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
International Nuclear Information System (INIS)
Quinn, Thomas P.
2005-01-01
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 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, 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 177 Lu-DOTA-Re(Arg11)CCMSH and
Raposinho, Paula D; Xavier, Catarina; Correia, João D G; Falcão, Soraia; Gomes, Paula; Santos, Isabel
2008-03-01
Early detection of primary melanoma tumors is essential because there is no effective treatment for metastatic melanoma. Several linear and cyclic radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analogs have been proposed to target the melanocortin type 1 receptor (MC1R) overexpressed in melanoma. The compact structure of a rhenium-cyclized alpha-MSH analog (Re-CCMSH) significantly enhanced its in vivo tumor uptake and retention. Melanotan II (MT-II), a cyclic lactam analog of alpha-MSH (Ac-Nle-cyclo[Asp-His-DPhe-Arg-Trp-Lys]-NH2]), is a very potent and stable agonist peptide largely used in the characterization of melanocortin receptors. Taking advantage of the superior biological features associated with the MT-II cyclic peptide, we assessed the effect of lactam-based cyclization on the tumor-seeking properties of alpha-MSH analogs by comparing the pharmacokinetics profile of the 99mTc-labeled cyclic peptide betaAla-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 with that of the linear analog betaAla-Nle-Asp-His-DPhe-Arg-Trp-Lys-NH2 in melanoma-bearing mice. We have synthesized and coupled the linear and cyclic peptides to a bifunctional chelator containing a pyrazolyl-diamine backbone (pz) through the amino group of betaAla, and the resulting pz-peptide conjugates were reacted with the fac-[99mTc(CO)3]+ moiety. The 99mTc(CO)3-labeled conjugates were obtained in high yield, high specific activity, and high radiochemical purity. The cyclic 99mTc(CO)3-labeled conjugate presents a remarkable internalization (87.1% of receptor-bound tracer and 50.5% of total applied activity, after 6 h at 37 degrees C) and cellular retention (only 24.7% released from the cells after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake and retention was obtained in melanoma-bearing C57BL6 mice for the cyclic radioconjugate [9.26 +/- 0.83 and 11.31 +/- 1.83% ID/g at 1 and 4 h after injection, respectively]. The linear 99mTc(CO)3-pz-peptide presented lower values for
Guo, Haixun; Yang, Jianquan; Gallazzi, Fabio; Prossnitz, Eric R; Sklar, Larry A; Miao, Yubin
2009-11-01
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 (alpha-MSH) peptide. A novel lactam bridge-cyclized alpha-MSH peptide, Ac-GluGlu-CycMSH[DOTA] {Ac-Glu-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Lys(DOTA)]}, was synthesized using standard 9-fluorenylmethyloxycarbonyl (Fmoc) chemistry. DOTA was directly attached to the alpha-amino group of Lys in the cyclic ring, while the N-terminus of the peptide was acetylated to generate Ac-GluGlu-CycMSH[DOTA]. The MC1 receptor binding affinity of Ac-GluGlu-CycMSH[DOTA] was determined in B16/F1 melanoma cells. Melanoma targeting and pharmacokinetic properties of Ac-GluGlu-CycMSH[DOTA]-111In were determined in B16/F1 melanoma-bearing C57 mice and compared to that of 111In-DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp] (111In-DOTA-GlyGlu-CycMSH; DOTA was coupled to the N-terminus of the peptide). Ac-GluGlu-CycMSH[DOTA] displayed 0.6 nM MC1 receptor binding affinity in B16/F1 cells. Ac-GluGlu-CycMSH[DOTA]-111In was readily prepared with greater than 95% radiolabeling yield. Ac-GluGlu-CycMSH[DOTA]-111In exhibited high tumor uptake (11.42 +/- 2.20% ID/g 2 h postinjection) and prolonged tumor retention (9.42 +/- 2.41% ID/g 4 h postinjection) in B16/F1 melanoma-bearing C57 mice. The uptake values for nontarget organs were generally low (<1.3% ID/g) except for the kidneys 2, 4, and 24 h postinjection. DOTA position exhibited profound effect on melanoma targeting and pharmacokinetic properties of Ac-GluGlu-CycMSH[DOTA]-111In, providing a new insight into the design of lactam bridge-cyclized peptide for melanoma imaging and therapy.
Guo, Haixun; Yang, Jianquan; Shenoy, Nalini; Miao, Yubin
2009-12-01
The purpose of this study was to examine the melanoma imaging properties of a novel 67Ga-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (alpha-MSH) peptide. A lactam bridge-cyclized alpha-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 pulmonary metastatic melanoma-bearing C57 mice. Flank primary melanoma and pulmonary metastatic melanoma imaging were performed by small animal single photon emission computed tomography (SPECT)/CT using 67Ga-DOTA-GlyGlu-CycMSH as an imaging probe. 67Ga-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. 67Ga-DOTA-GlyGlu-CycMSH exhibited substantial tumor uptake (12.93 +/- 1.63%ID/g at 2 h postinjection) and prolonged tumor retention (5.02 +/- 1.35%ID/g at 24 h postinjection) in B16/F1 melanoma-bearing C57 mice. The uptake values for nontarget organs were generally low (<0.30%ID/g) except for the kidneys at 2, 4, and 24 h postinjection. 67Ga-DOTA-GlyGlu-CycMSH exhibited significantly (p < 0.05) higher uptakes (1.44 +/- 0.75%ID/g at 2 h postinjection and 1.49 +/- 0.69%ID/g at 4 h postinjection) in metastatic melanoma-bearing lung than those in normal lung (0.15 +/- 0.10%ID/g and 0.17 +/- 0.11%ID/g at 2 and 4 h postinjection, respectively). Both flank primary B16/F1 melanoma and B16/F10 pulmonary melanoma metastases were clearly visualized by SPECT/CT using 67Ga-DOTA-GlyGlu-CycMSH as an imaging probe 2 h postinjection. 67Ga-DOTA-GlyGlu-CycMSH exhibited favorable melanoma targeting and imaging properties, highlighting its potential as an effective imaging probe for early detection of primary and metastatic melanoma.
Nicolaou, Anna; Estdale, Sian E; Tsatmali, Marina; Herrero, Daniel Pascual; Thody, Anthony J
2004-07-16
Prostaglandins are potent mediators of the inflammatory response and are also involved in cancer development. In this study, we show that human melanocytes and FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have the capability to produce prostaglandins. The FM55 cells produced predominantly PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly PGE2. The anti-inflammatory peptide, alpha-melanocyte stimulating hormone (alpha-MSH), reduced prostaglandin production in FM55 and HaCaT cells and reversed the effect of the pro-inflammatory cytokine TNF-alpha in the former. These results indicate that melanocytes produce prostaglandins and that alpha-MSH, by inhibiting this response, may play an important role in regulating inflammatory responses in the skin.
Miao, Yubin; Gallazzi, Fabio; Guo, Haixun; Quinn, Thomas P
2008-02-01
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 alpha-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 (111)In. The internalization and efflux of (111)In-labeled CycMSH peptides were examined in B16/F1 melanoma cells. The melanoma targeting properties, pharmacokinetics, and SPECT/CT imaging of (111)In-labeled CycMSH peptides were determined in B16/F1 melanoma-bearing C57 mice. Both (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH exhibited fast internalization and extended retention in B16/F1 cells. The tumor uptake values of (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH were 9.53+/-1.41% injected dose/gram (% ID/g) and 10.40+/-1.40% ID/g at 2 h postinjection, respectively. Flank melanoma tumors were clearly visualized with (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH by SPECT/CT images at 2 h postinjection. Whole-body clearance of the peptides was fast, with greater than 90% of the radioactivities cleared through urinary system by 2 h postinjection. There was low radioactivity (<0.8% ID/g) accumulated in blood and normal organs except kidneys at all time points investigated. Introduction of a negatively charged linker (-Gly-Glu-) into the peptide sequence decreased the renal uptake by 44% without affecting the tumor uptake at 4 h postinjection. High receptor-mediated melanoma uptakes coupled with fast whole-body clearance in B16/F1 melanoma-bearing C57 mice demonstrated the feasibility of using (111)In-labeled lactam bridge-cyclized alpha-MSH peptide analogues as a novel class of imaging probes for receptor-targeting melanoma imaging.
[Alpha-melanocyte-stimulating hormone. From bench to bedside].
Böhm, M; Luger, T A
2010-06-01
Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that is produced by the skin itself from the precursor proopiomelanocortin. It crucially mediates ultraviolet light-induced tanning after binding to melanocortin-1 receptors (MC-1R) expressed on the surface of epidermal melanocytes. The potent pigment-inducing and also cytoprotective actions of alpha-MSH are the rationale for the performance of first phase II clinical trials with Nle4-D-Phe7-alpha-MSH (NDP-alpha-MSH), a subcutaneously administered synthetic and superpotent alpha-MSH analogue, in patients with photodermatoses such as erythropoietic protoporphyria. Since alpha-MSH has shown promising anti-inflammatory and antifibrotic properties in numerous preclinical studies, it will be most interesting to evaluate these effects in further clinical pilot studies with NDP-alpha-MSH. In addition to alpha-MSH analogues, truncated tripeptides such as KDPT which do not bind to MC-1R but have sustained anti-inflammatory properties are currently emerging as another novel therapeutic strategy in dermatology.
Directory of Open Access Journals (Sweden)
Markus Böhm
2016-05-01
Full Text Available Alpha-melanocyte-stimulating hormone (alpha-MSH increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.
Improving the stability of alpha-conotoxin AuIB through N-to-C cyclization
DEFF Research Database (Denmark)
Armishaw, Christopher J; Jensen, Anders A; Balle, Lena D
2011-01-01
Modification of alpha-conotoxin frameworks through cyclization via an oligopeptide linker has previously been shown as an effective strategy for improving in vivo stability. We have extended this strategy by investigating cyclic analogs of alpha-conotoxin AuIB, a selective alpha3beta4 nicotinic a......-AuIB. As such, the cAuIB-2 globular isomer could constitute a useful probe for studying the role of the alpha3beta4 nicotinic acetylcholine receptor in a range of in vivo experimental paradigms....
International Nuclear Information System (INIS)
Croteau, R.; Satterwhite, D.M.; Wheeler, C.J.; Felton, N.M.
1989-01-01
The conversion of geranyl pyrophosphate to (+)-alpha-pinene and to (-)-beta-pinene is considered to proceed by the initial isomerization of the substrate to (-)-(3R)- and to (+)-(3S)-linalyl pyrophosphate, respectively, and the subsequent cyclization of the anti, endo-conformer of these bound intermediates by mirror-image sequences which should result in the net retention of configuration at C1 of the geranyl precursor. Incubation of (1R)-[2-14C,1-3H]- and (1S)-[2-14C,1-3H]geranyl pyrophosphate with (+)-pinene cyclase and with (-)-pinene cyclase from common sage (Salvia officinalis) gave labeled (+)-alpha- and (-)-beta-pinene of unchanged 3H/14C ratio in all cases, and the (+)- and (-)-olefins were stereoselectively converted to (+)- and (-)-borneol, respectively, which were oxidized to the corresponding (+)- and (-)-isomers of camphor, again without change in isotope ratio. The location of the tritium was determined in each case by stereoselective, base-catalyzed exchange of the exo-alpha-hydrogens of these derived ketones. The results indicated that the configuration at C1 of the substrate was retained in the enzymatic transformations to the (+)- and (-)-pinenes, which is entirely consistent with the syn-isomerization of geranyl pyrophosphate to linalyl pyrophosphate, transoid to cisoid rotation, and anti, endo-cyclization of the latter. The absolute stereochemical elements of the antipodal reaction sequences were confirmed by the selective enzymatic conversions of (3R)- and (3S)-1Z-[1-3H]linalyl pyrophosphate to (+)-alpha-pinene and (-)-beta-pinene, respectively, and by the location of the tritium in the derived camphors as before. The summation of the results fully defines the overall stereochemistry of the coupled isomerization and cyclization of geranyl pyrophosphate to the antipodal pinenes
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-(1......) were detected in lower amounts in both the intermediate lobe and the anterior lobe. ACTH-(1-17), ACTH-(1-13) and their acetylated analogues could not be detected in the anterior lobe or the intermediate lobe. The results suggest that an endopeptidase initially cleaves ACTH-(1-39) at the Lys-16-Arg-17...... bond. ACTH-(1-16) is then processed by a pituitary carboxypeptidase to ACTH-(1-14) and ACTH-(17-39) by the aminopeptidase to ACTH-(18-39)....
