkou; Ohmaru, Koichi; Koga, Noriyuki; Migita, Hisashi; Kiyokawa, Kensuke

    2011-01-01

    Background and Aims: A small mass of melanocytic nevi on the face is commonly treated by surgical resection. This method is associated with cosmetic complications, such as scarring and scar contracture. The use of CO2 Laser treatment to avoid these complications is increasing. However, scarring or recurrence may still occur after CO2 Laser treatment. To resolve these problems, we developed a new Combined Laser Therapy (CLT) protocol using three laser instruments.

  20. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation

    OpenAIRE

    Kadekaro, Ana Luisa; Leachman, Sancy; Kavanagh, Renny J.; Swope, Viki; Cassidy, Pamela; Supp, Dorothy; Sartor, Maureen; Schwemberger, Sandy; Babcock, George; Wakamatsu, Kazumasa; Ito, Shosuke; Koshoffer, Amy; Boissy, Raymond E.; Manga, Prashiela; Sturm, Richard A.

    2010-01-01

    The melanocortin 1 receptor gene is a main determinant of human pigmentation, and a melanoma susceptibility gene, because its variants that are strongly associated with red hair color increase melanoma risk. To test experimentally the association between melanocortin 1 receptor genotype and melanoma susceptibility, we compared the responses of primary human melanocyte cultures naturally expressing different melanocortin 1 receptor variants to α-melanocortin and ultraviolet radiation. We found...

  1. EdnrB Governs Regenerative Response of Melanocyte Stem Cells by Crosstalk with Wnt Signaling

    OpenAIRE

    Makoto Takeo; Wendy Lee; Piul Rabbani; Qi Sun; Hai Hu; Chae Ho Lim; Prashiela Manga; Mayumi Ito

    2016-01-01

    Delineating the crosstalk between distinct signaling pathways is key to understanding the diverse and dynamic responses of adult stem cells during tissue regeneration. Here, we demonstrate that the Edn/EdnrB signaling pathway can interact with other signaling pathways to elicit distinct stem cell functions during tissue regeneration. EdnrB signaling promotes proliferation and differentiation of melanocyte stem cells (McSCs), dramatically enhancing the regeneration of hair and epidermal melano...

  2. NFIB is a governor of epithelial–melanocyte stem cell behaviour in a shared niche

    OpenAIRE

    Chang, Chiung-Ying; Pasolli, H. Amalia; Giannopoulou, Eugenia G.; Guasch, Géraldine; Gronostajski, Richard M; Elemento, Olivier; Fuchs, Elaine

    2013-01-01

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation1–4. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment2,5. Dissecting the inter-stem-ce...

  3. Intracranial melanocytic meningeal tumours and melanosis oculi: case report and literature review

    International Nuclear Information System (INIS)

    Melanocytic meningeal tumours are rare extra-axial neoplasms of the nervous system, with only three reported cases in the cavernous sinus. Herein we describe for the first time the association of ocular melanosis and multiple intracranial melanocytic meningeal tumours, with the presenting lesion being in the cavernous sinus. The importance of this association is discussed together with the diagnostic and therapeutic challenges of the case. A 20-year-old man presented with a left sixth cranial nerve deficit; general examination documented only congenital melanosis of the homolateral eye. MRI examination showed a space occupying lesion in the left cavernous sinus, which was followed conservatively for 2 years, until a new space occupying lesion was evident at the level of the right frontal convexity: both lesions presented with neuroradiological characteristics suggestive of melanin content. The frontal convexity lesion was removed: intraoperatively the dura was markedly and diffusely melanotic. Histological examination documented a melanocytic meningeal tumour, with a proliferative index of 3 %. The patient underwent 3D-Conformal Radiation Therapy on the lesion of the cavernous sinus (total dose 5040 cGy), with initial tumour reduction. Three years later, due to a symptomatic growth, he underwent partial removal of the lesion in the cavernous sinus. Histological examination was unchanged. He then received adjuvant Temozolomide with Low Dose Fractionated Radiation Therapy (LD-FRT). Due to further disease progression cisplatin plus fotemustine were administered, concomitant with LD-FRT: after two cycles MRI documented significant disease regression. After a period of apparent disease control, the patient presented with persistent cough and evidence of multiple thoracic metastases, which lead to his death, seven years after presentation. Intracranial melanocytic meningeal tumours are challenging lesions, both from a diagnostic and therapeutic point of view; though rare

  4. The $\\alpha-\\alpha$ fishbone potential revisited

    CERN Document Server

    Day, J P; Elhanafy, M; Smith, E; Woodhouse, R; Papp, Z

    2011-01-01

    The fishbone potential of composite particles simulates the Pauli effect by nonlocal terms. We determine the $\\alpha-\\alpha$ fishbone potential by simultaneously fitting to two-$\\alpha$ resonance energies, experimental phase shifts and three-$\\alpha$ binding energies. We found that essentially a simple gaussian can provide a good description of two-$\\alpha$ and three-$\\alpha$ experimental data without invoking three-body potentials.

  5. Premature graying as a consequence of compromised antioxidant activity in hair bulb melanocytes and their precursors.

    Directory of Open Access Journals (Sweden)

    Ying Shi

    Full Text Available Intricate coordinated mechanisms that govern the synchrony of hair growth and melanin synthesis remain largely unclear. These two events can be uncoupled in prematurely gray hair, probably due to oxidative insults that lead to the death of oxidative stress-sensitive melanocytes. In this study, we examined the gene expression profiles of middle (bulge and lower (hair bulb segments that had been micro-dissected from unpigmented and from normally pigmented hair follicles from the same donors using quantitative real-time RT-PCR (qPCR arrays. We found a significant down-regulation of melanogenesis-related genes (TYR, TYRP1, MITF, PAX3, POMC in unpigmented hair bulbs and of marker genes typical for melanocyte precursor cells (PAX3, SOX10, DCT in unpigmented mid-segments compared with their pigmented analogues. qPCR, western blotting and spin trapping assays revealed that catalase protein expression and hydroxyl radical scavenging activities are strongly repressed in unpigmented hair follicles. These data provide the first clear evidence that compromised antioxidant activity in gray hair follicles simultaneously affects mature hair bulb melanocytes and their immature precursor cells in the bulge region.

  6. Mechanical properties of growing melanocytic nevi and the progression to melanoma

    Science.gov (United States)

    Taloni, Alessandro; Alemi, Alexander; Ciusani, Emilio; Sethna, James P.; Zapperi, Stefano; La Porta, Caterina A. M.; National Research Council Of Italy Team; Lassp, Department Of Physics, Cornell University Team; Istituto Neurologico Carlo Besta Collaboration; Department Of Biosciences, University Of Milano Team

    2015-03-01

    Melanocytic nevi are benign proliferations that sometimes turn into malignant melanoma in a way that is still unclear from the biochemical and genetic point of view. Diagnostic and prognostic tools are then mostly based on dermoscopic examination and morphological analysis of histological tissues. To investigate the role of mechanics and geometry in the morpholgical dynamics of melanocytic nevi, we present a computational model for cell proliferation in a layered non-linear elastic tissue. Our simulations show that the morphology of the nevus is correlated to the initial location of the proliferating cell starting the growth process and to the mechanical properties of the tissue. We also demonstrate that melanocytes are subject to compressive stresses that fluctuate widely in the nevus and depend on the growth stage. Numerical simulations of cells in the epidermis releasing matrix metalloproteinases display an accelerated invasion of the dermis by destroying the basal membrane. Moreover, we show experimentally that osmotic stress and collagen inhibit growth in primary melanoma cells while the effect is much weaker in metastatic cells.

  7. Ultrastructural inquiries of the effects of X-radiation on melanocytes in monolayer cultures

    International Nuclear Information System (INIS)

    Melanocytes (HPM-73 cells) in monolayer culture, which in the exponential growth phase were irradiated with an X-ray dose of 8 Gy (800 rad) and 16 Gy (1600 rad), showed ultrastructural changes in the cell wall (for example, microvilli), in elements of the cytoskeleton (microtubules and microfilaments), of the mitochondria and a change in structures containing melanin (melanosomes/pre-melanosomes). As a control, melanocytes incubated in a culture medium containing serum were used. The irradiated cells showed morphologically tangible cell changes. It resulted in a strong development of the cytoskeleton (microtubules and microfilaments), an increase in lysosome-like structures, a re-orientation of cell wall structures in the form of a reduction of wall extensions (decrease in size of microvilli) and an increase in structures containing melanin. It was also noticed that the cells which had received 16 Gy (1600 rad) were damaged more than the cells which had received 8 Gy (800 rad), whereby the more highly irradiated cells still were not understood to be in 'disintegration'. All of these changes should be considered under the aspect of repair mechanisms after cell damage (irradiation). Altogether melanocytes are in comparison to other tumor cells less radiation sensitive. (orig.)

  8. DMEM enhances tyrosinase activity in B16 mouse melanoma cells and human melanocytes

    Directory of Open Access Journals (Sweden)

    Panpen Diawpanich

    2008-07-01

    Full Text Available Media components may affect the activities of cultured cells. In this study, tyrosinase activity was evaluated by using B16-F10 mouse melanoma cell lines (B16-F10 and primary human melanocytes cultured in different media. An optical density measurement and a L-dopa reaction assay were used as the determination of the tyrosinase activity. The study of B16-F10 found the optical density to be 2010, 2246 and 2961 in cells cultured in RPMI Medium 1640 (RPMI1640,Minimum Essential Medium (MEM and Dulbecco’s Modified Eagle Medium (DMEM, respectively. Moreover, compared to RPMI 1640 and MEM, DMEM showed the darkest color of melanin formation in culture media and in cells after the L-dopa reaction assay. Addition of kojic acid showed a significant inhibitory effect on tyrosinase activity in all media.Whereas MCDB153 showed no significant effect on human melanocytes, DMEM caused a dramatic increase in tyrosinase activity after 4 days of cultivation. Addition of kojic acid showed a significant tyrosinase inhibitory effect in DMEM only. Furthermore, an active ingredient in green tea, epigallocathechin gallate (EGCG could inhibit tyrosinase activity in both B16-F10 and human melanocytes cultured in DMEM. In summary, these results suggest that DMEM is a suitable medium that provides high detection sensitivity in a tyrosinase inhibition assay.

  9. The Effect of Otic Melanocyte Destruction on Auditory and Vestibular Function: a Study on Vitiligo Patients.

    Science.gov (United States)

    Mahdi, Parvane; Amali, Amin; Ruzbahani, Masoumeh; Pourbakht, Akram; Mahdavi, Asadollah

    2016-02-01

    The hallmark of vitiligo is the disappearance of melanocytes from the skin. As a result, of melanocytes presence in the auditory and vestibular apparatus, the involvement of these systems in vitiligo which targets the melanocytes of the whole body is possible; suggesting that vitiligo is a systemic disease rather than a purely cutaneous problem. A total of 21 patients with vitiligo were enrolled in this study. A group of 20 healthy subjects served as a control group. Pure tone audiometry (PTA), auditory brainstem responses (ABR) and vestibular evoked myogenic potentials (VEMP) were carried out in all participants. High frequency sensory neural hearing loss was seen in 8 (38.09%) patients. ABR analysis revealed 10 (47.61%) had an abnormal increase in latency of wave III, and 6 (28.57%) had an abnormal prolongation of IPL I-III, however, regarding our VEMP findings, there were no recorded responses on left ear of 1 (4.76%) patient and latency of p13 was prolonged in 5(23.80%) patients. There was no correlation between ages, duration of disease, and any of the recorded parameters (P>0.05). In the present survey, we highlighted the auditory and vestibular involvement in vitiligo patients. PMID:26997595

  10. The Effect of Otic Melanocyte Destruction on Auditory and Vestibular Function: a Study on Vitiligo Patients

    Directory of Open Access Journals (Sweden)

    Parvane Mahdi

    2016-03-01

    Full Text Available The hallmark of vitiligo is the disappearance of melanocytes from the skin. As a result, of melanocytes presence in the auditory and vestibular apparatus, the involvement of these systems in vitiligo which targets the melanocytes of the whole body is possible; suggesting that vitiligo is a systemic disease rather than a purely cutaneous problem. A total of 21 patients with vitiligo were enrolled in this study. A group of 20 healthy subjects served as a control group. Pure tone audiometry (PTA, auditory brainstem responses (ABR and vestibular evoked myogenic potentials (VEMP were carried out in all participants. High frequency sensory neural hearing loss was seen in 8 (38.09% patients. ABR analysis revealed 10 (47.61% had an abnormal increase in latency of wave III, and 6 (28.57% had an abnormal prolongation of IPL I-III, however, regarding our VEMP findings, there were no recorded responses on left ear of 1 (4.76% patient and latency of p13 was prolonged in 5(23.80% patients. There was no correlation between ages, duration of disease, and any of the recorded parameters (P>0.05. In the present survey, we highlighted the auditory and vestibular involvement in vitiligo patients.

  11. Alpha One Foundation

    Science.gov (United States)

    ... Tested Find Support Find Doctor What Is Alpha-1? Alpha-1 Antitrypsin Deficiency (Alpha-1) is a ... results for inhaled augmentation More News Our Number One Goal: Find a cure for Alpha-1. Website ...

  12. Alpha-1 Antitrypsin Test

    Science.gov (United States)

    ... helpful? Also known as: Alpha 1 -antitrypsin; A1AT; AAT Formal name: Alpha 1 Antitrypsin; α1-antitrypsin Related ... know? How is it used? Alpha-1 antitrypsin (AAT) testing is used to help diagnose alpha-1 ...

  13. Alpha spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, Felix; Wilsenach, Heinrich; Zuber, Kai [IKTP TU-Dresden, Dresden (Germany)

    2014-07-01

    Alpha decays from long living isotopes are one of the limiting backgrounds for experiments searching for rare decays with stringent background constrains, such as neutrinoless double beta decay experiments. It is thus very important to accurately measure the half-lives of these decays, in order to properly model their background contribution. Therefore, it is important to be able to measure half-lives from alpha decays of the order of 1 x 10{sup 15} yr. A measurement of such a long lived decay imposes, however, a series of challenges, where the correct discrimination between background and true signal is critical. There is also a more general interest in such long living half-life measurements, as their value depends crucially on the underlying nuclear model. This work proposes a setup to measure long lived alpha decays, based on the design of the Frisch-Grid ionisation chamber. It is shown that the proposed design provides a good separation of signal and background events. It is also demonstrated that, with pulse shape analysis, it is possible to constrain the source position of the decay, further improving the quality of the data. A discussion of the characterisation of the detector is also presented as well as some results obtained with calibration sources.

  14. Alpha spectroscopy

    International Nuclear Information System (INIS)

    Alpha decays from long living isotopes are one of the limiting backgrounds for experiments searching for rare decays with stringent background constrains, such as neutrinoless double beta decay experiments. It is thus very important to accurately measure the half-lives of these decays, in order to properly model their background contribution. Therefore, it is important to be able to measure half-lives from alpha decays of the order of 1 x 1015 yr. A measurement of such a long lived decay imposes, however, a series of challenges, where the correct discrimination between background and true signal is critical. There is also a more general interest in such long living half-life measurements, as their value depends crucially on the underlying nuclear model. This work proposes a setup to measure long lived alpha decays, based on the design of the Frisch-Grid ionisation chamber. It is shown that the proposed design provides a good separation of signal and background events. It is also demonstrated that, with pulse shape analysis, it is possible to constrain the source position of the decay, further improving the quality of the data. A discussion of the characterisation of the detector is also presented as well as some results obtained with calibration sources.

  15. 基于磁刺激内关穴的脑电α波时频分析%Time-Frequency Analysis of Alpha Wave Based on EEG Signals Magnetic Stimulated at Acupoint of Neiguan (PC6)

    Institute of Scientific and Technical Information of China (English)

    李文文; 徐桂芝; 陈小刚; 杨硕; 于洪丽

    2011-01-01

    Objective This article combined the magnetic stimulation and traditional Chinese medicine acupuncture points, meridians conduction to study the effect of magnetic stimulation on wave α distribution and energy. Methods The brain electric activity mappings, which were of wave α distribution under different conditions, were drawn and utilized to analyze the effect of magnetic stimulation on wave α distribution. And Gabor wavelet and Hilbert transform were used to study the effect of magnetic stimulation on wave α energy.Results The magnetic stimulation at acupoint Neiguan could cause the changes of wave α distribution and energy. The distribution of wave α under magnetic stimulation state was enhanced than that of normal state.The power of wave α in the frontal and left occipital brain after magnetic stimulation was significantly higher than that before stimulation. Conclusion The study demonstrated that the subjects might be sober and quiet under the magnetic stimulation at acupoint Neiguan, and the magnetic stimulation might have a similar effect with acupuncture stimulation at Neiguan. The study verified the effectiveness of magnetic stimulation and laid the foundation for future research.%目的 本文将磁刺激和传统中医穴位、经络传导相结合,研究了磁刺激内关穴对大脑α波的分布及能量的影响.方法 绘制不同状态下的α波分布的脑电地形图,分析磁刺激对大脑α波分布的影响.采用Gabor小波和希尔伯特变换方法研究磁刺激对大脑α波能量的影响.结果 磁刺激内关穴能够引起被试者α波的分布及能量的变化,表现在:磁刺激时α波分布范围大于安静状态;与刺激前相比,磁刺激后大脑额叶和左侧枕叶的α波能量明显增强.结论 本研究表明磁刺激被试者的内关穴可能使被试者达到清醒和镇定的状态,与针刺内关穴的安神醒脑作用有着异曲同工之效.本研究验证了磁刺激穴位的有效性,为今后的相关研究奠定了基础.

  16. Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin.

    Directory of Open Access Journals (Sweden)

    Charles W Higdon

    Full Text Available In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology.

  17. A Varp-Binding Protein, RACK1, Regulates Dendrite Outgrowth through Stabilization of Varp Protein in Mouse Melanocytes.

    Science.gov (United States)

    Marubashi, Soujiro; Ohbayashi, Norihiko; Fukuda, Mitsunori

    2016-08-01

    Varp (VPS9-ankyrin repeat protein) in melanocytes is thought to function as a key player in the pigmentation of mammals. Varp regulates two different melanocyte functions: (i) transport of melanogenic enzymes to melanosomes by functioning as a Rab32/38 effector and (ii) promotion of dendrite outgrowth by functioning as a Rab21-guanine nucleotide exchange factor. The Varp protein level has recently been shown to be negatively regulated by proteasomal degradation through interaction of the ankyrin repeat 2 (ANKR2) domain of Varp with Rab40C. However, the molecular mechanisms by which Varp escapes from Rab40C and retains its own expression level remain completely unknown. Here, we identified RACK1 (receptor of activated protein kinase C 1) as a Varp-ANKR2 binding partner and investigated its involvement in Varp stabilization in mouse melanocytes. The results showed that knockdown of endogenous RACK1 in melanocytes caused dramatic reduction of the Varp protein level and inhibition of dendrite outgrowth, and intriguingly, overexpression of RACK1 inhibited the interaction between Varp and Rab40C and counteracted the negative effect of Rab40C on dendrite outgrowth. These findings indicated that RACK1 competes with Rab40C for binding to the ANKR2 domain of Varp and regulates dendrite outgrowth through stabilization of Varp in mouse melanocytes. PMID:27066885

  18. Influence of melanocytes in the ex-vivo reconstructed epidermal melanin unit following an acute UV irradiation; Role des melanocytes dans l'unite epidermique de melanisation reconstruite ex-vivo apres une irradiation UV aigue

    Energy Technology Data Exchange (ETDEWEB)

    Cario-Andre, M

    2000-11-15

    Influence of melanocytes in skin pigmentation is well documented, however its photo-protective role has given rise to controversy. The role of melanocytes have been investigated on reconstructed epidermis with 100 % of keratinocytes or 95 % of keratinocytes and 5 % of melanocytes. In a first time, the effect of an acute UVB dose has been studied on both reconstructed epidermis, next we have investigated UVA and UVA+B effects on these epidermis. Following irradiation, the presence of melanocytes in reconstructed epidermis protects against apoptosis without protecting significantly against DNA damage formation (CPD, 6-4PP) and protects against UV-induced unbalance of the SOD/catalase ratio (antioxidants enzymes). On the contrary, the presence of melanocytes in reconstructed epidermis amplifies lipids and proteins oxidations but seems to protect against DNA oxidations. Melanocytes differ from keratinocytes by their melanin content and their more important concentration in polyunsaturated fatty acids. To evaluate what is the part of melanin and the part of polyunsaturated fatty acids in epidermal UV responses, reconstructed epidermis with keratinocytes have been supplemented with polyunsaturated fatty acid. This study indicates that polyunsaturated fatty acids are responsible for lipids and proteins oxidations and that melanin protect against DNA oxidation induced by lipid peroxidation. All these studies demonstrate that, model of reconstructed epidermis and epidermis in-vivo have the same behaviour following UV irradiation. In the last part, sunscreens and antioxidants have been tested on reconstructed epidermis and have demonstrated that model of reconstructed epidermis is suitable for photo-protective molecules screening. (author)

  19. A murine model for the development of melanocytic nevi and their progression to melanoma.

    Science.gov (United States)

    Nasti, Tahseen H; Cochran, J Barry; Tsuruta, Yuko; Yusuf, Nabiha; McKay, Kristopher M; Athar, Mohammad; Timares, Laura; Elmets, Craig A

    2016-05-01

    Acquired melanocytic nevi are commonly found in sun exposed and unexposed human skin, but the potential for their transformation into invasive melanoma is not clear. Therefore, a mouse model of nevus initiation and progression was developed in C3H/HeN mice using a modified chemical carcinogenesis protocol. Nevi develop due to DNA damage initiated by dimethylbenz(a) anthracene (DMBA) followed by chronic promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Dysplastic pigmented skin lesions appeared in 7-9 wk with 100% penetrance. Nests of melanocytic cells appeared in a subset of skin draining lymph nodes (dLN) by 25 wk, but not in age matched controls. Immunohistochemistry, real-time PCR, and flow cytometric analyses confirmed their melanocytic origin. Transformed cells were present in a subset of nevi and dLNs, which exhibited anchorage-independent growth, tumor development, and metastasis in nude mice. Approximately 50% of the cell lines contained H-Ras mutations and lost tumor suppressor p16(Ink4a) expression. While most studies of melanoma focus on tumor progression in transgenic mouse models where the mutations are present from birth, our model permits investigation of acquired mutations at the earliest stages of nevus initiation and promotion of nevus cell transformation. This robust nevus/melanoma model may prove useful for identifying genetic loci associated with nevus formation, novel oncogenic pathways, tumor targets for immune-prevention, screening therapeutics, and elucidating mechanisms of immune surveillance and immune evasion. © 2015 The Authors. Molecular Carcinogenesis, published by Wiley Periodicals, Inc. PMID:25788145

  20. Premalignant quiescent melanocytic nevi do not express the MHC class I chain-related protein A

    Directory of Open Access Journals (Sweden)

    Mercedes B. Fuertes

    2011-08-01

    Full Text Available The MHC class I chain-related protein A (MICA is an inducible molecule almost not expressed by normal cells but strongly up-regulated in tumor cells. MICA-expressing cells are recognized by natural killer (NK cells, CD8+ aßTCR and ?dTCR T lymphocytes through the NKG2D receptor. Engagement of NKG2D by MICA triggers IFN-? secretion and cytotoxicity against malignant cells. Although most solid tumors express MICA and this molecule is a target during immune surveillance against tumors, it has been observed that high grade tumors from different histotypes express low amounts of cell surface MICA due to a metalloprotease- induced shedding. Also, melanomas develop after a complex process of neotransformation of normal melanocytes. However, the expression of MICA in premalignant stages (primary human quiescent melanocytic nevi remains unknown. Here, we assessed expression of MICA by flow cytometry using cell suspensions from 15 primary nevi isolated from 11 patients. When collected material was abundant, cell lysates were prepared and MICA expression was also analyzed by Western blot. We observed that MICA was undetectable in the 15 primary nevi (intradermic, junction, mixed, lentigo and congenital samples as well as in normal skin, benign lesions (seborrheic keratosis, premalignant lesions (actinic keratosis and benign basocellular cancer. Conversely, a primary recently diagnosed melanoma showed intense cell surface MICA. We conclude that the onset of MICA expression is a tightly regulated process that occurs after melanocytes trespass the stage of malignant transformation. Thus, analysis of MICA expression in tissue sections of skin samples may constitute a useful marker to differentiate between benign and malignant nevi.

  1. [The congenital melanocytic nevi of the face in child: What's new?].

    Science.gov (United States)

    Captier, G

    2015-09-01

    Congenital melanocytic nevi of the face are a frequent reason for consultation in paediatric plastic surgery. Usually of small size, they raise a complex problem of reconstruction when they are large and giant. The indication of excision is generally stated on aesthetic criteria whereas the risk of melanoma is especially important in the giant nevi. Simple suture, full thickness skin graft and expanded skin flaps are the techniques of choice. The treatment must be carried out precociously, follow a surgical planning, respect the aesthetic units of the face and the periorificial areas, adapt to the age of the child and bring psychological benefit to the child. PMID:26189003

  2. Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta

    DEFF Research Database (Denmark)

    Karlsen, Joachim R; Borregaard, Niels; Cowland, Jack B

    2010-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL) is a siderophore-binding antimicrobial protein that is up-regulated in epithelial tissues during inflammation. We demonstrated previously that the gene encoding NGAL (LCN2) is strongly up-regulated by interleukin (IL)-1beta in an NF-kappaB-depende......Neutrophil gelatinase-associated lipocalin (NGAL) is a siderophore-binding antimicrobial protein that is up-regulated in epithelial tissues during inflammation. We demonstrated previously that the gene encoding NGAL (LCN2) is strongly up-regulated by interleukin (IL)-1beta in an NF......-alpha in the presence of IL-17, a pro-inflammatory cytokine produced by the newly discovered subset of CD4(+) T helper cells, T(H)-17. In contrast to the murine NGAL orthologue, 24p3/lipocalin 2, we found no requirement for C/EBP-beta or C/EBP-delta for NGAL induction by IL-17 and TNF-alpha as neither...... small interfering RNAs against the two C/EBP mRNAs nor mutation of the C/EBP sites in the LCN2 promoter abolished IL-17- and TNF-alpha-induced up-regulation of NGAL. NGAL induction is governed solely by NF-kappaB and its co-factor IkappaB-zeta. This was demonstrated by a pronounced reduction in the...

  3. 白癜风皮损中非黑素细胞进展%Non-melanocytes in vitiligo lesions

    Institute of Scientific and Technical Information of China (English)

    金永红; 许爱娥

    2008-01-01

    The pathogenesis of vitiligo is still unclear.In addition to melanocytes,non-melanocytes are involved in the pathogenesis of vitiligo.More and more studies have been conducted on non.melanocytes in vitiligo recently.It has been shown that keratinocytes,Langerhans cells and fibroblasts affect the migration,proliteration and differentiation of melanocytes.The changes of cytokines secreted by and ultrastructural abnormality of non-melanocytes may affect the activity and apoptosis of melanocytes in vitiligo lesions,influence pigrnentogenesis in skin,thereafter,take part in the pathogenesis of vitiligo.This paper presents the latest investigation of keratinocytes,Langerhans cells and fibroblasts in vitiligo.%白癜风的发病机制尚未完全明了.其发病除黑素细胞异常外,还涉及非黑素细胞的变化,近年来非黑素细胞在白癜风中的研究逐渐增多.研究表明,一些皮肤非黑素细胞如角质形成细胞、朗格汉斯细胞、成纤维细胞等与黑素细胞关系密切,这些细胞影响黑素细胞的迁移、增殖、分化等功能.白癜风皮损中非黑素细胞超微结构的异常和分泌细胞因子的变化可影响黑素细胞的活性及凋亡,影响皮肤色素生成,从而参与白癜风发病.

  4. Influence of melanocytes in the ex-vivo reconstructed epidermal melanin unit following an acute UV irradiation

    International Nuclear Information System (INIS)

    Influence of melanocytes in skin pigmentation is well documented, however its photo-protective role has given rise to controversy. The role of melanocytes have been investigated on reconstructed epidermis with 100 % of keratinocytes or 95 % of keratinocytes and 5 % of melanocytes. In a first time, the effect of an acute UVB dose has been studied on both reconstructed epidermis, next we have investigated UVA and UVA+B effects on these epidermis. Following irradiation, the presence of melanocytes in reconstructed epidermis protects against apoptosis without protecting significantly against DNA damage formation (CPD, 6-4PP) and protects against UV-induced unbalance of the SOD/catalase ratio (antioxidants enzymes). On the contrary, the presence of melanocytes in reconstructed epidermis amplifies lipids and proteins oxidations but seems to protect against DNA oxidations. Melanocytes differ from keratinocytes by their melanin content and their more important concentration in polyunsaturated fatty acids. To evaluate what is the part of melanin and the part of polyunsaturated fatty acids in epidermal UV responses, reconstructed epidermis with keratinocytes have been supplemented with polyunsaturated fatty acid. This study indicates that polyunsaturated fatty acids are responsible for lipids and proteins oxidations and that melanin protect against DNA oxidation induced by lipid peroxidation. All these studies demonstrate that, model of reconstructed epidermis and epidermis in-vivo have the same behaviour following UV irradiation. In the last part, sunscreens and antioxidants have been tested on reconstructed epidermis and have demonstrated that model of reconstructed epidermis is suitable for photo-protective molecules screening. (author)

  5. EFFECTS OF BU GU ZHI(PSORALEA CORYLIFOLIA L) AND BAI ZHI (DAHURIAN ANGELICA ROOT) EXTRACTS ON MELANOCYTE ADHESION AND MIGRATION

    Institute of Scientific and Technical Information of China (English)

    Ma Huiqun; Feng Jie; Zhang Xianqi; Mu Kuanhou; Liu Chao; Niu Xinwu; Dang Qianli

    2005-01-01

    Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from two kind of Chinese medicinable herbs were tested. Human melanocytes were obtained from neonatal foreskins and 48-well culture dish covered with fibronectin were used to perform melanocyte adhesion assay; Motility was assessed using the micropore filter method. Results: The extracts of Bu Gu Zhi(Psoralea corylifolia L), Bai Zhi(Dahurian angelica root) obviously showed an effect in increasing of human melanocyte adhesion and migration on fibronectin. Conclusion It is suggested that Buguzhi(Fructus Psoraleae) and Baizhi(Radix Angelicae Dahuricae) might induce melanocyte adhesion and/or migration in the treatment of vitiligo.