International Nuclear Information System (INIS)
Carta, Davide; Salvarese, Nicola; Morellato, Nicolò; Gao, Feng; Sihver, Wiebke; Pietzsch, Hans Jurgen; Biondi, Barbara; Ruzza, Paolo; Refosco, Fiorenzo; Carpanese, Debora; Rosato, Antonio; Bolzati, Cristina
2016-01-01
The purpose of this study was to evaluate the effect of cyclization on the biological profile of a [ 99m Tc(N)(PNP3)]-labeled α-melanocyte stimulating hormone peptide analog. A lactam bridge-cyclized H-Cys-Ahx-βAla 3 -c[Lys 4 -Glu-His-D-Phe-Arg-Trp-Glu 10 ]-Arg 11 -Pro-Val-NH 2 (NAP―NS2) and the corresponding linear H-Cys-Ahx-βAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH 2 (NAP―NS1) peptide were synthetized, characterized by ESI-MS spectroscopy and their melanocortin-1 receptor (MC1R) binding affinity was determined in B16/F10 melanoma cells. The consistent [ 99m Tc(N)(PNP3)]-labeled compounds were readily obtained in high specific activity and their stability and biological properties were assessed. As an example, the chemical identity of [ 99m Tc(N)(NAP–NS1)(PNP3)] + was confirmed by carrier added experiments supported by radio/UV HPLC analysis combined with ESI(+)-MS. Compared with the linear peptide, cyclization negatively affected the biological properties of NAP–NS2 peptide by reducing its binding affinity for MC1R and by decreasing the overall excretion rate of the corresponding [ 99m Tc(N)(PNP3)]-labeled peptide from the body as well as its in vivo stability. [ 99m Tc(N)(NAP–NS1)(PNP3)] + was evaluated for its potential as melanoma imaging probe in murine melanoma model. Data from in vitro and in vivo studies on B16/F10 melanoma model of [ 99m Tc(N)(NAP–NS1)(PNP3)] + clearly evidenced that the radiolabeled linear peptide keeps its biological properties up on the conjugation to the [ 99m Tc(N)(PNP3)]-building block. The progressive increase of the tumor-to-nontarget ratios over the time indicates a quite stable interaction between the radio-complex and the MC1R.
Delgado Hernàndez, R; Demitri, M T; Carlin, A; Meazza, C; Villa, P; Ghezzi, P; Lipton, J M; Catania, A
1999-01-01
The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central alpha-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-alpha and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Lung myeloperoxidase activity, a marker of neutrophil infiltration, was increased in endotoxemic mice; the increase was significantly less in lungs of mice treated with central alpha-MSH. Intraperitoneal administration of the small dose of alpha-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central alpha-MSH, we tested the idea that endogenous peptide induced within the brain during systemic inflammation modulates host responses to endotoxic challenge in peripheral tissues. The data showed that proinflammatory agents induced by endotoxin in the circulation, lungs, and liver were significantly greater after blockade of central alpha-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation.
John, David A.; Seal, Robert R.; Polyak, Désirée E.; Schulz, Klaus J.; DeYoung,, John H.; Seal, Robert R.; Bradley, Dwight C.
2017-12-19
Rhenium is one of the rarest elements in Earth’s continental crust; its estimated average crustal abundance is less than 1 part per billion. Rhenium is a metal that has an extremely high melting point and a heat-stable crystalline structure. More than 80 percent of the rhenium consumed in the world is used in high-temperature superalloys, especially those used to make turbine blades for jet aircraft engines. Rhenium’s other major application is in platinum-rhenium catalysts used in petroleum refining.Rhenium rarely occurs as a native element or as its own sulfide mineral; most rhenium is present as a substitute for molybdenum in molybdenite. Annual world mine production of rhenium is about 50 metric tons. Nearly all primary rhenium production (that is, rhenium produced by mining rather than through recycling) is as a byproduct of copper mining, and about 80 percent of the rhenium obtained through mining is recovered from the flue dust produced during the roasting of molybdenite concentrates from porphyry copper deposits. Molybdenite in porphyry copper deposits can contain hundreds to several thousand grams per metric ton of rhenium, although the estimated rhenium grades of these deposits range from less than 0.1 gram per metric ton to about 0.6 gram per metric ton.Continental-arc porphyry copper-(molybdenum-gold) deposits supply most of the world’s rhenium production and have large inferred rhenium resources. Porphyry copper mines in Chile account for about 55 percent of the world’s mine production of rhenium; rhenium is also recovered from porphyry copper deposits in the United States, Armenia, Kazakhstan, Mexico, Peru, Russia, and Uzbekistan. Sediment-hosted strata-bound copper deposits in Kazakhstan (of the sandstone type) and in Poland (of the reduced-facies, or Kupferschiefer, type) account for most other rhenium produced by mining. These types of deposits also have large amounts of identified rhenium resources. The future supply of rhenium is likely
Airaghi, L; Garofalo, L; Cutuli, M G; Delgado, R; Carlin, A; Demitri, M T; Badalamenti, S; Graziani, G; Lipton, J M; Catania, A
2000-08-01
Clinical and/or laboratory signs of systemic inflammation occur frequently in patients undergoing long-term haemodialysis. It is likely, therefore, that a compensatory release of endogenous anti-inflammatory molecules occurs to limit host reactions. The aim of the present research was to determine if the potent anti-inflammatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin derivative, is increased in plasma of haemodialysis patients. Because endotoxin and cytokines induce alpha-MSH in vivo and in vitro, we also measured plasma concentrations of endotoxin, interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), and the two circulating products of activated monocytes, nitric oxide (NO) and neopterin. Thirty-five chronic haemodialysis patients, 20 patients with chronic renal failure not yet on dialysis, and 35 normal controls were included in the study. In the haemodialysis group, blood samples were obtained before and at the end of a dialysis session. Plasma alpha-MSH was measured using a double antibody radioimmunoassay, and IL-6, TNF-alpha, and neopterin using specific enzyme-linked immunosorbent assays. Plasma nitrites were determined by a colorimetric method, and endotoxin with the quantitative chromogenic LAL (limulus amoebocyte lysate) method. Mean plasma alpha-MSH was higher in haemodialysis patients than in control subjects, with the peptide concentrations being particularly elevated in dialysed patients with detectable endotoxin. High alpha-MSH concentrations were observed in the pre-dialysis samples, with no substantial change at the end of the dialysis session. Plasma concentrations of IL-6, TNF-alpha, neopterin, and NO were generally elevated in chronic haemodialysis patients and there was a negative correlation between circulating alpha-MSH and IL-6. In patients with renal failure not yet on dialysis, mean plasma alpha-MSH was similar to that of normal subjects. alpha-MSH is increased in the circulation of
DEFF Research Database (Denmark)
Fenger, M
1988-01-01
Pro-opiomelanocortin (POMC)-related peptides in extracts of anterior and neurointermediate pituitary lobes from pigs were characterized by gel chromatography, reversed-phase chromatography and radioimmunoassays. The peptide content was ca. 3-fold greater in the anterior lobe compared...... to the neurointermediate lobe (19.8 nmol POMC/anterior lobe vs 7.0 nmol/neurointermediate lobe). In the neurointermediate lobe 93% of POMC was processed to alpha-melanocyte-stimulating hormone (alpha-MSH) and analogs exclusively of low molecular weight. Most of the remaining adrenocorticotropic hormone (ACTH...... as alpha-MSH and analogs (94%). However, more than 95% of these peptides were of high molecular weight. In the anterior lobe 2.3% of N-POMC was processed and 94% was amidated gamma-MSH of only high molecular weight. These results show that gamma-MSH and alpha-MSH are amidated to the same extent...
Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma
International Nuclear Information System (INIS)
Frey, L. M.; Houben, R.; Brocker, E. B.
2011-01-01
Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues by means of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intra-tumoral melanocytes. Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.
Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I
1999-03-15
We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).
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
Guo, Haixun; Gallazzi, Fabio; Miao, Yubin
2013-04-01
The purpose of this study was to examine the melanoma targeting and imaging properties of new (99m)Tc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSH(hex), AcCG3-GGNle-CycMSH(hex), and HYNIC-GGNle-CycMSH(hex) peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of (99m)Tc-MAG3-GGNle-CycMSH(hex), (99m)Tc-AcCG3-GGNle-CycMSH(hex), (99m)Tc(CO)3-HYNIC-GGNle-CycMSH(hex), and (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice at 2 h postinjection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were further examined because of its high melanoma uptake and fast urinary clearance. The IC50 values of MAG3-GGNle-CycMSH(hex), AcCG3-GGNle-CycMSH(hex), and HYNIC-GGNle-CycMSH(hex) were 1.0 ± 0.05, 1.2 ± 0.19, and 0.6 ± 0.04 nM in B16/F1 melanoma cells, respectively. Among these four (99m)Tc-peptides, (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) exhibited the highest melanoma uptake (14.14 ± 4.90% ID/g) and fastest urinary clearance (91.26 ± 1.96% ID) at 2 h postinjection. (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) showed high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were 2.50 and 3.55 at 4 and 24 h postinjection. The melanoma lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) as an imaging probe at 2 h postinjection. Overall, high melanoma uptake coupled with fast urinary clearance of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) highlighted its potential for metastatic melanoma detection in the future.
Spherical rhenium metal powder
International Nuclear Information System (INIS)
Leonhardt, T.; Moore, N.; Hamister, M.
2001-01-01
The development of a high-density, spherical rhenium powder (SReP) possessing excellent flow characteristics has enabled the use of advanced processing techniques for the manufacture of rhenium components. The techniques that were investigated were vacuum plasma spraying (VPS), direct-hot isostatic pressing (D-HIP), and various other traditional powder metallurgy processing methods of forming rhenium powder into near-net shaped components. The principal disadvantages of standard rhenium metal powder (RMP) for advanced consolidation applications include: poor flow characteristics; high oxygen content; and low and varying packing densities. SReP will lower costs, reduce processing times, and improve yields when manufacturing powder metallurgy rhenium components. The results of the powder characterization of spherical rhenium powder and the consolidation of the SReP are further discussed. (author)
Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi
2014-12-01
Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medicinal amino acid used in skin whitening care. This study examined the effects of tranexamic acid on the melanocyte activation of the skin induced by an ultraviolet (UV) B eye irradiation. The eye or ear was locally exposed to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining body surface with aluminum foil. UVB eye irradiation induced melanocyte activation of the skin, similar to that observed following UVB ear irradiation, which was suppressed by the administration of tranexamic acid treatment. The plasma α-melanocyte-stimulating hormone (α-MSH) content was increased by UVB irradiation of the eye; however, the increase in α-MSH was suppressed by tranexamic acid treatment. In addition, UVB eye irradiation induced the up-regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid treatment. These results clearly indicate that tranexamic acid decreases the expression of PC2, which cleavages from proopiomelanocortin to α-MSH in the pituitary gland, thereby suppressing melanocyte activation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Rhenium radioisotopes for therapeutic radiopharmaceutical development
International Nuclear Information System (INIS)
Knapp, F.F. Jr.; Beets, A.L.; Pinkert, J.; Kropp, J.; Lin, W.Y.; Wang, S.Y.
2001-01-01
Rhenium-186 and rhenium-188 represent two important radioisotopes which are of interest for a variety of therapeutic applications in oncology, nuclear medicine and interventional cardiology. Rhenium-186 is directly produced in a nuclear reactor and the 90 hour half-life allows distribution to distant sites. The relatively low specific activity of rhenium-186 produced in most reactors, however, permits use of phosphonates, but limits use for labelled peptides and antibodies. Rhenium-188 has a much shorter 16.9 hour half-life which makes distribution from direct reactor production difficult. However, rhenium-188 can be obtained carrier-free from a tungsten-188/rhenium-188 generator, which has a long useful shelf-life of several months which is cost-effective, especially for developing regions. In this paper we discuss the issues associated with the production of rhenium-186- and rhenium-188 and the development and use of various radiopharmaceuticals and devices labelled with these radioisotopes for bone pain palliation, endoradiotherapy of tumours by selective catheterization and tumour therapy using radiolabelled peptides and antibodies, radionuclide synovectomy and the new field of vascular radiation therapy. (author)
ELECTROPHILIC CYCLIZATION OF DITERPENOIDS
Directory of Open Access Journals (Sweden)
Veaceslav Kulciţki
2006-06-01
Full Text Available A review of diterpenoid cyclization initiated by electrophilic reagents is provided. Conventional protonic and Lewis acids are examined along with superacids as initiators of cyclization cascade. An emphasis is placed on the use of cyclization reactions as a tool for the synthesis of compounds with potential practical utility. The review contains 74 references.
Kholmanskikh, Olga; van Baren, Nicolas; Brasseur, Francis; Ottaviani, Sabrina; Vanacker, Julie; Arts, Nathalie; van der Bruggen, Pierre; Coulie, Pierre; De Plaen, Etienne
2010-10-01
We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1beta. This effect is NF-kappaB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1beta reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1alpha or IL-1beta secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that approximately 13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.
International Nuclear Information System (INIS)
Busev, A.I.; Tiptsova, V.G.; Ivanov, V.M.