  6. Reduced WIF-1 expression stimulates skin hyperpigmentation in patients with melasma.

    Science.gov (United States)

    Kim, Ji-Young; Lee, Tae-Ryong; Lee, Ai-Young

    2013-01-01

    The expression of Wnt inhibitory factor-1 (WIF-1) gene, which was detected by a microarray analysis of hyperpigmented and normally pigmented skin sets of melasma patients, was significantly reduced in the hyperpigmented skin from melasma patients, but not in healthy controls, regardless of UV irradiation. Wnt signals regulate skin pigmentation; however, WIF-1 is expressed in cultured skin keratinocytes and fibroblasts, but not in melanocytes. Therefore, we examined whether WIF-1 knockdown in neighboring keratinocytes and fibroblasts plays a role in melasma. Additionally, the effect of WIF-1 overexpression on the amelioration of hyperpigmentation was examined. WIF-1 knockdown, either in fibroblasts or in keratinocytes, significantly stimulated tyrosinase expression and melanosome transfer, whereas melanocytes with WIF-1 overexpression significantly reduced those parameters. The WIF-1 knockdown decreased glycogen synthase kinase-3β (GSK-3β), β-catenin, and NFATc2 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 2) phosphorylation and increased microphthalmia-associated transcription factor (MITF) expression as in melanocytes with Wnt-1 overexpression, whereas the WIF-1 overexpression reversed the results. Expression of Wnts, both canonical and noncanonical, was increased in the hyperpigmented skin of melasma patients. Collectively, WIF-1 downregulation, which may occur in epidermal keratinocytes and in dermal fibroblasts, is involved in melasma development because of the stimulation of melanogenesis and melanosome transfer through upregulation of the canonical and the noncanonical Wnt signaling pathway. PMID:22951732

  7. Malignant Tumor Derived from Skin Melanocytes of a Bovine of Unusual Presentation: A Case Study

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Chaves Velásquez

    2015-05-01

    Full Text Available Melanocytic tumors and melanomas in domestic animals include neoplasms composed of melanin-producing cells. In cattle, these tumors are rare and mostly benign, while malignant tumors are almost non-existent. The article reports the case of a female crossbred cow 38 months of age with a fluctuating mass located between the mandibular border and the left parotid region, about three months duration, with evident growth in the last thirty days. After surgical excision, a sample preserved in buffered formalin (10% was sent to the Laboratory of Pathology (University of Nariño—consisting of a fragment of 7.0 × 10.5 × 8.0 cm, ellipsoid, with skin and hair on one side, irregular surface, blackish brown, semi-soft consistency, and presence of shear translucent slimy content—for processing and inclusion in paraffin, cut to 5 μm thickness and stained with hematoxylin-eosin coloration. The forwarded tissue was classified as a neoplasm of malignant behavior derived from melanocytes, due to its cellular characteristics: growth pattern, pattern of distribution, severe cellular pleomorphism, anisocytosis, megalocytosis, nuclear pleomorphism, anisokaryosis, megalokaryosis, and involvement of blood vessel walls; additionally, the paraffin block was cut for immunohistochemical processing using monoclonal markers (S-100 DAKO® and Melan A DAKO®, contrasted with Mayer’s hematoxylin. Strong immunostaining of neoplastic cells is evident, and it constitutes the first reported case of this disease in Nariño (Colombia.

  8. Multidirectional Vector Excision Leads to Better Outcomes than Traditional Elliptical Excision of Facial Congenital Melanocytic Nevus

    Directory of Open Access Journals (Sweden)

    Seung Il Oh

    2013-09-01

    Full Text Available Background The elliptical excision is the standard method of removing benign skin lesions,such as congenital melanocytic nevi. This technique allows for primary closure, with little to nodog-ear deformity, but may sacrifice normal tissue adjacent to the lesion, resulting in scarswhich are unnecessarily long. This study was designed to compare the predicted results ofelliptical excision with those resulting from our excision technique.Methods Eighty-two patients with congenital melanocytic nevus on the face were prospectivelystudied. Each lesion was examined and an optimal ellipse was designed and marked onthe skin. After an incision on one side of the nevus margin, subcutaneous undermining wasperformed in the appropriate direction. The skin flap was pulled up and approximated alongseveral vectors to minimize the occurrence of dog-ear deformity.Results Overall, the final wound length was 21.1% shorter than that achieved by ellipticalexcision. Only 8.5% of the patients required dog-ear repair. There was no significant distortionof critical facial structures. All of the scars were deemed aesthetically acceptable based ontheir Patient and Observer Scar Assessment Scale scores.Conclusions When compared to elliptical excision, our technique appears to minimize dogeardeformity and decrease the final wound length. This technique should be considered analternative method for excision of facial nevi.

  9. Comparison of growth factor signalling pathway utilisation in cultured normal melanocytes and melanoma cell lines

    International Nuclear Information System (INIS)

    The phosphatidylinositol-3-kinase (PI3K-PKB), mitogen activated protein kinase (MEK-ERK) and the mammalian target of rapamycin (mTOR- p70S6K), are thought to regulate many aspects of tumour cell proliferation and survival. We have examined the utilisation of these three signalling pathways in a number of cell lines derived from patients with metastatic malignant melanoma of known PIK3CA, PTEN, NRAS and BRAF mutational status. Western blotting was used to compare the phosphorylation status of components of the PI3K-PKB, MEK-ERK and mTOR-p70S6K signalling pathways, as indices of pathway utilisation. Normal melanocytes could not be distinguished from melanoma cells on the basis of pathway utilisation when grown in the presence of serum, but could be distinguished upon serum starvation, where signalling protein phosphorylation was generally abrogated. Surprisingly, the differential utilisation of individual pathways was not consistently associated with the presence of an oncogenic or tumour suppressor mutation of genes in these pathways. Utilisation of the PI3K-PKB, MEK-ERK and mTOR-p70S6K signalling pathways in melanoma, as determined by phosphorylation of signalling components, varies widely across a series of cell lines, and does not directly reflect mutation of genes coding these components. The main difference between cultured normal melanocytes and melanoma cells is not the pathway utilisation itself, but rather in the serum dependence of pathway utilisation

  10. Toll-Like Receptor 2- and 6-Mediated Stimulation by Macrophage-Activating Lipopeptide 2 Induces Lipopolysaccharide (LPS) Cross Tolerance in Mice, Which Results in Protection from Tumor Necrosis Factor Alpha but in Only Partial Protection from Lethal LPS Doses

    OpenAIRE

    Deiters, Ursula; Gumenscheimer, Marina; Galanos, Chris; Mühlradt, Peter F.

    2003-01-01

    Patients or experimental animals previously exposed to lipopolysaccharide (LPS) become tolerant to further LPS challenge. We investigated the potential of the macrophage-activating lipopeptide 2 (MALP-2) to induce in vivo cross tolerance to tumor necrosis factor alpha (TNF-α) and LPS. MALP-2-induced tolerance could be of practical interest, as MALP-2 proved much less pyrogenic in rabbits than LPS. Whereas LPS signals via Toll-like receptor 4 (TLR4), MALP-2 uses TLR2 and TLR6. LPS-mediated cyt...

  11. Neuropeptide Y and gamma-melanocyte stimulating hormone (γ-MSH) share a common pressor mechanism of action

    OpenAIRE

    Gruber, Kenneth A.; Fan, Wei (David); Akerberg, Helena; Larhammar, Dan; Chee, Melissa J. S.; Colmers, William F.; Cone, Roger D.

    2009-01-01

    Central circuits known to regulate food intake and energy expenditure also affect central cardiovascular regulation. For example, both the melanocortin and neuropeptide Y (NPY) peptide families, known to regulate food intake, also produce central hypertensive effects. Members of both families share a similar C-terminal amino acid residue sequence, RF(Y) amide, a sequence distinct from that required for melanocortin receptor binding. A recently delineated family of RFamide receptors recognizes...

  12. Metastatic melanoma imaging with an 111In-labeled lactam bridge-cyclized α-melanocyte-stimulating hormone peptide

    International Nuclear Information System (INIS)

    Introduction: The purpose of this study was to examine whether a novel lactam bridge-cyclized 111In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Gly-Glu-c[Lys-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-Asp] {DOTA-GlyGlu-CycMSH} could be an effective imaging probe for metastatic melanoma detection. Methods: 111In-DOTA-GlyGlu-CycMSH was prepared and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of 111In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of 111In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission computed tomography (SPECT)/CT (Nano-SPECT/CT) using 111In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) imaging. Results: 111In-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. 111In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. 111In-DOTA-GlyGlu-CycMSH exhibited significantly (P111In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [18F]FDG 1 h post-injection. Conclusions: 111In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting and -imaging properties, highlighting its potential as an effective imaging probe for metastatic melanoma detection.

  13. Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4.

    Science.gov (United States)

    Costin, Gertrude-E; Valencia, Julio C; Vieira, Wilfred D; Lamoreux, M Lynn; Hearing, Vincent J

    2003-08-01

    Oculocutaneous albinism (OCA) type 4 is a newly identified human autosomal recessive hypopigmentary disorder that disrupts pigmentation in the skin, hair and eyes. Three other forms of OCA have been previously characterized, each resulting from the aberrant processing and/or sorting of tyrosinase, the enzyme critical to pigment production in mammals. The disruption of tyrosinase trafficking occurs at the level of the endoplasmic reticulum (ER) in OCA1 and OCA3, but at the post-Golgi level in OCA2. The gene responsible for OCA4 is the human homologue of the mouse underwhite (uw) gene, which encodes the membrane-associated transporter protein (MATP). To characterize OCA4, we investigated the processing and sorting of melanogenic proteins in primary melanocytes derived from uw/uw mice and from wild-type mice. OCA4 melanocytes were found to be constantly secreted into the medium dark vesicles that contain tyrosinase and two other melanogenic enzymes, Tyrp1 (tyrosinase-related protein 1) and Dct (DOPAchrome tautomerase); this secretory process is not seen in wild-type melanocytes. Although tyrosinase was synthesized at comparable rates in wild-type and in uw-mutant melanocytes, tyrosinase activity in uw-mutant melanocytes was only about 20% of that found in wild-type melanocytes, and was enriched only about threefold in melanosomes compared with the ninefold enrichment in wild-type melanocytes. OCA4 melanocytes showed a marked difference from wild-type melanocytes in that tyrosinase was abnormally secreted from the cells, a process similar to that seen in OCA2 melanocytes, which results from a mutation of the pink-eyed dilution (P) gene. The P protein and MATP have 12 transmembrane regions and are predicted to function as transporters. Ultrastructural analysis shows that the vesicles secreted from OCA4 melanocytes are mostly early stage melanosomes. Taken together, our results show that in OCA4 melanocytes, tyrosinase processing and intracellular trafficking to the

  14. Transplantation of melanocytes obtained from the skin ameliorates apomorphine-induced abnormal behavior in rodent hemi-parkinsonian models.

    Directory of Open Access Journals (Sweden)

    Masato Asanuma

    Full Text Available Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine. Marked improvement in apomorphine-induced rotation was noted at day 40 after intrastriatal melanoma cell transplantation. Transplantation of tyrosinase cDNA-transfected hepatoma cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice and the effect was present up to 2 months. Moreover, parkinsonian mice transplanted with melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior up to 3 months after the transplantation. Dopamine-positive signals were seen around the surviving transplants in these experiments. Taken together with previous studies showing dopamine synthesis and metabolism by tyrosinase, these results highlight therapeutic potential of intrastriatal autograft cell transplantation of melanocytes in patients with Parkinson's disease.

  15. Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes.

    Science.gov (United States)

    Cheng, Tsing; Orlow, Seth J; Manga, Prashiela

    2013-11-01

    Accumulation of proteins in the endoplasmic reticulum (ER) typically induces stress and initiates the unfolded protein response (UPR) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR activation can increase resistance to subsequent acute ER stress. We therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2 (Oca2)-null melanocytes where UPR signaling is arrested despite continued tyrosinase accumulation leading to resistance to the chemical ER stressor thapsigargin. Although thapsigargin triggers UPR activation, instead of Perk-mediated phosphorylation of eIF2α, in Oca2-null melanocytes, eIF2α was rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the Gadd34-PP1α phosphatase complex. Gadd34-complex inhibition blocked eIF2α dephosphorylation and significantly increased Oca2-null melanocyte sensitivity to thapsigargin. Thus, Oca2-null melanocytes adapt to acute ER stress by disruption of pro-apoptotic Perk signaling, which promotes cell survival. This is the first study to demonstrate rapid eIF2α dephosphorylation as an adaptive mechanism to ER stress. PMID:23962237

  16. Polycaprolactone fiber meshes provide a 3D environment suitable for cultivation and differentiation of melanocytes from the outer root sheath of hair follicle.

    Science.gov (United States)

    Savkovic, Vuk; Flämig, Franziska; Schneider, Marie; Sülflow, Katharina; Loth, Tina; Lohrenz, Andrea; Hacker, Michael Christian; Schulz-Siegmund, Michaela; Simon, Jan-Christoph

    2016-01-01

    Melanocytes differentiated from the stem cells of human hair follicle outer root sheath (ORS) have the potential for developing non-invasive treatments for skin disorders out of a minimal sample: of hair root. With a robust procedure for melanocyte cultivation from the ORS of human hair follicle at hand, this study focused on the identification of a suitable biocompatible, biodegradable carrier as the next step toward their clinical implementation. Polycaprolactone (PCL) is a known biocompatible material used for a number of medical devices. In this study, we have populated electrospun PCL fiber meshes with normal human epidermal melanocytes (NHEM) as well as with hair-follicle-derived human melanocytes from the outer root sheath (HUMORS) and tested their functionality in vitro. PCL fiber meshes evidently provided a niche for melanocytes and supported their melanotic properties. The cells were tested for gene expression of PAX3, PMEL, TYR and MITF, as well as for proliferation, expression of melanocyte marker proteins tyrosinase and glycoprotein 100 (gp100), L-DOPA-tautomerase enzymatic activity and melanin content. Reduced mitochondrial activity and PAX-3 gene expression indicated that the three-dimensional PCL scaffold supported differentiation rather than proliferation of melanocytes. The monitored melanotic features of both the NHEM and HUMORS cultivated on PCL scaffolds significantly exceeded those of two-dimensional adherent cultures. PMID:26126647

  17. Selective cytotoxicity of 4-S-cysteaminylphenol on follicular melanocytes of the black mouse: rational basis for its application to melanoma chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Y.; Jimbow, K.

    1987-06-15

    We have previously shown that 4-S-cysteaminylphenol (4-S-CAP) causes a significant inhibition of in vivo melanoma growth. To clarify the mechanism of the in vivo antimelanoma effect, this study evaluated the cellular and subcellular changes of follicular melanocytes after s.c. administration of 4-S-CAP on the lumbar areas of black and albino mice. 4-S-CAP produced a prompt, selective swelling and lysis of melanocytes, resulting eventually in the necrosis of melanocytes and the depigmentation of black hair follicles. None of the degenerative changes were seen in melanocytes and keratinocytes of control albino follicles. Comparison of melanocytes in black and albino follicles revealed that melanin synthesis is highly active in the melanocytes of black follicles while melanin and tyrosinase synthesis is not seen in the melanocytes of albino follicles. The findings indicate that the selective melanocytotoxicity of 4-S-CAP is manifested by lysis and necrosis of cells which are actively engaged in melanin synthesis. 4-S-CAP appears to provide a new modality for rational chemotherapy of malignant melanoma.

  18. Differentiating intratumoral melanocytes from Langerhans cells in nonmelanocytic pigmented skin tumors in vivo by label-free third-harmonic generation microscopy

    Science.gov (United States)

    Weng, Wei-Hung; Liao, Yi-Hua; Tsai, Ming-Rung; Wei, Ming-Liang; Huang, Hsin-Yi; Sun, Chi-Kuang

    2016-07-01

    Morphology and distribution of melanocytes are critical imaging information for the diagnosis of melanocytic lesions. However, how to image intratumoral melanocytes noninvasively in pigmented skin tumors is seldom investigated. Third-harmonic generation (THG) is shown to be enhanced by melanin, whereas high accuracy has been demonstrated using THG microscopy for in vivo differential diagnosis of nonmelanocytic pigmented skin tumors. It is thus desirable to investigate if label-free THG microscopy was capable to in vivo identify intratumoral melanocytes. In this study, histopathological correlations of label-free THG images with the immunohistochemical images stained with human melanoma black (HMB)-45 and cluster of differentiation 1a (CD1a) were made. The correlation results indicated that the intratumoral THG-bright dendritic-cell-like signals were endogenously derived from melanocytes rather than Langerhans cells (LCs). The consistency between THG-bright dendritic-cell-like signals and HMB-45 melanocyte staining showed a kappa coefficient of 0.807, 84.6% sensitivity, and 95% specificity. In contrast, a kappa coefficient of -0.37, 21.7% sensitivity, and 30% specificity were noted between the THG-bright dendritic-cell-like signals and CD1a staining for LCs. Our study indicates the capability of noninvasive label-free THG microscopy to differentiate intratumoral melanocytes from LCs, which is not feasible in previous in vivo label-free clinical-imaging modalities.

  19. CASH algorithm versus 3-point checklist and its modified version in evaluation of melanocytic pigmented skin lesions: The 4-point checklist.

    Science.gov (United States)

    di Meo, Nicola; Stinco, Giuseppe; Bonin, Serena; Gatti, Alessandro; Trevisini, Sara; Damiani, Giovanni; Vichi, Silvia; Trevisan, Giusto

    2016-06-01

    Dermoscopy, in expert hands, increases accuracy, sensitivity and specificity in diagnosis of pigmented skin lesions of a single operator, compared with clinical examination. Simplified algorithmic methods have been developed to help less expert dermoscopists in diagnosis of melanocytic lesions. This study included 125 melanocytic skin lesions divided into melanocytic nevi, dysplastic nevi and thin melanomas (<1 mm). We compared the 3-point checklist and CASH algorithm to analyze different pigmented skin lesions. Based on preliminary results, we proposed a new modified algorithm, called the 4-point checklist, whose accuracy is similar to the CASH algorithm and whose simplicity is similar to the 3-point checklist. PMID:26589251

  20. Supplementing alpha-tocopherol (vitamin E and vitamin D3 in high fat diet decrease IL-6 production in murine epididymal adipose tissue and 3T3-L1 adipocytes following LPS stimulation

    Directory of Open Access Journals (Sweden)

    Oller do Nascimento Claudia

    2011-02-01

    Full Text Available Abstract Background It is well known that high fat diets (HFDs induce obesity and an increase in proinflammatory adipokines. Interleukin-6 (IL-6 is considered the major inflammatory mediator in obesity. Obesity is associated with a vitamin deficiency, especially of vitamins E and D3. We examined the effects of vitamin D3 and vitamin E supplementation on levels of IL-6 and IL-10 (as a marker of anti-inflammatory cytokines since, a balance between pro- and anti-inflammatory cytokines is maintained protein expression in adipose tissue of mice provided with an HFD. Additionally, we measured the effects of vitamin E and vitamin D3 treatment on LPS-stimulated 3T3-L1 adipocytes IL-6 and IL-10 secretion. Results IL-6 protein levels and the IL-6/IL-10 ratio were decreased in epididymal white adipose tissue in groups receiving vitamins E and D3 supplementation compared to the HFD group. A 24-hour treatment of vitamin D3 and vitamin E significantly reduced the IL-6 levels in the adipocytes culture medium without affecting IL-10 levels. Conclusions Vitamin D3 and vitamin E supplementation in an HFD had an anti-inflammatory effect by decreasing IL-6 production in epididymal adipose tissue in mice and in 3T3-L1 adipocytes stimulated with LPS. Our results suggest that vitamin E and D3 supplementation can be used as an adjunctive therapy to reduce the proinflammatory cytokines present in obese patients.

  1. Comparative action spectrum for ultraviolet light killing of mouse melanocytes from different genetic coat color backgrounds

    International Nuclear Information System (INIS)

    The photobiology of mouse melanocyte lines with different pigment genotypes was studied by measuring colony-forming ability after irradiation. The cell lines were wild-type black (melan-a) and the mutants brown (melan-b) and albino (melan-c). Four lamps emitting various UV wavelengths were used. These were germicidal (UVC, 200-280 nm), 82.3% output at 254 nm, TL01 (UVB, 280-320 nm), 64.2% at 310-311 nm, FS20, broadband with peak output at 312 nm and Alisun-S (UVA, 320-400 nm), broadband with peak output at 350-354 nm. Appropriate filtration reduced the contaminating UVC to nonlethal levels for the longer waverange lamps. It is clear from these studies that, in pigment cells, monochromatic results cannot predict polychromatic responses and that cell death from solar irradiations is a complex phenomenon that depends on more than DNA damage. (author)

  2. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism

    DEFF Research Database (Denmark)

    Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet;

    2013-01-01

    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family......, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional...... individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in...

  3. Anti-melanogenic effects of black, green, and white tea extracts on immortalized melanocytes.

    Science.gov (United States)

    Kim, Young Chul; Choi, So Young; Park, Eun Ye

    2015-01-01

    Tea contains polyphenols and is one of the most popular beverages consumed worldwide. Because most tyrosinase inhibitors that regulate melanogenesis are phenol/catechol derivatives, this study investigated the inhibitory effects of Camellia sinensis water extracts (CSWEs), including black tea, green tea, and white tea extracts, on melanogenesis using immortalized melanocytes. CSWEs inhibited melanin accumulation and melanin synthesis along with tyrosinase activity in a concentration-dependent manner. These inhibitory effects were superior to those of arbutin, a well-known depigmenting agent. The anti-melanogenic activity of black (fermented) tea was higher than that of a predominant tea catecholamine, epigallocatechin gallate. CSWEs, especially black tea extract, decreased tyrosinase protein levels in a concentration-dependent manner. These results suggest that the anti-melanogenic effect of CSWEs is mediated by a decrease in both tyrosinase activity and protein expression, and may be augmented by fermentation. Thus, CSWEs could be useful skin-whitening agents in the cosmetic industry. PMID:25643794

  4. FBH1 protects melanocytes from transformation and is deregulated in melanomas.

    Science.gov (United States)

    Jeong, Yeon-Tae; Cermak, Lukas; Guijarro, Maria V; Hernando, Eva; Pagano, Michele

    2013-04-01

    FBH1 is a member of the UvrD family of DNA helicases and plays a crucial role in the response to DNA replication stress. In particular, upon DNA replication stress, FBH1 promotes double-strand breakage and activation of the DNA-PK and ATM signaling cascades in a helicase-dependent manner. In the present manuscript, we show that FBH1 is often deleted or mutated in melanoma cells, which results in their increased survival in response to replicative stress. Accordingly, FBH1 depletion promotes UV-mediated transformation of human melanocytes. Thus, FBH1 inactivation appears to contribute to oncogenic transformation by allowing survival of cells undergoing replicative stress due to external factors such as UV irradiation. PMID:23466708

  5. Effects of low dose tritium on differentiation of melanocytes of hair follicles in mice

    International Nuclear Information System (INIS)

    Tritium water was injected to pregnant C57BL mice intraperitoneally with the accumulated absorbed dose of 0.2 Gy, 0.4 Gy and 0.6 Gy at 7, 12 and 16 days of embryonic development. The effects were examined by scoring changes in frequencies of the abnormal melanocytes in the hair follicles from dorsal skin of F1 offspring 3.5 days after birth by means of light microscope. The results demonstrate that the frequencies of abnormal hair follicles increased linearly with increasing absorbed dose of animals with the same time of administration. The highest frequencies were found in the mice receiving tritium at earlier stage of gestation, and the frequencies decreased as fetal development advanced

  6. The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma

    International Nuclear Information System (INIS)

    Recent evidence demonstrates that 14-3-3σ acts as a tumor suppressor gene inactivated by methylation of its 5' CpG islands in epithelial tumor cells, while remaining un-methylated in normal human epithelia. The methylation analysis of 14-3-3σ has been largely overlooked in melanoma. The methylation status of 14-3-3σ CpG island in melanocytes and melanoma cells was analyzed by methylation-specific sequencing (MSS) and quantitative methylation-specific PCR (Q-MSP). 14-3-3σ mRNA and protein expression in cell lines was detected by real-time RT-PCR and western blot. Melanoma cells were also treated by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, and/or histone deacetylase inhibitor, Trichostatin A (TSA), to evaluate their effects on 14-3-3σ gene expression. 14-3-3σ is hypermethylated in both human melanocytes and most melanoma cells in a lineage-specific manner, resulting in the silencing of 14-3-3σ gene expression and the active induction of 14-3-3σ mRNA and protein expression following treatment with DAC. We also observed a synergistic effect upon gene expression when DAC was combined with TSA. The promoter methylation status of 14-3-3σ was analyzed utilizing Q-MSP in 20 melanoma tissue samples and 10 cell lines derived from these samples, showing that the majority of melanoma samples maintain their hypermethylation status of the 14-3-3σ gene. 14-3-3σ is hypermethylated in human melanoma in a cell-linage specific manner. Spontaneous demethylation and re-expression of 14-3-3σ is a rare event in melanoma, indicating 14-3-3σ might have a tentative role in the pathogenesis of melanoma

  7. Comparative effect of recombinant IL-1, -2, -3, -4, and -6, IFN-gamma, granulocyte-macrophage-colony-stimulating factor, tumor necrosis factor-alpha, and histamine-releasing factors on the secretion of histamine from basophils

    International Nuclear Information System (INIS)

    Most cytokines possess multiple biologic activities. This study was undertaken to investigate the effect of rIL-1 beta, -2, -3, -4 and -6, IFN-gamma, TNF-alpha, and granulocyte-macrophage (GM)-CSF on basophils from 16 donors and the amount of histamine released was compared with that by partially purified mononuclear cell-derived histamine-releasing factor (HRF) and anti-IgE. We found that only IL-3 and GM-CSF at relatively high doses (50 to 500 ng/ml) released small amounts of histamine (3 to 14%) from two allergic donors. In contrast, both HRF and anti-IgE released significant amounts of histamine from all donors. Other cytokines did not release any measurable quantity of histamine. Simultaneous addition of several cytokines to the basophils also failed to release histamine. IL-3, GM-CSF, and IL-1 can also release histamine at lower concentrations (less than 5 ng/ml) when incubated with basophils in the presence of D2O. Basophils from 6 out of 13 allergic donors released histamine in response to IL-3, whereas three donors responded to IL-1 beta and two responded to GM-CSF. The results of this study demonstrated that although IL-3 and GM-CSF release small amounts of histamine only from a select group of allergic patients, mononuclear cell-derived HRF is more potent in their action and release histamine from normals as well as allergic patients

  8. Ab initio alpha-alpha scattering.

    Science.gov (United States)

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-12-01

    Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei--nuclei with even and equal numbers of protons and neutrons--is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the 'adiabatic projection method' to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  9. Ab initio alpha-alpha scattering

    Science.gov (United States)

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A.; Luu, Thomas; Meißner, Ulf-G.

    2015-12-01

    Processes such as the scattering of alpha particles (4He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei—nuclei with even and equal numbers of protons and neutrons—is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the ‘adiabatic projection method’ to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  10. Secreted Frizzled-Related Protein 2 (sFRP2) Functions as a Melanogenic Stimulator; the Role of sFRP2 in UV-Induced Hyperpigmentary Disorders.

    Science.gov (United States)

    Kim, Misun; Han, Jae Ho; Kim, Jang-Hee; Park, Tae Jun; Kang, Hee Young

    2016-01-01

    In this study, we found that secreted frizzled-related protein 2 (sFRP2) is overexpressed in the hyperpigmentary skin of melasma and solar lentigo and in acutely UV-irradiated skin. To investigate the effect of sFRP2 on melanogenesis, normal human melanocytes were infected with sFRP2-lentivirus or sh-sFRP2. It was found that sFRP2 stimulates melanogenesis through microphthalmia-associated transcription factor and/or tyrosinase upregulation via β-catenin signaling. The stimulatory action of sFRP2 in pigmentation was further confirmed in melanocytes cocultured with fibroblasts and in ex vivo cultured skin. The findings suggest that sFRP2 functions as a melanogenic stimulator and that it plays a role in the development of UV-induced hyperpigmentary disorders. PMID:26763443

  11. In vitro anti-inflammatory activities of new steroidal antedrugs: [16alpha,17alpha-d] Isoxazoline and [16alpha,17alpha-d]-3'-hydroxy-iminoformyl isoxazoline derivatives of prednisolone and 9alpha-fluoroprednisolone.