1978-01-01
The basic methods for determining rhenium in various objects are presented. The gravimetric determination of rhenium is based on a quantitative precipitation of ReO 4 - ions with tetraphenylarsonium chloride. The determination is not hindered by tungstates and molybdates. The potentiometric determination of rhenium in alloys (>=0.5% Re) is based on perrhenate ion reduction to Re(4) with the titrated solution of the Cr(2) salt. Re(7) is titrated in a hot sulfuric acid solution in the presence of KJ. The relative error of the method is 1 to 3%. The photometric determination of rhenium is performed by the rhodamide method in molybdenum-and tungsten-containing alloys and catalytically, in rocks, after it has been separated in the form of sulfide. The extraction-photometric determination of rhenium is carried out with the aid of methyl violet (analysis of a stock with a high content of Mo, W, Ta, Nb, Ti ahd Zr) and thio-oxine (the determination of Re is hindered by Au, Pt, Pd, Ru, Os, Rh, Ir). Also described are methods for differential-spectrophotometric determination of Re with the aid of thiocarbamide, as well as with the aid of dimethylglyoxime in the presence of SnCl 2 in an acid medium when Re is determined in its alloys with niobium and hafnium. It takes 2 hours to analyze the Hf-Re alloy and 3 hours to analyze the Nb-Re alloy, the standard deviation being 0.005 at 30-50% Re and 0.027 to 0.019 at 10-50% Re
Evidence for alpha-MSH binding sites on human scalp hair follicles: preliminary results
Nanninga, P. B.; Ghanem, G. E.; Lejeune, F. J.; Bos, J. D.; Westerhof, W.
1991-01-01
Alpha-MSH, considered an important pigmentation hormone, binds to melanocytes and is thought to stimulate melanogenesis through a cyclic-AMP-dependent mechanism. The binding of alpha-MSH to follicular melanocytes has been investigated in human hair of different colors, ranging from black to blond
International Nuclear Information System (INIS)
Croteau, R.; Gershenzon, J.; Wheeler, C.J.; Satterwhite, D.M.
1990-01-01
The conversion of geranyl pyrophosphate to (+)-bornyl pyrophosphate and (+)-camphene is considered to proceed by the initial isomerization of the substrate to (-)-(3R)-linalyl pyrophosphate and the subsequent cyclization of this bound intermediate. In the case of (-)-bornyl pyrophosphate and (-)-camphene, isomerization of the substrate to the (+)-(3S)-linalyl intermediate precedes cyclization. The geranyl and linalyl precursors were shown to be mutually competitive substrates (inhibitors) of the relevant cyclization enzymes isolated from Salvia officinalis (sage) and Tanacetum vulgare (tansy) by the mixed substrate analysis method, demonstrating that isomerization and cyclization take place at the same active site. Incubation of partially purified enzyme preparations with (3R)-[1Z-3H]linalyl pyrophosphate plus [1-14C]geranyl pyrophosphate gave rise to double-labeled (+)-bornyl pyrophosphate and (+)-camphene, whereas incubation of enzyme preparations catalyzing the antipodal cyclizations with (3S)-[1Z-3H]-linalyl pyrophosphate plus [1-14C]geranyl pyrophosphate yielded double-labeled (-)-bornyl pyrophosphate and (-)-camphene. Each product was then transformed to the corresponding (+)- or (-)-camphor without change in the 3H:14C isotope ratio, and the location of the tritium label was deduced in each case by stereoselective, base-catalyzed exchange of the exo-alpha-hydrogen of the derived ketone. The finding that the 1Z-3H of the linalyl precursor was positioned at the endo-alpha-hydrogen of the corresponding camphor in all cases, coupled to the previously demonstrated retention of configuration at C1 of the geranyl substrate in these transformations, confirmed the syn-isomerization of geranyl pyrophosphate to linalyl pyrophosphate and the cyclization of the latter via the anti,endo- conformer
Electrochemical behaviour of rhenium-graphite electrode
International Nuclear Information System (INIS)
Varypaev, V.N.; Krasikov, V.L.
1980-01-01
Electrochemical behaviour of combination electrode from graphite with electrodeposited thin coating of electrolytic rhenium is studied. Solution of 0.5 m NaCl+0.04 m AlCl 3 served as an electrolite. Polarization galvanostatic curves of hydrogen evolution upon electrodes with conditional rhenium thickness of 3.5 and 0.35 μm, 35 and 3.5 nm are obtained. Possibility of preparation of rhenium-graphite cathode with extremely low rhenium consume, electro-chemical properties of which are simu-lar to purely rhenium cathode is shown. Such electrode is characterized with stable in time low cathode potential of hydrogen evolution in chloride electrolyte and during cathode polarization it is not affected by corrosion
Feller, Liviu; Chandran, Rakesh; Kramer, Beverley; Khammissa, Razia A G; Altini, Mario; Lemmer, Johan
2014-09-01
The color of normal skin and of oral mucosa is not determined by the number of melanocytes in the epithelium but rather by their melanogenic activity. Pigmented biopolymers or melanins are synthesized in melanosomes. Tyrosinase is the critical enzyme in the biosynthesis of both brown/black eumelanin and yellow/red pheomelanin. The number of the melanosomes within the melanocytes, the type of melanin within the melanosomes, and the efficacy of the transfer of melanosomes from the melanocytes to the neighboring keratinocytes all play an important role in tissue pigmentation. Melanin production is regulated by locally produced factors including proopiomelanocortin and its derivative peptides, particularly alpha-melanocyte-stimulating hormone (α-MSH), melanocortin 1 receptor (MC1R), adrenergic and cholinergic agents, growth factors, cytokines, and nitric oxide. Both eumelanin and pheomelanin can be produced by the same melanocytes, and the proportion of the two melanin types is influenced by the degree of functional activity of the α-MSH/MC1R intracellular pathway. The cause of HIV oral melanosis is not fully understood but may be associated with HIV-induced cytokine dysregulation, with the medications commonly prescribed to HIV-seropositive persons, and with adrenocortical dysfunction, which is not uncommon in HIV-seropositive subjects with AIDS. The purpose of this article is to discuss some aspects of melanocyte biology and HIV-associated oral melanin hyperpigmentation.
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
Rhenium carbene complexes and their applications; Rhenium-Carben-Komplexe und ihre Anwendungen
Energy Technology Data Exchange (ETDEWEB)
Hille, Claudia Heidi
2016-01-25
New pharmaceutically suitable metal complexes play an important role in the development of diagnostic and therapeutic agents for cancer treatment. One option concerning new radiopharmaceuticals, is the application of the rhenium isotopes {sup 186}Re and {sup 188}Re. Therefore, water soluble but at the same time stable complexes, which can be synthesized straightforward, are required. In this thesis, several synthetic pathways to such rhenium complexes bearing Nheterocyclic carbenes are presented and applicability tests of literature known complexes conducted. The selected target structures based on monocarbenes turned out to be inappropriate for use in radiopharmaceutical applications, due to their long reaction times and purification issues. Additionally, sterical and electronical effects of the carbene ligands concerning complex formation have been investigated. Possibilities of functionalization at different positions on the heterocycle as well as hydrophilic wingtips - to achieve a better stability in an aqueous media - have been examined to gain information about chemical and physical properties of the resulting complexes. Furthermore, experiments regarding the coordination of various biscarbene ligands, which provides besides the stable chelatisation additionally the possibility of varying the linking bridge, to rhenium(I/V) precursors, have been performed. Dioxo-bis-(1,1{sup '}-methylene-bis(3,3{sup '}-diisopropylimidazolium-2-ylidene)) rhenium(V )-hexafluorophosphate was synthesized via a transmetalation reaction of the corresponding silver carbene with ReOCl{sub 3}(PPh{sub 3}){sub 2} and silver hexafluorophosphate. This complex provided the basis for the first radiolabeled {sup 188}Rhenium NHC complex later on. An enhancement of the kinetic and thermodynamic stability of potential rhenium biscarbene complexes based on modifications concerning the length and character of the bridging moiety between the chelating NHC rings as well as the nature of
Torres, Cristian Gabriel; Pino, Ana María; Sierralta, Walter Daniel
2009-06-01
The effects of estradiol (E2) and of an AFP-derived cyclized peptide (cP) on the proliferation of primary cultures of cancer cells isolated from spontaneous canine mammary tumors were studied. The cellular response to E2 and cP was related to the expression of estradiol receptor (isoforms alpha and beta). In ER-positive cells, 2 nM estradiol increased cell proliferation and the phosphorylation of ERK1/2; 2 microg/ml cP inhibited all these effects. Estradiol also increased HER2 immunoreactivity in ER-positive cells, an effect that was reverted to its basal values by cP. Estradiol stimulated in these cells the release of MMP2 and MMP9 and the shedding of HB-EGF, effects that the cP did not affect. ER-negative cells were refractory to estradiol or cP. All canine mammary tumor cells in culture responded to treatments analogously to human mammary cancer cells. Our results support the proposal of cP as a new, potentially effective therapeutic agent for the management of mammary cancer.
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.
The Cyclization of natural rubber
International Nuclear Information System (INIS)
Mirzataheri, M.
2000-01-01
The effect of solvent, temperature, time, weight percent of catalyst on the rate and mechanism of cyclization of natural rubber was studied in toluene and xylene solutions having tin tetra chloride catalyst (SnCl 4 ). Iodo metric titration show, with 8% SnCl 4 (based on polymer weight) cyclization occurs, leaving 27.4% of the total unsaturation. Infrared spectra of cyclized natural rubber show decreased absorption intensity at 840 and 780 cm -1 which are characteristic bands of the linear polymer and the appearance of absorption band at 890 cm -1 as cycles were formed. By using this chemical modification, natural rubber is transformed into a resinous thermoplastic, hard, non rubbery cyclized material with much less unsaturation than the original rubber, which could find commercial applications ad adhesives, printing inks, industrial and ship paints
Rhenium Rocket Manufacturing Technology
1997-01-01
The NASA Lewis Research Center's On-Board Propulsion Branch has a research and technology program to develop high-temperature (2200 C), iridium-coated rhenium rocket chamber materials for radiation-cooled rockets in satellite propulsion systems. Although successful material demonstrations have gained much industry interest, acceptance of the technology has been hindered by a lack of demonstrated joining technologies and a sparse materials property data base. To alleviate these concerns, we fabricated rhenium to C-103 alloy joints by three methods: explosive bonding, diffusion bonding, and brazing. The joints were tested by simulating their incorporation into a structure by welding and by simulating high-temperature operation. Test results show that the shear strength of the joints degrades with welding and elevated temperature operation but that it is adequate for the application. Rhenium is known to form brittle intermetallics with a number of elements, and this phenomena is suspected to cause the strength degradation. Further bonding tests with a tantalum diffusion barrier between the rhenium and C-103 is planned to prevent the formation of brittle intermetallics.
Near-Net Shape Powder Metallurgy Rhenium Thruster
Leonhardt, Todd; Hamister, Mark; Carlen, Jan C.; Biaglow, James; Reed, Brian
2001-01-01
This paper describes the development of a method to produce a near-net shape (NNS) powder metallurgy (PM) rhenium combustion chamber of the size 445 N (100 lbf) used in a high performance liquid apogee engine. These engines are used in low earth Orbit and geostationary orbit for satellite positioning systems. The developments in near-net shape powder metallurgy rhenium combustion chambers reported in this paper will reduce manufacturing cost of the rhenium chambers by 25 percent, and reduce the manufacturing time by 30 to 40 percent. The quantity of rhenium metal powder used to produce a rhenium chamber is reduced by approximately 70 percent and the subsequent reduction in machining schedule and costs is nearly 50 percent.
Choi, Hyunjung; Jin, Sun Hee; Han, Mi Hwa; Lee, Jinyoung; Ahn, Seyeon; Seong, Minjeong; Choi, Hyun; Han, Jiyeon; Cho, Eun-Gyung; Lee, Tae Ryong; Noh, Minsoo
2014-10-01
The interactions between human epidermal melanocytes and their cellular microenvironment are important in the regulation of human melanocyte functions or in their malignant transformation into melanoma. Although the basement membrane extracellular matrix (BM-ECM) is one of major melanocyte microenvironments, the effects of BM-ECM on the human melanocyte functions are not fully explained at a molecular level. This study was aimed to characterize the molecular and cellular interactions between normal human melanocytes (NHMs) and BM-ECM. We investigated cell culture models of normal human melanocytes or melanoma cells on three-dimensional (3D) Matrigel to understand the roles of the basement membrane microenvironment in human melanocyte functions. Melanogenesis and melanobast biomarker expression in both primary human melanocytes and melanoma cells on 3D Matrigel were evaluated. We found that NHMs migrated and formed reversible paired box 3 (PAX3) expressing cell clusters on three-dimensional (3D) Matrigel. The melanogenesis was significantly decreased in the PAX3 expressing cell cluster. The expression profile of PAX3, SOX10, and MITF in the melanocyte cluster on 3D Matrigel was similar to that of melanoblasts. Interestingly, PAX3 and SOX10 showed an inverse expression profile in NHMs, whereas the inverse expression pattern of PAX3 and SOX10 was disrupted in melanoma MNT1 and WM266-4 cells. The human melanocyte culture on 3D Matrigel provides an alternative model system to study functions of human melanoblasts. In addition, this system will contribute to the elucidation of PAX3-related tumorigenic mechanisms to understand human melanoma. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Directed light fabrication of rhenium components
Energy Technology Data Exchange (ETDEWEB)
Milewski, J.O.; Thoma, D.J.; Lewis, G.K.