    Science.gov (United States)

    Park, Kwan-K; Ko, Dong-H; You, Z; Khan, M Omar F; Lee, Henry J

    2006-03-01

    A series of new anti-inflammatory steroidal antedrugs with C-16,17-isoxazoline ring system were synthesized and their pharmacological activities were evaluated. We reported earlier that these compounds are promising antedrugs based on the results of 5-day rat croton oil ear edema assay. In the present study, most of these compounds showed high binding affinities to the glucocorticoid receptor of liver cytosol. 21-acetyloxy-9alpha-fluoro-11beta-hydroxy-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d] isoxazoline (FP-ISO-21AC) and 11beta,21-dihydroxy-9alpha-fluoro-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d] isoxazoline (FP-ISO-21OH) were found 5.0-, 5.3-fold more potent than prednisolone, respectively. Inhibitory effects of the antedrugs on the nitric oxide (NO) production were assessed using LPS-stimulated RAW 264.7 murine macrophage cells. All these steroidal antedrugs exhibited concentration-dependent inhibition of NO production, but their relative potencies were lower than prednisolone. In vitro metabolism study in rat plasma showed that FP-ISO-21AC and 21-acetyloxy-9alpha-fluoro-11beta-hydroxy-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d]-3'-hydroxyiminoformyl isoxazoline (FP-OXIM-21AC) were hydrolyzed rapidly, with the half-lives of 2.1 and 4.2 min, respectively. The half-lives of FP-ISO-21OH and 11beta,21-dihydroxy-9alpha-fluoro-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d]-3'-hydroxyiminoformyl isoxazoline (FP-OXIM-21OH) were 92.2 and 110.2 min, respectively. PMID:16309722

  12. Faddeev calculation of 3 alpha and alpha alpha Lambda systems using alpha alpha resonating-group method kernel

    CERN Document Server

    Fujiwara, Y; Kohno, M; Suzuki, Y; Baye, D; Sparenberg, J M

    2004-01-01

    We carry out Faddeev calculations of three-alpha (3 alpha) and two-alpha plus Lambda (alpha alpha Lambda) systems, using two-cluster resonating-group method kernels. The input includes an effective two-nucleon force for the alpha alpha resonating-group method and a new effective Lambda N force for the Lambda alpha interaction. The latter force is a simple two-range Gaussian potential for each spin-singlet and triplet state, generated from the phase-shift behavior of the quark-model hyperon-nucleon interaction, fss2, by using an inversion method based on supersymmetric quantum mechanics. Owing to the exact treatment of the Pauli-forbidden states between the clusters, the present three-cluster Faddeev formalism can describe the mutually related, alpha alpha, 3 alpha and alpha alpha Lambda systems, in terms of a unique set of the baryon-baryon interactions. For the three-range Minnesota force which describes the alpha alpha phase shifts quite accurately, the ground-state and excitation energies of 9Be Lambda are...

  13. Effects of low-dose heavy ions on embryonic development in mice and on melanocyte differentiation in the epidermis and hair bulb

    International Nuclear Information System (INIS)

    The effects of prenatal low-dose irradiation with heavy ions on embryonic development in mice and on melanocyte differentiation are not well understood. We performed whole-body irradiation of pregnant C57BL/10J mice at embryonic Day 9 (E9) with a single dose of γ-rays, silicon, argon or iron ions. The number of living embryos and embryonic body weight at E18 decreased after exposure to heavy ions at high doses. Malformations such as small eyes and limb anomalies were observed in heavy-ion-treated embryos, but not in γ-ray-treated embryos. The frequency of abnormally curved tails was increased by exposure to γ-rays and argon and iron ions even at a dose of 0.1 Gy (P<0.05). In contrast, a dose-dependent decrease in the number of epidermal melanoblasts/melanocytes and hair bulb melanocytes was observed after 0.1 Gy irradiation with γ-rays or heavy ions (P<0.01). The decrease in the number of dorsal hair bulb melanocytes, dorsal and ventral epidermal melanoblasts/melanocytes and ventral hair bulb melanocytes was not necessarily correlated with the linear energy transfer of the radiation tested. Moreover, the effects of heavy ions were larger on the ventral skin than on the dorsal skin, indicating that the sensitivity of melanocytes to heavy ions differs between the dorsal and ventral skin. Taken together, these results suggest that the effects of the low-dose heavy ions differ between cell types and tissues, and the effects on the prenatal development of mice and melanocyte development are not necessarily greater than those of γ-rays. (author)

  14. Malarial pigment haemozoin, IFN-gamma, TNF-alpha, IL-1beta and LPS do not stimulate expression of inducible nitric oxide synthase and production of nitric oxide in immuno-purified human monocytes

    Directory of Open Access Journals (Sweden)

    Ceretto Monica

    2007-06-01

    Full Text Available Abstract Background Enhanced production of nitric oxide (NO following upmodulation of the inducible isoform of NO synthase (iNOS by haemozoin (HZ, inflammatory cytokines and LPS may provide protection against Plasmodium falciparum malaria by killing hepatic and blood forms of parasites and inhibiting the cytoadherence of parasitized erythrocytes (RBC to endothelial cells. Monocytes and macrophages are considered to contribute importantly to protective upregulation of iNOS and production of NO. Data obtained with murine phagocytes fed with human HZ and synthetic HZ (sHZ indicate that supplemental treatment of those cells with IFN-gamma elicited significant increases in protein and mRNA expression of iNOS and NO production, providing a potential mechanism linking HZ phagocytosis and increased production of NO. Purpose of this study was to analyse the effect of P. falciparum HZ and sHZ supplemental to treatment with IFN-gamma and/or a stimulatory cytokine-LPS mix on iNOS protein and mRNA expression in immuno-purified human monocytes. Methods Adherent immunopurified human monocytes (purity >85%, and murine phagocytic cell lines RAW 264.7, N11 and ANA1 were fed or not with P. falciparum HZ or sHZ and treated or not with IFN-gamma or a stimulatory cytokine-LPS mix. Production of NO was quantified in supernatants, iNOS protein and mRNA expression were measured after immunoprecipitation and Western blotting and quantitative RT-PCT, respectively. Results Phagocytosis of HZ/sHZ by human monocytes did not increase iNOS protein and mRNA expression and NO production either after stimulation by IFN-gamma or the cytokine-LPS mix. By contrast, in HZ/sHZ-laden murine macrophages, identical treatment with IFN-gamma and the cytokine-LPS mix elicited significant increases in protein and mRNA expression of iNOS and NOS metabolites production, in agreement with literature data. Conclusion Results indicate that human monocytes fed or not with HZ/sHZ were constantly

  15. Phorbol esters promote alpha 1-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism.

    OpenAIRE

    Leeb-Lundberg, L M; Cotecchia, S; Lomasney, J W; DeBernardis, J F; Lefkowitz, R J; Caron, M G

    1985-01-01

    DDT1 MF-2 cells, which are derived from hamster vas deferens smooth muscle, contain alpha 1-adrenergic receptors (54,800 +/- 2700 sites per cell) that are coupled to stimulation of inositol phospholipid metabolism. Incubation of these cells with tumor-promoting phorbol esters, which stimulate calcium- and phospholipid-dependent protein kinase, leads to a marked attenuation of the ability of alpha 1-receptor agonists such as norepinephrine to stimulate the turnover of inositol phospholipids. T...

  16. Neurofibroma and lipoma in association with giant congenital melanocytic nevus coexisting in one nodule: a case report.

    Science.gov (United States)

    Shang, Zhiwei; Dai, Tao; Ren, Yongqiang

    2015-01-01

    Giant congenital melanocytic nevi (GCMN) are rare conditions that defined as melanocytic lesion recognized at birth, which will reach a diameter larger than 20 cm, and they occur in about 1 per 500,000 newborns. Despite its rarity, they may associate with severe abnormalities like spina bifida occulta, meningocele, club foot and hypertrophy or atrophy of deeper structures of a limb, Carney complex, premature aging syndromes, neurofibroma, vitiligo, lipoma and dysplasia of bilateral hip impact on the patient. In this case, we report a 3-years-old male child presenting a GCMN with large, blackish, and thick nevus covering over the entire neck, back, and lower to the waist level. We highlight the importance of proper histopathological examination of the biopsy taken from the single huge nodule which revealed features of both neurofibroma and lipoma coexisting. The objective of this paper is to report a rare case with the clinical and pathologic findings. PMID:26379904

  17. Melanoma inhibitor of apoptosis protein is expressed differentially in melanoma and melanocytic naevus, but similarly in primary and metastatic melanomas

    OpenAIRE

    Gong, J; Chen, N; Zhou, Q; Yang, B.; Wang, Y; Wang, X.

    2005-01-01

    Background: Malignant melanoma is highly resistant to current treatments. The inhibitor of apoptosis protein (IAP) family member, melanoma IAP (ML-IAP), is overexpressed in some melanoma cell lines, rendering them resistant to apoptotic signals. Targeting ML-IAP is a promising approach to treating melanoma. However, the status of ML-IAP expression in human melanoma tissues and the difference in expression between melanoma and melanocytic naevus are not known.

  18. Human Breast Cancer Cell Lines Co-Express Neuronal, Epithelial, and Melanocytic Differentiation Markers In Vitro and In Vivo

    OpenAIRE

    Qingbei Zhang; Hanli Fan; Jikun Shen; Hoffman, Robert M.; H Rosie Xing

    2010-01-01

    Differentiation programs are aberrant in cancer cells allowing them to express differentiation markers in addition to their tissue of origin. In the present study, we demonstrate the multi-lineage differentiation potential of breast cancer cell lines to express multiple neuronal/glial lineage-specific markers as well as mammary epithelial and melanocytic-specific markers. Multilineage expression was detected in luminal (MCF-7 and SKBR3) and basal (MDA-MB-231) types of human breast cancer cell...

  19. Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes

    OpenAIRE

    Cheng, Tsing; Orlow, Seth J.; Manga, Prashiela

    2013-01-01

    Accumulation of proteins in the endoplasmic reticulum (ER) typically induces stress and initiates the unfolded protein response (UPR) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR activation can increase resistance to subsequent acute ER stress. We therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2 (Oca2)-null melanocytes where UPR signaling is arrested despite continued tyrosinase accumulation leadin...

  20. Differential inhibition of lipopolysaccharide-induced phenomena by anti-tumor necrosis factor alpha antibody.

    OpenAIRE

    Vogel, S N; Havell, E A

    1990-01-01

    Tumor necrosis factor alpha (TNF alpha) has been implicated as a major mediator of lipopolysaccharide (LPS)-induced phenomena. Administration to mice of a polyclonal, monospecific antibody prepared against recombinant murine TNF alpha abolished detection of LPS-induced TNF alpha activity and significantly reduced levels of LPS-induced colony-stimulating factor but failed to reduce the production of LPS-induced interferon, corticosterone, or LPS-induced hypoglycemia.

  1. Review of alpha_s determinations

    CERN Document Server

    Pich, Antonio

    2013-01-01

    The present knowledge on the strong coupling is briefly summarized. The most precise determinations of alpha_s, at different energies, are reviewed and compared at the Z mass scale, using the predicted QCD running. The impressive agreement achieved between experimental measurements and theoretical predictions constitutes a beautiful and very significant test of Asymptotic Freedom, establishing QCD as the fundamental theory of the strong interaction. The world average value of the strong coupling is found to be alpha_s(M_Z^2)= 0.1186 \\pm 0.0007.

  2. Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Amrita [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Katdare, Meena, E-mail: mkatdare@gmail.com [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507 (United States)

    2015-08-14

    Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

  3. Pyrimidine dimer induction and repair in cultured human skin keratinocytes or melanocytes after irradiation with monochromatic ultraviolet radiation

    International Nuclear Information System (INIS)

    We compared the susceptibilities of cultured melanocytes and keratinocytes to dimer induction in DNA by monochromatic ultraviolet (UV) radiation. Keratinocytes as well as melanocytes were derived from human foreskin, grown as a monolayer in petri dishes, covered with phosphate-buffered saline containing 0.1% glucose, and irradiated. UV irradiation was carried out at 254, 297, and 302 nm as well as with a light source emitting predominantly 312 nm. The induction of pyrmidine dimers was assessed by determination of the number of T4 endonuclease V-sensitive sites (ESS). We found a slightly higher response for dimer induction in melanocytes at 254, 297, and 302 nm; this difference was only significant at the 297-nm wavelength. Action spectra for pyrimidine dimer induction were derived from the exposure-response data obtained. The action spectra mimic to a large degree the action spectra for dimer induction in other cultured mammalian cells. The repair rate during a post-irradiation period lasting up to 24 h was substantially the same for the two cell types. The percentage of T4 endonuclease V-sensitive sites (ESS) remaining 9 and 24 h after irradiation was 45% and 30%, respectively

  4. Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

    International Nuclear Information System (INIS)

    Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics

  5. Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as "OCA3".

    OpenAIRE

    Boissy, R. E.; Zhao, H.; Oetting, W S; Austin, L. M.; Wildenberg, S C; Boissy, Y. L.; Zhao, Y.; Sturm, R. A.; Hearing, V J; King, R A; Nordlund, J. J.

    1996-01-01

    Most types of human oculocutaneous albinism (OCA) result from mutations in the gene for tyrosinase (OCA1) or the P protein (OCA2), although other types of OCA have been described but have not been mapped to specific loci. Melanocytes were cultured from an African-American with OCA, who exhibited the phenotype of Brown OCA, and his normal fraternal twin. Melanocytes cultured from the patient with OCA and the normal twin appeared brown versus black, respectively. Melanocytes from both the patie...

  6. Benzophenone-1 stimulated the growth of BG-1 ovarian cancer cells by cell cycle regulation via an estrogen receptor alpha-mediated signaling pathway in cellular and xenograft mouse models

    International Nuclear Information System (INIS)

    results suggest that BP-1 is an endocrine disrupting chemical (EDC) that exerts xenoestrogenic effects by stimulating the proliferation of BG-1 ovarian cancer via ER signaling pathway associated with cell cycle as did E2

  7. IGFBP-3, hypoxia and TNF-{alpha} inhibit adiponectin transcription

    Energy Technology Data Exchange (ETDEWEB)

    Zappala, Giovanna, E-mail: zappalag@mail.nih.gov [Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States); Rechler, Matthew M. [Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States); Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States)

    2009-05-15

    The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-{gamma}, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin. It activates PPAR-{gamma}-RXR-{alpha} heterodimers bound to PPAR-{gamma} response elements in the adiponectin promoter. Rosiglitazone-stimulated adiponectin protein synthesis in 3T3-L1 mouse adipocytes has been shown to be inhibited by IGFBP-3, which can be induced by hypoxia and the proinflammatory cytokine, TNF-{alpha}, two inhibitors of adiponectin transcription. The present study demonstrates that IGFBP-3, the hypoxia-mimetic agent cobalt chloride, and TNF-{alpha} inhibit rosiglitazone-induced adiponectin transcription in mouse embryo fibroblasts that stably express PPAR-{gamma}2. Native IGFBP-3 can bind RXR-{alpha} and inhibited rosiglitazone stimulated promoter activity, whereas an IGFBP-3 mutant that does not bind RXR-{alpha} did not. These results suggest that IGFBP-3 may mediate the inhibition of adiponectin transcription by hypoxia and TNF-{alpha}, and that IGFBP-3 binding to RXR-{alpha} may be required for the observed inhibition.

  8. Review of alpha_s determinations

    OpenAIRE

    Pich, Antonio

    2013-01-01

    The present knowledge on the strong coupling is briefly summarized. The most precise determinations of alpha_s, at different energies, are reviewed and compared at the Z mass scale, using the predicted QCD running. The impressive agreement achieved between experimental measurements and theoretical predictions constitutes a beautiful and very significant test of Asymptotic Freedom, establishing QCD as the fundamental theory of the strong interaction. The world average value of the strong coupl...

  9. World Summary of $\\alpha_s$ (2015)

    CERN Document Server

    Bethke, Siegfried; Salam, Gavin P

    2015-01-01

    This is a preliminary update of the measurements of α s and the determination of the world average value of α s (M Z 2 ) presented in the 2013/2014 edition of the Review of Particle Properties [1]. A number of studies which became available since late 2013 provide new results for each of the (previously 5, now) 6 subclasses of measurements for which pre-average values of $\\alpha_s (M_Z^2)$ are determined.

  10. Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

  11. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  12. The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes.

    Science.gov (United States)

    Silver, Debra L; Leeds, Karen E; Hwang, Hun-Way; Miller, Emily E; Pavan, William J

    2013-03-15

    Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waardenburg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haploinsufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis. Strikingly, while Magoh haploinsufficiency severely reduces epidermal melanoblasts, it does not significantly affect the number of dermal melanoblasts. These data indicate Magoh impacts melanoblast development by disproportionately affecting expansion of epidermal melanoblast populations. We probed the cellular basis for melanoblast reduction and discovered that Magoh mutant melanoblasts do not undergo increased apoptosis, but instead are arrested in mitosis. Mitotic arrest is evident in both Magoh haploinsufficient embryos and in Magoh siRNA treated melanoma cell lines. Together our findings indicate that Magoh-regulated proliferation of melanoblasts in the dermis may be critical for production of epidermally-bound melanoblasts. Our results point to a central role for Magoh in melanocyte development. PMID:23333945

  13. Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF.

    Science.gov (United States)

    Pogenberg, Vivian; Ogmundsdóttir, Margrét H; Bergsteinsdóttir, Kristín; Schepsky, Alexander; Phung, Bengt; Deineko, Viktor; Milewski, Morlin; Steingrímsson, Eiríkur; Wilmanns, Matthias

    2012-12-01

    Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte development and an important oncogene in melanoma. MITF heterodimeric assembly with related basic helix-loop-helix leucine zipper transcription factors is highly restricted, and its binding profile to cognate DNA sequences is distinct. Here, we determined the crystal structure of MITF in its apo conformation and in the presence of two related DNA response elements, the E-box and M-box. In addition, we investigated mouse and human Mitf mutations to dissect the functional significance of structural features. Owing to an unusual three-residue shift in the leucine zipper register, the MITF homodimer shows a marked kink in one of the two zipper helices to allow an out-of-register assembly. Removal of this insertion relieves restricted heterodimerization by MITF and permits assembly with the transcription factor MAX. Binding of MITF to the M-box motif is mediated by an unusual nonpolar interaction by Ile212, a residue that is mutated in mice and humans with Waardenburg syndrome. As several related transcription factors have low affinity for the M-box sequence, our analysis unravels how these proteins discriminate between similar target sequences. Our data provide a rational basis for targeting MITF in the treatment of important hereditary diseases and cancer. PMID:23207919

  14. Suppression of autophagy dysregulates the antioxidant response and causes premature senescence of melanocytes.

    Science.gov (United States)

    Zhang, Cheng-Feng; Gruber, Florian; Ni, Chunya; Mildner, Michael; Koenig, Ulrich; Karner, Susanne; Barresi, Caterina; Rossiter, Heidemarie; Narzt, Marie-Sophie; Nagelreiter, Ionela M; Larue, Lionel; Tobin, Desmond J; Eckhart, Leopold; Tschachler, Erwin

    2015-05-01

    Autophagy is the central cellular mechanism for delivering organelles and cytoplasm to lysosomes for degradation and recycling of their molecular components. To determine the contribution of autophagy to melanocyte (MC) biology, we inactivated the essential autophagy gene Atg7 specifically in MCs using the Cre-loxP system. This gene deletion efficiently suppressed a key step in autophagy, lipidation of microtubule-associated protein 1 light chain 3 beta (LC3), in MCs and induced slight hypopigmentation of the epidermis in mice. The melanin content of hair was decreased by 10-15% in mice with autophagy-deficient MC as compared with control animals. When cultured in vitro, MCs from mutant and control mice produced equal amounts of melanin per cell. However, Atg7-deficient MCs entered into premature growth arrest and accumulated reactive oxygen species (ROS) damage, ubiquitinated proteins, and the multi-functional adapter protein SQSTM1/p62. Moreover, nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent expression of NAD(P)H dehydrogenase, quinone 1, and glutathione S-transferase Mu 1 was increased, indicating a contribution of autophagy to redox homeostasis in MCs. In summary, the results of our study suggest that Atg7-dependent autophagy is dispensable for melanogenesis but necessary for achieving the full proliferative capacity of MCs. PMID:25290687

  15. BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma

    International Nuclear Information System (INIS)

    Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression. Uveal melanoma cells were studied following RNAi-mediated depletion of BAP1 using proliferation, BrdU incorporation, flow cytometry, migration, invasion, differentiation and clonogenic assays, as well as in vivo tumorigenicity experiments in NOD-SCID-Gamma mice. Depletion of BAP1 in uveal melanoma cells resulted in a loss of differentiation and gain of stem-like properties, including expression of stem cell markers, increased capacity for self-replication, and enhanced ability to grow in stem cell conditions. BAP1 depletion did not result in increased proliferation, migration, invasion or tumorigenicity. BAP1 appears to function in the uveal melanocyte lineage primarily as a regulator of differentiation, with cells deficient for BAP1 exhibiting stem-like qualities. It will be important to elucidate how this effect of BAP1 loss promotes metastasis and how to reverse this effect therapeutically

  16. The influence of clinical information in the histopathologic diagnosis of melanocytic skin neoplasms.

    Directory of Open Access Journals (Sweden)

    Gerardo Ferrara

    Full Text Available BACKGROUND: We tested the relevance of clinical information in the histopathologic evaluation of melanocytic skin neoplasm (MSN. METHODS: Histopathologic specimens from 99 clinically atypical MSN were circulated among ten histopathologists; each case had clinical information available in a database with a five-step procedure (no information; age/sex/location; clinical diagnosis; clinical image; dermoscopic image; each step had a histopathologic diagnosis (D1 through D5; each diagnostic step had a level of diagnostic confidence (LDC ranging from 1 (no diagnostic certainty to 5 (absolute diagnostic certainty. The comparison of the LDC was employed with an analysis of variance (ANOVA for repeated measures. FINDINGS: In D1 (no information, 36/99 cases (36.3% had unanimous diagnosis; in D5 (full information available, 51/99 cases (51.5% had unanimous diagnosis (p for difference between proportions <0.001. The observer agreement expressed as kappa increased significantly from D1 to D5. The mean LDC linearly increased for each observer from D1 through D5 (p for linear trend <0.001. On average, each histopathologist changed his initial diagnosis in 7 cases (range: 2-23. Most diagnostic changes were in D2 (age/sex/location. INTERPRETATION: The histopathologic criteria for the diagnosis of MSN can work as such, but the final histopathologic diagnosis is a clinically-aided interpretation. Clinical data sometimes reverse the initial histopathologic evaluation.

  17. Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes.

    Science.gov (United States)

    Lavezzo, Marcelo Mendes; Sakata, Viviane Mayumi; Morita, Celso; Rodriguez, Ever Ernesto Caso; Abdallah, Smairah Frutuoso; da Silva, Felipe T G; Hirata, Carlos Eduardo; Yamamoto, Joyce Hisae

    2016-01-01

    Vogt-Koyanagi-Harada disease (VKHD) is a rare granulomatous inflammatory disease that affects pigmented structures, such as eye, inner ear, meninges, skin and hair. This disease is mainly a Th1 lymphocyte mediated aggression to melanocytes after a viral trigger in the presence of HLA-DRB1*0405 allele. The absence of ocular trauma or previous intraocular surgery sets VKHD appart from sympathetic ophthalmia, its main differential diagnosis. The disease has an acute onset of bilateral blurred vision with hyperemia preceded by flu-like symptoms. The acute uveitic stage is characterized by a diffuse choroiditis with serous retinal detachment and optic disc hyperemia and edema. Fluorescein angiography in this phase demonstrates multiple early hyperfluorescent points. After the acute uveitic stage, ocular and integumentary system pigmentary changes may appear. Ocular findings may be accompanied by lymphocytic meningitis, hearing impairment and/or tinnitus in a variable proportion of patients. Prompt diagnosis followed by early, aggressive and long-term treatment with high-dose corticosteroids is most often ensued by good visual outcomes. However, some patients may experience chronic uveal inflammation with functional eye deterioration. The current review discusses the general features of VKHD, including epidemiology, classification into categories, differential diagnosis and current therapeutic approaches. PMID:27008848

  18. A distinctive melanocytic lesion associated with melanoma-prone dysplastic naevus syndrome: the hybrid naevus.

    Science.gov (United States)

    Schubert, C; Parwaresch, R; Rudolph, P

    2001-02-01

    Clinically and histologically, the concept of dysplastic nevi remains controversial. To elaborate more precise criteria for the nevi of patients with dysplastic naevus syndrome (DNS), we examined 58 nevi from seven DNS patients who developed one or several malignant melanomas. Clinical presentation and histomorphology were evaluated, and immunohistochemistry was performed using proliferation marker Ki-S5 and antibody DO-7 to the p53 protein. Sixty nevi from individuals without history of melanoma served as controls. Of the DNS nevi, 21 (36.2%) exhibited no morphological particularities. The remaining 37 nevi presented distinctive histological features consisting of a slight epidermal acanthosis, spitzoid vertically oriented nests of dyscohesive nevus cells, and single-standing atypical melanocytes in the basal cell layer of the epidermis. Immunohistochemical analysis revealed an average proliferation index of 2.5%, which significantly surpassed the mean growth fraction of conventional dysplastic nevi (DNS possess distinctive features. The newly characterized criteria may provide a basis for the diagnosis of DNS and might help to identify patients at increased risk for malignant melanoma by examination of a single biopsy. PMID:11253119

  19. Applying a Dermal Regenerative Template in Management of Congenital Melanocytic Nevi of the Hand.

    Science.gov (United States)

    Kumbla, Pallavi A; Yuen, James C; Tait, Mark A

    2015-09-01

    Congenital melanocytic nevus of the hand in the pediatric population is an uncommon diagnosis. These lesions have malignant potential and can cause psychosocial effects from cosmetic deformity. Early surgical intervention is recommended in these cases. The literature suggests that full-thickness skin grafting is to be performed in the hand to maintain functionality and avoid contracture and scarring. This creates a large donor-site defect and increased risk of graft loss due to slow revascularization from graft thickness. In addition, for large defects, the full-thickness skin graft donor site would require a split-thickness graft. However, split-thickness skin grafting is avoided in the hand due to increased scarring and contracture and decreased range of motion despite decreased donor-site morbidity and better revascularization. We describe a novel reconstructive technique that uses a dermal regenerative template (Integra) with split-thickness grafting. Having performed in 2 pediatric patients, we demonstrate that aesthetic and functional outcomes are equivalent to full-thickness grafting while creating a superficial donor site and allowing for improved revascularization from decreased graft thickness. PMID:26495228

  20. The Effects of Biological Agents on Melanocytic Nevi: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Nurşah Doğan

    2016-03-01

    Full Text Available Objective: The aim of our study was to evaluate the changes of the melanocytic nevi during the biological agent therapy. Methods: For this purpose, 40 index nevi of 25 adult patients who were treated with infliximab, adalimumab, etanercept or rituximab were included in this study. All of the patients underwent clinical and dermoscopic evaluation before the beginning of the treatment, 6 months and 1 year after the beginning of the treatment. Among dermoscopic examination methods, pattern analysis, ABCD score system and three-point checklist were performed. Results: In terms of the diameter of the index nevi, there was no statistically significant difference between the first examination and that of the sixth month, but differences was observed between the first examination and that of the twelfth month. There was also no statistically significant difference in total dermoscopy scores calculated by ABCD score system application on 31 nevi at the times of assessment. At the end of the study, we detected 24 new nevi formation in 7 patients, whom all of were over 35 years of age, however no eruptive nevi or melanoma formation were observed. Conclusion: An increase in the diameters of the present nevi and formation of new nevi may be seen with biological agent therapy in one-year-follow-up.

  1. Lyman Alpha Control

    CERN Document Server

    Nielsen, Daniel Stefaniak

    2015-01-01

    This document gives an overview of how to operate the Lyman Alpha Control application written in LabVIEW along with things to watch out for. Overview of the LabVIEW code itself as well as the physical wiring of and connections from/to the NI PCI-6229 DAQ box is also included. The Lyman Alpha Control application is the interface between the ALPHA sequencer and the HighFinesse Wavelength Meter as well as the Lyman Alpha laser setup. The application measures the wavelength of the output light from the Lyman Alpha cavity through the Wavelength Meter. The application can use the Wavelength Meter’s PID capabilities to stabilize the Lyman Alpha laser output as well as switch between up to three frequencies.

  2. New ALPHA-2 magnet

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    On 21 June, members of the ALPHA collaboration celebrated the handover of the first solenoid designed for the ALPHA-2 experiment. The magnet has since been successfully installed and is working well.   Khalid Mansoor, Sumera Yamin and Jeffrey Hangst in front of the new ALPHA-2 solenoid. “This was the first of three identical solenoids that will be installed between now and September, as the rest of the ALPHA-2 device is installed and commissioned,” explains ALPHA spokesperson Jeffrey Hangst. “These magnets are designed to allow us to transfer particles - antiprotons, electrons and positrons - between various parts of the new ALPHA-2 device by controlling the transverse size of the particle bunch that is being transferred.” Sumera Yamin and Khalid Mansoor, two Pakistani scientists from the National Centre for Physics in Islamabad, came to CERN in February specifically to design and manufacture these magnets. “We had the chance to work on act...

  3. Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells

    DEFF Research Database (Denmark)

    Nordentoft, Iver; Jeppesen, Per B; Nielsen, Anders L;

    2007-01-01

    In the present study we investigate the expression levels of cytosolic phospholipase A2 alpha (cPLA2alpha) interacting histone acetyl transferase proteins TIP60alpha and TIP60beta in non-diabetic C57BL wild-type mice and obese type 2 diabetic KKAy model mice. The aim was to test our hypothesis that...

  4. Regional Fluctuation in the Functional Consequence of LINE-1 Insertion in the Mitf Gene: The Black Spotting Phenotype Arisen from the Mitfmi-bw Mouse Lacking Melanocytes.

    Directory of Open Access Journals (Sweden)

    Kazuhisa Takeda

    Full Text Available Microphthalmia-associated transcription factor (Mitf is a key regulator for differentiation of melanoblasts, precursors to melanocytes. The mouse homozygous for the black-eyed white (Mitfmi-bw allele is characterized by the white-coat color and deafness with black eyes due to the lack of melanocytes. The Mitfmi-bw allele carries LINE-1, a retrotransposable element, which results in the Mitf deficiency. Here, we have established the black spotting mouse that was spontaneously arisen from the homozygous Mitfmi-bw mouse lacking melanocytes. The black spotting mouse shows multiple black patches on the white coat, with age-related graying. Importantly, each black patch also contains hair follicles lacking melanocytes, whereas the white-coat area completely lacks melanocytes. RT-PCR analyses of the pigmented patches confirmed that the LINE-1 insertion is retained in the Mitf gene of the black spotting mouse, thereby excluding the possibility of the somatic reversion of the Mitfmi-bw allele. The immunohistochemical analysis revealed that the staining intensity for beta-catenin was noticeably lower in hair follicles lacking melanocytes of the homozygous Mitfmi-bw mouse and the black spotting mouse, compared to the control mouse. In contrast, the staining intensity for beta-catenin and cyclin D1 was higher in keratinocytes of the black spotting mouse, compared to keratinocytes of the control mouse and the Mitfmi-bw mouse. Moreover, the keratinocyte layer appears thicker in the Mitfmi-bw mouse, with the overexpression of Ki-67, a marker for cell proliferation. We also show that the presumptive black spots are formed by embryonic day 15.5. Thus, the black spotting mouse provides the unique model to explore the molecular basis for the survival and death of developing melanoblasts and melanocyte stem cells in the epidermis. These results indicate that follicular melanocytes are responsible for maintaining the epidermal homeostasis; namely, the present study

  5. Alpha Shapes and Proteins

    DEFF Research Database (Denmark)

    Winter, Pawel; Sterner, Henrik; Sterner, Peter

    We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

  6. Targeted Alpha Therapy: From Alpha to Omega

    International Nuclear Information System (INIS)

    This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

  7. "Virtual microscopy" and the internet as telepathology consultation tools: diagnostic accuracy in evaluating melanocytic skin lesions.

    Science.gov (United States)

    Okada, D H; Binder, S W; Felten, C L; Strauss, J S; Marchevsky, A M

    1999-12-01

    The Internet offers a widely available, inexpensive tool for telepathology consultations. It allows the transfer of image and text files through electronic mail (e-mail) or file transfer protocols (FTP), using a variety of microcomputer platforms. We studied the use of the Internet and "virtual microscopy" tools for the diagnosis of 35 skin biopsies, including a variety of benign and malignant melanocytic lesions. Digitized images from these lesions were obtained at 40x and 100x optical magnification, using a high resolution digital camera (Microlumina, Leaf Systems, Southborough, MA), a light microscope with a phototube adapter and a microcomputer with a Pentium 166 MHz microprocessor. Two to four images of each case were arranged on a "canvas" to represent the majority or an entire biopsy level, using Photoshop software (Adobe Systems Inc., San Jose, CA). The images were compressed using Joint Photographers Expert Group (JPEG) format. The images were then viewed on a computer video monitor in a manner that closely resembles light microscopy, including scrolling by using the "hand tool" of Photoshop and changing magnification digitally up to 4 times without visible image degradation. The image files, ranging in size from 700 kilobytes to 2.1 megabytes (average 1.6 megabytes) were attached to e-mail messages that contained clinical information, using standard Multipurpose Internet Mail Extension (MIME) protocols and sent through the Internet, for interpretation by a dermatopathologist. The consultant could open the images from the e-mail message, using Microsoft Outlook Express (Microsoft Corp., Redmond, WA) and Photoshop software, scroll them, change magnification and render a diagnosis in a manner that closely simulates light microscopy. One hundred percent concordance was obtained between the telepathology and traditional hematoxylin and eosin slide diagnoses. The Internet and relatively inexpensive "virtual microscopy" tools offer a novel technology for

  8. Laser Erbium: YAG no tratamento de nevos melanocíticos Erbium: YAG laser in treatment of acquired melanocytic nevi

    Directory of Open Access Journals (Sweden)

    Mauricio Martins

    2008-12-01

    Full Text Available FUNDAMENTOS - Os nevos melanocíticos adquiridos são observados em grande parte da população e o resultado da sua excisão, dependendo da localização, extensão e fatores inerentes ao paciente, pode ser insatisfatório. OBJETIVO - Avaliar o uso do laser Erbium: YAG no tratamento de nevos melanocíticos adquiridos MÉTODOS - Foram selecionados nove pacientes, seis homens e três mulheres, brancos, com idade entre 20 e 60 anos e desejo de remover um nevo melanocítico composto no tronco. Metade do nevo foi tratada com laser, e a outra metade foi utilizada como controle. Após um mês da aplicação, foram avaliados a cicatrização, o resultado estético e a persistência de células névicas e melanina. RESULTADOS - Houve rápida cicatrização e ótimo resultado estético, no entanto, o exame histopatológico demonstrou a permanência de células névicas e melanina em sete e em nove das amostras examinadas, respectivamente. CONCLUSÃO - A utilização do laser Erbium:YAG, com os parâmetros utilizados neste estudo, não foi capaz de destruir completamente as células névicas melanocíticas e a melanina, não sendo, portanto, recomendada para o tratamento dessas lesões, dada a possibilidade de transformação maligna futura.BACKGROUND- Acquired melanocytic nevi are commonly found and the result of their excision may not be satisfactory depending on their location, extension and factors associated to the patient. OBJECTIVE - To evaluate the use of Erbium:YAG laser in treatment of acquired melanocytic nevi. METHOD - Nine white-skinned patients were selected, six men and three women with aged 20-60 years. All desired to remove one compound acquired melanocytic nevus on the trunk. Half of the nevi was treated with Erbium YAG laser while the remaining were used as control. One month after application, healing, aesthetic results and persistence of melanocytic cells and melanin were evaluated. RESULTS - All patients presented fast healing and

  9. HGF/SF increases number of skin melanocytes but does not alter quality or quantity of follicular melanogenesis.

    Directory of Open Access Journals (Sweden)

    Agnieszka Wolnicka-Glubisz

    Full Text Available Melanins are an important factor determining the vulnerability of mammalian skin to UV radiation and thus to UV-induced skin cancers. Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF have extra-follicular dermal melanocytes, notably in the papillary upper dermis, and are susceptible to UV-induced melanoma. Pigmented HGF/SF neonatal mice are more susceptible than albino HGF/SF animals to UVA -induced melanoma, indicating an involvement of melanin in melanoma formation. This raises the question of the effect of transgenic HGF/SF on melanization. We developed a methodology to accurately quantitate both the production of melanin and the efficiency of melanogenesis in normal, and HGF/SF transgenic mice in vivo. Skin and hair shafts of 5 day old and adult (3 week old C57BL/6-HGF/SF and corresponding C57BL/6 wild type mice were investigated by electron paramagnetic resonance spectroscopy (EPR to quantitate melanin, by transmission electron microscopy (TEM for the presence of melanosomes, and by standard histology and by Western blotting and zymography to determine the expression and activity of melanogenesis-related proteins. Eumelanin but no phaeomelanin was detected in transgenic C57BL/6-HGF and C57BL/6 wild type mice. Transgenic HGF/SF overexpression did not change the type of melanin produced in the skin or hair, did not affect the terminal content of melanin production in standard samples of hair and did not influence hair cycle/morphogenesis-related changes in skin thickness. No melanocytes were found in the epidermis and no melanosomes were found in epidermal keratinocytes. HGF/SF transgenic mice thus lack the epidermal melanin UV-protection found in constitutively dark human skin. We conclude that melanocytes in the HGF/SF transgenic mouse, particularly in the papillary dermis, are vulnerable to UVA which interacts with eumelanin but not phaeomelanin to induce melanoma.

  10. The effect of white light on normal and malignant murine melanocytes: A link between opsins, clock genes, and melanogenesis.

    Science.gov (United States)

    de Assis, L V M; Moraes, M N; da Silveira Cruz-Machado, S; Castrucci, A M L

    2016-06-01

    The skin possesses a photosensitive system comprised of opsins whose function is not fully understood, and clock genes which exert an important regulatory role in skin biology. Here, we evaluated the presence of opsins in normal (Melan-a cells) and malignant (B16-F10 cells) murine melanocytes. Both cell lines express Opn2, Opn4 - for the first time reported in these cell types - as well as S-opsin. OPN4 protein was found in a small area capping the cell nuclei of B16-F10 cells kept in constant dark (DD); twenty-four hours after the white light pulse (WLP), OPN4 was found in the cell membrane. Despite the fact that B16-F10 cells expressed less Opn2 and Opn4 than Melan-a cells, our data indicate that the malignant melanocytes exhibited increased photoresponsiveness. The clock gene machinery is also severely downregulated in B16-F10 cells as compared to Melan-a cells. Per1, Per2, and Bmal1 expression increased in B16-F10 cells in response to WLP. Although no response in clock gene expression to WLP was observed in Melan-a cells, gene correlational data suggest a minor effect of WLP. In contrast to opsins and clock genes, melanogenesis is significantly upregulated in malignant melanocytes in comparison to Melan-a cells. Tyrosinase expression increased after WLP only in B16-F10 cells; however no increase in melanin content after WLP was seen in either cell line. Our findings may prove useful in the treatment and the development of new pharmacological approaches of depigmentation diseases and skin cancer. PMID:26947915

  11. Alpha-particle diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Young, K.M.

    1991-01-01

    This paper will focus on the state of development of diagnostics which are expected to provide the information needed for {alpha}- physics studies in the future. Conventional measurement of detailed temporal and spatial profiles of background plasma properties in DT will be essential for such aspects as determining heating effectiveness, shaping of the plasma profiles and effects of MHD, but will not be addressed here. This paper will address (1) the measurement of the neutron source, and hence {alpha}-particle birth profile, (2) measurement of the escaping {alpha}-particles and (3) measurement of the confined {alpha}-particles over their full energy range. There will also be a brief discussion of (4) the concerns about instabilities being generated by {alpha}-particles and the methods necessary for measuring these effects. 51 refs., 10 figs.

  12. Imaging alpha particle detector

    Science.gov (United States)

    Anderson, D.F.

    1980-10-29

    A method and apparatus for detecting and imaging alpha particles sources is described. A dielectric coated high voltage electrode and a tungsten wire grid constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source to be quantitatively or qualitatively analyzed. A thin polyester film window allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  13. MicroRNA expression in melanocytic nevi: the usefulness of formalin-fixed, paraffin-embedded material for miRNA microarray profiling

    DEFF Research Database (Denmark)

    Glud, M.; Klausen, M.; Gniadecki, R.;

    2009-01-01

    surgical specimens are formalin fixed and paraffin embedded (FFPE). To explore whether FFPE material would be suitable for miRNA profiling in melanocytic lesions, we compared miRNA expression patterns in FFPE versus fresh frozen samples, obtained from 15 human melanocytic nevi. Out of microarray data, we...... therefore serve as biomarkers that may be useful in a clinical environment for diagnosis of various diseases. Most miRNA profiling studies have used fresh tissue samples. However, in some types of cancer, including malignant melanoma, fresh material is difficult to obtain from primary tumors, and most...... identified 84 miRNAs that were expressed in both types of samples and represented an miRNA profile of melanocytic nevi. Our results showed a high correlation in miRNA expression (Spearman r-value of 0.80) between paired FFPE and fresh frozen material. The data were further validated by quantitative RT...

  14. Tumor necrosis factor alpha polymorphism in heart failure/cardiomyopathy.

    Science.gov (United States)

    Vadlamani, Lou; Iyengar, Srinivas

    2004-01-01

    Tumor necrosis factor a (TNF-alpha) is a proinflammatory cytokine that is produced by activated macrophages. It has been shown to stimulate the release of endothelial cytokines and NO, increase vascular permeability, decrease contractility, and induce a prothrombotic state. The most studied TNF-a gene mutation in heart disease is a gamma to alpha substitution, which occurs when 308 nucleotides move upstream from the transcription initiation site in the TNF promoter and has been associated with elevated levels of TNF-alpha. The TNF1 allele (wild type) contains gamma at this site, while the TNF2 allele has an alpha substitution at the site. The TNF2 allele is a more powerful transcriptional activator, therefore leading to higher TNF-alpha levels. Most of the studies to date have failed to conclusively show any link between the polymorphism and heart disease, both coronary artery disease and cardiomyopathy/heart failure. PMID:15591843

  15. PD-L1 expression in melanocytic lesions does not correlate with the BRAF V600E mutation

    OpenAIRE

    Rodić, Nemanja; Anders, Robert A.; Eshleman, James R.; Lin, Ming-Tseh; Xu, Haiying; Kim, Jung H.; Beierl, Katie; Chen, Shuming; Luber, Brandon S.; Wang, Hao; Topalian, Suzanne L.; Pardoll, Drew M.; Taube, Janis M.

    2014-01-01

    PD-L1 expression in melanoma correlates with response to PD-1 pathway-blocking antibodies. Aberrant tumor-cell PD-L1 expression may be oncogene-driven and/or induced by interferon-gamma (IFNγ). Melanomas express PD-L1 in association with tumor-infiltrating lymphocytes (TIL), but the potential contribution of the BRAF V600E mutation (BRAFmut) to induced PD-L1 expression has not been determined. Fifty-two archival melanocytic lesions were assessed for PD-L1 expression, TIL infiltration and BRAF...

  16. Transplante de melanócitos no piebaldismo: relato de caso Melanocyte transplant in piebaldism: case report

    Directory of Open Access Journals (Sweden)

    Daniela Rezende Neves

    2010-06-01

    Full Text Available O piebaldismo é uma genodermatose rara onde as lesões acrômicas não respondem aos tratamentos tópico e fototerápico. Este artigo tem como objetivo demonstrar a importância do transplante de melanócitos, usando a técnica de minigrafting no tratamento do piebaldismo.Piebaldism is a rare genodermatosis in which depigmented skin areas are unresponsive to topical or light treatment. This article describes the importance of transplant techniques using noncultured melanocytes (minigrafting in the treatment of piebaldism.

  17. Melanocortin systems on pigment dispersion in fish chromatophores

    OpenAIRE

    AkiyoshiTakahashi; YumikoSaito

    2012-01-01

    Alpha-Melanocyte-stimulating hormone (alpha-MSH) is responsible for pigment dispersion in the chromatophores of fish and other tetrapods such as amphibians and reptiles. Recently, we discovered that alpha-MSH did not always stimulate pigment dispersion because this hormonal peptide exerted no effects on the melanophores of flounders. We assumed that the reduction of alpha-MSH activity was related to the co-expression of different alpha-MSH receptor subtypes—termed melanocortin receptors (MC...

  18. Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation

    Directory of Open Access Journals (Sweden)

    Vincent-Naulleau Silvia

    2008-04-01

    Full Text Available Abstract Background Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. Results We compared the serial analysis of gene expression (SAGE between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including GNB2L1 which was found upregulated in the melanoma library. In situ hybridisation confirmed GNB2L1 overexpression in MeLiM melanocytic lesions. GNB2L1 encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKCαβ. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low. Conclusion RACK1 overexpression detected in situ in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma

  19. 白介素-8对体外培养黑素细胞的影响%Effects of Interleukin-8 on Human Melanocytes in Vitro

    Institute of Scientific and Technical Information of China (English)

    陈静宇; 林新瑜; 王芳; 林鸿刚

    2012-01-01

    Objective: To establish the culture system of human normal melanocytes in vitro, and to study the effects of interleukin-8 at different concentrations on the proliferation of human melanocytes and melanin synthesis. Methods: MTT method and NaOH lysis method were employed to measure the effects of interleukin-8 at different concentrations on the proliferation of human melanocytes and melanin respectively. Apoptosis rates of melanocytes were detected with flow cytometer. Results: Interleukin-8 promotes melanocyte proliferation and melanin synthesis. Conclusions: Interleukin-8 enhances melanocyte proliferation and melanin synthesis.%目的:建立正常人表皮黑素细胞体外培养体系,观察不同浓度白介素-8对体外培养正常人黑素细胞的细胞增殖及黑素合成的影响.方法:采用四甲基偶氮唑盐(MTr)法测定不同浓度白介素-8对黑素细胞增值的影响,NaOH裂解法测定黑素生成量,流式细胞仪检测黑素细胞的凋亡率.结果:白介素-8对黑素细胞活力有增强作用,能使细胞增殖能力增加,黑素合成增加,但对黑素细胞的凋亡率无显著性影响.结论:白介素-8对体外培养的黑素细胞增殖及黑素生成都有增强作用.

  20. Molecular determinants of desensitization and assembly of the chimeric GABA(A) receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2 and gamma2

    DEFF Research Database (Denmark)

    Elster, L; Kristiansen, U; Pickering, D S;

    2001-01-01

    Two gamma-aminobutyric acid(A) (GABA(A)) receptor chimeras were designed in order to elucidate the structural requirements for GABA(A) receptor desensitization and assembly. The (alpha1/gamma2) and (gamma2/alpha1) chimeric subunits representing the extracellular N-terminal domain of alpha1 or gamma...... opposed to the staining of the (gamma2/alpha1)-containing receptors, which was only slightly higher than background. To explain this, the (alpha1/gamma2) and (gamma2/alpha1) chimeras may act like alpha1 and gamma2 subunits, respectively, indicating that the extracellular N-terminal segment is important...... for assembly. However, the (alpha1/gamma2) chimeric subunit had characteristics different from the alpha1 subunit, since the (alpha1/gamma2) chimera gave rise to no desensitization after GABA stimulation in whole-cell patch-clamp recordings, which was independent of whether the chimera was expressed...

  1. Rare Skin Adnexal and Melanocytic Tumors Arising in Ovarian Mature Cystic Teratomas: A Report of 3 Cases and Review of the Literature.

    Science.gov (United States)

    Moulla, Alexandra A; Magdy, Nesreen; Francis, Nicholas; Taube, Janis; Ronnett, Brigitte M; El-Bahrawy, Mona

    2016-09-01

    Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas. PMID:26974995

  2. Identification of multiple post-translational modifications in the porcine brain specific p25alpha

    DEFF Research Database (Denmark)

    Kleinnijenhuis, Anne J; Hedegaard, Claus; Lundvig, Ditte; Sundbye, Sabrina; Issinger, Olaf Georg; Jensen, Ole Nørregaard; Jensen, Poul Henning

    2008-01-01

    -synuclein and is a potent stimulator of alpha-synuclein aggregation. P25alpha is a phosphoprotein and post-translational modifications (PTMs) may play a role in its disease-related abnormalities. To investigate the spectrum of PTMs on p25alpha we cloned porcine p25alpha and isolated the protein from porcine...... brain. Using several complementary tandem mass spectrometry techniques for peptide mass analysis and amino acid sequencing, a comprehensive analysis of the PTMs on porcine p25alpha was performed. It was found that porcine p25alpha is heavily modified with a variety of modifications: phosphorylation, di......- and trimethylation, citrullination and a HexNAc group. The modifications are localized within p25alpha's unfolded terminal domains and suggest that their functional states are regulated. This comprehensive mapping of p25alpha's PTMs will form the basis for future functional studies and investigations...

  3. The alpha channeling effect

    Energy Technology Data Exchange (ETDEWEB)

    Fisch, N. J.

    2015-12-10

    Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

  4. Alpha and beta adrenergic effects on metabolism in contracting, perfused muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Ruderman, N B; Galbo, H

    1982-01-01

    The role of alpha- and beta-adrenergic receptor stimulation for the effect of epinephrine on muscle glycogenolysis, glucose- and oxygen uptake and muscle performance was studied in the perfused rat hindquarter at rest and during electrical stimulation (60 contractions/min). Adrenergic stimulation...... was obtained by epinephrine in a physiological concentration (2.4 X 10(-8) M) and alpha- and beta-adrenergic blockade by 10(-5) M phentolamine and propranolol, respectively. Epinephrine enhanced net glycogenolysis during contractions most markedly in slow-twitch red fibers. In these fibers the effect...... stimulation of alpha-adrenergic receptors and had a positive inotropic effect during contractions which was abolished by alpha- as well as by beta-adrenergic blockade. The results indicate that epinephrine has profound effects on contracting muscle, and that these effects are elicited through different...

  5. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Maëlle Lempereur

    2016-01-01

    Full Text Available Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L. which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box. In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells. Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif.

  6. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells.

    Science.gov (United States)

    Lempereur, Maëlle; Majewska, Claire; Brunquers, Amandine; Wongpramud, Sumalee; Valet, Bénédicte; Janssens, Philippe; Dillemans, Monique; Van Nedervelde, Laurence; Gallo, Dominique

    2016-01-01

    Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif. PMID:27190515

  7. Overexpression of protein tyrosine phosphatase-alpha (PTP-alpha) but not PTP-kappa inhibits translocation of GLUT4 in rat adipose cells

    DEFF Research Database (Denmark)

    Cong, L N; Chen, H; Li, Y;

    1999-01-01

    Protein tyrosine phosphatases (PTPases) are likely to play important roles in insulin action. We recently demonstrated that the nontransmembrane PTPase PTP1B can act as a negative modulator of insulin-stimulated translocation of GLUT4. We now examine the role of PTP-alpha and PTP-kappa (two trans......-stimulated glucose transport....

  8. The Alpha-1A Adrenergic Receptor in the Rabbit Heart.

    Directory of Open Access Journals (Sweden)

    R Croft Thomas

    Full Text Available The alpha-1A-adrenergic receptor (AR subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse.

  9. Local versus nonlocal $\\alpha\\alpha$ interactions in $3\\alpha$ description of $^{12}$C

    CERN Document Server

    Suzuki, Y; Descouvemont, P; Fujiwara, Y; Matsumura, H; Orabi, M; Theeten, M

    2008-01-01

    Local $\\alpha \\alpha$ potentials fail to describe $^{12}$C as a $3\\alpha$ system. Nonlocal $\\alpha \\alpha$ potentials that renormalize the energy-dependent kernel of the resonating group method allow interpreting simultaneously the ground state and $0^+_2$ resonance of $^{12}$C as $3\\alpha$ states. A comparison with fully microscopic calculations provides a measure of the importance of three-cluster exchanges in those states.

  10. New Whitening Constituents from Taiwan-Native Pyracantha koidzumii: Structures and Tyrosinase Inhibitory Analysis in Human Epidermal Melanocytes

    Directory of Open Access Journals (Sweden)

    Rong-Dih Lin

    2015-12-01

    Full Text Available Nontoxic natural products useful in skin care cosmetics are of considerable interest. Tyrosinase is a rate-limiting enzyme for which its inhibitor is useful in developing whitening cosmetics. Pyracantha koidzumii (Hayata Rehder is an endemic species in Taiwan that exhibits tyrosinase-inhibitory activity. To find new active natural compounds from P. koidzumii, we performed bioguided isolation and studied the related activity in human epidermal melanocytes. In total, 13 compounds were identified from P. koidzumii in the present study, including two new compounds, 3,6-dihydroxy-2,4-dimethoxy-dibenzofuran (9 and 3,4-dihydroxy-5-methoxybiphenyl-2ʹ-O-β-d-glucopyranoside (13, as well as 11 known compounds. The new compound 13 exhibited maximum potency in inhibiting cellular tyrosinase activity, the protein expression of cellular tyrosinase and tyrosinase-related protein-2, as well as the mRNA expression of Paired box 3 and microphthalmia-associated transcription factor in a concentration-dependent manner. In the enzyme kinetic assay, the new compound 13 acted as an uncompetitive mixed-type inhibitor against the substrate l-3,4-dihydroxyphenylalanine and had a Km value against this substrate of 0.262 mM, as calculated using the Lineweaver–Burk plots. Taken together, our findings show compound 13 exhibits tyrosinase inhibition in human melanocytes and compound 13 may be a potential candidate for use in cosmetics.

  11. Sustained Aftereffect of α-tACS Lasts Up to 70 min after Stimulation

    Science.gov (United States)

    Kasten, Florian H.; Dowsett, James; Herrmann, Christoph S.

    2016-01-01

    Transcranial alternating current stimulation (tACS) has been repeatedly demonstrated to increase power of endogenous brain oscillations in the range of the stimulated frequency after stimulation. In the alpha band this aftereffect has been shown to persist for at least 30 min. However, in most experiments the aftereffect exceeded the duration of the measurement. Thus, it remains unclear how the effect develops beyond these 30 min and when it decays. The current study aimed to extend existing findings by monitoring the physiological aftereffect of tACS in the alpha range for an extended period of 90 min post-stimulation. To this end participants received either 20 min of tACS or sham stimulation with intensities below their individual sensation threshold at the individual alpha frequency (IAF). Electroencephalogram (EEG) was acquired during 3 min before and 90 min after stimulation. Subjects performed a visual vigilance task during the whole measurement. While the enhanced power in the individual alpha band did not return back to pre-stimulation baseline in the stimulation group, the difference between stimulation and sham diminishes after 70 min due to a natural alpha increase of the sham group. PMID:27252642

  12. Bremsstrahlung in $\\alpha$ Decay

    CERN Document Server

    Takigawa, N; Hagino, K; Ono, A; Brink, D M

    1999-01-01

    A quantum mechanical analysis of the bremsstrahlung in $\\alpha$ decay of $^{210}$Po is performed in close reference to a semiclassical theory. We clarify the contribution from the tunneling, mixed, outside barrier regions and from the wall of the inner potential well to the final spectral distribution, and discuss their interplay. We also comment on the validity of semiclassical calculations, and the possibility to eliminate the ambiguity in the nuclear potential between the alpha particle and daughter nucleus using the bremsstrahlung spectrum.

  13. Unified model for alpha-decay and alpha-capture

    International Nuclear Information System (INIS)

    A unified model for alpha-decay and alpha-capture is discussed. Simultaneously the half-lives for alpha-transition between ground states as well as ground and excited states and alpha-capture cross-sections by spherical magic or near-magic nuclei are well described in the framework of this model. Using these data the alpha-nucleus potential is obtained. The simple empirical relations for handy evaluation of the half-lives for alpha-transition, which take into account both the angular momentum and parity of alpha-transition, are presented

  14. ALPHA-2: the sequel

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    While many experiments are methodically planning for intense works over the long shutdown, there is one experiment that is already working at full steam: ALPHA-2. Its final components arrived last month and will completely replace the previous ALPHA set-up. Unlike its predecessor, this next generation experiment has been specifically designed to measure the properties of antimatter.   The ALPHA team lower the new superconducting solenoid magnet into place. The ALPHA collaboration is working at full speed to complete the ALPHA-2 set-up for mid-November – this will give them a few weeks of running before the AD shutdown on 17 December. “We really want to get some experience with this device this year so that, if we need to make any changes, we will have time during the long shutdown in which to make them,” says Jeffrey Hangst, ALPHA spokesperson. “Rather than starting the 2014 run in the commissioning stage, we will be up and running from the get go.&...

  15. Alpha Particle Diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, Ray, K.

    2009-05-13

    The study of burning plasmas is the next frontier in fusion energy research, and will be a major objective of the U.S. fusion program through U.S. collaboration with our international partners on the ITER Project. For DT magnetic fusion to be useful for energy production, it is essential that the energetic alpha particles produced by the fusion reactions be confined long enough to deposit a significant fraction of their initial ~3.5 MeV energy in the plasma before they are lost. Development of diagnostics to study the behavior of energetic confined alpha particles is a very important if not essential part of burning plasma research. Despite the clear need for these measurements, development of diagnostics to study confined the fast confined alphas to date has proven extremely difficult, and the available techniques remain for the most part unproven and with significant uncertainties. Research under this grant had the goal of developing diagnostics of fast confined alphas, primarily based on measurements of the neutron and ion tails resulting from alpha particle knock-on collisions with the plasma deuterium and tritium fuel ions. One of the strengths of this approach is the ability to measure the alphas in the hot plasma core where the interesting ignition physics will occur.

  16. Alpha Background Rejection in Bolometer Detectors

    Science.gov (United States)

    Deporzio, Nicholas

    2016-03-01

    This study presents the modification of bolometer detectors used in particle searches to veto or otherwise reject alpha radiation background and the statistical advantages of doing so. Several techniques are presented in detail - plastic film scintillator vetoes, metallic film ionization vetoes, and scintillating bolometer vetoes. Plastic scintillator films are cooled to bolometer temperatures and bombarded with 1.4MeV to 6.0MeV alpha particles representative of documented detector background. Photomultipliers detect this scintillation light and produce a veto signal. Layered metallic films of a primary metal, dielectric, and secondary metal, such as gold-polyethylene-gold films, are cooled to milli-kelvin temperatures and biased to produce a current signal veto when incident 1.4MeV to 6.0MeV alpha particles ionize conduction paths through the film. Modified Zinc Molybdate Bolometers are used to produce scintillation light when stimulated by alpha background. Calibration of veto signal to background energy is presented. Results are used to quantify the statistical impact of such modifications on bolometer searches.

  17. Resting alpha activity predicts learning ability in alpha neurofeedback

    OpenAIRE

    Wenya eNan; Feng eWan; Mang I eVai; Agostinho eRosa

    2014-01-01

    Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the tr...

  18. Pharmacological evidence that alpha2A- and alpha2C-adrenoceptors mediate the inhibition of cardioaccelerator sympathetic outflow in pithed rats.

    Science.gov (United States)

    Cobos-Puc, Luis E; Villalón, Carlos M; Sánchez-López, Araceli; Lozano-Cuenca, Jair; Pertz, Heinz H; Görnemann, Tilo; Centurión, David

    2007-01-12

    It has been suggested that the alpha(2)-adrenoceptors mediating cardiac sympatho-inhibition in pithed rats closely resemble the pharmacological profile of the alpha(2A)-adrenoceptor subtype. However, several lines of evidence suggest that more than one subtype may be involved. Thus, the present study has pharmacologically re-evaluated the receptor subtype(s) involved in the inhibitory effect of the alpha(2)-adrenoceptor agonist, B-HT 933, on the tachycardic responses elicited by selective cardiac sympathetic stimulation (0.03, 0.1, 0.3, 1 and 3 Hz) in desipramine-pretreated pithed rats. I.v. continuous infusions of B-HT 933 (30 microg/kg min), which failed to modify the tachycardic responses to exogenous noradrenaline, inhibited those induced by preganglionic (C(7)-T(1)) stimulation of the cardiac sympathetic outflow at all frequencies of stimulation (0.03-3 Hz). This cardiac sympatho-inhibitory response to B-HT 933 was: (1) unaltered by saline (1 ml/kg) or the antagonists BRL44408 (100 microg/kg; alpha(2A)) or imiloxan (3000 and 10,000 microg/kg; alpha(2B)); (2) partially antagonized by BRL44408 (300 microg/kg) or MK912 (10 microg/kg; alpha(2C)) given separately; and (3) completely antagonized by rauwolscine (300 microg/kg; alpha(2)), MK912 (30 microg/kg) or the combination of BRL44408 (300 microg/kg) plus MK912 (10 microg/kg). Moreover, the above doses of antagonists, which are high enough to block their respective receptors, failed to block per se the tachycardic responses to sympathetic stimulation. These results suggest that the cardiac sympatho-inhibition induced by B-HT 933 in pithed rats is mainly mediated by stimulation of alpha(2A)- and alpha(2C)-adrenoceptors. PMID:17109851

  19. Alpha particles in fusion research

    International Nuclear Information System (INIS)

    This collection of 39 (mostly view graph) presentations addresses various aspects of alpha particle physics in thermonuclear fusion research, including energy balance and alpha particle losses, transport, the influence of alpha particles on plasma stability, helium ash, the transition to and sustainment of a burning fusion plasma, as well as alpha particle diagnostics. Refs, figs and tabs

  20. Stereological estimation of nuclear volume in benign and malignant melanocytic lesions of the skin. Inter- and intraobserver variability of malignancy grading

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Ottosen, P D

    1991-01-01

    tumors, the observer variability of estimates of nuclear vv is studied. Routinely processed, paraffin embedded tissue specimens from 22 malignant melanomas and nine benign melanocytic cutaneous lesions are retrospectively investigated. The sampling scheme for estimation of nuclear vv is easy to use and...