1997-02-01
Directed Light Fabrication (DLF) is a direct metal deposition process that fuses powder, delivered by gas into the focal zone of a high powered laser beam to form fully dense near-net shaped components. This is accomplished in one step without the use of molds, dies, forming, pressing, sintering or forging equipment. DLF is performed in a high purity inert environment free from the contaminants associated with conventional processing such as oxide and carbon pickup, lubricants, binding agents, cooling or cleaning agents. Applications using rhenium have historically been limited in part by its workability and cost. This study demonstrates the ability to fuse rhenium metal powder, using a DLF machine, into free standing rods and describes the associated parameter study. Microstructural comparisons between DLF deposited rhenium and commercial rhenium sheet product is performed. This research combined with existing DLF technology demonstrates the feasibility of forming complex rhenium, metal shapes directly from powder.
Breman, A.C.; Dijkink, J.; van Maarseveen, J.H.; Kinderman, S.S.; Hiemstra, H.
2009-01-01
A reaction sequence, involving the addition of (substituted) propargylsilanes to lactate-derived N-acyliminium ions followed by gold-catalyzed cyclization of the resulting alpha-allenyl amide, is applied in expedient syntheses of pyrrolizidine alkaloids heliotridine and ent-retronecine in five steps
Nickel-catalyzed cyclization of alpha, omega-dienes: formation vs. cleavage of C-C bonds
Czech Academy of Sciences Publication Activity Database
Nečas, D.; Turský, M.; Tišlerová, I.; Kotora, Martin
2006-01-01
Roč. 30, č. 4 (2006), s. 671-674 ISSN 1144-0546 R&D Projects: GA MŠk 1M0508; GA ČR GD203/03/H140 Institutional research plan: CEZ:AV0Z40550506 Keywords : catalysis * nickel * cyclization * diene * cyclopentane Subject RIV: CC - Organic Chemistry Impact factor: 2.647, year: 2006
International Nuclear Information System (INIS)
Pozdnyak, N.Z.; Belyaev, R.A.; Vavilov, Yu.V.; Vinogradov, Yu.G.; Serykh, G.M.
1978-01-01
Preparation technology (by powder metallurgy methods) of sintered rhenium and tungsten-rhenium VR-5, VR-10, and VR-20 alloys is described. Thermal conduction of rhenium and VR-20 alloy has been measured in the temperature range from 300 to 1000 K. The value obtained turned out to be considerably less than those published elsewhere, this testifies to the great thermal contact resistance between the material grains. Also measured is the mean linear expansion coefficient for the mentioned above materials in the same temperature range. Linear expansion increases with rhenium content increase
Rhenium-osmium geochemistry: method and applications
International Nuclear Information System (INIS)
Luck, J.M.
1982-03-01
Experimental methods for chemical separation and isotopic analysis of rhenium-osmium are described. Accurate determinations are obtained for a quantity ratio around 10 -6 -10 -7 g. Development as a geochemical tracer is examined. Study of rhenium-osmium in meteorites allows the determination of solar system chronology and age of the galaxy. Rhenium-osmium chronology in meteorites is improved and osmium isotopes are used as petrogenetic and geological tracers. Molybdenites are studied through 187 Re- 187 Os dating [fr
Crystallochemistry of rhenium compounds with metal-metal bonds
International Nuclear Information System (INIS)
Koz'min, P.A.; Surazhskaya, M.D.
1980-01-01
A review is presented including a brief description of atomic structure of 59 coordination rhenium compounds with metal-metal bond. The most important bond lengths and valent angles are presented for each compound. The dependence of rhenium-rhenium bond length on its multiplicity is discussed and possible causes of deviations from this dependence (namely, axial ligand presence, steric repulsion of ligands) are considered. On the basis of qualitative comparison of electronegativity of ligands in dimer compounds with quarternary bond of rhenium-rhenium a supposition is made on the influence of formal charge of atomic group and summary electro-negativity of ligands on the possibility of the metal-metal bond formation
International Nuclear Information System (INIS)
Croteau, R.; Satterwhite, D.M.; Cane, D.E.; Chang, C.C.
1988-01-01
Cyclase I from Salvia officinalis leaf catalyzes the conversion of geranyl pyrophosphate to the stereo-chemically related bicyclic monoterpenes (+)-alpha-pinene and (+)-camphene and to lesser quantities of monocyclic and acyclic olefins, whereas cyclase II from this plant tissue converts the same acyclic precursor to (-)-alpha-pinene, (-)-beta-pinene and (-)-camphene as well as to lesser amounts of monocyclics and acyclics. These antipodal cyclizations are considered to proceed by the initial isomerization of the substrate to the respective bound tertiary allylic intermediates (-)-(3R)- and (+)-(3S)-linalyl pyrophosphate. [(3R)-8,9-14C,(3RS)-1E-3H]Linalyl pyrophosphate (3H:14C = 5.14) was tested as a substrate with both cyclases to determine the configuration of the cyclizing intermediate. This substrate with cyclase I yielded alpha-pinene and camphene with 3H:14C ratios of 3.1 and 4.2, respectively, indicating preferential, but not exclusive, utilization of the (3R)-enantiomer. With cyclase II, the doubly labeled substrate gave bicyclic olefins with 3H:14C ratios of from 13 to 20, indicating preferential, but not exclusive, utilization of the (3S)-enantiomer in this case. (3R)- and (3S)-[1Z-3H]linalyl pyrophosphate were separately compared to the achiral precursors [1-3H]geranyl pyrophosphate and [1-3H]neryl pyrophosphate (cis-isomer) as substrates for the cyclizations. With cyclase I, geranyl, neryl, and (3R)-linalyl pyrophosphate gave rise exclusively to (+)-alpha-pinene and (+)-camphene, whereas (3S)-linayl pyrophosphate produced, at relatively low rates, the (-)-isomers. With cyclase II, geranyl, neryl, and (3S)-linalyl pyrophosphate yielded exclusively the (-)-isomer series, whereas (3R)-linalyl pyrophosphate afforded the (+)-isomers at low rates
Rhenium Nanochemistry for Catalyst Preparation
Directory of Open Access Journals (Sweden)
Vadim G. Kessler
2012-08-01
Full Text Available The review presents synthetic approaches to modern rhenium-based catalysts. Creation of an active center is considered as a process of obtaining a nanoparticle or a molecule, immobilized within a matrix of the substrate. Selective chemical routes to preparation of particles of rhenium alloys, rhenium oxides and the molecules of alkyltrioxorhenium, and their insertion into porous structure of zeolites, ordered mesoporous MCM matrices, anodic mesoporous alumina, and porous transition metal oxides are considered. Structure-property relationships are traced for these catalysts in relation to such processes as alkylation and isomerization, olefin metathesis, selective oxidation of olefins, methanol to formaldehyde conversion, etc.
Rhenium corrosion in chloride melts
International Nuclear Information System (INIS)
Stepanov, A.D.; Shkol'nikov, S.N.; Vetyukov, M.M.
1989-01-01
The results investigating rhenium corrosion in chloride melts containing sodium, potassium and chromium ions by a gravimetry potentials in argon atmosphere in a sealing quarth cell are described. Rhenium corrosion is shown to be rather considerable in melts containing CrCl 2 . The value of corrosion rate depending on temperature is determined
Thiocarbonyl complexes of rhenium. Pt. 1
International Nuclear Information System (INIS)
Abram, U.
1993-01-01
Novel rhenium complexes with terminal thiocarbonyl groups have been synthesized from ReCl 3 (Me 2 PhP) 3 and sodium diethyldithiocarbamate. mer-(Diethyldithiocarbamato)tris-(dimethylphenylphosphine)(thiocarbonyl)rhenium( I), mer-[Re(CS)(Me 2 PhP) 3 (Et 2 dtc)], and tris(diethyldithiocarbamato)(thiocarbonyl)rhenium(III), [Re(CS)(Et 2 dtc) 3 ] have been studied by infrared and NMR spectroscopy, mass spectrometry and X-ray diffraction. mer-[Re(CS)(Me 2 PhP) 3 (Et 2 dtc)] crystallizes orthorhombic in the space group P na 2 1 with a=1516.1(2), b=2189.8(2) and c=1035.6(1) pm. Structure solution and refinement converged at R=0.042. The coordination geometry is a distorted octahedron. The Re-C bond length is found to be 184(2) pm. [Re(CS)(Et 2 dtc) 3 ] crystallizes monoclinic in the space group P2 1 /c with a=962.2(6), b=1744.0(2), c=1537.4(6) pm and β=96.21(1) . The final R value is 0.028. In the monomeric complex the rhenium atom is seven-coordinate with an approximate pentagonal-bipyramidal coordination sphere and a rhenium-carbon distance of 181(1) pm. (orig.)
Energy Technology Data Exchange (ETDEWEB)
Yang Jianquan; Guo Haixun [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin, E-mail: ymiao@salud.unm.ed [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)
2010-11-15
Introduction: The purpose of this study was to examine whether {sup 99m}Tc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone ({alpha}-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and {alpha}{sub v{beta}3} integrin receptors was superior in melanoma targeting to {sup 99m}Tc-labeled {alpha}-MSH or RGD peptide targeting only the MC1 or {alpha}{sub v{beta}3} integrin receptor. Methods: RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were designed to target both MC1 and {alpha}{sub v{beta}3} integrin receptors, MC1 receptor only and {alpha}{sub v{beta}3} integrin receptor only, respectively. The MC1 or {alpha}{sub v{beta}3} integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of {sup 99m}Tc-labeled RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts. Results: RGD-Lys-(Arg{sup 11})CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and {alpha}{sub v{beta}3} integrin receptors, whereas RAD-Lys-(Arg{sup 11})CCMSH or RGD-Lys-(Arg{sup 11})CCMSHscramble lost their {alpha}{sub v{beta}3} integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was 2.49 and 2.24 times (P < .05) the melanoma uptakes of {sup 99m}Tc-RAD-Lys-(Arg{sup 11})CCMSH and {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg{sup 11})CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH, whereas the coinjection of RGD+(Arg{sup 11})CCMSH peptide mixture
Near net shape of powder metallurgy rhenium parts
International Nuclear Information System (INIS)
Leonhardt, T.; Downs, J.
2001-01-01
In this paper, a description of the stages of processing necessary to produce a near-net shape (NNS) powder metallurgy (PM) rhenium component through the use of cold isostatic pressing (CIP) to form a complex shape will be explained. This method was primarily developed for the production of the 440 N and 490 N liquid apogee engine combustion chambers used in satellite positioning systems. The CIP to NNS process has been used in the manufacture and production of other rhenium aerospace components as well. Cold isostatic pressing (CIP) to a near net shape utilizing a one or two-part mandrel greatly reduces the quantity of rhenium required to produce the component, and also significantly reduces the number of secondary machining operations necessary to complete the manufacturing process. Further, the developments in near-net shape powder metallurgy rhenium manufacturing techniques have generated significant savings in the area of both time and budget. Overall, cost declined by as much as 35 % for the quantity of rhenium chambers, and manufacturing time was decreased by 30-40 %. The quantity of rhenium metal powder used to produce a rhenium chamber was reduced by approximately 70 %, with a subsequent reduction of nearly 50 % in secondary machining operation schedules. Thus, it is apparent that the overall savings provided by the production of near-net shape powder metallurgy rhenium components will be more than merely another aspect of any project involving high temperature applications, it will constitute significant benefit. (author)
Development of industrial hydrogenating catalyst on rhenium base
International Nuclear Information System (INIS)
Chistyakova, G.A.; Bat', I.I.; Rebrova, V.V.
1975-01-01
Processes for forming rhenium catalysts on carbon carrier and their catalytic properties in nitrobenzene (NB) reduction were studied. Application of an ammonia preparation to the carbon surface produced impregnated carbon saturated at room temperature with a water solution of the ammonia preparation, taken in a volume equal to the volumetric capacity of the carbon. With one impregnation, 2% rhenium was taken up. Catalysts containing more than 5% rhenium were obtained by impregnating the carbon with heating and use of more concentrated solutions. Catalysts made in this way and dried at 100 0 C had the composition Re 2 OH/carbon/. The most active catalysts were those reduced at 200-250 0 C; higher temperatures, up to 300-500 0 C, decreased the activity. Study of the catalytic properties of the rhenium catalysts in a liquid phase reduction of NB showed that the specific activity of rhenium depends only slightly on the content of the active component in the catalyst and is close to the specific activity of palladium and considerably exceeds that of nickel. Study of the effect of the NB concentration and hydrogen pressure on the activity and stability of the 5% rhenium catalyst indicated that with NB concentrations from 50 to 10% the process takes place at an essentially constant rate; the order of the reaction was close to zero with an apparent activation energy of about 7000 cal/mole. At pressures of 15-200 atm the yield with the 5% catalyst was proportional to the hydrogen pressure. A big advantage of the rhenium catalysts in the reduction of NB is their high selectivity. With a higher activity than palladium and nickel catalysts, 5% rhenium catalyst produces a high operating capacity in a wide range of contact charges, which has considerable significance for industrial use in contact apparatus of the column type. Comparison of the costs of rhenium catalysts and granular carbon carrier with those of nickel, platinum, and palladium showed that 5% rhenium catalyst can
Ultraviolet radiation directly induces pigment production by cultured human melanocytes
International Nuclear Information System (INIS)
Friedmann, P.S.; Gilchrest, B.A.