  1. Quantitative real-time RT-PCR in sentinel lymph nodes from melanoma patients. Detection of melanocytic mRNA predicts disease-free survival

    DEFF Research Database (Denmark)

    Riber-Hansen, Rikke; Abrahamsen, Helene Nortvig; Sorensen, Boe Sandahl;

    2008-01-01

    Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) for specific melanoma markers is more sensitive than histology for detecting cells of melanocytic origin in sentinel lymph nodes (SLNs) in cutaneous melanoma. The clinical significance of a positive qRT-PCR analysis ...

  2. The microRNA molecular signature of atypic and common acquired melanocytic nevi: differential expression of miR-125b and let-7c

    DEFF Research Database (Denmark)

    Holst, Line Marie Broksø; Kaczkowski, Bogumil; Glud, Martin;

    2011-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression through base pairing with mRNA and which are crucially involved in carcinogenesis (the so-called oncomiRs). We compared the miRNA signature between acquired melanocytic nevi showing clinical atypia (atypic nevi, AN) and ...

  3. Nevo melanocítico congénito gigante: presentación de tres casos Giants congenital melanocytic nevus: Report of three cases

    Directory of Open Access Journals (Sweden)

    V Estrella

    Full Text Available Los Nevos Melanocíticos Congénitos (NMC son lesiones pigmentarias, que pueden aparecer en el nacimiento, aunque hay casos comunicados hasta el primer año de vida (Nevo Melanocítico Congénito Tardío. Presentan ciertas características clínicas y evolutivas de gran importancia: el compromiso estético de las formas gigantes, la asociación con melanocitosis meníngea y su transformación maligna de la lesión cutánea o meníngea. Presentamos tres casos de nevos melanocíticos congénitos gigantes. Cabe destacar, que el objetivo de este artículo es realizar una revisión del tema, orientar al seguimiento y control de los mismos y destacar la dificultad para su tratamiento debido a su gran tamaño.The Congenital Melanocytic Nevus are lesions melanocytic pigmented. Already apparent at birth but there are cases reported to the first year of life (Late Congenital Melanocytic Nevus. Certain features and evolution clinics that are important: the great compromise of aesthetic forms giant, meningeal melanocitosis association and its malignant transformation. We present three cases of Giants Congenital Melanocytic Nevus. It should be noted, that the purpose of this article is a review of the issue and guide the monitoring and control of them and point out the difficult treatment.

  4. Intercomparison of alpha particle spectrometry software packages

    International Nuclear Information System (INIS)

    Software has reached an important level as the 'logical controller' at different levels, from a single instrument to an entire computer-controlled experiment. This is also the case for software packages in nuclear instruments and experiments. In particular, because of the range of applications of alpha-particle spectrometry, software packages in this field are often used. It is the aim of this intercomparison to test and describe the abilities of four such software packages. The main objectives of the intercomparison were the ability of the programs to determine the peak areas and the peak area uncertainties, and the statistical control and stability of reported results. In this report, the task, methods and results of the intercomparison are presented in order to asist the potential users of such software and to stimulate the development of even better alpha-particle spectrum analysis software

  5. Prejunctional alpha2A-autoreceptors in the canine saphenous vein.

    Science.gov (United States)

    Paiva, M Q; Mota, A; Moura, D; Guimarães, S

    1997-09-01

    The aim of the study was to determine the subtype of prejunctional alpha2-autoreceptors in the canine saphenous vein. Segments of the vein were incubated with 3H-noradrenaline and subsequently perifused with modified Krebs-Henseleit solution. Five periods of electrical stimulation were applied (S1-S5; each for 2 min, 1 Hz). Concentration-response curves for the inhibitory effect of the alpha2-adrenoceptor agonists oxymetazoline and UK-14,304 and for the facilitatory effect of nine antagonists were determined. Correlations between the pEC30%s for the antagonists obtained in the present study and the pKis for the same antagonists obtained in tissues expressing only alpha2A- (HT29 cells), alpha2B- (neonatal rat lung), alpha2C- (OK cells) or alpha2D-adrenoceptors (rat submaxillary gland) showed that the alpha2-autoreceptors in the canine saphenous vein resemble most closely the alpha2A-subtype. Furthermore, oxymetazoline was a highly potent agonist (pIC50% = 8.10) and prazosin was a weak antagonist (pEC30% = 6.46), confirming that the alpha2-adrenoceptors involved in the modulation of the response to electrical stimulation of the canine saphenous vein do not belong to either the alpha2B- or alpha2C-subtype. On the other hand, the EC30% ratios phentolamine/rauwolscine and idazoxan/rauwolscine were much closer to the ratios obtained at alpha2-autoreceptors of the rabbit- (alpha2A) than of the guinea-pig brain cortex (alpha2D). The results suggest that the sympathetic nerves of the canine saphenous vein are endowed with alpha2A-adrenoceptors. PMID:9303575

  6. Transcranial alternating current stimulation with sawtooth waves: simultaneous stimulation and EEG recording

    Directory of Open Access Journals (Sweden)

    James eDowsett

    2016-03-01

    Full Text Available Transcranial alternating current stimulation (tACS has until now mostly been administered as an alternating sinusoidal wave. Despite modern tACS stimulators being able to deliver alternating current with any arbitrary shape there has been no systematic exploration into the relative benefits of different waveforms. As tACS is a relatively new technique there is a huge parameter space of unexplored possibilities which may prove superior or complimentary to the traditional sinusoidal waveform. Here we begin to address this with an investigation into the effects of sawtooth wave tACS on individual alpha power. Evidence from animal models suggests that the gradient and direction of an electric current should be important factors for the subsequent neural firing rate; we compared positive and negative ramp sawtooth waves to test this. An additional advantage of sawtooth waves is that the resulting artefact in the electroencephalogram (EEG recording is significantly simpler to remove than a sine wave; accordingly we were able to observe alpha oscillations both during and after stimulation.We found that positive ramp sawtooth, but not negative ramp sawtooth, significantly enhanced alpha power during stimulation relative to sham (p<0.01. In addition we tested for an after-effect of both sawtooth and sinusoidal stimulation on alpha power but in this case did not find any significant effect. This preliminary study paves the way for further investigations into the effect of the gradient and direction of the current in tACS which could significantly improve the usefulness of this technique.

  7. Fibroblast interleukin 1 beta: synergistic stimulation by recombinant interleukin 1 and tumor necrosis factor and posttranscriptional regulation.

    OpenAIRE

    Elias, J. A.; Reynolds, M M; Kotloff, R M; Kern, J A

    1989-01-01

    To understand the role fibroblasts play in mediating and amplifying the effects of inflammatory cytokines, we determined whether recombinant interleukin 1 (IL-1) and recombinant tumor necrosis factor (TNF), alone and in combination, stimulated fibroblasts to produce IL-1 beta. Recombinant IL-1 (alpha and beta) stimulated fibroblast IL-1 beta mRNA accumulation, whereas recombinant TNF did not. In addition, simultaneous stimulation with recombinant IL-1 (alpha or beta) and recombinant TNF resul...

  8. Updata on transplantion of melanocytes in the treatment of vitiligo%黑素细胞移植治疗白癜风的研究进展

    Institute of Scientific and Technical Information of China (English)

    秦晓明; 柯国琳; 杨孔超

    2015-01-01

    Transplantion of melanocytes is one of the methods in the treatment of vitiligo at stable stage, including cultured melanocyte transplantation and epidermal cells suspension transplantation. Co-culturing of melanocytes with adipose-derived stem cells may be a potential substitute for co-culturing with keratino-cytes. The efficiency of autologous melanocytes transplantation in vitiligo patients may be predicted by perile-sional skin-homing CD8+T cell activities and the dermal mesenchymal stem cells might be used as auxiliary agent to improve the efficacy. The progress on transplantion of melanocytes in the treatment of vitiligo is re-viewed.%黑素细胞移植是治疗稳定期白癜风的方法之一,主要包括培养的黑素细胞移植和表皮细胞悬液移植。近年来动物实验证实脂肪干细胞可代替角质形成细胞与黑素细胞共培养移植治疗白癜风。白癜风患者自体黑素细胞的移植效率可通过皮损周围皮肤归巢CD8+T细胞活动性来进行预测,真皮间充质干细胞可作为黑素细胞移植治疗白癜风的辅助剂。本文综述黑素细胞移植治疗白癜风的国内外进展,旨在为临床提供参考。

  9. An unusual case of congenital melanocytic nevus presenting as neurocutaneous melanoma coexisting with Tuberous Sclerosis complex: A case report

    Directory of Open Access Journals (Sweden)

    Thacker Purujit J

    2011-07-01

    Full Text Available Abstract Introduction Congenital melanocytic nevi are among the several known risk factors for the development of melanoma. Neurocutaneous melanosis is a rare, congenital, non-hereditary disorder characterized by the presence of multiple and/or giant congenital melanocytic nevi. It is a rare condition, with fewer than 200 cases reported in the literature. Its association with tuberous sclerosis complex, a form of the neurocutaneous syndrome, is an unusual finding which, to the best of our knowledge, has not been documented in the English literature so far. Herein we present the first case documenting such an association in a 16-year-old post-pubertal Indian girl. Case presentation In this report, we describe the case of a 16-year-old Indian girl who presented to our hospital with swelling on the scalp which had progressed from the hairline to just above the left brow, causing mechanical ptosis. She was born with a black-pigmented triangular patch covered with hair over the scalp which had increased in size over a period of eight years after birth. An X-ray of her skull and ultrasonography revealed soft tissue swelling in the left temporofrontoparietal region. Magnetic resonance imaging of her brain showed the presence of 8.99 cm × 2.26 cm abnormal signal intensity involving the scalp, a few small tubers with cortical dysplasia in the left frontoparietal region with asymmetric dilatation, and the presence of calcified subependymal nodules within the left lateral ventricle. These findings were suggestive of tuberous sclerosis. A histopathological examination of the swelling was suggestive of congenital melanocytic nevi. The patient underwent surgery. Excision of the tumor with primary skin grafting was done, with the graft being taken from the medial aspect of the right thigh. Conclusion This case warrants further research to provide concrete evidence of an association of neurocutaneous melanoma with tuberous sclerosis complex. Research should be

  10. Neural dynamics during repetitive visual stimulation

    Science.gov (United States)

    Tsoneva, Tsvetomira; Garcia-Molina, Gary; Desain, Peter

    2015-12-01

    Objective. Steady-state visual evoked potentials (SSVEPs), the brain responses to repetitive visual stimulation (RVS), are widely utilized in neuroscience. Their high signal-to-noise ratio and ability to entrain oscillatory brain activity are beneficial for their applications in brain-computer interfaces, investigation of neural processes underlying brain rhythmic activity (steady-state topography) and probing the causal role of brain rhythms in cognition and emotion. This paper aims at analyzing the space and time EEG dynamics in response to RVS at the frequency of stimulation and ongoing rhythms in the delta, theta, alpha, beta, and gamma bands. Approach.We used electroencephalography (EEG) to study the oscillatory brain dynamics during RVS at 10 frequencies in the gamma band (40-60 Hz). We collected an extensive EEG data set from 32 participants and analyzed the RVS evoked and induced responses in the time-frequency domain. Main results. Stable SSVEP over parieto-occipital sites was observed at each of the fundamental frequencies and their harmonics and sub-harmonics. Both the strength and the spatial propagation of the SSVEP response seem sensitive to stimulus frequency. The SSVEP was more localized around the parieto-occipital sites for higher frequencies (>54 Hz) and spread to fronto-central locations for lower frequencies. We observed a strong negative correlation between stimulation frequency and relative power change at that frequency, the first harmonic and the sub-harmonic components over occipital sites. Interestingly, over parietal sites for sub-harmonics a positive correlation of relative power change and stimulation frequency was found. A number of distinct patterns in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz) and beta (15-30 Hz) bands were also observed. The transient response, from 0 to about 300 ms after stimulation onset, was accompanied by increase in delta and theta power over fronto-central and occipital sites, which returned to baseline

  11. Release of endogenous ATP during sympathetic nerve stimulation.

    OpenAIRE

    Lew, M. J.; White, T. D.

    1987-01-01

    1 Vas deferens from guinea-pig was stimulated with a suction electrode and both contractions and release of endogenous ATP monitored 2 Release of ATP was tetrodotoxin-sensitive and increased when the number of stimuli was increased. 3 Release of ATP was not due to contraction of the muscle and persisted following block of contractions with prazosin and alpha, beta-methylene ATP. 4 These results indicate that stimulation of the sympathetic nerves in the vas deferens releases endogenous ATP pre...

  12. Potential relevance of alpha(1-adrenergic receptor autoantibodies in refractory hypertension.

    Directory of Open Access Journals (Sweden)

    Katrin Wenzel

    Full Text Available BACKGROUND: Agonistic autoantibodies directed at the alpha(1-adrenergic receptor (alpha(1-AAB have been described in patients with hypertension. We implied earlier that alpha(1-AAB might have a mechanistic role and could represent a therapeutic target. METHODOLOGY/PRINCIPAL FINDINGS: To pursue the issue, we performed clinical and basic studies. We observed that 41 of 81 patients with refractory hypertension had alpha(1-AAB; after immunoadsorption blood pressure was significantly reduced in these patients. Rabbits were immunized to generate alpha(1-adrenergic receptor antibodies (alpha(1-AB. Patient alpha(1-AAB and rabbit alpha(1-AB were purified using affinity chromatography and characterized both by epitope mapping and surface plasmon resonance measurements. Neonatal rat cardiomyocytes, rat vascular smooth muscle cells (VSMC, and Chinese hamster ovary cells transfected with the human alpha(1A-adrenergic receptor were incubated with patient alpha(1-AAB and rabbit alpha(1-AB and the activation of signal transduction pathways was investigated by Western blot, confocal laser scanning microscopy, and gene expression. We found that phospholipase A2 group IIA (PLA2-IIA and L-type calcium channel (Cacna1c genes were upregulated in cardiomyocytes and VSMC after stimulation with both purified antibodies. We showed that patient alpha(1-AAB and rabbit alpha(1-AB result in protein kinase C alpha activation and transient extracellular-related kinase (EKR1/2 phosphorylation. Finally, we showed that the antibodies exert acute effects on intracellular Ca(2+ in cardiomyocytes and induce mesentery artery segment contraction. CONCLUSIONS/SIGNIFICANCE: Patient alpha(1-AAB and rabbit alpha(1-AB can induce signaling pathways important for hypertension and cardiac remodeling. Our data provide evidence for a potential clinical relevance for alpha(1-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension.

  13. ALPHA MIS: Reference manual

    Energy Technology Data Exchange (ETDEWEB)

    Lovin, J.K.; Haese, R.L.; Heatherly, R.D.; Hughes, S.E.; Ishee, J.S.; Pratt, S.M.; Smith, D.W.

    1992-02-01

    ALPHA is a powerful and versatile management information system (MIS) initiated and sponsored and by the Finance and Business Management Division of Oak Ridge National Laboratory, who maintain and develop it in concert with the Business Systems Division for its Information Center. A general-purpose MIS, ALPHA allows users to access System 1022 and System 1032 databases to obtain and manage information. From a personal computer or a data terminal, Energy Systems employees can use ALPHA to control their own report reprocessing. Using four general commands (Database, Select, Sort, and Report) they can (1) choose a mainframe database, (2) define subsets within it, (3) sequentially order a subset by one or more variables, and (4) generate a report with their own or a canned format.

  14. mc1r Pathway regulation of zebrafish melanosome dispersion

    DEFF Research Database (Denmark)

    Richardson, Jennifer; Lundegaard, Pia Rengtved; Reynolds, Natalie L;

    2008-01-01

    Zebrafish rapidly alter their pigmentation in response to environmental changes. For black melanocytes, this change is due to aggregation or dispersion of melanin in the cell. Dispersion and aggregation are controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, which increase...... upon stimulation by alpha melanocyte-stimulating hormone (alpha-MSH) or reduce with melanin-concentrating hormone (MCH). In mammals and birds, the melanocortin-1-receptor (MC1R) responds to MSH, and stimulates the synthesis of black eumelanin. While MSH-cAMP signaling stimulates melanogenesis in...

  15. Immunohistochemical localization of cathepsin D and a possible role of melanocytes during tail resorption in tadpoles of a tropical toad.

    Science.gov (United States)

    Mahapatra, Cuckoo; Mahapatra, Pravati Kumari

    2012-07-01

    Programmed cell death during anuran tail resorption is primarily brought about by apoptosis. Cathepsin D, a lysosomal aspartyl protease, is involved in the death of tail tissues. Thus, anuran tail resorption presents an ideal model to study cathepsin-mediated cell death during vertebrate development. Present study describes the trend of specific activity of cathepsin D in the tail of different developmental stages and immunohistochemical localization of cathepsin D in the tail tissues of the common Asian toad, Duttaphrynus melanostictus. Cathepsin D was involved in programmed cell death in epidermis, muscle, spinal cord, and blood cells in the resorbing tail. Interestingly, it was also involved in the pre-resorbing tail before visible tail resorption which indicates initiation of cell death even before actually the tail resorbs. Melanocytes were found to be one of the causative agents in degrading tail tissues and were associated with the degradation of muscle, epidermis and spinal cord of the resorbing tail. PMID:22505219

  16. Detection of alpha particles with undoped poly (ethylene naphthalate)

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hidehito, E-mail: hidehito@rri.kyoto-u.ac.jp [Kyoto University, 2, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan); National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shirakawa, Yoshiyuki; Kitamura, Hisashi [National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Sato, Nobuhiro; Takahashi, Sentaro [Kyoto University, 2, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan)

    2014-03-01

    There has been recent interest in the use of undoped, aromatic-ring polymers as organic scintillation materials for radiation detectors. Here, we characterise the response of poly (ethylene naphthalate) (PEN) to alpha particles. The energy response to 5486 keV alpha particles emitted from {sup 241}Am was 554±45 keV electron equivalents (keVee), with an energy resolution of 11.2±0.1%. The energy response to 6118 keV alpha particles emitted from {sup 252}Cf was 618±45 keVee, with a resolution of 8.8±0.1%. It is also important to characterise the refractive index because it determines how efficiently light propagates in scintillation materials to the photodetector. By taking into account the PEN emission spectrum, it was revealed that its effective refractive index was 1.70. Overall, the results indicate that PEN has potential as a scintillation material for the detection of alpha particles. - Highlights: • PEN is characterised as a scintillation material for alpha particles. • The effective refractive index for PEN is 1.70 in its emission spectrum. • The response to 5486 (6118) keV alpha particles was 554±45 (618±45) keVee. • The energy resolution for 5486 (6118) keV alpha particles was 11.2±0.1 (8.8±0.1) %. • This work will stimulate future use of PEN for radiation detection.

  17. Feldspar, Infrared Stimulated Luminescence

    DEFF Research Database (Denmark)

    Jain, Mayank

    2014-01-01

    This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars.......This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars....

  18. Transcranial Electric Field Stimulation

    OpenAIRE

    Arfaee, Arash

    2015-01-01

    Nervous stimulation with electric methods not only has a long history in the treatment of many conditions but also in the last two decades has been used increasingly as a powerful functional brain mapping tool alongside other imaging techniques. This technology has been used to record the stimulation-evoked activity of the stimulated location. This research describes work surrounding a novel technique for brain and nervous stimulation using the electric field as the medium; particularly tra...

  19. Alpha and evangelical conversion

    OpenAIRE

    Stout, A.; Dein, S.

    2013-01-01

    A semi-structured interview study was conducted among 11 ‘Born Again’ Christians eliciting their conversion narratives. Informants emphasised the importance of embodying the Holy Spirit and developing a personal relationship with Christ in the process of conversion. The Alpha Course played an important role in this process.

  20. Alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line; Stensland, Hilde Monica Frostad Riise; Olsen, Klaus Juul;

    2015-01-01

    the three subgroups of genotype/subcellular localisation and the clinical and biochemical data were done to investigate the potential relationship between genotype and phenotype in alpha-mannosidosis. Statistical analyses were performed using the SPSS software. Analyses of covariance were performed to...

  1. The $\\alpha_S$ Dependence of Parton Distributions

    OpenAIRE

    Martin, A. D.; Stirling, W. J.; Roberts, R G

    1995-01-01

    We perform next-to-leading order global analyses of deep inelastic and related data for different fixed values of $\\alpha_S (M_Z^2)$. We present sets of parton distributions for six values of $\\alpha_S$ in the range 0.105 to 0.130. We display the $(x, Q^2)$ domains with the largest parton uncertainty and we discuss how forthcoming data may be able to improve the determination of the parton densities.

  2. Functional role of frontal alpha oscillations in creativity.

    Science.gov (United States)

    Lustenberger, Caroline; Boyle, Michael R; Foulser, A Alban; Mellin, Juliann M; Fröhlich, Flavio

    2015-06-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent electroencephalography (EEG) data suggests that cortical oscillations in the alpha frequency band (8-12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a functional role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10 Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking (TTCT), a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40 Hz-tACS was used instead of 10 Hz-tACS to rule out a general "electrical stimulation" effect. No significant change in the Creativity Index was found for such frontal 40 Hz stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. PMID:25913062

  3. Genetics Home Reference: alpha thalassemia

    Science.gov (United States)

    ... for Disease Control and Prevention Centre for Genetics Education (Australia) Cooley's Anemia Foundation: Fact sheet about alpha thalassemia Disease InfoSearch: Alpha-Thalassemia Genomics Education Programme (UK) Information Center for Sickle Cell and ...

  4. Comparison of the effect of alpha1- and alpha2-adrenoceptor agonists and antagonists on muscle contractility of the rabbit abdominal aorta in vitro.

    Science.gov (United States)

    Gnus, Jan; Rusiecka, Agnieszka; Czerski, Albert; Zawadzki, Wojciech; Witkiewicz, Wojciech; Hauzer, Willy

    2013-01-01

    The aim of the study was to demonstrate the effect of selected agonists and antagonists of alpha-adrenergic receptors on muscle contractility of the rabbit abdominal aorta in vitro with particular emphasis on alpha2-adrenergic receptor subtypes. The study was conducted on 30 New Zealand breed rabbits from which specimens of the abdominal aorta were collected. The sections were set up in an automatic water bath in a Krebs-Henseleit buffer at 37 degrees C. The experiments showed that alpha1-adrenergic receptors played the main role in the contractile response ofthe rabbit abdominal aorta. Stimulation of alpha1-adrenergic receptor by administration ofphenylephrine resulted in an increase in smooth muscle tonus ofthe rabbit abdominal aorta by an average of 4.75 mN. The reaction after stimulation of alpha2-adrenergic receptors by similar doses of their agonists was much weaker. Prolonged tissue response time and time needed to reach maximum tonus for alpha2-adrenergic receptor agonists were observed. The obtained results confirm the thesis that the alpha1-adrenergic receptor is the most important factor controlling the contractility of the rabbit abdominal aorta, but the alpha2-adrenergic receptor is also involved in maintaining muscle tissue tonus. PMID:23767297

  5. $\\alpha$-minimal Banach spaces

    CERN Document Server

    Rosendal, Christian

    2011-01-01

    A Banach space with a Schauder basis is said to be $\\alpha$-minimal for some countable ordinal $\\alpha$ if, for any two block subspaces, the Bourgain embeddability index of one into the other is at least $\\alpha$. We prove a dichotomy that characterises when a Banach space has an $\\alpha$-minimal subspace, which contributes to the ongoing project, initiated by W. T. Gowers, of classifying separable Banach spaces by identifying characteristic subspaces.

  6. Analgesic effect of interferon-alpha via mu opioid receptor in the rat.

    Science.gov (United States)

    Jiang, C L; Son, L X; Lu, C L; You, Z D; Wang, Y X; Sun, L Y; Cui, R Y; Liu, X Y

    2000-03-01

    Using the tail-flick induced by electro-stimulation as a pain marker, it was found that pain threshold (PT) was significantly increased after injecting interferon-alpha (IFN alpha) into the lateral ventricle of rats. This effect was dosage-dependent and abolished by monoclonal antibody (McAb) to IFN alpha. Naloxone could inhibit the analgesic effect of IFN alpha, suggesting that the analgesic effect of IFN alpha be related to the opioid receptors. Beta-funaltrexamine (beta-FNA), the mu specific receptor antagonist could completely block the analgesic effect of IFN alpha. The selective delta-opioid receptor antagonist, ICI174,864 and the kappa-opioid receptor antagonist, nor-BNI both failed to prevent the analgesic effect of IFN alpha. IFN alpha could significantly inhibit the production of the cAMP stimulated by forskolin in SK-N-SH cells expressing the mu-opioid receptor, not in NG108-15 cells expressing the delta-opioid receptor uniformly. The results obtained provide further evidence for opioid activity of IFN alpha and suggest that this effect is mediated by central opioid receptors of the mu subtype. The evidence is consistent with the hypothesis that multiple actions of cytokines, such as immunoregulatory and neuroregulatory effects, might be mediated by distinct domains of cytokines interacting with different receptors. PMID:10676852

  7. Resting alpha activity predicts learning ability in alpha neurofeedback

    Directory of Open Access Journals (Sweden)

    Wenya eNan

    2014-07-01

    Full Text Available Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the training parameter changes between two periods, within a short period and across the whole training time. It was found that the resting alpha amplitude measured before training had significant positive correlations with all learning indices and could be used as a predictor for the learning ability prediction. This finding would help the researchers in not only predicting the training efficacy in individuals but also gaining further insight into the mechanisms of alpha neurofeedback.

  8. Alpha scintillation radon counting

    International Nuclear Information System (INIS)

    Radon counting chambers which utilize the alpha-scintillation properties of silver activated zinc sulfide are simple to construct, have a high efficiency, and, with proper design, may be relatively insensitive to variations in the pressure or purity of the counter filling. Chambers which were constructed from glass, metal, or plastic in a wide variety of shapes and sizes were evaluated for the accuracy and the precision of the radon counting. The principles affecting the alpha-scintillation radon counting chamber design and an analytic system suitable for a large scale study of the 222Rn and 226Ra content of either air or other environmental samples are described. Particular note is taken of those factors which affect the accuracy and the precision of the method for monitoring radioactivity around uranium mines

  9. MicroRNA expression in melanocytic nevi: the usefulness of formalin-fixed, paraffin-embedded material for miRNA microarray profiling

    DEFF Research Database (Denmark)

    Glud, Martin; Klausen, Mikkel; Gniadecki, Robert;

    2009-01-01

    MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate cellular differentiation, proliferation, and apoptosis. MiRNAs are expressed in a developmentally regulated and tissue-specific manner. Aberrant expression may contribute to pathological processes such as cancer, and miRNA may...... therefore serve as biomarkers that may be useful in a clinical environment for diagnosis of various diseases. Most miRNA profiling studies have used fresh tissue samples. However, in some types of cancer, including malignant melanoma, fresh material is difficult to obtain from primary tumors, and most...... surgical specimens are formalin fixed and paraffin embedded (FFPE). To explore whether FFPE material would be suitable for miRNA profiling in melanocytic lesions, we compared miRNA expression patterns in FFPE versus fresh frozen samples, obtained from 15 human melanocytic nevi. Out of microarray data, we...

  10. The temperature dependence of optically stimulated luminescence from α-Al2O3:C

    DEFF Research Database (Denmark)

    Markey, B.G.; McKeever, S.W.S.; Akselrod, M.S.;

    1996-01-01

    The results of experimental measurements and computer simulations on optically stimulated luminescence (OSL) from alpha-Al2O3:C are described. The intensity of the OSL observed during illumination of irradiated specimens with visible light is temperature dependent. Optical stimulation is observed...

  11. Rossi Alpha Method

    International Nuclear Information System (INIS)

    The Rossi Alpha Method has proved to be valuable for the determination of prompt neutron lifetimes in fissile assemblies having known reproduction numbers at or near delayed critical. This workshop report emphasizes the pioneering applications of the method by Dr. John D. Orndoff to fast-neutron critical assemblies at Los Alamos. The value of the method appears to disappear for subcritical systems where the Rossi-α is no longer an α-eigenvalue

  12. The anti-inflammatory mechanisms of α-melanocyte-stimulating hormone%α-黑色素细胞刺激素的抗炎机制

    Institute of Scientific and Technical Information of China (English)

    陈波; 胡巢凤; 王华东; 林晨; 李楚杰

    2001-01-01

    α-MSH is an endogenous neuropetide that is effective of all categories of expreimental inflammation. The mechanisms underlying the anti-inflammatory influence of α-MSH are reviewed in the article. α-MSH suppresses inflammation in the CNS and periphery by downregulating the activation of NF-κB, then inhibiting production of proinflammatory cytokines, nitric oxide, chemokines and adhension molecules, and increasing synthesis of anti-inflammatory cytokines. α-MSH is useful in the treatment of many pathological situations in humans.

  13. Enhanced Cationic Charge is a Key Factor in Promoting Staphylocidal Activity of α-Melanocyte Stimulating Hormone via Selective Lipid Affinity.

    Science.gov (United States)

    Singh, Jyotsna; Joshi, Seema; Mumtaz, Sana; Maurya, Nancy; Ghosh, Ilora; Khanna, Shivangi; Natarajan, Vivek T; Mukhopadhyay, Kasturi

    2016-01-01

    The steady rise in antimicrobial resistance poses a severe threat to global public health by hindering treatment of an escalating spectrum of infections. We have previously established the potent activity of α-MSH, a 13 residue antimicrobial peptide, against the opportunistic pathogen Staphylococcus aureus. Here, we sought to determine whether an increase in cationic charge in α-MSH could contribute towards improving its staphylocidal potential by increasing its interaction with anionic bacterial membranes. For this we designed novel α-MSH analogues by replacing polar uncharged residues with lysine and alanine. Similar to α-MSH, the designed peptides preserved turn/random coil conformation in artificial bacterial mimic 1,2-dimyristoyl-sn-glycero-3-phosphocholine:1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (7:3, w/w) vesicles and showed preferential insertion in the hydrophobic core of anionic membranes. Increased cationic charge resulted in considerable augmentation of antibacterial potency against MSSA and MRSA. With ~18-fold better binding than α-MSH to bacterial mimic vesicles, the most charged peptide KKK-MSH showed enhanced membrane permeabilization and depolarization activity against intact S. aureus. Scanning electron microscopy confirmed a membrane disruptive mode of action for KKK-MSH. Overall, increasing the cationic charge improved the staphylocidal activity of α-MSH without compromising its cell selectivity. The present study would help in designing more effective α-MSH-based peptides to combat clinically relevant staphylococcal infections. PMID:27526963

  14. Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in α-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells

    OpenAIRE

    Yoon, Hoon-Seok; Hyun, Chang-Gu; Lee, Nam-Ho; Park, Sung-Soo; Shin, Dong-Bum

    2016-01-01

    Previous research showed that resveratrol (trans-3,4′,5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4′,5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. ...

  15. Efficacy of the melanocortin analogue Nle4-D-Phe7-α-melanocyte-stimulating hormone in the treatment of patients with Hailey–Hailey disease

    OpenAIRE

    Biolcati, G; Aurizi, C; Barbieri, L; Cialfi, S; Screpanti, I; Talora, C

    2013-01-01

    Background Hailey–Hailey disease (HHD) is a rare, chronic and recurrent blistering disorder, which is characterized clinically by erosions occurring primarily in intertriginous regions, and histologically by suprabasal acantholysis. Oxidative stress plays a specific role in the pathogenesis of HHD, by regulating the expression of factors playing an important role in keratinocyte proliferation and differentiation. Aim Given the significance of oxidative stress in HHD, we investigated the poten...

  16. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-11-01

    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  17. Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation

    OpenAIRE

    Vincent-Naulleau Silvia; Geffrotin Claudine; Bernex Florence; Bossé Philippe; Julé Sophia; Egidy Giorgia; Horak Vratislav; Sastre-Garau Xavier; Panthier Jean-Jacques

    2008-01-01

    Abstract Background Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. Results We compared the serial analysis of gene expression (SAGE) between n...

  18. Alpha-globin loci in homozygous beta-thalassemia intermedia.

    Science.gov (United States)

    Triadou, P; Lapoumeroulie, C; Girot, R; Labie, D

    1983-01-01

    Homozygous beta-thalassemia intermediate (TI) differs from thalassemia major (TM) in being less severe clinically. Associated alpha-thalassemia could account for the TI phenotype by reducing the alpha/non-alpha chain imbalance. We have analyzed the alpha loci of 9 TI and 11 TM patients by restriction endonuclease mapping. All the TM and 7 of the TI patients have the normal complement of four alpha-globin genes (alpha alpha/alpha alpha). One TI patient has three alpha-globin genes (alpha alpha/-alpha), and another TI patient has five alpha genes (alpha alpha/alpha alpha alpha). PMID:6305827

  19. MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes.

    Science.gov (United States)

    Wang, Pengchao; Zhao, Yuanyuan; Fan, Ruiwen; Chen, Tianzhi; Dong, Changsheng

    2016-01-01

    MicroRNAs (miRNAs) play an important role in regulating almost all biological processes. miRNAs bind to the 3' untranslated region (UTR) of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3' UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF) and Tyrosinase (TYR) were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5. PMID:27347933

  20. MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes

    Directory of Open Access Journals (Sweden)

    Pengchao Wang

    2016-06-01

    Full Text Available MicroRNAs (miRNAs play an important role in regulating almost all biological processes. miRNAs bind to the 3′ untranslated region (UTR of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3′ UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF and Tyrosinase (TYR were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5.

  1. High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes

    DEFF Research Database (Denmark)

    Sandmand, Marie; Bruunsgaard, Helle; Kemp, Kåre;

    2003-01-01

    humans. METHODS: TNF-alpha production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14, 81-year-olds and 25 centenarians. RESULTS: Plasma levels of TNF-alpha increased with increasing age. An...

  2. Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.;

    1999-01-01

    Ageing is associated with decreased resistance to bacterial infections and concomitant increased circulating levels of inflammatory cytokines. The purpose of the present study was to research age-related changes in levels of early mediators of the acute-phase response in whole blood supernatants...... following LPS stimulation, representing an ex vivo model of sepsis. Levels of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6 in whole blood supernatants were measured after in vitro LPS stimulation for 24 h in 168 elderly humans aged 81 years from the 1914 cohort in Glostrup, Denmark and in 91...... proinflammatory cytokines compared with young men, but this difference was blurred by ageing. No relation was found between circulating plasma levels of TNF-alpha and levels after in vitro LPS stimulation. In conclusion, decreased production of TNF-alpha and IL-1 beta after exposure to LPS may reflect impaired...

  3. Perineural alpha(2A)-adrenoceptor activation inhibits spinal cord neuroplasticity and tactile allodynia after nerve injury.

    OpenAIRE

    Lavand'homme, Patricia; Ma, Weiya; Kock, Marc De; Eisenach, James C.

    2002-01-01

    BACKGROUND: Nerve injury in animals increases alpha(2)-adrenoceptor expression in dorsal root ganglion cells and results in novel excitatory responses to their activation, perhaps leading to the phenomenon of sympathetically maintained pain. In contrast to this notion, peripheral alpha(2)-adrenoceptor stimulation fails to induce pain in patients with chronic pain. We hypothesized that alpha(2) adrenoceptors at the site of nerve injury play an inhibitory, not excitatory role. METHODS: Partial ...

  4. Deep Brain Stimulation

    OpenAIRE

    Perlmutter, Joel. S.; Mink, Jonathan W.

    2006-01-01

    Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting t...

  5. On the possible role of stimulation duration for after-effects of transcranial alternating current stimulation

    Directory of Open Access Journals (Sweden)

    Stefan Rach

    2015-08-01

    Full Text Available Transcranial alternating current stimulation is a novel method that allows application of sinusoidal currents to modulate brain oscillations and cognitive processes. Studies in humans have demonstrated tACS after-effects following stimulation durations in the range of minutes. However, such after-effects are absent in animal studies using much shorter stimulation protocols in the range of seconds. Thus, stimulation duration might be a critical parameter for after-effects to occur. To test this hypothesis, we repeated a recent human tACS experiment with a short duration. We applied alpha tACS intermittently for one second duration while keeping other parameters identical. The results demonstrate that this very short intermittent protocol did not produce after-effects on amplitude or phase of the electroencephalogram. Since synaptic plasticity has been suggested as a possible mechanism for after-effects, our results indicate that a stimulation duration of one second is too short to induce synaptic plasticity. Future studies in animals are required that use extended stimulation durations to reveal the neuronal underpinnings. A better understanding of the mechanisms of tACS after-effects is crucial for potential clinical applications.

  6. A modified fluorimetric host cell reactivation assay to determine the repair capacity of primary keratinocytes, melanocytes and fibroblasts

    Directory of Open Access Journals (Sweden)

    Gebhard Daniel

    2010-06-01

    Full Text Available Abstract Background The Host Cell Reactivation Assay (HCRA is widely used to identify circumstances and substances affecting the repair capacity of cells, however, it is restricted by the transfection procedure used and the sensitivity of the detection method. Primary skin cells are particularly difficult to transfect, and therefore sensitive methods are needed to detect any variations due to the cell-type or inter-individual differences or changes induced by diverse substances. A sensitive and repeatable method to detect the repair capacity of skin cells would be useful in two different aspects: On the one hand, to identify substances influencing the repair capacity in a positive manner (these substances could be promising ingredients for cosmetic products and on the other hand, to exclude the negative effects of substances on the repair capacity (this could serve as one step further towards replacing or at least reducing animal testing. Results In this paper, we present a rapid and sensitive assay to determine the repair capacity of primary keratinocytes, melanocytes and fibroblasts based on two wave-length Green Fluorescent Protein (GFP and DsRed reporter technology in order to test different substances and their potential to influence the DNA repair capacity. For the detection of plasmid restoration, we used FACS technology, which, in comparison to luminometer technology, is highly sensitive and allows single cell based analysis. The usefulness of this assay and studying the repair capacity is demonstrated by the evidence that DNA repair is repressed by Cyclosporin A in fibroblasts. Conclusions The methodology described in this paper determines the DNA repair capacity in different types of human skin cells. The described transfection protocol is suitable for the transfection of melanocytes, keratinocytes and fibroblasts, reaching efficacies suitable for the detection of the restored plasmids by FACS technology. Therefore the repair capacity

  7. Stimulant Use Disorders.

    Science.gov (United States)

    Park, Taryn M; Haning, William F

    2016-07-01

    Compared with other illicit substances, stimulants are not commonly used by adolescents; however, they represent a serious concern regarding substance use among youths. This article uses methamphetamine as a model for stimulant use in adolescents; cocaine and prescription stimulants are also mentioned. Methamphetamine use among adolescents and young adults is a serious health concern with potentially long-term physical, cognitive, and psychiatric consequences. Brain development and the effects of misusing stimulants align such that usage in adolescents can more dangerous than during adulthood. It seems helpful to keep in mind the differences between adolescents and young adults when implementing interventions. PMID:27338967

  8. The Response of microRNAs to Solar UVR in Skin-Resident Melanocytes Differs between Melanoma Patients and Healthy Persons.

    Directory of Open Access Journals (Sweden)

    Jingfeng Sha

    Full Text Available The conversion of melanocytes into cutaneous melanoma is largely dictated by the effects of solar ultraviolet radiation (UVR. Yet to be described, however, is exactly how these cells are affected by intense solar UVR while residing in their natural microenvironment, and whether their response differs in persons with a history of melanoma when compared to that of healthy individuals. By using laser capture microdissection (LCM to isolate a pure population of melanocytes from a small area of skin that had been intermittingly exposed or un-exposed to physiological doses of solar UVR, we can now report for the first time that the majority of UV-responsive microRNAs (miRNAs in the melanocytes of a group of women with a history of melanoma are down-regulated when compared to those in the melanocytes of healthy controls. Among the miRNAs that were commonly and significantly down-regulated in each of these women were miR-193b (P<0.003, miR-342-3p (P<0.003, miR186 (P<0.007, miR-130a (P<0.007, and miR-146a (P<0.007. To identify genes potentially released from inhibition by these repressed UV-miRNAs, we analyzed databases (e.g., DIANA-TarBase containing experimentally validated microRNA-gene interactions. In the end, this enabled us to construct UV-miRNA-gene regulatory networks consisting of individual genes with a probable gain-of-function being intersected not by one, but by several down-regulated UV-miRNAs. Most striking, however, was that these networks typified well-known regulatory modules involved in controlling the epithelial-to-mesenchymal transition and processes associated with the regulation of immune-evasion. We speculate that these pathways become activated by UVR resulting in miRNA down regulation only in melanocytes susceptible to melanoma, and that these changes could be partially responsible for empowering these cells toward tumor progression.

  9. The Response of microRNAs to Solar UVR in Skin-Resident Melanocytes Differs between Melanoma Patients and Healthy Persons.

    Science.gov (United States)

    Sha, Jingfeng; Gastman, Brian R; Morris, Nathan; Mesinkovska, Natasha A; Baron, Elma D; Cooper, Kevin D; McCormick, Thomas; Arbesman, Joshua; Harter, Marian L

    2016-01-01

    The conversion of melanocytes into cutaneous melanoma is largely dictated by the effects of solar ultraviolet radiation (UVR). Yet to be described, however, is exactly how these cells are affected by intense solar UVR while residing in their natural microenvironment, and whether their response differs in persons with a history of melanoma when compared to that of healthy individuals. By using laser capture microdissection (LCM) to isolate a pure population of melanocytes from a small area of skin that had been intermittingly exposed or un-exposed to physiological doses of solar UVR, we can now report for the first time that the majority of UV-responsive microRNAs (miRNAs) in the melanocytes of a group of women with a history of melanoma are down-regulated when compared to those in the melanocytes of healthy controls. Among the miRNAs that were commonly and significantly down-regulated in each of these women were miR-193b (P<0.003), miR-342-3p (P<0.003), miR186 (P<0.007), miR-130a (P<0.007), and miR-146a (P<0.007). To identify genes potentially released from inhibition by these repressed UV-miRNAs, we analyzed databases (e.g., DIANA-TarBase) containing experimentally validated microRNA-gene interactions. In the end, this enabled us to construct UV-miRNA-gene regulatory networks consisting of individual genes with a probable gain-of-function being intersected not by one, but by several down-regulated UV-miRNAs. Most striking, however, was that these networks typified well-known regulatory modules involved in controlling the epithelial-to-mesenchymal transition and processes associated with the regulation of immune-evasion. We speculate that these pathways become activated by UVR resulting in miRNA down regulation only in melanocytes susceptible to melanoma, and that these changes could be partially responsible for empowering these cells toward tumor progression. PMID:27149382

  10. Interferon-alpha induced depressive-like behavior in rats

    DEFF Research Database (Denmark)

    Fischer, C. W.; Liebenberg, N.; Elfving, B.;

    2013-01-01

    Background: A subpopulation of individuals with major depressive disorder (MDD) show increased levels of peripheral inflammatory biomarkers, indicating an association of MDD with a chronically activated immune system. Administration of the immune stimulating cytokine, interferon-alpha (IFN......-(alpha)), also used in the treatment of cancer and hepatitis, commonly leads to neuropsychiatric side effects with approximately 16- 45% of patients developing depressive-like symptoms during the course of therapy. Given that treatmentresistant depression has been associated with increased levels of inflammatory...... markers, the development of an inflammation-induced model of depression is highly relevant. Aim: The objective of this study was to investigate whether IFN-(alpha) can induce a chronic low-grade inflammatory state in rats, and whether this may lead to a depressive phenotype. Methods: Male Sprague...

  11. Unfolding domains of recombinant fusion alpha alpha-tropomyosin.

    OpenAIRE

    Ishii, Y; Hitchcock-DeGregori, S.; Mabuchi, K; Lehrer, S S

    1992-01-01

    The thermal unfolding of the coiled-coil alpha-helix of recombinant alpha alpha-tropomyosin from rat striated muscle containing an additional 80-residue peptide of influenza virus NS1 protein at the N-terminus (fusion-tropomyosin) was studied with circular dichroism and fluorescence techniques. Fusion-tropomyosin unfolded in four cooperative transitions: (1) a pretransition starting at 35 degrees C involving the middle of the molecule; (2) a major transition at 46 degrees C involving no more ...

  12. Bi209 alpha activity

    International Nuclear Information System (INIS)

    The study for measuring Bi209 alpha activity is presented. Ilford L4 nuclear emulsion pellicles loaded with bismuth citrate to obtain a load of 100 mg/cm3 of dry emulsion, were prepared. Other pellicles were prepared with the same. Ilford L4 gel to estimate the background radiation. To observe 'fading' effect, pellicles loaded with bismuth were submitted to neutrons of high energy, aiming to record recoil proton tracks. The pellicles were confined in nitrogen atmosphere at temperature lower than -100C. The Bi209 experimental half-life was obtained and compared with the estimated theoretical data. (M.C.K.)

  13. PANP is a novel O-glycosylated PILR{alpha} ligand expressed in neural tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kogure, Amane [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Shiratori, Ikuo [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Wang, Jing [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Lanier, Lewis L. [Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 (United States); Arase, Hisashi, E-mail: arase@biken.osaka-u.ac.jp [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); JST CREST, Saitama 332-0012 (Japan)

    2011-02-18

    Research highlights: {yields} A Novel molecule, PANP, was identified to be a PILR{alpha} ligand. {yields} Sialylated O-glycan structures on PANP were required for PILR{alpha} recognition. {yields} Transcription of PANP was mainly observed in neural tissues. {yields} PANP seems to be involved in immune regulation as a ligand for PILR{alpha}. -- Abstract: PILR{alpha} is an immune inhibitory receptor possessing an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain enabling it to deliver inhibitory signals. Binding of PILR{alpha} to its ligand CD99 is involved in immune regulation; however, whether there are other PILR{alpha} ligands in addition to CD99 is not known. Here, we report that a novel molecule, PILR-associating neural protein (PANP), acts as an additional ligand for PILR{alpha}. Transcription of PANP was mainly observed in neural tissues. PILR{alpha}-Ig fusion protein bound cells transfected with PANP and the transfectants stimulated PILR{alpha} reporter cells. Specific O-glycan structures on PANP were found to be required for PILR recognition of this ligand. These results suggest that PANP is involved in immune regulation as a ligand of the PILR{alpha}.

  14. Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: A new subtype of albinism classified as {open_quotes}OCA3{close_quotes}

    Energy Technology Data Exchange (ETDEWEB)

    Boissy, R.E.; Zhao, H.; Austin, L.M.; Boissy, Y.L.; Zhao, Y. [Univ. of Cincinnati College of Medicine, OH (United States)] [and others

    1996-06-01

    Most types of human oculocutaneous albinism (OCA) result from mutations in the gene for tyrosinase (OCA1) or the P protein (OCA2), although other types of OCA have been described but have not been mapped to specific loci. Melanocytes were cultured from an African-American with OCA, who exhibited the phenotype of Brown OCA, and his normal fraternal twin. Melanocytes cultured from the patient with OCA and the normal twin appeared brown versus black, respectively. Melanocytes from both the patient with OCA and the normal twin demonstrated equal amounts of NP-40-soluble melanin; however, melanocytes from the patient with OCA contained only 7% of the amount of insoluble melanin found from the normal twin. Tyrosinase-related protein-1 (TRP-1) was not detected in the OCA melanocytes by use of various anti-TRP-1 probes. Furthermore, transcripts for TRP-1 were absent in cultured OCA melanocytes. The affected twin was homozygous for a single-bp deletion in exon 6, removing an A in codon 368 and leading to a premature stop at codon 384. Tyrosine hydroxylase activity of the OCA melanocytes was comparable to controls when assayed in cell lysates but was only 30% of controls when assayed in intact cells. We conclude that this mutation of the human TRP-1 gene affects its interaction with tyrosinase, resulting in dysregulation of tyrosinase activity, promotes the synthesis of brown versus black melanin, and is responsible for a third genetic type of OCA in humans, which we classify as {open_quotes}OCA3.{close_quotes} 69 refs., 7 figs., 3 tabs.

  15. Epidemiology of Melanocytic Naevi in Children from Lleida, Catalonia, Spain: Protective Role of Sunscreen in the Development of Acquired Moles.

    Science.gov (United States)

    Moreno, Sara; Soria, Xavier; Martínez, Montserrat; Martí, Rosa M; Casanova, Josep M

    2016-04-12

    The worldwide incidence of malignant melanoma is increasing. The number of pigmented naevi and amount of solar exposure are important risk factors. The aim of this study was to characterize a paediatric population (from Lleida, Catalonia, Spain) in terms of phenotype, sun behaviour and naevi prevalence. Data on the numbers and distributions of acquired naevi in 369 children, aged 4, 8 and 14 years, were collected and correlated with age, sex, skin phototype and environmental factors (annual/lifetime intermittent and chronic sun exposure, sunburns and sunscreen use). The density of naevi increased with age. Boys had more naevi on the trunk and girls had more naevi on the legs. Children with light skin phototype had more naevi. A higher level of accumulated sun exposure correlated with a higher number of naevi in children with non-adequate sunscreen use. In conclusion, several risk factors associated with naevi density and distribution were found, as previously reported by others. Multivariate analysis confirmed a protective role of sunscreen in the development of acquired melanocytic naevi. PMID:26551264

  16. Correction of defective early tyrosinase processing by bafilomycin A1 and monensin in pink-eyed dilution melanocytes.

    Science.gov (United States)

    Chen, Kun; Minwalla, Ljiljana; Ni, Li; Orlow, Seth J

    2004-02-01

    Mutations in the human P gene result in oculocutaneous albinism type 2, the most common form of albinism. Mouse melan-p1 melanocytes, cultured from mice null at the homologous pink-eyed dilution (p) locus, exhibit defective melanin production. A variety of compounds including tyrosine, NH4Cl, bafilomycin A1, concanamycin, monensin, and nigericin are capable of restoring melanin synthesis in these cells. In the current study, we investigated the subcellular effects of bafilomycin A1 and monensin treatment of melan-p1 cells. Both agents play two roles in the processing of tyrosinase (Tyr) in melan-p1 cells. First, combined glycosidase digestion and immunoblotting analysis showed that these agents reduce levels of Tyr retained in the endoplasmic reticulum (ER) and facilitate the release of Tyr from the ER to the Golgi. Secondly, treatment with these compounds resulted in the stabilization of Tyr. Surprisingly, induction of melanin synthesis corresponds more closely with diminution of ER-retained Tyr, rather than the absolute amount of Tyr. Our results suggest that bafilomycin A1 and monensin induce melanin synthesis in melan-p1 cells mainly by facilitating Tyr processing from the ER to the Golgi by increasing the pH in either the ER or the ER-Golgi intermediate compartment. PMID:14717843

  17. Altered melanocyte differentiation and retinal pigmented epithelium transdifferentiation induced by Mash1 expression in pigment cell precursors.

    Science.gov (United States)

    Lanning, Jessica L; Wallace, Jaclyn S; Zhang, Deming; Diwakar, Ganesh; Jiao, Zhongxian; Hornyak, Thomas J

    2005-10-01

    Transcription factor genes governing pigment cell development that are associated with spotting mutations in mice include members of several structural transcription factor classes but not members of the basic helix-loop-helix (bHLH) class, important for neurogenesis and myogenesis. To determine the effects of bHLH factor expression on pigment cell development, the neurogenic bHLH factor Mash1 was expressed early in pigment cell development in transgenic mice from the dopachrome tautomerase (Dct) promoter. Dct:Mash1 transgenic founders exhibit variable microphthalmia and patchy coat color hypopigmentation. Transgenic F1 mice exhibit microphthalmia with complete coat color dilution. Marker analysis demonstrates that Mash1 expression in the retinal pigmented epithelium (RPE) initiates neurogenesis in this cell layer, whereas expression in remaining neural crest-derived melanocytes alters their differentiation, in part by profoundly downregulating expression of the p (pink-eyed dilution) gene, while maintaining their cell fate. The effects of transcriptional perturbation of pigment cell precursors by Mash1 further highlight differences between pigment cells of distinct developmental origins, and suggest a mechanism for the alteration of melanogenesis to result in marked coat color dilution. PMID:16185282

  18. Human breast cancer cell lines co-express neuronal, epithelial, and melanocytic differentiation markers in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Qingbei Zhang

    Full Text Available Differentiation programs are aberrant in cancer cells allowing them to express differentiation markers in addition to their tissue of origin. In the present study, we demonstrate the multi-lineage differentiation potential of breast cancer cell lines to express multiple neuronal/glial lineage-specific markers as well as mammary epithelial and melanocytic-specific markers. Multilineage expression was detected in luminal (MCF-7 and SKBR3 and basal (MDA-MB-231 types of human breast cancer cell lines. We also observed comparable co-expression of these three cell lineage markers in MDA-MB-435 cells in vitro, in MDA-MB-435 primary tumors derived from parental and single cell clones and in lung metastases in vivo. Furthermore, ectoderm multi-lineage transdifferentiation was also found in human melanoma (Ul-MeL and glioblastoma cell lines (U87 and D54. These observations indicate that aberrant multi-lineage transdifferentiation or lineage infidelity may be a wide spread phenomenon in cancer.

  19. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-04-22

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

  20. Background canceling surface alpha detector

    International Nuclear Information System (INIS)

    A background canceling long range alpha detector which is capable of providing output proportional to both the alpha radiation emitted from a surface and to radioactive gas emanating from the surface. The detector operates by using an electrical field between first and second signal planes, an enclosure and the surface or substance to be monitored for alpha radiation. The first and second signal planes are maintained at the same voltage with respect to the electrically conductive enclosure, reducing leakage currents. In the presence of alpha radiation and radioactive gas decay, the signal from the first signal plane is proportional to both the surface alpha radiation and to the airborne radioactive gas, while the signal from the second signal plane is proportional only to the airborne radioactive gas. The difference between these two signals is proportional to the surface alpha radiation alone. 5 figs

  1. Alpha activity measurement with lsc

    International Nuclear Information System (INIS)

    Recently, we showed that the alpha activity in liquid samples can be measured using a liquid scintillation analyzer without alpha/beta discrimination capability. The purpose of this work was to evaluate the performances of the method and to optimize the procedure of the sample preparation. A series of tests was performed to validate the procedure of alpha emitting radionuclides extraction in aqueous samples with Actinide Resin, especially regarding to the contact time required to extract all alpha nuclides. The main conclusions were that a minimum 18 hours stirring time is needed to achieve a percent recovery of the alpha nuclides grater than 90% and that the counting efficiency of alphas measurements with LSC is nearly 100%. (authors)

  2. Robust Estimation of Cronbach's Alpha

    OpenAIRE

    Christmann, A.; Van Aelst, Stefan

    2002-01-01

    Cronbach’s alpha is a popular method to measure reliability, e.g. in quantifying the reliability of a score to summarize the information of several items in question- naires. The alpha coefficient is known to be non-robust. We study the behavior of this coefficient in different settings to identify situations, which can easily occur in practice, but under which the Cronbach’s alpha coefficient is extremely sensitive to violations of the classical model assumptions. Furthermore,...

  3. Mathematical model of cAMP-dependent signaling pathway in constitutive and UV-induced melanogenesis

    Science.gov (United States)

    Stolnitz, Mikhail M.; Peshkova, Anna Y.

    2002-07-01

    Cascade of reactions of cAMP-dependent signaling pathway in melanocytes is investigated by mathematical modeling. Model takes into account (alpha) -melanocyte stimulating hormone binding to melanocortin-1 receptor, adenylate cyclase activation by G-protein, increase of the intracellular cAMP concentration, PKA activation by cAMP, CREB phosphorylation by PKA, microphthalmia gene expression, microphthalmia binding to tyrosinase gene promoter, increase of tyrosinase synthesis. Positive and negative feedback loops of this system are analyzed.

  4. Sequenciamento e análise dos genes das subunidades alfa e beta do hormônio folículo estimulante de bovino (Bos taurus indicus Sequencing and analysis of subunits alpha and beta of the follicle stimulating hormone from bovine (Bos taurus indicus

    Directory of Open Access Journals (Sweden)

    Luci Sayori Murata

    2008-07-01

    of the subunits alpha and beta of the Bos taurus indicus follicle stimulated hormone (FSH. It to compare the results of sequencing these subunits between subunits aplha and beta from swine and Bos taurus taurus previouly published in GenBank. There was a high similarity between nucleotides and predicted amino acids in the αFSH chain of Bos taurus indicus and those of swine and buffalo. In the compare the sequence of the subunit of αFSH of Bos taurus indicus with swine showed differences in three aminoacid residues with ßFSH there was a modification in the first base of the codon, which had to an alteration in the 83 amino acid residue which in Bos taurus indicus and a glycin, this was serine in Bos taurus taurus. This modification, as well as those indentyfied in cDNA of the αFSH and ßFSH chains were confirmed by cloning. The modification of serine for glycine in position 83 was the only substitute that altered the residue in the comparson between ßFSH subunit of Bos taurus indicus and Bos taurus taurus. Nevertheles this modification showld not significantly alter the physiological properties of FSH as the glycine residue was also found in the swine ßFSH, it is therefore a specific modification which distinguishes between the ßFSH of Bos taurus taurus and Bos taurus indicus.

     

    KEY WORDS: Bovine, cloning, FSH, hormone.

  5. Effect of chemicals on fungal alpha-amylase activity.

    Science.gov (United States)

    Ali, F S; Abdel-Moneim, A A

    1989-01-01

    The effect of 8 growth regulators at concentrations of 1,000, 5,000 and 10,000 ppm on the activity of fungal (Aspergillus flavus var. columnaris) alpha-amylase was studied. Indol acetic acid (IAA) and naphthalene acetic acid (NAA) inhibited alpha-amylase activity by 2% and 7% at 1,000 ppm. The other 6 growth regulators, indol butyric acid (IBA), gibberellic acid, cumarin, cycocel (CCC), atonik-G and kylar, did not inhibit but stimulated alpha-amylase activity (0 to 9%) at 1,000 ppm. All growth regulators studied inhibited alpha-amylase activity at 5,000 and 10,000 ppm concentration except kylar. The effect of organic acids and formaldehyde at 0.01, 0.005, and 0.001 M was studied. Acetic acid stimulated alpha-amylase at all concentrations, but formic acid, oxalic acid, lactic acid and citric acid inhibited alpha-amylase activity by 91, 100, 100 and 79%, respectively, at a concentration of 0.01 M, while by 31, 100, 15 and 20%, respectively, at 0.005 M. Formaldehyde induced 7, 3 and 2% inhibition at 0.01, 0.005 and 0.001 M, respectively. At 0.01 M either sorbitol or fructose inhibited alpha-amylase by 8%, Maltose 7%, sucrose 6%, phenol, glucose and galactose each by 5%, ethanol, glycerol, arabinose and sodium benzoate each by 4%, isopropanol and mannitol 1%, but methanol and ammonium citrate dibasic did not inhibit alpha-amylase. The results indicate that CuCl2, SnCl2, AgNO3 and Fe2(SO4)3 were the strongest inhibitors, followed by Cd(C2H3O2), HgCl2, Na2-EDTA, Na2HPO4, and CaCl2 in decreasing order. NaCl, NaBr and Mn SO4 did not inhibit alpha-amylase at concentrations from 10 mM to 0.01 mM. PMID:2515680

  6. The vascular smooth muscle alpha-actin gene is reactivated during cardiac hypertrophy provoked by load.

    OpenAIRE

    Black, F M; Packer, S E; Parker, T G; Michael, L H; Roberts, R; R J Schwartz; Schneider, M D

    1991-01-01

    Cardiac hypertrophy triggered by mechanical load possesses features in common with growth factor signal transduction. A hemodynamic load provokes rapid expression of the growth factor-inducible nuclear oncogene, c-fos, and certain peptide growth factors specifically stimulate the "fetal" cardiac genes associated with hypertrophy, even in the absence of load. These include the gene encoding vascular smooth muscle alpha-actin, the earliest alpha-actin expressed during cardiac myogenesis; howeve...