1987-01-01
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 14 C-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
Growth of melanocytes in human epidermal cell cultures
International Nuclear Information System (INIS)
Staiano-Coico, L.; Hefton, J.M.; Amadeo, C.; Pagan-Charry, I.; Madden, M.R.; Cardon-Cardo, C.
1990-01-01
Epidermal cell cultures were grown in keratinocyte-conditioned medium for use as burn wound grafts; the melanocyte composition of the grafts was studied under a variety of conditions. Melanocytes were identified by immunohistochemistry based on a monoclonal antibody (MEL-5) that has previously been shown to react specifically with melanocytes. During the first 7 days of growth in primary culture, the total number of melanocytes in the epidermal cultures decreased to 10% of the number present in normal skin. Beginning on day 2 of culture, bipolar melanocytes were present at a mean cell density of 116 +/- 2/mm2; the keratinocyte to melanocyte ratio was preserved during further primary culture and through three subpassages. Moreover, exposure of cultures to mild UVB irradiation stimulated the melanocytes to proliferate, suggesting that the melanocytes growing in culture maintained their responsiveness to external stimuli. When the sheets of cultured cells were enzymatically detached from the plastic culture flasks before grafting, melanocytes remained in the basal layer of cells as part of the graft applied to the patient
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...... (ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH and ACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. The hinge peptides were amidated to an extent two to three orders...... amidated POMC-related peptides are present in normal human pituitary. It also shows that cleavage in vivo at all dibasic amino acids but one, takes place at the N-terminal POMC region; the exception is at the POMC-(49-50) N-terminal of the gamma MSH sequence. The pattern of peptides produced suggests...
Synthesis of fused azole-piperidionoses: A free radical cyclization approach
Energy Technology Data Exchange (ETDEWEB)
Marco-Contelles, Jose; Alhambra Jimenez, Carolina [Instituto de Quimica Organica General (CSIC), Madrid (Spain)
1999-08-01
A new strategy has been reported for the synthesis of fused azole-piperidinoses featuring and unprecedented and very efficient 6-exo-trig free radical cyclization onto heterocyclic sugar templates. These compounds are key intermediates for the synthesis of known or analogues of azole-glycosidase inhibitors. In this communication we describe our recent and successful results on the synthesis of fused triazole-piperidinoses. Radical precursors have been prepared by standard methodologies from 1, 2:5, 6-bis-O-isopropylidene-{alpha}-D-glucofuranose (4) via triazoles linked at C3 with {beta}-orientation, readily obtained by 1, 3-dipolar cycloaddition of azide 5 with diethyl acetylenedicarboxylate or methyl propiolate, and by S{sub N}2 displacement of the tosylate at C3 with 1, 2, 4-triazole in compound 20. The key 6-exp-trig free radical cyclizations proceeded in the usual conditions [tributyltin hydride or tris(trimethylsily)silane, AIBN, toluene] yielding the azaannulated sugars 9, 11, 19 and 23 in good or excellent yields. A mechanism for these cyclizations has been proposed. [Spanish] Se ha informado una nueva estrategia para la sintesis azol-piperidinosas fusionadas mediante una ciclizacion 6-exo-trig muy eficiente y sin precedentes, sobre plantillas de azucares heterociclicos. Estos compuestos son intermediarios claves para la sintesis de inhibidores de azol-glicosidasa conocidos analogos de ellos. En esta comunicacion describimos nuestros resultados recientes y exitosos sobre la sintesis de triazol-piperidinosas. Los precursores de radicales fueron preparados por la metodologia usual a partir de 1, 2:5, 6-bis-O-isopropiliden-{alpha}-D-glucofuranosa (4) via triazoles unidos en C3, con orientacion {beta}, los cuales se obtienen facilmente por cicloadicion 1, 3-dipolar de la azida 5 con acetilendicarboxilato de dietilo o propiolato de metilo y por desplazamiento S{sub N}2 del tosilato en C3 con 1, 2, 4-triazol en el compuesto 20. Las ciclizaciones 6-exo
Guo, Haixun; Yang, Jianquan; Gallazzi, Fabio; Miao, Yubin
2011-04-01
The purpose of this study was to examine the profound effects of the amino acid linkers on the melanoma-targeting and pharmacokinetic properties of (111)In-labeled lactam bridge-cyclized DOTA-[X]-CycMSH(hex) {1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[X]-c[Asp-His-dPhe-Arg-Trp-Lys]-CONH(2); X = GGNle, GENle, or NleGE; GG = -Gly-Gly- and GE = -Gly-Glu-} peptides. Three novel peptides (DOTA-GGNle-CycMSH(hex), DOTA-GENle-CycMSH(hex), and DOTA-NleGE-CycMSH(hex)) were designed and synthesized. The melanocortin-1 (MC1) receptor-binding affinities of the peptides were determined in B16/F1 melanoma cells. The melanoma-targeting and pharmacokinetic properties of (111)In-DOTA-GGNle-CycMSH(hex) and (111)In-DOTA-GENle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice. DOTA-GGNle-CycMSH(hex) and DOTA-GENle-CycMSH(hex) displayed 2.1 and 11.5 nM MC1 receptor-binding affinities, whereas DOTA-NleGE-CycMSH(hex) showed 873.4 nM MC1 receptor-binding affinity. The introduction of the -GG- linker maintained high melanoma uptake while decreasing kidney and liver uptake of (111)In-DOTA-GGNle-CycMSH(hex). The tumor uptake of (111)In-DOTA-GGNle-CycMSH(hex) was 19.05 ± 5.04 and 18.6 ± 3.56 percentage injected dose per gram at 2 and 4 h after injection, respectively. (111)In-DOTA-GGNle-CycMSH(hex) exhibited 28%, 32%, and 42% less kidney uptake than (111)In-DOTA-Nle-CycMSH(hex) we reported previously, and 61%, 65%, and 68% less liver uptake than (111)In-DOTA-Nle-CycMSH(hex) at 2, 4, and 24 h after injection, respectively. The amino acid linkers exhibited profound effects on the melanoma-targeting and pharmacokinetic properties of the (111)In-labeled lactam bridge-cyclized α-melanocyte-stimulating hormone peptides. Introduction of the -GG- linker maintained high melanoma uptake while reducing kidney and liver uptake of (111)In-DOTA-GGNle-CycMSH(hex), highlighting its potential as an effective imaging probe for melanoma detection, as well as a therapeutic peptide
Conjunctival Melanocytic Tumors-New Developments
Directory of Open Access Journals (Sweden)
Hülya Gökmen Soysal
2014-09-01
Full Text Available Melanocytic lesions of the conjunctiva represent a wide spectrum of tumors that include benign, premalignant, and malignant tumors. There are many ongoing arguments about the definition, classification, and therapeutic options of the conjunctival melanocytic tumors with many different suggestions. Conjunctival nevi are the most common melanocytic tumors and their risk of malignant transformation is less than1%. Primary acquired melanosis (PAM histopathologically includes various types of lesions from increased melanin pigmentation without melanocyte proliferation to melanoma in situ and is accepted as a clinical definition, so that a new classification is recommended which is based on more objective criteria than before. Although conjunctival melanoma is seen rarely, it is associated with a high mortality rate. Management of these tumors mainly involves surgery and adjuvant topical chemotherapy, cryotherapy, and radiation therapy that help improving the survival, however, new options are being investigated related to genetic and molecular researches. (Turk J Ophthalmol 2014; 44: Supplement 15-21
Engineering an Affinity-Enhanced Peptide through Optimization of Cyclization Chemistry.
Ngambenjawong, Chayanon; Pineda, Julio Marco B; Pun, Suzie H
2016-12-21
Peptide cyclization is a strategy used to improve stability and activity of peptides. The most commonly used cyclization method is disulfide bridge formation of cysteine-containing peptides, as is typically found in nature. Over the years, an increasing number of alternative chemistries for peptide cyclization with improved efficiency, kinetics, orthogonality, and stability have been reported. However, there has been less appreciation for the opportunity to fine-tune peptide activity via the diverse chemical entities introduced at the site of linkage by different cyclization strategies. Here, we demonstrate how cyclization optimization of an M2 "anti-inflammatory" macrophage-binding peptide (M2pep) resulted in a significant increase in binding affinity of the optimized analog to M2 macrophages while maintaining binding selectivity compared to M1 "pro-inflammatory" macrophages. In this study, we report synthesis and evaluation of four cyclic M2pep(RY) analogs with diverse cyclization strategies: (1) Asp-[amide]-Lys, (2) azido-Lys-[triazole(copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC))]-propargyl-Gly, (3) Cys-[decafluorobiphenyl (DFBP)]-Cys, and (4) Cys-[decafluorobiphenyl sulfone (DFS)]-Cys, whereby the chemical entity or linker at the linkage site is shown in the square bracket and is between the residues involved in cyclization. These peptides are compared to a disulfide-cyclized M2pep(RY) that we previously reported as a serum-stable, affinity-enhanced analog to the original linear M2pep. DFBP-cyclized M2pep(RY) exhibits the highest binding activity to M2 macrophages with apparent dissociation constant (K D ) about 2.03 μM compared to 36.3 μM for the original disulfide-cyclized M2pep(RY) and 220 μM for the original linear peptide. DFS-cyclized M2pep(RY) also binds more strongly than the original cyclized analog, whereas amide- and triazole-cyclized M2pep(RY) analogs bind less strongly. We verified that DFBP alone has negligible binding to M2
Enantioselective cyclizations and cyclization cascades of samarium ketyl radicals
Kern, Nicolas; Plesniak, Mateusz P.; McDouall, Joseph J. W.; Procter, David J.
2017-12-01
The rapid generation of molecular complexity from simple starting materials is a key challenge in synthesis. Enantioselective radical cyclization cascades have the potential to deliver complex, densely packed, polycyclic architectures, with control of three-dimensional shape, in one step. Unfortunately, carrying out reactions with radicals in an enantiocontrolled fashion remains challenging due to their high reactivity. This is particularly the case for reactions of radicals generated using the classical reagent, SmI2. Here, we demonstrate that enantioselective SmI2-mediated radical cyclizations and cascades that exploit a simple, recyclable chiral ligand can convert symmetrical ketoesters to complex carbocyclic products bearing multiple stereocentres with high enantio- and diastereocontrol. A computational study has been used to probe the origin of the enantioselectivity. Our studies suggest that many processes that rely on SmI2 can be rendered enantioselective by the design of suitable ligands.
First principles calculations of interstitial and lamellar rhenium nitrides
Energy Technology Data Exchange (ETDEWEB)
Soto, G., E-mail: gerardo@cnyn.unam.mx [Universidad Nacional Autonoma de Mexico, Centro de Nanociencias y Nanotecnologia, Km 107 Carretera Tijuana-Ensenada, Ensenada Baja California (Mexico); Tiznado, H.; Reyes, A.; Cruz, W. de la [Universidad Nacional Autonoma de Mexico, Centro de Nanociencias y Nanotecnologia, Km 107 Carretera Tijuana-Ensenada, Ensenada Baja California (Mexico)
2012-02-15
Highlights: Black-Right-Pointing-Pointer The possible structures of rhenium nitride as a function of composition are analyzed. Black-Right-Pointing-Pointer The alloying energy is favorable for rhenium nitride in lamellar arrangements. Black-Right-Pointing-Pointer The structures produced by magnetron sputtering are metastable variations. Black-Right-Pointing-Pointer The structures produced by high-pressure high-temperature are stable configurations. Black-Right-Pointing-Pointer The lamellar structures are a new category of interstitial dissolutions. - Abstract: We report here a systematic first principles study of two classes of variable-composition rhenium nitride: i, interstitial rhenium nitride as a solid solution and ii, rhenium nitride in lamellar structures. The compounds in class i are cubic and hexagonal close-packed rhenium phases, with nitrogen in the octahedral and tetrahedral interstices of the metal, and they are formed without changes to the structure, except for slight distortions of the unit cells. In the compounds in class ii, by contrast, the nitrogen inclusion provokes stacking faults in the parent metal structure. These faults create trigonal-prismatic sites where the nitrogen residence is energetically favored. This second class of compounds produces lamellar structures, where the nitrogen lamellas are inserted among multiple rhenium layers. The Re{sub 3}N and Re{sub 2}N phases produced recently by high-temperature and high-pressure synthesis belong to this class. The ratio of the nitrogen layers to the rhenium layers is given by the composition. While the first principle calculations point to higher stability for the lamellar structures as opposed to the interstitial phases, the experimental evidence presented here demonstrates that the interstitial classes are synthesizable by plasma methods. We conclude that rhenium nitrides possess polymorphism and that the two-dimensional lamellar structures might represent an emerging class of materials
First principles calculations of interstitial and lamellar rhenium nitrides
International Nuclear Information System (INIS)
Soto, G.; Tiznado, H.; Reyes, A.; Cruz, W. de la
2012-01-01
Highlights: ► The possible structures of rhenium nitride as a function of composition are analyzed. ► The alloying energy is favorable for rhenium nitride in lamellar arrangements. ► The structures produced by magnetron sputtering are metastable variations. ► The structures produced by high-pressure high-temperature are stable configurations. ► The lamellar structures are a new category of interstitial dissolutions. - Abstract: We report here a systematic first principles study of two classes of variable-composition rhenium nitride: i, interstitial rhenium nitride as a solid solution and ii, rhenium nitride in lamellar structures. The compounds in class i are cubic and hexagonal close-packed rhenium phases, with nitrogen in the octahedral and tetrahedral interstices of the metal, and they are formed without changes to the structure, except for slight distortions of the unit cells. In the compounds in class ii, by contrast, the nitrogen inclusion provokes stacking faults in the parent metal structure. These faults create trigonal-prismatic sites where the nitrogen residence is energetically favored. This second class of compounds produces lamellar structures, where the nitrogen lamellas are inserted among multiple rhenium layers. The Re 3 N and Re 2 N phases produced recently by high-temperature and high-pressure synthesis belong to this class. The ratio of the nitrogen layers to the rhenium layers is given by the composition. While the first principle calculations point to higher stability for the lamellar structures as opposed to the interstitial phases, the experimental evidence presented here demonstrates that the interstitial classes are synthesizable by plasma methods. We conclude that rhenium nitrides possess polymorphism and that the two-dimensional lamellar structures might represent an emerging class of materials within binary nitride chemistry.