  7. Characterization of a mutant calcineurin A alpha gene expressed by EL4 lymphoma cells.

    OpenAIRE

    Fruman, D A; Pai, S Y; Burakoff, S J; Bierer, B E

    1995-01-01

    The calmodulin-stimulated phosphatase calcineurin plays a critical role in calcium-dependent T-lymphocyte activation pathways. Here, we report the identification of a missense mutation in the calcineurin A alpha gene expressed by EL4 T-lymphoma cells. This mutation changes an evolutionarily conserved aspartic acid to asparagine within the autoinhibitory domain of the calcineurin A alpha protein. A comparison of wild-type and mutant autoinhibitory peptides indicates that this amino acid substi...

  8. TNF-alpha impairs the S-G2/M cell cycle checkpoint and cyclobutane pyrimidine dimer repair in premalignant skin cells: Role of the PI3K-Akt pathway

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.; Calay, D.;

    2008-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is induced by UVB radiation and has been implicated in the early stages of skin carcinogenesis. Here, we show that in normal keratinocytes and the transformed keratinocyte cell lines, HaCaT and A431, TNF-alpha stimulates protein kinase B/Akt, which results ...

  9. Lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells : Intracellular localization of tumor necrosis factor alpha and interleukin 1 beta detected with a three-color immunofluorescence technique

    NARCIS (Netherlands)

    deBont, ESJM; Niemarkt, AE; Tamminga, RYJ; Kimpen, JLL; Kamps, WA; deLeij, LHMF

    1996-01-01

    Lipopolysaccharide (LPS) can induce monocytes to produce various cytokines such as tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta). In the present study, the kinetics of both intracellular and extra cellular accumulation of TNF alpha and IL-1 beta in LPS stimulated mononuc

  10. The regulatory mechanism of Hsp90{alpha} secretion from endothelial cells and its role in angiogenesis during wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xiaomin [National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Luo, Yongzhang, E-mail: yluo@tsinghua.edu.cn [National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084 (China)

    2010-07-16

    Research highlights: {yields} Growth factors such as bFGF, VEGF, PDGF and SDF-1 stimulate Hsp90{alpha} secretion from endothelial cells. {yields} Secreted Hsp90{alpha} localizes on the leading edge of activated endothelial cells. {yields} Secreted Hsp90{alpha} promotes angiogenesis in wound healing. -- Abstract: Heat shock protein 90{alpha} (Hsp90{alpha}) is a ubiquitously expressed molecular chaperone, which is essential for the maintenance of eukaryote homeostasis. Hsp90{alpha} can also be secreted extracellularly and is associated with several physiological and pathological processes including wound healing, cancer, infectious diseases and diabetes. Angiogenesis, defined as the sprouting of new blood vessels from pre-existing capillaries via endothelial cell proliferation and migration, commonly occurs in and contributes to the above mentioned processes. However, the secretion of Hsp90{alpha} from endothelial cells and also its function in angiogenesis are still unclear. Here we investigated the role of extracellular Hsp90{alpha} in angiogenesis using dermal endothelial cells in vitro and a wound healing model in vivo. We find that the secretion of Hsp90{alpha} but not Hsp90{beta} is increased in activated endothelial cells with the induction of angiogenic factors and matrix proteins. Secreted Hsp90{alpha} localizes on the leading edge of endothelial cells and promotes their angiogenic activities, whereas Hsp90{alpha} neutralizing antibodies reverse the effect. Furthermore, using a mouse skin wound healing model in vivo, we demonstrate that extracellular Hsp90{alpha} localizes on blood vessels in granulation tissues of wounded skin and promotes angiogenesis during wound healing. Taken together, our study reveals that Hsp90{alpha} can be secreted by activated endothelial cells and is a positive regulator of angiogenesis, suggesting the potential application of Hsp90{alpha} as a stimulator for wound repair.

  11. TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C-alpha

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Lifen [Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan (China); Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637 (United States); The Committees on Immunology, The University of Chicago, Chicago, IL 60637 (United States); Qiao, Guilin; Ying, Haiyan [Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637 (United States); The Committees on Immunology, The University of Chicago, Chicago, IL 60637 (United States); Zhang, Jian, E-mail: jzhang@medicine.bsd.uchicago.edu [Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan (China); Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637 (United States); The Committees on Immunology, The University of Chicago, Chicago, IL 60637 (United States); The Committees on Molecular Medicine, The University of Chicago, Chicago, IL 60637 (United States); Yin, Fei, E-mail: yf2323@hotmail.com [Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan (China)

    2010-09-10

    Research highlights: {yields} Conventional PKC positively regulates TCR-induced phosphorylation of Akt. {yields} PKC-alpha is the PDK-2 responsible for phosphorylating Akt at Ser{sup 473} upon TCR stimulation. {yields} Knockdown of PKC-alpha decreases TCR-induced Akt phosphorylation. -- Abstract: Akt signaling plays a central role in T cell functions, such as proliferation, apoptosis, and regulatory T cell development. Phosphorylation at Ser{sup 473} in the hydrophobic motif, along with Thr{sup 308} in its activation loop, is considered necessary for Akt function. It is widely accepted that phosphoinositide-dependent kinase 1 (PDK-1) phosphorylates Akt at Thr{sup 308}, but the kinase(s) responsible for phosphorylating Akt at Ser{sup 473} (PDK-2) remains elusive. The existence of PDK-2 is considered to be specific to cell type and stimulus. PDK-2 in T cells in response to TCR stimulation has not been clearly defined. In this study, we found that conventional PKC positively regulated TCR-induced Akt Ser{sup 473} phosphorylation. PKC-alpha purified from T cells can phosphorylate Akt at Ser{sup 473} in vitro upon TCR stimulation. Knockdown of PKC-alpha in T-cell-line Jurkat cells reduced TCR-induced phosphorylation of Akt as well as its downstream targets. Thus our results suggest that PKC-alpha is a candidate for PDK-2 in T cells upon TCR stimulation.

  12. Stimulated Resonant Radiation

    CERN Document Server

    Clerici, M; Rubino, E; Moss, D; Couairon, A; Légaré, F; Morandotti, R; Faccio, D

    2014-01-01

    Resonant radiation (RR) is emitted by solitons propagating in a waveguide or by filamenting pulses in bulk media. Recent studies have highlighted the possibility to stimulate RR also in weaker pulses that co-propogate with a pump pulse. We numerically and experimentally demonstrate that RR radiation can be stimulated employing a THz seed co-propagating in diamond with an intense 800 nm pulse. This way we predict and observe the stimulated emission of RR at 425 nm, thus bridging a spectral gap of more than six octaves and allowing the detection of THz pulses by means of a silicon-based device.

  13. 玻璃酸钠对黑素细胞生物学活性的影响%Effects of hyaluronic acid on biological activity of melanocytes

    Institute of Scientific and Technical Information of China (English)

    洪为松; 钱国培; 许爱娥

    2011-01-01

    Objective To observe the effect of hyaluronic acid on the proliferation of and tyrosinase activity in melanocytes.Methods Normal primary human melanocytes were isolated from infant foreskin tissue and cultured.Different concentrations(0 to 10 g/L)of hyaluronic acid wero added to the culture medium immediately or 8 hours after the inoculation of melanocytes.MTT assay was performed to detect the proliferation of melanocytes,and tyrosinase activity was determined to evaluate the effect of hyaluronic acid on the melanin synthesis by melanocytes.Results The proliferation level (absorbance at 490 am,A490)of melanocytes was 0.14±0.02,0.37±0.08,0.45±0.11,0.49±0.07,0.55±0.12,0.52±0.11,0.49±0.07,0.39±0.05,0.19±0.03 and 0.01 4-0.01 when treated with hyaluronic acid of 0,0.008,0.016,0.313,0.625,1.250,2.500,5.000,7.500 and 10.000 g/L,respectively.The hyaluronic acid of 0.08 to 5 g/L markedly accelerated the proliferation of melanocytes,while that of 10 g/L inhibited their proliferation.The tyrosinase activity in melanocytes was promoted by hyaluronie acid of 0.2 to 5 g/L,but suppressed by that of 10 g/L.The proliferation of melanocytes treated with hyaluronic acid immediately after the inoculation was more rapid than that treated with hyaluronic acid 8 hours after the inoculation.Conclusion The hyaluronic acid of 0.2 to 5 g/L can enhance the proliferation of and tyrosinase activity in melanocytes.%目的 观察玻璃酸钠对黑素细胞增殖及酪氨酸酶活性的影响.方法 噻唑蓝法和酪氨酸酶活性测定法分别检测不同浓度玻璃酸钠对正常人黑素细胞生长和黑素合成能力的影响.结果 玻璃酸钠质量浓度为0,0.008、0.016、0.313、0.625、1.250、2.500、5.000、7.500、10.000 g/L时,黑素细胞增殖活性(A490)分别为0.14±0.02、0.37±0.08、0.45±0.11、0.49±0.07、0.55±0.12、0.52±0.11、0.49±0.07、0.39±0.05、0.19±0.03、0.01±0.01,玻璃酸钠质量浓度在0.08~5 g/L范围内时,对黑素细胞的

  14. Effect of Low-Level Laser Stimulation on EEG

    Directory of Open Access Journals (Sweden)

    Jih-Huah Wu

    2012-01-01

    Full Text Available Conventional laser stimulation at the acupoint can induce significant brain activation, and the activation is theoretically conveyed by the sensory afferents. Whether the insensible low-level Laser stimulation outside the acupoint could also evoke electroencephalographic (EEG changes is not known. We designed a low-level laser array stimulator (6 pcs laser diode, wavelength 830 nm, output power 7 mW, and operation frequency 10 Hz to deliver insensible laser stimulations to the palm. EEG activities before, during, and after the laser stimulation were collected. The amplitude powers of each EEG frequency band were analyzed. We found that the low-level laser stimulation was able to increase the power of alpha rhythms and theta waves, mainly in the posterior head regions. These effects lasted at least 15 minutes after cessation of the laser stimulation. The amplitude power of beta activities in the anterior head regions decreased after laser stimulation. We thought these EEG changes comparable to those in meditation.

  15. Alpha glucosidase inhibitors.

    Science.gov (United States)

    Kalra, Sanjay

    2014-04-01

    Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs. Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a pancreato -centred mechanism of action. Working to delay carbohydrate absorption in the gastrointestinal tract, they control postprandial hyperglycaemia and provide unquestioned cardiovascular benefit. Specially suited for a traditional Pakistani carbohydrate-rich diet, AGIs have been termed the 'untapped diamonds' of diabetology. The use of these oral antidiabetic drugs (OADs) that target pathophysiology in the early stages of type 2 diabetes, notably to reduce postprandial hyperglycaemia and hyperinsulinaemia will inevitably increase with time. This review describes the history of their development, mechanism of action, basic and clinical pharmacology, and suggests practical, evidence-based guidance for their optimal use. PMID:24864650

  16. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    International Nuclear Information System (INIS)

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with 125I-lipoproteins [human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)]. The media were then analyzed for lipoprotein protein coat degradation products (mainly 125I-monoiodotyrosine) and progestin [mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)]. In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production

  17. Thyrotropin-releasing hormone-induced depletion of G(q)alpha/G(11)alpha proteins from detergent-insensitive membrane domains.

    Science.gov (United States)

    Pesanová, Z; Novotný, J; Cerný, J; Milligan, G; Svoboda, P

    1999-12-24

    The role of detergent-insensitive membrane domains (DIMs) in desensitisation of the G protein-coupled receptor-mediated hormone response was studied in clone E2M11 of HEK293 cells which stably express high levels of both thyrotropin-releasing hormone (TRH) receptors and G(11)alpha G protein. DIMs were prepared by flotation in equilibrium sucrose density gradients and characterised by a panel of membrane markers representing peripheral, glycosylphosphatidylinositol-bound as well as integral membrane proteins (caveolin, CD29, CD55, CD59, CD147, the alpha subunit of Na, K-ATPase) and enzyme activities (alkaline phosphatase, adenylyl cyclase). Caveolin-containing DIMs represented only a small fraction of the overall pool of G(q)alpha/G(11)alpha-rich domains. Prolonged stimulation of E2M11 cells with TRH resulted in dramatic depletion of G(q)alpha/G(11)alpha from all DIMs, which was paralleled by a concomitant G(q)alpha/G(11)alpha increase in the high-density gradient fractions containing the bulk-phase membrane constituents soluble in 1% Triton X-100. Distribution of membrane markers was unchanged under these conditions. Membrane domains thus represent a substantial structural determinant of the G protein pool relevant to desensitisation of hormone action. PMID:10611479

  18. Insurance - Piper Alpha ''et al''

    International Nuclear Information System (INIS)

    This paper opens with some brief information about the Piper Alpha loss, how the loss was handled and its final cost. More importantly, it discusses the effect of the Piper Alpha loss on the world insurance market including the oil insurance captives such as O.I.L Limited. Finally, the insurance market current status and prognosis for the future are considered. (Author)

  19. Long-range alpha detector

    International Nuclear Information System (INIS)

    Historically, alpha-particle and alpha-contamination detectors have been limited by the very short range of alpha particles in air and by relatively poor sensitivity even if the particles are intercepted. Alpha detectors have had to be operated in a vacuum or in close proximity to the source if reasonable efficiency is desired. Alpha particles interact with the ambient air, producing ionization in the air at the rate of ∼30,000 ion pairs per mega-electron-volt of alpha energy. These charges can be transported over significant distances (several meters) in a moving current of air generated by a small fan. An ion chamber located in front of the fan measures the current carried by the moving ions. The long-range alpha detector (LRAD) offers several advantages over more traditional alpha detectors. First and foremost, it can operate efficiently even if the contamination is not easily accessible. Second, ions generated by contamination in crevices and other unmonitorable locations can be detected if the airflow penetrates those areas. Third, all of the contamination on a large surface will generate ions that can be detected in a single detector; hence, the detector's sensitivity to distributed sources is not limited by the size of the probe. Finally, a simple ion chamber can detect very small electric currents, making this technique potentially quite sensitive

  20. Alpha particle emitters in medicine

    International Nuclear Information System (INIS)

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 (211At) and natural bismuth-212 (212Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 (223Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs

  1. The Lyman alpha reference sample

    DEFF Research Database (Denmark)

    Hayes, M.; Östlin, G.; Schaerer, D.; Verhamme, A.; Mas-Hesse, J.M.; Adamo, A.; Atek, H.; Cannon, J.M.; Duval, F.; Guaita, L.; Herenz, E.C.; Kunth, D.; Laursen, Peter; Melinder, J.; Orlitová, I.; Otí-Floranes, H.; Sandberg, A.

    2013-01-01

    We report on new imaging observations of the Lyman alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028

  2. Growth hormone stimulation test

    Science.gov (United States)

    The growth hormone (GH) stimulation test measures the ability of the body to produce GH. ... killing medicine (antiseptic). The first sample is drawn early in the morning. Medicine is given through the ...

  3. Geothermal Well Stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, D. A.; Morris, C. W.; Sinclair, A. R.; Hanold, R. J.; Vetter, O. J.

    1981-03-01

    The stimulation of geothermal wells presents some new and challenging problems. Formation temperatures in the 300-600 F range can be expected. The behavior of stimulation fluids, frac proppants, and equipment at these temperatures in a hostile brine environment must be carefully evaluated before performance expectations can be determined. In order to avoid possible damage to the producing horizon of the formation, high temperature chemical compatibility between the in situ materials and the stimulation materials must be verified. Perhaps most significant of all, in geothermal wells the required techniques must be capable of bringing about the production of very large amounts of fluid. This necessity for high flow rates represents a significant departure from conventional petroleum well stimulation and demands the creation of very high near-wellbore permeability and/or fractures with very high flow conductivity.

  4. Constitutive phosphorylation of I kappa B alpha by casein kinase II.

    OpenAIRE

    Barroga, C F; Stevenson, J K; Schwarz, E M; Verma, I M

    1995-01-01

    The NF-kappa B/Rel proteins are sequestered in the cytoplasm in association with the phosphorylated form of I kappa B alpha. Upon induction with a wide variety of agents, the activity of NF-kappa B/Rel proteins is preceded by the rapid degradation of I kappa B alpha protein. We report the identification and partial purification of a cellular kinase from unstimulated or stimulated murine cells, which specifically phosphorylates the C terminus of I kappa B alpha. There are several consensus sit...

  5. Isoprostane 8-epi-prostaglandin F2 alpha is a potent contractor of human peripheral lymphatics.

    Science.gov (United States)

    Sinzinger, H; Oguogho, A; Kaliman, J

    1997-09-01

    Isoprostanes are products of free radical-catalyzed peroxidation and 8-epi-prostaglandin (PG) F2 alpha is the most important vasomodulator of this group of compounds. In human lower leg lymphatics isolated from 5 different patients without a smoking history or hyperlipidemia, 8-epi-PGF2 alpha stimulated in vitro contraction more strongly than the thromboxane receptor agonist U46619. Other isoprostanes (8-epi-PGE1, 8-epi-PGE2) had only limited lymphatic contractile potency. These data suggest a potentially relevant role for epi-8-PGF2 alpha in facilitating lymph transport especially in conditions of inflammation. PMID:9313207

  6. The Effects of Endothelin-3 on the Melanocyte Characteristic and Expression of Hair Color Genes in Melanocytes from Alpaca (Lama Pacos) in vitro%内皮素-3对羊驼黑色素细胞特征及细胞内毛色基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    耿建军; 白俊明; 范瑞文; 杨姗姗; 庞亚妙; 董常生

    2013-01-01

    The study aimed to investigate the effects of endothelin-3 (EDN3) on the expression of hair color genes of alpaca.The activity of melanocyte,the production of melanin in melanocytes and the expressions of related genes and proteins including Endothelin receptor B (EDNRB),KIT,Microphthalmia-associtated transcription factor (MITF) and Tyrosinase (TYR) in alpaca melanocytes in cultures with addition of different dose of EDN3(0,10-9,10-8,10-7mol · L-1),were examined by MTT,ultraviolet spectrophotometry,qRT-PCR and Western blotting,respectively.The results showed that the amount of melanocytes was increased with the increasing double-or tri-dendrites; At the addition dose of 10-8 mol · L-1 for 72 h after adding EDN3,compared to control group,the proliferation of melanocytes was obvious and the expressions of EDNRB,KIT,MITF and TYR significantly up-regulated at the level of both transcription and translation in melanocytes(P<0.05).Moreover,the production of melanin in melanocytes significantly increased(P<0.05).These findings indicate that EDN3 play an important role in regulating melanins production in melanocytes in alpaca.%为了研究内皮素-3(Endothelin-3,EDN3)对羊驼皮肤黑色素细胞内毛色形成相关基因的影响.本研究在体外培养的羊驼皮肤黑色素细胞中添加不同浓度(0、10-9、10-8、10-7mol· L-1)的EDN3,通过MTT法、紫外分光光度法、qRT-PCR和Western blotting技术分别检测黑色素细胞活力、黑色素产量、相关基因和蛋白(包括内皮素受体B(Endothelin receptor B,EDNRB)、KIT、小眼畸形相关转录因子(Microphthalmia-associtated transcription factor,MITF)和酪氨酸酶(Tyrosinase,TYR))的表达情况.结果表明,在羊驼皮肤黑色素细胞添加EDN3 72 h 后,黑色素细胞呈双树突或三树突状,且细胞数量明显增加;在添加适当浓度10-8mol·L-1时,细胞具有明显的增殖,细胞内EDNRB、KIT、MITF和TRY在转录水平和蛋白水平的表达量被上调,

  7. Alpha Schottky junction energy source

    Science.gov (United States)

    Litz, Marc S.; Fan, Zhaoyang; Carroll, James J.; Bayne, Stephen

    2012-06-01

    Isotope batteries offer solutions for long-lived low-power sensor requirements. Alpha emitting isotopes have energy per decay 103 times that of beta emitters. Alpha particles are absorbed within 20 μm of most materials reducing shielding mitigation. However, damage to materials from the alphas limits their practical use. A Schottky Barrier Diode (SBD) geometry is considered with an alpha emitting contact-layer on a diamond-like crystal semiconductor region. The radiation tolerance of diamond, the safety of alpha particles, combined with the internal field of the SBD is expected to generate current useful for low-power electronic devices over decades. Device design parameters and calculations of the expected current are described.

  8. Stimulated Thomson scattering

    International Nuclear Information System (INIS)

    The theory of stimulated Thomson scattering is investigated both quantum mechanically and classically. In the interaction of a collisionless plasma with two electromagnetic waves, both with frequencies well above the plasma frequency, energy is transferred from the high-frequency wave to the low-frequency wave via stimulated Thomson scattering. This process is mediated by the nonlinear interaction of the plasma electrons with a beat wave at the difference frequency between the two waves; this beat frequency must be well above the plasma frequency. The gain coefficient for stimulated Thomson scattering is calculated both quantum mechanically and classically, and identical results are obtained. The classical calculation also yields the first nonlinear term in the index of refraction due to stimulated Thomson scattering, as well as the details of the saturation of the gain and the index of refraction. The authors present explicit formulas for the gain coefficient and the index of refraction, in the unsaturated limit, for both very cold and very hot plasmas. The calculations indicate that it should be possible to detect stimulated Thomson scattering experimentally by means of polarization enhancement. In an appendix, the theory of stimulated Thomson scattering is used to treat the free-electron amplifier

  9. Levels of eicosanoids (6-oxo-PGF1 alpha and 8-epi-PGF2 alpha) in human and porcine lymphatics and lymph.

    Science.gov (United States)

    Oguogho, A; Kaliman, J; Sinzinger, H

    1998-12-01

    Prostaglandin (PG)I2 is the primary eicosanoid synthesized by human lymphatics and 8-epi-PGF2 alpha, an isoprostane formed during free radical catalyzed peroxidation, is the most potent stimulator of lymphatic contraction tested thus far. We now examine the respective concentrations in the lymphatic wall of both human and porcine lymphatics and lymph fluid using specific immunoassays. Although both compounds are detectable in the lymphatic wall and lymph fluid, PGI2- (via its main metabolite 6-oxo-PGF1 alpha) is greater in the lymphatic wall whereas 8-epi-PGF2 alpha dominates in lymph fluid. Because inflammation is associated with oxidative injury, which in turn stimulates release of isoprostane, eicosanoid derivatives may modulate lymphatic tone during acute tissue reaction. PMID:9949390

  10. Expression of cyclins A and E in melanocytic skin lesions and its correlation with some clinicopathologic features

    Directory of Open Access Journals (Sweden)

    Ana Alekseenko

    2012-07-01

    Full Text Available Cyclins play a fundamental role in the cell cycle. Recent studies have focused on their role in the development of various malignancies. The objective of this study was to evaluate and compare the expression of cyclins A and E in common nevi, dysplastic nevi and malignant melanomas, and to investigate the relationship between cyclin expression and some pathological parameters such as tumor thickness, ulceration, regression, and mitotic rate, as well as several clinical and phenotypic parameters such as skin phototype, hair and eye color, number of nevi, personal or family melanoma history, and personal history of nonmelanoma skin cancer (NMSC. A total of 102 melanocytic skin lesions, including 30 common nevi, 38 dysplastic nevi and 34 melanomas, were examined. Expression of cyclins was detected by immunohistochemistry and quantified as a percentage of immunostained cell nuclei in each sample. Significant differences in expression of both cyclins were found between all lesion types: the median percentage of cyclin A-positive nuclei was 8.2% in melanomas, 3.4% in dysplastic nevi, and 0.95% in common nevi (p < 0.001. The corresponding percentages for cyclin E were 9.5%, 4.25% and 1.44% (p < 0.001. Expression of both cyclins was significantly higher among patients with a personal history of NMSC. Cyclin A was also significantly overexpressed in patients with a high total nevus count (TNC compared to moderate and low TNC. Expression of cyclins did not significantly correlate with the other clinicopathologic features investigated. These findings indicate the possible involvement of cyclins A and E in the pathogenesis of malignant melanoma. Our results also show a potential diagnostic significance of these cyclins as markers allowing discrimination between dysplastic nevi and melanoma.

  11. Spontaneous CD8 T cell responses against the melanocyte differentiation antigen RAB38/NY-MEL-1 in melanoma patients.

    Science.gov (United States)

    Walton, Senta M; Gerlinger, Marco; de la Rosa, Olga; Nuber, Natko; Knights, Ashley; Gati, Asma; Laumer, Monika; Strauss, Laura; Exner, Carolin; Schäfer, Niklaus; Urosevic, Mirjana; Dummer, Reinhard; Tiercy, Jean-Marie; Mackensen, Andreas; Jaeger, Elke; Lévy, Frédéric; Knuth, Alexander; Jäger, Dirk; Zippelius, Alfred

    2006-12-01

    The melanocyte differentiation Ag RAB38/NY-MEL-1 was identified by serological expression cloning (SEREX) and is expressed in the vast majority of melanoma lesions. The immunogenicity of RAB38/NY-MEL-1 has been corroborated previously by the frequent occurrence of specific Ab responses in melanoma patients. To elucidate potential CD8 T cell responses, we applied in vitro sensitization with overlapping peptides spanning the RAB38/NY-MEL-1 protein sequence and the reverse immunology approach. The identified peptide RAB38/NY-MEL-1(50-58) exhibited a marked response in ELISPOT assays after in vitro sensitization of CD8 T cells from HLA-A *0201(+) melanoma patients. In vitro digestion assays using purified proteasomes provided evidence of natural processing of RAB38/NY-MEL-1(50-58) peptide. Accordingly, monoclonal RAB38/NY-MEL-1(50-58)-specific T cell populations were capable of specifically recognizing HLA-A2(+) melanoma cell lines expressing RAB38/NY-MEL-1. Applying fluorescent HLA-A2/RAB38/NY-MEL-1(50-58) multimeric constructs, we were able to document a spontaneously developed memory/effector CD8 T cell response against this peptide in a melanoma patient. To elucidate the Ag-processing pathway, we demonstrate that RAB38/NY-MEL-1(50-58) is produced efficiently by the standard proteasome and the immunoproteasome. In addition to the identification of a RAB38/NY-MEL-1-derived immunogenic CD8 T cell epitope, this study is instrumental for both the onset and monitoring of future RAB38/NY-MEL-1-based vaccination trials. PMID:17114498

  12. Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene

    OpenAIRE

    Lécine, P; Algarté, M; Rameil, P; Beadling, C; Bucher, P.; Nabholz, M; Imbert, J

    1997-01-01

    The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is a key regulator of lymphocyte proliferation. IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli. Interleukin 2 (IL-2) stimulates IL-2R alpha. transcription, thereby amplifying expression of its own high-affinity receptor. IL-2R alpha transcription is at least in part controlled by two positive regulatory regions, PRRI and PRRII. PRRI is an inducible proximal enhancer, located between nucleotides ...

  13. Case Report: melanoma and melanocytic nevus differentiation with reflectance confocal microscopy. [v1; ref status: indexed, http://f1000r.es/5mr

    Directory of Open Access Journals (Sweden)

    Joanna Łudzik

    2015-07-01

    Full Text Available Historically, melanoma has been typically diagnosed by naked-eye examination and confirmed with invasive biopsy. However, recently the use of reflectance confocal microscopy enables non-invasive bedside diagnosis of clinically equivocal lesions. We present a case in which reflectance confocal microscopy was used to evaluate two skin lesions in the same patient confirming the diagnosis of a melanoma and potentially avoiding invasive biopsy in the second benign melanocytic lesion.  Clinicians should be aware of the availability of new non-invasive technologies that can aid in early diagnosis of malignant skin tumors and potentially reduce the number of benign lesion excisions.

  14. Effects of interleukin-6 on cultured human melanocytes in vitro%白介素-6对体外培养的黑素细胞影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    林新瑜; 段西凌; 林鸿刚; 何飞

    2011-01-01

    Objective Establishing the culture of human normal melanocytes in vitro, and studying effects of Interleukin-6 on cultured human melanocytes. Methods MTT method, NaOH 2 assay were employed to measure the cell viability, melanin synthesis of melanocytes, apoptosis rates of melanocytes were detected by using flow cytometer. Results Interleukin-6 induced a mild effect on melanocytic viability, while it showed a significant decrease in the cell counts, melanin synthesis and cell apoptosis. Conclusion Interleukin-6 can inhibit melanocytic proliferation and melanin synthesis. It is worth to study later. It makes valid to make use of Interleukin-6 for treatment of the pigmented skin diseases.%目的 建立正常人表皮黑素细胞体外培养体系,研究白介素-6(Interleukin-6,IL-6)对体外培养的黑素细胞的影响.方法 采用四甲基偶氮唑盐(MTT)法测定白介素-6对黑素细胞活力的影响,NaOH裂解法测定黑素合成,流式细胞仪检测黑素细胞的凋亡率.结果 白介素-6对黑素细胞活力有抑制作用,能使细胞增殖力降低,黑素合成减少,增加黑素细胞的凋亡率.结论 白介素-6对体外培养的黑素细胞增殖及黑素生成都有抑制作用,这为临床应用白介素-6治疗色素性疾病提供了实验依据.

  15. ALPHA freezes antiprotons

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    Laboratories like CERN can routinely produce many different types of antiparticles. In 1995, the PS210 experiment formed the first antihydrogen atoms and a few years later, in 2002, ATRAP and ATHENA were already able to produce several thousand of them. However, no experiment in the world has succeeded in ‘trapping’ these anti-atoms in order to study them. This is the goal of the ALPHA experiment, which has recently managed to cool down the antiprotons to just a few Kelvin. This represents a major step towards trapping the anti-atom, thus opening a new avenue into the investigation of antimatter properties.   Members of the ALPHA collaboration working on the apparatus in the Antiproton Decelerator experimental hall at CERN. Just like the atom, the anti-atom is neutral. Unlike the atom, the anti-atom is made up of antiprotons (as opposed to protons in the atom) and positrons (as opposed to electrons). In order to thoroughly study the properties of the anti-atoms, scien...