Iodine - catalyzed prins cyclization of aliphatic and aromatic ketones
International Nuclear Information System (INIS)
Kishore, K.R.; Reddy, K.; Silva Junior, Luiz F.
2013-01-01
Iodine-catalyzed Prins cyclization of homoallylic alcohols and ketones was investigated. Anhydrous conditions and inert atmosphere are not required in this metal-free protocol. The reaction of 2-(3,4-dihydronaphthalene-1-yl)propan-1-ol with six aliphatic symmetric ketones gave the desired products in 67-77% yield. Cyclization was performed with four aliphatic unsymmetric ketones, leading to corresponding pyrans in 66-76% yield. Prins cyclization was also accomplished with four aromatic ketones in 37-66% yield. Finally, Prins cyclization of the monoterpene isopulegol and acetone was successfully achieved. (author)
Iodine - catalyzed prins cyclization of aliphatic and aromatic ketones
Energy Technology Data Exchange (ETDEWEB)
Kishore, K.R.; Reddy, K.; Silva Junior, Luiz F., E-mail: luizfsjr@iq.usp.br [Universidade de Sao Paulo (IQ/USP), SP (Brazil). Inst. de Quimica. Dept. de Quimica Fundamental
2013-09-15
Iodine-catalyzed Prins cyclization of homoallylic alcohols and ketones was investigated. Anhydrous conditions and inert atmosphere are not required in this metal-free protocol. The reaction of 2-(3,4-dihydronaphthalene-1-yl)propan-1-ol with six aliphatic symmetric ketones gave the desired products in 67-77% yield. Cyclization was performed with four aliphatic unsymmetric ketones, leading to corresponding pyrans in 66-76% yield. Prins cyclization was also accomplished with four aromatic ketones in 37-66% yield. Finally, Prins cyclization of the monoterpene isopulegol and acetone was successfully achieved. (author)
Concentration of rhenium from dilute sodium chloride solutions
Directory of Open Access Journals (Sweden)
DRAGOLJUB M. LUKIC
2008-03-01
Full Text Available The conditions for the desorption of rhenium from the anion exchange resin Dowex 1-x8 by HNO3, HCl, H2SO4 and NaOH were determined. The solution (5.0´10-3 mol dm-3 Re in 0.15 mol dm-3 NaCl was passed through a column containing 0.10 g of the resin. The total sorbed amount of rhenium was 0.20 g/g of the resin. It was then eluted by the corresponding eluent in the concentration range up to about 3.0 mol dm-3. The highest elution efficiency and the most favourable elution profile were found with 3.0 mol dm-3 HNO3. Over 77 % of the sorbed rhenium was found in the first 5 ml of the eluate. Practically all the rhenium was recovered with 20 ml of the acid. Under the given experimental conditions, HCl and H2SO4 were less favourable while NaOH was not applicable, due to very low efficiency of rhenium elution.
Study of cyclization of chelating compounds using electrospray ionization mass spectrometry
International Nuclear Information System (INIS)
Shi Ying; Campbell, J.A.
2000-01-01
Electrospray ionization mass spectrometry (ESI-MS) was used for the study of cyclization of organic chelating compounds (chelators). Four chelating compounds were studied: Symmetrical ethylenediaminediacetic acid (s-EDDA), Unsymmetrical ethylenediaminediacetic acid (u-EDDA), N-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), and N-(2-hydroxyethyl)iminodiacetic acid (HEIDA). The chelators were cyclized with treatments of acids and heating. The open and cyclized form of the chelators were semi-quantified by both positive and negative ion modes ESI-MS. The kinetics of chelator cyclization was studied as a function of reaction temperature and the pH of the matrix. The cyclization of s-EDDA was found to be a pseudo-first order reaction in s-EDDA and overall second order. The cyclizations of HEIDA and HEDTA are reversible reactions. Higher temperature and lower pH favors cyclization. (author)
Directory of Open Access Journals (Sweden)
Joseph M. Mannion
2017-01-01
Full Text Available Degassing is a common preparation technique for rhenium filaments used for thermal ionization mass spectrometric analysis of actinides, including plutonium. Although optimization studies regarding degassing conditions have been reported, little work has been done to characterize filament aging after degassing. In this study, the effects of filament aging after degassing were explored to determine a “shelf-life” for degassed rhenium filaments, and methods to limit filament aging were investigated. Zone-refined rhenium filaments were degassed by resistance heating under high vacuum before exposure to ambient atmosphere for up to 2 months. After degassing the nucleation and preferential growth of oxo-rhenium crystallites on the surface of polycrystalline rhenium filaments was observed by atomic force microscopy and scanning electron microscopy (SEM. Compositional analysis of the crystallites was conducted using SEM-Raman spectroscopy and SEM energy dispersive X-ray spectroscopy, and grain orientation at the metal surface was investigated by electron back-scatter diffraction mapping. Spectra collected by SEM-Raman suggest crystallites are composed primarily of perrhenic acid. The relative extent of growth and crystallite morphology were found to be grain dependent and affected by the dissolution of carbon into filaments during annealing (often referred to as carbonization or carburization. Crystallites were observed to nucleate in region specific modes and grow over time through transfer of material from the surface. Factors most likely to affect the rates of crystallite growth include rhenium substrate properties such as grain size, orientation, levels of dissolved carbon, and relative abundance of defect sites; as well as environmental factors such as length of exposure to oxygen and relative humidity. Thin (∼180 nm hydrophobic films of poly(vinylbenzyl chloride were found to slow the growth of oxo-rhenium crystallites on the filament
Energy Technology Data Exchange (ETDEWEB)
Castillo Gomez, Juan Daniel
2015-04-27
Bioconjugation reactions with Rhenium and Technetium are of high importance for the development of novel radiopharmaceuticals for nuclear medicine. In this thesis the possibilities for bioconjugation using linkable Thiocarmbamoylbenzamidines as ligands for the complexation of Rhenium and Technetium were examined.
The kinetics of anodic dissolution of rhenium in aqueous electrolyte solutions
International Nuclear Information System (INIS)
Atanasyants, A.G.; Kornienko, V.A.
1986-01-01
The kinetics of anodic rhenium dissolution was investigated by means of potentiodynamic and potentiostatic polarization curves recorded at temperature from 293 to 333 K in different media (NaOH, KOH, NaCl, NaBr, HCl, H 2 SO 4 ) using the rotating disc technique. It is shown that the kinetics of anodic rhenium dissolution and effective activation energy depend not only on the composition and pH value of the solutions but also on the structure of the dissolving rhenium surface. The investigation of the anodic behaviour of the rhenium monocrystal revealed the existence of anisotropy of the monocrystal electrochemical properties. The experimental results point to an important role of adsorption processes in anodic rhenium dissolution. Rhenium dissolution proceeds with formation of intermediate surface adsorption complexes between the metal and the components of the solution
In vitro structure-activity relationship of Re-cyclized octreotide analogues
Energy Technology Data Exchange (ETDEWEB)
Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)
2010-07-15
Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.
Thermophysical measurements on solid and liquid rhenium
International Nuclear Information System (INIS)
Pottlacher, G.; Jager, H.; Neger, T.
1986-01-01
A fast resistive heating technique was used to measure such thermophysical data of solid and liquid rhenium as enthalpy, specific heat, thermal volume expansion, and electrical resistivity. The measurements are performed with heating rates of slightly more than 10 9 K s -1 up to states of superheated liquid rhenium (7500 K)
Effect of Temperature and Mole Ratio on the Synthesis Yield of Rhenium-Tetrofosmin
Directory of Open Access Journals (Sweden)
Widyastuti
2015-08-01
Full Text Available Technetium-99m (99mTc tetrofosmin is widely used in nuclear medicine as a diagnostic agent for myocardial perfusion and as a tumor imaging agent. As a parenteral preparation it requires an evaluation of its pharmacokinetics and stability in-vivo. Since 99mTc has a short half-life and is only available in very low concentrations, it is impossible to characterize its chemical properties and presence in the body. Due to this reason, only technetium-99 (T1/2 = 5 × 105 years, which is available in macro quantities, or natural rhenium can be used for this purpose. In this study rhenium-188 (188Re tetrofosmin will be synthesized and applied, because non-radioactive Re can be easily obtained. Synthesis and radiochemical purity analysis of carrier-added 188Re-tetrofosmin were carried out as a model to study the in-vivo stability of technetium-99m tetrofosmin. Rhenium-188 was used as a tracer to identify the formation of rhenium tetrofosmin. Rhenium gluconate was synthesized first prior to the formation of rhenium tetrofosmin. The quality of labeling for both rhenium gluconate and rhenium tetrofosmin was analyzed using paper- and thin-layer chromatography, respectively. Rhenium gluconate can be synthesized with high labeling yield within 1 hour, whereas rhenium tetrofosmin was synthesized both in room temperature and in an elevated temperature with various tetrofosmin-to-rhenium mole ratios.The results showed that heating at 95oC led to a higher yield of more than 90% within 30 minutes. Rhenium tetrofosmin could be produced in high radiochemical purity using an excess of tetrofosmin with mole ratio of 2000. It is concluded that rhenium tetrofosmin could be synthesized through the formation of rhenium gluconate, and a higher yield could be obtained in a shorter time by heating process.
Feichtinger, René G; Pétervári, Erika; Zopf, Michaela; Vidali, Silvia; Aminzadeh-Gohari, Sepideh; Mayr, Johannes A; Kofler, Barbara; Balaskó, Márta
2017-08-01
Hypothalamic alpha-melanocyte-stimulating hormone (α-MSH) is a key catabolic mediator of energy homeostasis. Its anorexigenic and hypermetabolic effects show characteristic age-related alterations that may be part of the mechanism of middle-aged obesity and geriatric anorexia/cachexia seen in humans and other mammals. We aimed to investigate the role of α-MSH in mitochondrial energy metabolism during the course of aging in a rodent model. To determine the role of α-MSH in mitochondrial energy metabolism in muscle, we administered intracerebroventricular (ICV) infusions of α-MSH for 7-days to different age-groups of male Wistar rats. The activities of oxidative phosphorylation complexes I to V and citrate synthase were determined and compared to those of age-matched controls. We also quantified mitochondrial DNA (mtDNA) copy number and measured the expression of the master regulators of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPARγ). The peptide reduced weight gain in juvenile rats to one fifth of that of controls and increased the weight loss in older animals by about five fold. Mitochondrial DNA copy number inversely correlated with changes in body weight in controls, but not in α-MSH-treated animals. The strong increase in body weight in young rats was associated with a low mtDNA copy number and high PPARγ mRNA levels in controls. Expression of PGC-1α and PPARγ declined with age, whereas OXPHOS and citrate synthase enzyme activities were unchanged. In contrast, α-MSH treatment suppressed OXPHOS enzyme and citrate synthase activity. In conclusion, our results showed age-related differences in the metabolic effects of α-MSH. In addition, administration of α-MSH suppressed citrate synthase and OXPHOS activities independent of age. These findings suggest that α-MSH exposure may inhibit mitochondrial biogenesis. Copyright © 2016 Elsevier
Melanocyte colonization and pigmentation of breast carcinoma
DEFF Research Database (Denmark)
Mele, Marco; Laurberg, Tinne; Engberg Damsgaard, Tine
2012-01-01
. The pathogenesis by which melanocyte migration takes place is not known, but a breached basement membrane is considered essential. Conclusion. Histological examination and additional staining of skin are essential to differentiate breast cancer melanosis from malignant melanoma.......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...
Okugawa, Seigo; Masu, Hyuma; Yamaguchi, Kentaro; Takeda, Kei
2005-12-09
[reactions: see text] The reaction of delta-silyl-gamma,delta-epoxypentanenitrile derivatives 9-12 with a base and an alkylating agent affords (Z)-delta-siloxy-gamma,delta-unsaturated pentanenitrile derivatives via a tandem process that involves the formation of a cyclopropane derivative by epoxy nitrile cyclization followed by Brook rearrangement and an anion-induced cleavage of the cyclopropane ring. Exclusive formation of a (Z)-derivative from trans-epoxides is explained by the reaction pathway that involves a backside displacement of the epoxide by the alpha-nitrile carbanion and the O-Si bond formation followed by concerted processes involving Brook rearrangement and the anti-mode of eliminative ring fission of the cyclopropane from the rotamer 19. The fact that (E)-isomers are exclusively obtained from cis-epoxides and alpha-cyclopropyl-alpha-silylcarbinol derivative 26 provides experimental support for the proposed pathway.
Determination of rhenium in geologic samples of sandstone-type uranium deposit
International Nuclear Information System (INIS)
Li Yanan; Wang Xiuqin; Yin Jinshuang
1997-01-01
The thiourea colorimetry method suitable for the determination of samples with rhenium content higher than 5 μg/g is described. The method is characterized by many advantages: stability of analytical results, simplicity and cheapness of reagent, and wide range of analysed samples. The catalytic colorimetry is also applied to determine trace rhenium meeting the demand for comprehensive appraisal of prospecting and exploration, recovery and utilization of rhenium. This method can also be applied to analyse rhenium of other samples
Kurouchi, Hiroaki; Sugimoto, Hiromichi; Otani, Yuko; Ohwada, Tomohiko
2010-01-20
The chemical features, such as substrate stability, product distribution, and substrate generality, and the reaction mechanism of Brønsted superacid-catalyzed cyclization reactions of aromatic ring-containing acetoacetates (beta-ketoesters) were examined in detail. While two types of carbonyl cyclization are possible, i.e., keto cyclization and ester cyclization, the former was found to take place exclusively. The reaction constitutes an efficient method to synthesize indene and 3,4-dihydronapthalene derivatives. Acid-base titration monitored with (13)C NMR spectroscopy showed that the acetoacetates are fully O(1),O(3)-diprotonated at H(0) = -11. While the five-membered ring cyclization of the arylacetoacetates proceeded slowly at H(0) = -11, a linear increase in the rate of the cyclization was found with increasing acidity in the high acidity region of H(0) = -11.8 to -13.3. Therefore, the O(1),O(3)-diprotonated acetoacetates exhibited some cyclizing reactivity, but they are not the reactive intermediates responsible for the acceleration of the cyclization in the high acidity region. The reactive cationic species might be formed by further protonation (or protosolvation) of the O(1),O(3)-diprotonated acetoacetates; i.e., they may be tricationic species. Thermochemical data on the acid-catalyzed cyclization of the arylacetoacetates showed that the activation energy is decreased significantly as compared with that of the related acid-catalyzed cyclization reaction of a compound bearing a single functional group, such as a ketone. These findings indicate that intervention of the trication contributes to the activation of the cyclization of arylacetoacetates in strong acid, and the electron-withdrawing nature of the O-protonated ester functionality significantly increases the electrophilicity of the ketone moiety.
Work function of carburized rhenium
International Nuclear Information System (INIS)
Pallmer, P.G. Jr.; Gordon, R.L.; Dresser, M.J.
1980-01-01
Variations of the electronic work function of carburized rhenium foils containing approximately 5 at.% carbon have been observed using the contact potential difference technique. Surface work function was observed to vary between 5.25 and 4.1 eV, with the work function of pure rhenium taken as 5.0 eV. Decrease in work function has been ascribed to the formation of graphitic layers on the surface at temperatures below the temperature of saturated solubility. The high work function surface was observed with all carbon in solution and has been ascribed to the presence of amorphous carbon near the surface
Accelerator Production and Separations for High Specific Activity Rhenium-186
Energy Technology Data Exchange (ETDEWEB)
Jurisson, Silvia S. [Univ. of Missouri, Columbia, MO (United States); Wilbur, D. Scott [Univ. of Washington, Seattle, WA (United States)
2016-04-01
Tungsten and osmium targets were evaluated for the production of high specific activity rhenium-186. Rhenium-186 has potential applications in radiotherapy for the treatment of a variety of diseases, including targeting with monoclonal antibodies and peptides. Methods were evaluated using tungsten metal, tungsten dioxide, tungsten disulfide and osmium disulfide. Separation of the rhenium-186 produced and recycling of the enriched tungsten-186 and osmium-189 enriched targets were developed.
International Nuclear Information System (INIS)
Vargas-Uscategui, Alejandro; Mosquera, Edgar; Chornik, Boris; Cifuentes, Luis
2015-01-01
Highlights: • Rhenium oxides were produced by means of pulsed current electrodeposition over ITO. • The electrocatalytic behavior of rhenium oxides electrodeposited over ITO was studied. • Electrodeposited rhenium oxides showed electrocatalytic behavior increasing the rate of the hydrogen evolution reaction. • The electrocatalysis behavior was explained considering the relative abundance of Re species on the surface of the electrodeposited material. - Abstract: Rhenium oxides are materials of interest for applications in the catalysis of reactions such as those occurring in fuel cells and photoelectrochemical cells. This research work was devoted to the production of rhenium oxide by means of pulsed current electrodeposition for the electrocatalysis of the hydrogen evolution reaction (HER). Rhenium oxides were electrodeposited over a transparent conductive oxide substrate (Indium Tin-doped Oxide – ITO) in an alkaline aqueous electrolyte. The electrodeposition process allowed the production of rhenium oxides islands (200–600 nm) with the presence of three oxidized rhenium species: Re"I"V associated to ReO_2, Re"V"I associated to ReO_3 and Re"V"I"I associated to H(ReO_4)H_2O. Electrodeposited rhenium oxides showed electrocatalytic behavior over the HER and an increase of one order of magnitude of the exchange current density was observed compared to the reaction taking place on the bare substrate. The electrocatalytic behavior varied with the morphology and relative abundance of oxidized rhenium species in the electrodeposits. Finally, two mechanisms of electrocatalysis were proposed to explain experimental results.
Cancer therapy with alpha-emitters labeled peptides.
Dadachova, Ekaterina
2010-05-01
Actively targeted alpha-particles offer specific tumor cell killing action with less collateral damage to surrounding normal tissues than beta-emitters. During the last decade, radiolabeled peptides that bind to different receptors on the tumors have been investigated as potential therapeutic agents both in the preclinical and clinical settings. Advantages of radiolabeled peptides over antibodies include relatively straightforward chemical synthesis, versatility, easier radiolabeling, rapid clearance from the circulation, faster penetration and more uniform distribution into tissues, and less immunogenicity. Rapid internalization of the radiolabeled peptides with equally rapid re-expression of the cell surface target is a highly desirable property that enhances the total delivery of these radionuclides into malignant sites. Peptides, such as octreotide, alpha-melanocyte-stimulating hormone analogues, arginine-glycine-aspartic acid-containing peptides, bombesin derivatives, and others may all be feasible for use with alpha-emitters. The on-going preclinical work has primarily concentrated on octreotide and octreotate analogues labeled with Bismuth-213 and Astatine-211. In addition, alpha-melanocyte-stimulating hormone analogue has been labeled with Lead-212/Bismuth-212 in vivo generator and demonstrated the encouraging therapeutic efficacy in treatment of experimental melanoma. Obstacles that continue to obstruct widespread acceptance of alpha-emitter-labeled peptides are primarily the supply of these radionuclides and concerns about potential kidney toxicity. New sources and methods for production of these medically valuable radionuclides and better understanding of mechanisms related to the peptide renal uptake and clearance should speed up the introduction of alpha-emitter-labeled peptides into the clinic. Copyright 2010 Elsevier Inc. All rights reserved.
In situ cyclization modification in polymerization of butadiene by rare earth coordination catalyst
International Nuclear Information System (INIS)
Wang Chaoyang
2005-01-01
Butadiene was polymerized to a certain extent in the presence of a rare earth coordination catalyst, neodymium compound of neodymium chloride and i-propyl alcohol and triethyl aluminum (NdCl 3 ·3i-PrOH-AlEt 3 ) in toluene and the allyl chloride was then added to the reactive solution in order to in situ cyclize the formed polybutadiene and cyclopolymerize the unreacted butadiene monomers. Effects of molar ratio of allylchloride to AlEt 3 (Cl/Al), cyclization reaction time and temperature, butadiene and NdCl 3 ·3i-PrOH concentrations on the cyclization reaction have been investigated. The cyclization reaction is very quick, only several minutes. The cyclization reaction temperature has few effects on the properties of the cyclized product. Cl/Al is a very important condition for this reaction system. Cyclized polybutadiene has a low value of intrinsic viscosity, free gelling and high yield at high Cl/Al. The microstructures and properties of the cyclized products have been characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and gel permeation chromatography. The cyclization mechanism is put forward
Rhenium: a rare metal critical in modern transportation
John, David A.
2015-01-01
Rhenium is a silvery-white, metallic element with an extremely high melting point (3,180 degrees Celsius) and a heat-stable crystalline structure, making it exceptionally resistant to heat and wear. Since the late 1980s, rhenium has been critical for superalloys used in turbine blades and in catalysts used to produce lead-free gasoline.
Structural determinants of reductive terpene cyclization in iridoid biosynthesis
DEFF Research Database (Denmark)
Kries, Hajo; Caputi, Lorenzo; Stevenson, Clare E M
2016-01-01
The carbon skeleton of ecologically and pharmacologically important iridoid monoterpenes is formed in a reductive cyclization reaction unrelated to canonical terpene cyclization. Here we report the crystal structure of the recently discovered iridoid cyclase (from Catharanthus roseus) bound...
Effect of rhenium addition on tungsten fuzz formation in helium plasmas
Energy Technology Data Exchange (ETDEWEB)
Khan, Aneeqa, E-mail: aneeqa.khan-3@postgrad.manchester.ac.uk [School of Mechanical, Aerospace and Civil Engineering, The University of Manchester, M13 9PL (United Kingdom); De Temmerman, Gregory [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046 - 13067 St Paul Lez Durance Cedex (France); Morgan, Thomas W. [FOM Institute DIFFER – Dutch Institute for Fundamental Energy Research, Partner in the Trilateral Euregio Cluster, Eindhoven (Netherlands); Ward, Michael B. [Institute for Materials Research, School of Chemical Process Engineering, University of Leeds, Leeds, LS2 9JT (United Kingdom)
2016-06-15
The effect of the addition of rhenium to tungsten on the formation of a nanostructure referred to as ‘fuzz’ when exposed to helium plasmas at fusion relevant ion fluxes was investigated in the Magnum and Pilot PSI devices at the FOM Institute DIFFER. The effect rhenium had on fuzz growth was seen to be dependent on time, temperature and flux. Initial fuzz growth was seen to be highly dependent on grain orientation, with rhenium having little effect. Once the fuzz was fully developed, the effect of grain orientation disappeared and the rhenium had an inhibiting effect on growth. This could be beneficial for inhibiting fuzz growth in a future fusion reactor, where transmutation of tungsten to rhenium is expected. It also appears that erosion or annealing of the fuzz is limiting growth of fuzz at higher temperatures in the range of ∼1340 °C.
Effect of rhenium addition on tungsten fuzz formation in helium plasmas
International Nuclear Information System (INIS)
Khan, Aneeqa; De Temmerman, Gregory; Morgan, Thomas W.; Ward, Michael B.
2016-01-01
The effect of the addition of rhenium to tungsten on the formation of a nanostructure referred to as ‘fuzz’ when exposed to helium plasmas at fusion relevant ion fluxes was investigated in the Magnum and Pilot PSI devices at the FOM Institute DIFFER. The effect rhenium had on fuzz growth was seen to be dependent on time, temperature and flux. Initial fuzz growth was seen to be highly dependent on grain orientation, with rhenium having little effect. Once the fuzz was fully developed, the effect of grain orientation disappeared and the rhenium had an inhibiting effect on growth. This could be beneficial for inhibiting fuzz growth in a future fusion reactor, where transmutation of tungsten to rhenium is expected. It also appears that erosion or annealing of the fuzz is limiting growth of fuzz at higher temperatures in the range of ∼1340 °C.
Early diagnosis and successful treatment of paraneoplastic melanocytic proliferation.
Jansen, Joyce C G; Van Calster, Joachim; Pulido, Jose S; Miles, Sarah L; Vile, Richard G; Van Bergen, Tine; Cassiman, Catherine; Spielberg, Leigh H; Leys, Anita M
2015-07-01
Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue. In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy. The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients. In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Determination of rhenium in ores of complex composition by the kinetic method
Energy Technology Data Exchange (ETDEWEB)
Pavlova, L G; Gurkina, T V [Kazakhskij Gosudarstvennyj Univ., Alma-Ata (USSR); Tsentral' naya Lab. Yuzhno-Kazakhstanskogo Geologicheskogo Upravleniya, Alma-Ata (USSR))
1979-09-01
The kinetic rhenium determination method is proposed based on rhenium catalytic effect in the reaction of malachite green with thiourea. The accompanying elements, excluding molybdenum, do not interfere with the rhenium determination at their concentration of up to 0.1 M. The interfering influence of molybdenum can be eliminated by addition of tartaric acid to the solution up to the concentration of 0.1 M. This enables to determine rhenium in presence of 1000-fold quantity of molybdenum. The method is applicable for the analysis of complex copper-zinc sulphide ores.
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.