  16. Synthesis of a precursor for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha,17 beta-diol 17-glucuronide

    International Nuclear Information System (INIS)

    Starting from 11 beta-hydroxytestosterone, the synthesis of a strategic precursor, C-9 (11) unsaturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (9a), for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide has been achieved. The authors optimized the reaction conditions for catalytic reduction employing hydrogen and subsequent base hydrolysis followed by purification on Amberlite XAD-2 resin to obtain the saturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide

  17. Measurement of $\\alpha_{s}$ with Radiative Hadronic Events

    CERN Document Server

    Abbiendi, G; Åkesson, P F; Alexander, G; Anagnostou, G; Anderson, K J; Asai, S; Axen, D; Bailey, I; Barberio, E; Barillari, T; Barlow, R J; Batley, R J; Bechtle, P; Behnke, T; Bell, K W; Bell, P J; Bella, G; Bellerive, A; Benelli, G; Bethke, S; Biebel, O; Boeriu, O; Bock, P; Boutemeur, M; Braibant, S; Brown, R M; Burckhart, H J; Campana, S; Capiluppi, P; Carnegie, R K; Carter, A A; Carter, J R; Chang, C Y; Charlton, D G; Ciocca, C; Csilling, A; Cuffiani, M; Dado, S; Dallavalle, M; de Roeck, A; De Wolf, E A; Desch, K; Dienes, B; Dubbert, J; Duchovni, E; Duckeck, G; Duerdoth, I P; Etzion, E; Fabbri, F; Ferrari, P; Fiedler, F; Fleck, I; Ford, M; Frey, A; Gagnon, P; Gary, J W; Geich-Gimbel, C; Giacomelli, G; Giacomelli, P; Giunta, M; Goldberg, J; Gross, E; Grunhaus, J; Gruwé, M; Sen-Gupta, A; Hajdu, C; Hamann, M; Hanson, G G; Harel, A; Hauschild, M; Hawkes, C M; Hawkings, R; Herten, G; Heuer, R D; Hill, J C; Horváth, D; Igo-Kemenes, P; Ishii, K; Jeremie, H; Jovanovic, P; Junk, T R; Kanzaki, J; Karlen, D; Kawagoe, K; Kawamoto, T; Keeler, R K; Kellogg, R G; Kennedy, B W; Kluth, S; Kobayashi, T; Kobel, M; Komamiya, S; Kramer, T; Krasznahorkays, A Jr; Krieger, P; Von Krogh, J; Kühl, T; Kupper, M; Lafferty, G D; Landsman, H; Lanske, D; Lellouch, D; Letts, J; Levinson, L; Lillich, J; Lloyd, S L; Loebinger, F K; Lü, J; Ludwig, A; Ludwig, J; Mader, W; Marcellini, S; Martin, A J; Mashimo, T; Mättig, P; McKenna, J; McPherson, R A; Meijers, F; Menges, W; Merritt, F S; Mes, H; Meyer, N; Michelini, A; Mihara, S; Mikenberg, G; Miller, D J; Mohr, W; Mori, T; Mutter, A; Nagai, K; Nakamura, I; Nanjo, H; Neal, H A; O'Neale, S W; Oh, A; Oreglia, M J; Orito, S; Pahl, C; Pásztor, G; Pater, J R; Pilcher, J E; Pinfold, J L; Plane, D E; Pooth, O; Przybycien, M; Quadt, A; Rabbertz, K; Rembser, C; Renkel, P; Roney, J M; Rossi, A M; Rozen, Y; Runge, K; Sachs, K; Saeki, T; Sarkisyan-Grinbaum, E; Schaile, A D; Schaile, O; Scharff-Hansen, P; Schiecks, J; Schörner-Sadenius, T; Schröder, M; Schumacher, M; Seuster, R; Shears, T G; Shen, B C; Sherwood, P; Skuja, A; Smith, A M; Sobie, R J; Söldner-Rembold, S; Spanó, F; Stahl, A; Strom, D; Ströhmer, R; Tarem, S; Tasevsky, M; Teuscher, R; Thomson, M A; Torrence, E; Toya, D; Trigger, I; Trócsányi, Z L; Tsur, E; Turner-Watson, M F; Ueda, I; Ujvári, B; Vollmer, C F; Vannerem, P; Vertesi, R; Verzocchi, M; Voss, H; Vossebeld, J; Ward, C P; Ward, D R; Watkins, P M; Watson, A T; Watson, N K; Wells, P S; Wengler, T; Wermes, N; Wilson, G W; Wilson, J A; Wolf, G; Wyatt, T R; Yamashita, S; Zer-Zion, D; Zivkovic, L

    2008-01-01

    Hadronic final states with a hard isolated photon are studied using data taken at centre-of-mass energies around the mass of the Z0 boson with the OPAL detector at LEP. The strong coupling alpha S is extracted by comparing data and QCD predictions for event shape observables at average reduced centre-of-mass energies ranging from 24 GeV to 78 GeV, and the energy dependence of alpha S is studied. Our results are consistent with the running of alpha S as predicted by QCD and show that within the uncertainties of our analysis event shapes in hadronic Z0 decays with hard and isolated photon radiation can be described by QCD at reduced centre-of-mass energies. Combining all values from different event shape observables and energies gives alpha S (Mz)=0.1182 pm 0.0015(stat.) pm 0.0101(syst.).

  18. Pivotal role of the alpha(2A-adrenoceptor in producing inflammation and organ injury in a rat model of sepsis.

    Directory of Open Access Journals (Sweden)

    Michael Miksa

    Full Text Available BACKGROUND: Norepinephrine (NE modulates the responsiveness of macrophages to proinflammatory stimuli through the activation of adrenergic receptors (ARs. Being part of the stress response, early increases of NE in sepsis sustain adverse systemic inflammatory responses. The intestine is an important source of NE release in the early stage of cecal ligation and puncture (CLP-induced sepsis in rats, which then stimulates TNF-alpha production in Kupffer cells (KCs through the activation of the alpha(2-AR. It is important to know which of the three alpha(2-AR subtypes (i.e., alpha(2A, alpha(2B or alpha(2C is responsible for the upregulation of TNF-alpha production. The aim of this study was to determine the contribution of alpha(2A-AR in this process. METHODOLOGY/PRINCIPAL FINDINGS: Adult male rats underwent CLP and KCs were isolated 2 h later. Gene expression of alpha(2A-AR was determined. In additional experiments, cultured KCs were incubated with NE with or without BRL-44408 maleate, a specific alpha(2A-AR antagonist, and intraportal infusion of NE for 2 h with or without BRL-44408 maleate was carried out in normal animals. Finally, the impact of alpha(2A-AR activation by NE was investigated under inflammatory conditions (i.e., endotoxemia and CLP. Gene expression of the alpha(2A-AR subtype was significantly upregulated after CLP. NE increased the release of TNF-alpha in cultured KCs, which was specifically inhibited by the alpha(2A-AR antagonist BRL-44408. Equally, intraportal NE infusion increased TNF-alpha gene expression in KCs and plasma TNF-alpha which was also abrogated by co-administration of BRL-44408. NE also potentiated LPS-induced TNF-alpha release via the alpha(2A-AR in vitro and in vivo. This potentiation of TNF-alpha release by NE was mediated through the alpha(2A-AR coupled Galphai protein and the activation of the p38 MAP kinase. Treatment of septic animals with BRL-44408 suppressed TNF-alpha, prevented multiple organ injury and

  19. Nitric oxide produced by ultraviolet-irradiated keratinocytes stimulates melanogenesis.

    OpenAIRE

    Roméro-Graillet, C; Aberdam, E; Clément, M.; Ortonne, J P; Ballotti, R

    1997-01-01

    Ultraviolet (UV) radiation is the main physiological stimulus for human skin pigmentation. Within the epidermal-melanin unit, melanocytes synthesize and transfer melanin to the surrounding keratinocytes. Keratinocytes produce paracrine factors that affect melanocyte proliferation, dendricity, and melanin synthesis. In this report, we show that normal human keratinocytes secrete nitric oxide (NO) in response to UVA and UVB radiation, and we demonstrate that the constitutive isoform of keratino...

  20. Dosimetry based on thermally and optically stimulated luminescence

    Energy Technology Data Exchange (ETDEWEB)

    Agersnap Larsen, Niels

    1999-01-01

    Thermally Stimulated Luminescence (TL) and Optically Stimulated Luminescence (OSL) properties of quartz and {alpha}-Al{sub 2}O{sub 3} have been investigated. Anneling-induced OSL and TL sensitivity changes in quartz has been investigated by experiments and modelling. This study does not support a pre-dose effect to account for the observed annealing-induced sensitivity change. The experimental data indicates a more simple mechanism that involves alteration of the concentration of the defect centers. Results from modelling of removal or creation of defect centers comparing well with experimentally obtained data. Thermal quenching of luminescence for the main emission center, the F-center, in {alpha}-Al{sub 2}O{sub 3}:C has been investigated by analysing TL curves obtained at different heating rates. The thermal quenching dependence of luminescence is found to follow the classical Mott-Seitz expression. Basic investigations of OSL properties of {alpha}Al{sub 2}O{sub 3}:C, including: the thermal depth of the OSL traps, the temperature dependence of OSL, and the OSL stimulation spectra. Simultaneous measurements of TL and thermally stimulated conductivity (TSC) are presented for {gamma}-irradiated {alpha}Al{sub 2}O{sub 3}:C. Activation energy analysis of the data reveals a superposition of several first-order TL and TSC peaks caused by release of charge carriers from a distribution of trapping states. Furthermore a description of an experimental method developed to determine the sign of the thermally released charge carriers has been presented. (au) 8 tabs., 59 ills., 90 refs.

  1. What Powers Lyman alpha Blobs?

    OpenAIRE

    Ao, Y.; Matsuda, Y; Beelen, A.; Henkel, C.; Cen, R.; De Breuck, C.; Francis, P; Kovacs, A.; Lagache, G.; Lehnert, M.; Mao, M; Menten, K. M.; Norris, R; Omont, A.; Tatemastu, K.

    2015-01-01

    Lyman alpha blobs (LABs) are spatially extended lyman alpha nebulae seen at high redshift. The origin of Lyman alpha emission in the LABs is still unclear and under debate. To study their heating mechanism(s), we present Australia Telescope Compact Array (ATCA) observations of the 20 cm radio emission and Herschel PACS and SPIRE measurements of the far-infrared (FIR) emission towards the four LABs in the protocluster J2143-4423 at z=2.38. Among the four LABs, B6 and B7 are detected in the rad...

  2. Sparse Coding for Alpha Matting

    OpenAIRE

    Johnson, Jubin; Varnousfaderani, Ehsan Shahrian; Cholakkal, Hisham; Rajan, Deepu

    2016-01-01

    Existing color sampling based alpha matting methods use the compositing equation to estimate alpha at a pixel from pairs of foreground (F) and background (B) samples. The quality of the matte depends on the selected (F,B) pairs. In this paper, the matting problem is reinterpreted as a sparse coding of pixel features, wherein the sum of the codes gives the estimate of the alpha matte from a set of unpaired F and B samples. A non-parametric probabilistic segmentation provides a certainty measur...

  3. Bovine intermediate pituitary alpha-amidation enzyme: preliminary characterization

    International Nuclear Information System (INIS)

    A secretory granule-associated enzymatic activity that converts mono-[125I]-D-Tyr-Val-Gly into mono-[125I]-D-Tyr-Val-NH2 has been studied. The activity is primarily soluble and shows optimal activity at pH 7 to pH 8. Amidation activity was stimulated 9-fold by addition of optimal amounts of copper (3 microM). In the presence of optimal copper, ascorbate stimulated the reaction 7-fold; none of the other reduced or oxidized cofactors tested was as effective. Taking into account the dependence of the reaction on ascorbate and molecular oxygen and the production of glyoxylate [2], it is suggested that the alpha-amidation enzyme is a monooxygenase. Lineweaver Burk plots with D-Tyr-Val-Gly as the varied substrate demonstrated Michelis-Menten type kinetics with the values of K/sub m/ and V/sub max/ increasing with the addition of ascorbate to the assay. A variety of peptides ending with a COOH-terminal Gly residue act as inhibitors of the reaction. Two synthetic peptides, gamma 2MSH and ACTH(1-14), with carboxyl termini similar to the presumed physiological substrates for the enzyme, act as competitive inhibitors with similar K1 values. It is likely that this secretory granule alpha-amidation activity is involved in the physiological biosynthetic alpha-amidation of a wide range of bioactive peptides

  4. Factors stimulating content marketing

    OpenAIRE

    Naser Azad; Seyed Mohsen Seyed AliAkbar; Sima Zomorodian

    2016-01-01

    This paper presents an empirical investigation to determine factors influencing on content marketing in banking industry. The study designs a questionnaire consists of 40 questions in Likert scale and distributes it among 550 randomly selected regular customers of Bank Mellat in city of Tehran, Iran and 400 properly filled questionnaires are collected. Cronbach alphas for all components of the survey are well above desirable level. Using principle component analysis with Varimax rotation, the...

  5. Dynamic fibrils in Ly alpha

    CERN Document Server

    Koza, J; Vourlidas, A

    2008-01-01

    The solar chromosphere and transition region are highly structured regimes of large complexity. A recent breakthrough concerns the identification of dynamic fibrils seen in Halpha. An aim is to find out whether dynamic fibrils are also observable in Ly alpha. We use a brief sequence of four high-resolution Ly alpha filtergrams of the solar limb taken by the Very high Angular resolution ULtraviolet Telescope (VAULT) to identify 50 dynamic fibrils, measure their top trajectories, and fit these with parabolas. Most fibril tops move supersonically. Their decelerations vary from sub- to superballistic. About half show outward acceleration, which may be an artifact from the poor sampling. The similarity between these dynamic fibrils observed in Ly alpha and the ones observed in Halpha suggests that the magnetoacoustic shock excitation proposed for the Halpha dynamic fibrils is also valid for the Ly alpha ones.

  6. Almost Redundant Components in the 3 alpha Faddeev Equation for the Buck, Friedlich and Wheatly alpha alpha Potential

    CERN Document Server

    Fujiwara, Y; Kohno, M

    2004-01-01

    The 3 alpha orthogonality condition model using the Pauli-forbidden bound states of the Buck, Friedlich and Wheatly alpha alpha potential can yield a compact 3 alpha ground state with a large binding energy, in which a small admixture of the redundant components can never be eliminated.

  7. 热处理对体外培养正常人黑素细胞活性的影响%Effect of heat treatment on the viability of cultured normal human melanocytes

    Institute of Scientific and Technical Information of China (English)

    牛建荣; 杨庆琪; 孟如松; 成玉; 赵广

    2011-01-01

    Objective To investigate the effect of heat treatment on the proliferation of, melanin synthesis and tyrosinase activity in cultured normal human melanocytes. Methods Normal human foreskin tissue was obtained by sterile circumcision and melanocytes were harvested by using methods for epidermal cell culture. Basic fibroblast growth factor (bFGF) was utilized as the primary mitogen to establish the culture system of normal human epidermal melanocytes. Masson-Fontana staining was proformed to identify melanocytes.Third-passage melanocytes were treated with hyperthermia at various temperatures (39 ℃, 41 ℃, 42 ℃, 43 ℃ and 45℃) for 1 hour a day for consecutive 3 days followed by the measurement of cell viability with MTT assay. The hyperthermia at optimized temperature was used to treat fourth-passage melanocytes for 1 hour a day for consecutive 3 days; subsequently, the tyrosinase activity were detected with L-Dopa as the substrate, and melanin content was determined in heat-treated and untreated (control) melanocytes. Results The hyperthermia at 42 ℃ exhibited the strongest promotive effect on the proliferation of melanocytes among these 5 hyperthermia conditions. After treatment with hyperthermia at 42 ℃ for 1 hour a day for consecutive 3 days, melanocytes showed an increment in tyrosinase activity by 36.4% and melanin synthesis by 78% compared with the untreated melanocytes (both P<0.05). Conclusions Heat treatment can enhance the proliferation of cultured human melanocytes, promote their melanin synthesis and tyrosinase activity.%目的 探讨热处理对体外培养的正常人黑素细胞的增殖活性、黑素合成及其酪氨酸酶活性的影响.方法 无菌操作获取正常人包皮环切术后的包皮,按照皮肤表皮细胞培养法获取黑素细胞,利用碱性成纤维细胞生长因子(bFGF)为主要有丝分裂原建立正常人表皮黑素细胞培养系,采用Masson-Fontana染色法对培养细胞进行鉴定,确定细胞种系,

  8. Alpha thalassaemia in British people.

    OpenAIRE

    Higgs, D R; Ayyub, H.; Clegg, J B; Hill, A V; Nicholls, R D; Teal, H; Wainscoat, J.S. (James S.); Weatherall, D. J.

    1985-01-01

    Although alpha thalassaemia is rare in north Europeans, it has been identified in British people with no known foreign ancestry. Twelve such patients were studied, of whom eight shared a distinctive molecular defect, which was clearly different from defects seen in subjects of Mediterranean or South East Asian origin. A rare but specific form of alpha thalassaemia is therefore present in the British population. In addition, two patients from families of mixed racial origin were encountered wh...

  9. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    International Nuclear Information System (INIS)

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals

  10. Assessment of the effect of phenytoin on cutaneous healing from excision of melanocytic nevi on the face and on the back

    Directory of Open Access Journals (Sweden)

    Pereira Carlos

    2010-08-01

    Full Text Available Abstract Background Topical phenytoin is a powerful skin wounds healing and it may be useful in clinical practice. The purpose of this study was to evaluate the effect of topical phenytoin 0.5%, by comparing it with cream (control in wounds resulting from excision of two melanocytic nevi in the same patient. Our purpose was also to assess if phenytoin had better therapeutic and cosmetic outcomes when compared with cream (control. Methods This study evaluated 100 patients with skin wounds from excision of melanocytic nevi. 50 patients with lesions on the face and 50 patients with lesions on the back, totalizing 200 lesions excised with modified punch. The resulting superficial skin wounds had the same diameter and depth, and second intention healing followed. Patients were followed for 60 days. Student's t-test, Mann Whitney nonparametric test, analysis of variance, LSD test, Shapiro-Wilks test and Fisher test were used to analyze the results, depending on the nature of the variables being studied. Results Phenytoin showed better therapeutic and cosmetic results, by healing faster, with more intense epithelization in wounds in comparison with cream (control. Phenytoin showed a statistically significant difference regarding the following parameters (p Conclusions Phenytoin showed better therapeutic and cosmetic results compared with cream (control. Phenytoin is a low cost drug, which accelerates skin wounds healing in human patients. Trial registration: ISRCTN96539803

  11. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    Energy Technology Data Exchange (ETDEWEB)

    Shimabukuro, Junji; Yamaoka, Ayako; Murata, Ken-ichi [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Kotani, Eiji [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan); Hirano, Tomoko [Venture Laboratory, Kyoto Institute of Technology, Kyoto (Japan); Nakajima, Yumiko [Functional Genomics Group, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa (Japan); Matsumoto, Goichi [Division of Oral Surgery, Yokohama Clinical Education Center of Kanagawa Dental University, Yokohama (Japan); Mori, Hajime, E-mail: hmori@kit.ac.jp [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan)

    2014-09-01

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals.

  12. Alpha Particle Emission in Fission

    International Nuclear Information System (INIS)

    Soon after it was discovered that alpha particles are occasionally emitted in fission, it was concluded, on the basis of the energy and angular distributions of these particles, that they are emitted from the space between the fragments at times close to that of the snapping of the neck that connects them. It is shown that, independent of any (still unknown) dynamic features of the alpha-particle ejection process, the energy required to emit alpha particles from between the fragments at the indicated time is barely available. Presumably the rareness of alpha particles in fission, and the apparent absence of still heavier ''third'' particles, is associated with the marginal energy supply at the time of actual fragment division. The fact that the total kinetic energy release in so-called ternary fission is roughly equal to that in normal binary fission instead of being about 20 MeV larger is shown to imply that the mean fragment separation at the division time is larger in ternary fission. This is interpreted to indicate that alpha particles are emitted with greatest probability n those fissions where ample energy happens to be provided through the stretching of an abnormally long neck between the fragments before they actually divide. It is suggested that the release of the alpha particles is a sudden rather than adiabatic process. (author)

  13. Alpha particle physics for ITER

    International Nuclear Information System (INIS)

    The paper is devoted to the analysis of a variety of physical processes which, in the ITER EDA configuration, determine the nature of alpha particle heating in the plasma interior and alpha particle losses to the first wall. The paper consists of results from the alpha particle toroidal field (TF) ripple loss calculations and an analysis of alpha particle collective effects including Alfven modes, sawtooth stabilization, etc. It is shown that the ripple loss in the present ITER configuration is only a few per cent, which cannot directly affect the achievement of ignition. In spite of the up-down asymmetry, the loss fraction does not strongly depend on the toroidal drift direction. However, the heat load is highly localized and can be as high as 1 MW/m2 on the top of the protective limiters. Preliminary calculations of toroidicity induced Alfven eigenmode (TAE) stability indicate that high n numbers may be unstable, but the computational tools, needed for reliable quantitative predictions, are still in a state of development. The likelihood of appreciable alpha particle loss will depend on whether TAE modes produce stochastic alpha particle diffusion or not. The effect of fast particles on the m = 1 mode is also discussed. (author). 15 refs, 2 figs, 1 tab

  14. Cytosolic PLA2(alpha) activation in Purkinje neurons and its role in AMPA-receptor trafficking.

    Science.gov (United States)

    Mashimo, Masato; Hirabayashi, Tetsuya; Murayama, Toshihiko; Shimizu, Takao

    2008-09-15

    Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) selectively releases arachidonic acid from membrane phospholipids and has been proposed to be involved in the induction of long-term depression (LTD), a form of synaptic plasticity in the cerebellum. This enzyme requires two events for its full activation: Ca(2+)-dependent translocation from the cytosol to organelle membranes in order to access phospholipids as substrates, and phosphorylation by several kinases. However, the subcellular distribution and activation of cPLA(2)alpha in Purkinje cells and the role of arachidonic acid in cerebellar LTD have not been fully elucidated. In cultured Purkinje cells, stimulation of AMPA receptors, but not metabotropic glutamate receptors, triggered translocation of cPLA(2)alpha to the somatic and dendritic Golgi compartments. This translocation required Ca(2+) influx through P-type Ca(2+) channels. AMPA plus PMA, a chemical method for inducing LTD, released arachidonic acid via phosphorylation of cPLA(2)alpha. AMPA plus PMA induced a decrease in surface GluR2 for more than 2 hours. Interestingly, this reduction was occluded by a cPLA(2)alpha-specific inhibitor. Furthermore, PMA plus arachidonic acid caused the prolonged internalization of GluR2 without activating AMPA receptors. These results suggest that cPLA(2)alpha regulates the persistent decrease in the expression of AMPA receptors, underscoring the role of cPLA(2)alpha in cerebellar LTD. PMID:18713832

  15. Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

    Science.gov (United States)

    Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

  16. Alpha/sub 1/ receptor coupling events initiated by methoxy-substituted tolazoline partial agonists

    Energy Technology Data Exchange (ETDEWEB)

    Wick, P.; Keung, A.; Deth, R.

    1986-03-01

    A series of mono- and dimethyoxy substituted tolazoline derivatives, known to be partial agonists at the alpha/sub 1/ receptor, were compared with the ..cap alpha../sub 1/ selective full agonist phenylephrine (PE) on isolated strips of rabbit aorta Agonist activity was evaluated in contraction, /sup 45/Ca influx, /sup 45/Ca efflux, and /sup 32/P-Phospholipid labelling studies. Maximum contractile responses for the 2-, 3-, and 3, 5- methoxy substituted tolazoline derivatives (10/sup -5/M) were 53.8, 67.6 and 99.7% of the PE (10/sup -5/M) response respectively. These same partial agonists caused a stimulation of /sup 45/Ca influx to the extent of 64, 86, and 95% of the PE response respectively. In /sup 45/Ca efflux studies, (a measure of the intracellular Ca/sup +2/ release) the tolazolines caused: 30%, 63%, and 78% of the PE stimulated level. /sup 32/P-Phosphatidic acid (PA) labelling was measured as an index of PI turnover after ..cap alpha../sub 1/ receptor stimulation. Compared to PE, the 2-, 3-, and 3,5- methoxy substituted tolazoline derivatives caused 22, 46, and 72% PA labelling. The above values are all in reasonable accord with the rank order or agonist activity shown in maximum contractile responses. The results of this investigation suggest that partial agonists stimulate ..cap alpha.. receptor coupling events at a level which is quantitatively comparable to their potencies in causing contraction of arterial smooth muscle.

  17. PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites

    DEFF Research Database (Denmark)

    Andersen, Gitte; Wegner, Lise; Jensen, Dorit Packert;

    2005-01-01

    PGC-1alpha is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The...

  18. Estudo comparativo morfofuncional de melanócitos em lesões de melasma Morphological and functional comparative study of melanocytes in melasma lesions

    Directory of Open Access Journals (Sweden)

    Luciane Donida Bartoli Miot

    2007-12-01

    Full Text Available FUNDAMENTOS - Melasma é hipermelanose comum caracterizada por máculas acastanhadas em áreas fotoexpostas, cuja fisiopatogenia não é totalmente esclarecida. OBJETIVOS - Caracterizar e comparar morfologica e funcionalmente os melanócitos da epiderme sã com os da pele afetada por melasma. MÉTODOS - Avaliaram-se 12 pacientes portadores de melasma facial, sendo realizadas biópsias da pele lesada e pele sã adjacente. Os cortes foram corados por hematoxilina-eosina, Fontana-Masson, marcados pelo Melan-A e submetidos à microscopia eletrônica. A quantificação epidérmica de melanina e melanócitos foi estimada a partir de análise citomorfométrica digital. RESULTADOS - Todas as pacientes eram mulheres com média de idade 41,3±2,8 anos. Ao Fontana-Masson evidenciou-se importante aumento da melanina epidérmica na pele lesada em relação à pele sã. A marcação pelo Melan-A demonstrou melanócitos maiores com dendritos proeminentes na pele lesada. Observou-se maior densidade de melanina epidérmica na pele lesada, e a análise digital do número de melanócitos da epiderme não demonstrou diferença significativa entre pele lesada e sã. À microscopia eletrônica, observaram-se número aumentado de melanossomas maduros nos ceratinócitos e melanócitos com organelas citoplasmáticas proeminentes na pele lesada. CONCLUSÕES - Melanogênese aumentada na epiderme com melasma em relação à epiderme normal adjacente.BACKGROUND - Melasma is a common hypermelanosis characterized by symmetric brownish macules on photoexposed areas, most frequently on the face of women. Its pathophysiology is still unknown. OBJECTIVES - To morphologically and functionally characterize and compare melanocytes of normal skin and of melasma. METHODS - Twelve patients with facial melasma were assessed and biopsies of lesions and adjacent healthy skin were performed. The slices were stained with hematoxylin-eosin and Fontana-Masson, immunohistochemically marked for

  19. Copeptin under glucagon stimulation.

    Science.gov (United States)

    Lewandowski, Krzysztof C; Lewiński, Andrzej; Skowrońska-Jóźwiak, Elżbieta; Stasiak, Magdalena; Horzelski, Wojciech; Brabant, Georg

    2016-05-01

    Stimulation of growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion by glucagon is a standard procedure to assess pituitary dysfunction but the pathomechanism of glucagon action remains unclear. As arginine vasopressin (AVP) may act on the release of both, GH and ACTH, we tested here the role of AVP in GST by measuring a stable precursor fragment, copeptin, which is stoichiometrically secreted with AVP in a 1:1 ratio. ACTH, cortisol, GH, and copeptin were measured at 0, 60, 90, 120, 150, and 180 min during GST in 79 subjects: healthy controls (Group 1, n = 32), subjects with pituitary disease, but with adequate cortisol and GH responses during GST (Group 2, n = 29), and those with overt hypopituitarism (Group 3, n = 18). Copeptin concentrations significantly increased over baseline 150 and 180 min following glucagon stimulation in controls and patients with intact pituitary function but not in hypopituitarism. Copeptin concentrations were stimulated over time and the maximal increment correlated with ACTH, while correlations between copeptin and GH were weaker. Interestingly, copeptin as well as GH secretion was significantly attenuated when comparing subjects within the highest to those in the lowest BMI quartile (p < 0.05). Copeptin is significantly released following glucagon stimulation. As this release is BMI-dependent, the time-dependent relation between copeptin and GH may be obscured, whereas the close relation to ACTH suggests that AVP/copeptin release might be linked to the activation of the adrenal axis. PMID:26578365

  20. Systematics of Alpha-Radioactivity

    Energy Technology Data Exchange (ETDEWEB)

    Perlman, I.; Ghiorso, A.; Seaborg, G.T.

    1949-09-12

    Correlations of alpha-decay energies in terms of mass number and atomic number have been made for all of the alpha-emitting species now numbering over 100. For each element isotopes show increase in alpha-energy with decrease in mass number except in the region of 126 neutrons where there is an explainable reversal. This reversal has the effect of creating a region of relatively low alpha-energy and long half-life at low mass numbers for such elements as astatine, emanation, francium, and possibly higher elements as had been noted already for bismuth and polonium. Methods and examples of using alpha-decay data to define the energy surface in the heavy element region are discussed. The regularities in alpha-decay are used for predictions of nuclear properties including prediction of the beta-stable nuclides among the heavy elements. The half-life vs. energy correlations show that the even-even nuclides conform well with existing alpha-decay theory, but all nuclear types with odd nucleons show prohibited decay. The reason for this prohibition is not found in spin changes in the alpha-emission but in the assembly of the components of the alpha particle, and this theory is discussed further in terms of observations made on nuclides having two or more alpha-groups. Using most of the even-even nuclei to define 'normal nuclear radius' calculations are now able to show the shrinkage in the regions of lead and of 126 neutrons to amount to about 10%. The much greater change in 'effective radius' for bismuth isotopes can be dissociated into the effects of odd nucleons superimposed on the actual decrease in nuclear radius. The simple expression r = 1.48 A{sup 1/3} {center_dot} 10{sup -13} cm seems to fit the data for the even-even nuclei outside of the region of 126 neutrons better than more complex functions.