Nipponium, the element ascribable to rhenium from the modern chemical viewpoint
Energy Technology Data Exchange (ETDEWEB)
Yoshihara, H.K. [Japan Isotope Data Inst., Sendai (Japan)
1997-11-01
Though the discovery of nipponium by Ogawa in 1908 was judged to be false and his work was forgotten for many years, the new element he believed to have found should be ascribed to rhenium (z = 75) by the following reasons: (1) the spectral line of 4882 A agrees well with the present data of rhenium, (2) recalculation of the atomic weight of the element supports the value in the neighbourhood of 185 which is very close to the present value 186.2 of rhenium, and (3) rhenium is actually present in Japanese molybdenite he studied. Therefore, it is concluded that his discovery of the `new` element was correct, but assignment of z = 43 was wrong. (orig.)
Method of stably radiolabeling antibodies with technetium and rhenium
International Nuclear Information System (INIS)
Paik, C.H.; Reba, R.C.; Eckelman, W.C.
1987-01-01
A method is described for labeling antibodies or antibody fragments with radionuclides of technetium or rhenium to obtain stable labeling, comprising: reacting a reduced radioisotope of technetium or rhenium with an antibody or antibody fragment, or a diethylenetriaminepentaacetic acid conjugated antibody or antibody fragment, in the presence of free or carrier-bound diethylenetriaminepentaacetic acid (DTPA). The amount of DTPA is sufficient to substantially completely inhibit binding of the reduced technetium or rhenium to nonstable binding sites of the antibody or antibody fragment, or the DTPA-conjugated antibody or antibody fragment. The resultant stably labeled antibody or antibody fragment, or DTPA[conjugated antibody or antibody fragment is recovered
Does Melanoma Begin in a Melanocyte Stem Cell
International Nuclear Information System (INIS)
Hoerter, J. D.; Bradley, P.; Casillas, A.; Chambers, D.; Weiswasser, B.; Clements, L.; Gilbert, S.; Jiao, A.
2012-01-01
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 zebra fish model. Zebra fish 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 zebra fish to investigate how UVA- (320-400nm) and UVB- (290-320nm) 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.
Separation of Rhenium (VII) from Tungsten (VI)
International Nuclear Information System (INIS)
Vucina, J.; Lukic, D.; Stoiljkovic, M.; Milosevic, M.; Orlic, M.
2004-01-01
Examined were the conditions for an effective separation of tungsten (VI) and rhenium (VII) on alumina if the solution of 0.20 mol dm -3 NaCl, ph=2.6 is used as the aqueous phase. Under the given experimental conditions alumina was found to be much better adsorbent for tungsten than for rhenium. The breakthrough and saturation capacities of alumina at pH=2 are 24 and 78 mg W/g Al 2 O 3 , respectively. With the increase of pH these values decrease. So, at pH=6 they are only 4 and 13 mg W/g Al 2 O 3 respectively. The elution volume for rhenium for the given column dimensions and quantity of the adsorbent is about 16 ml. These results were confirmed by the experiments of the radiological separations. Tungsten-187 remains firmly bound to the alumina. The radionuclide purity of the eluted 186'188 Re at pH=2 is very high. (authors)
PREFERENTIAL SECRETION OF INDUCIBLE HSP70 BY VITILIGO MELANOCYTES UNDER STRESS
Mosenson, Jeffrey A.; Flood, Kelsey; Klarquist, Jared; Eby, Jonathan M.; Koshoffer, Amy; Boissy, Raymond E.; Overbeck, Andreas; C.Tung, Rebecca; Poole, I. Caroline Le
2014-01-01
SUMMARY Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes. PMID:24354861
Determination of rhenium in molybdenite by neutron-activation analysis.
Terada, K; Yoshimura, Y; Osaki, S; Kiba, T
1967-01-01
A neutron-activation method is described for the determination of rhenium in molybdenite. Radiochemical separation by a carrier technique was carried out very rapidly by means of successive liquid-liquid extraction processes. The recovery of rhenium, which was determined by a spectrophotometric method, was about 93%. About 10 samples could be analysed within 6 hr in parallel runs.
Melanogenesis in dermal melanocytes of Japanese Silky chicken embryos.
Ortolani-Machado, C F; Freitas, P F; Faraco, C D
2009-08-01
The Japanese Silky chicken (SK) shows dermal and visceral hyperpigmentation. This study characterizes ultrastructurally the melanin granules developing in dermal melanocytes of the dorsal skin of SK, in an attempt to better understand the processes of melanogenesis in these permanently ectopic cells. The steps of melanogenesis are similar to those described for epidermal melanocytes, with melanosomes going from stage I to IV but, in SK, the maturation occurs in the cell body, as well as in the cytoplasmic processes. At stage III, the deposition of melanin is cumulative and can aggregate in rounded structures, which combine to turn into the mature granule. The final destiny of mature melanosomes is still unclear, although it was observed that dermal macrophages can accumulate melanin granules in their phagosomes. Even with the close proximity between melanocytes and other dermal cells, the transference of melanosomes was not observed. Our findings indicate that melanogenesis in dermal melanocytes in SK has the same morphological characteristics found in epidermal melanocytes, but the functional aspect still remains to be elucidated.
Hesperetin induces melanin production in adult human epidermal melanocytes.
Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban
2015-06-01
One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p melanin production in human melanocyte cultures could be reproduced on human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.
Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species
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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.
Knottin cyclization: impact on structure and dynamics
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Gracy Jérôme
2008-12-01
Full Text Available Abstract Background Present in various species, the knottins (also referred to as inhibitor cystine knots constitute a group of extremely stable miniproteins with a plethora of biological activities. Owing to their small size and their high stability, knottins are considered as excellent leads or scaffolds in drug design. Two knottin families contain macrocyclic compounds, namely the cyclotides and the squash inhibitors. The cyclotide family nearly exclusively contains head-to-tail cyclized members. On the other hand, the squash family predominantly contains linear members. Head-to-tail cyclization is intuitively expected to improve bioactivities by increasing stability and lowering flexibility as well as sensitivity to proteolytic attack. Results In this paper, we report data on solution structure, thermal stability, and flexibility as inferred from NMR experiments and molecular dynamics simulations of a linear squash inhibitor EETI-II, a circular squash inhibitor MCoTI-II, and a linear analog lin-MCoTI. Strikingly, the head-to-tail linker in cyclic MCoTI-II is by far the most flexible region of all three compounds. Moreover, we show that cyclic and linear squash inhibitors do not display large differences in structure or flexibility in standard conditions, raising the question as to why few squash inhibitors have evolved into cyclic compounds. The simulations revealed however that the cyclization increases resistance to high temperatures by limiting structure unfolding. Conclusion In this work, we show that, in contrast to what could have been intuitively expected, cyclization of squash inhibitors does not provide clear stability or flexibility modification. Overall, our results suggest that, for squash inhibitors in standard conditions, the circularization impact might come from incorporation of an additional loop sequence, that can contribute to the miniprotein specificity and affinity, rather than from an increase in conformational rigidity
Energy Technology Data Exchange (ETDEWEB)
Zerbino, Jorge O.; Castro Luna, Ana M.; Martins, M. E. [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires (Argentina). Inst. de Investigaciones Fisico-Quimicas, Teoricas y Aplicadas (INIFTA)]. E-mail: mmartins@inifta.unlp.edu.ar; Zinola, Carlos F.; Mendez, Eduardo [Universidad de la Republica, Montevideo (Uruguay). Facultad de Ciencias. Lab. de Electroquimica Fundamental
2002-08-01
Rhenium-containing films were grown on gold and platinum after different potentiostatic and potentiodynamic polarizations in the - 0.20 V to 0.70 V range (vs rhe) in aqueous acid perrhenate. Experimental data were obtained using cyclic voltammetry and ellipsometry, from which the thickness and optical indices of the electrodeposited rhenium layer were calculated. Metallic rhenium deposition on gold takes place at potentials within the hydrogen evolution reaction. Rhenium oxide on platinum is formed in the hydrogen adatom potential domain, whereas metallic rhenium is deposited concurrently with the hydrogen adsorption and evolution reactions on the same metal. (author)
Directory of Open Access Journals (Sweden)
Zerbino Jorge O.
2002-01-01
Full Text Available Rhenium-containing films were grown on gold and platinum after different potentiostatic and potentiodynamic polarizations in the - 0.20 V to 0.70 V range (vs rhe in aqueous acid perrhenate. Experimental data were obtained using cyclic voltammetry and ellipsometry, from which the thickness and optical indices of the electrodeposited rhenium layer were calculated. Metallic rhenium deposition on gold takes place at potentials within the hydrogen evolution reaction. Rhenium oxide on platinum is formed in the hydrogen adatom potential domain, whereas metallic rhenium is deposited concurrently with the hydrogen adsorption and evolution reactions on the same metal.
Synthesis of anatoxin a via intramolecular cyclization of iminium salts
International Nuclear Information System (INIS)
Bates, H.A.; Rapoport, H.
1979-01-01
Anatoxin a (1) has been synthesized by exploiting intramolecular cyclization between an iminium salt and a nucleophilic carbon to construct the 9-azabicyclo[4.2.1]nonane ring system. Cyclization of malonate iminiumsalt 16 at alkaline pH afforded a low yield of bicyclic malonate 18 owing to an unfavorable equilibrium constant and lability of the iminium salt in base. In contrast, cyclization of ketoiminium salt 31 afforded a good yield of bicyclic ketone 34 in acidic methanol. Dihydropyrrolium salts 16 and 31 were generated quantitatively by decarbonylation of substituted N-methylprolines 15 and 30b, obtained by reduction of the corresponding pyrroles
New leads for fragment-based design of rhenium/technetium radiopharmaceutical agents.
Brink, Alice; Helliwell, John R
2017-05-01
Multiple possibilities for the coordination of fac -[Re(CO) 3 (H 2 O) 3 ] + to a protein have been determined and include binding to Asp, Glu, Arg and His amino-acid residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro. The large number of rhenium metal complex binding sites that have been identified on specific residues thereby allow increased target identification for the design of future radiopharmaceuticals. The core experimental concept involved the use of state-of-art tuneable synchrotron radiation at the Diamond Light Source to optimize the rhenium anomalous dispersion signal to a large value ( f '' of 12.1 electrons) at its L I absorption edge with a selected X-ray wavelength of 0.9763 Å. At the Cu K α X-ray wavelength (1.5418 Å) the f '' for rhenium is 5.9 electrons. The expected peak-height increase owing to the optimization of the Re f '' was therefore 2.1. This X-ray wavelength tuning methodology thereby showed the lower occupancy rhenium binding sites as well as the occupancies of the higher occupancy rhenium binding sites.
New leads for fragment-based design of rhenium/technetium radiopharmaceutical agents
Directory of Open Access Journals (Sweden)
Alice Brink
2017-05-01
Full Text Available Multiple possibilities for the coordination of fac-[Re(CO3(H2O3]+ to a protein have been determined and include binding to Asp, Glu, Arg and His amino-acid residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro. The large number of rhenium metal complex binding sites that have been identified on specific residues thereby allow increased target identification for the design of future radiopharmaceuticals. The core experimental concept involved the use of state-of-art tuneable synchrotron radiation at the Diamond Light Source to optimize the rhenium anomalous dispersion signal to a large value (f′′ of 12.1 electrons at its LI absorption edge with a selected X-ray wavelength of 0.9763 Å. At the Cu Kα X-ray wavelength (1.5418 Å the f′′ for rhenium is 5.9 electrons. The expected peak-height increase owing to the optimization of the Re f′′ was therefore 2.1. This X-ray wavelength tuning methodology thereby showed the lower occupancy rhenium binding sites as well as the occupancies of the higher occupancy rhenium binding sites.
Monoclonal Antibodies Radiolabeling with Rhenium-188 for Radioimmunotherapy
Martini, Petra; Pasquali, Micol
2017-01-01
Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining 188Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain 188Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [188Re]ReO4−. The aim of this paper is to provide a short overview on 188Re-labeled (Mo)Abs, focusing in particular on the radiolabeling methods, quality control of radioimmunoconjugates, and their in vitro stability for radioimmunotherapy (RIT), with particular reference to the most important contributions published in literature in this topic. PMID:28951872
Manufacture and properties of molybdenum-rhenium alloys
International Nuclear Information System (INIS)
Fischer, B.; Freund, D.
2001-01-01
It is necessary to measure strength and creep behavior to guarantee the safe and reliable usage of refractory alloys at extremely high temperatures. In the literature there is very little information available about the properties of Mo-Re alloys at temperatures higher than 1000 C. A special test facility has been designed and built for stress-rupture testing at very high temperatures (up to 3000 C) of refractory metals and alloys in inert atmospheres. - The stress-rupture strength as well as the creep behavior of molybdenum-rhenium alloys with rhenium contents between 41 and 51 wt.% have been determined at temperatures ranging from 1200 to 2000 C, and rupture times of up to 10 hours using this facility. Previous measurements of stress-rupture strength and creep behavior of pure rhenium have been compared with the measurement results of Mo-Re alloys. - The discussion of the values measured is based on metallographic test results and scanning electron microscopy (SEM) images of Mo-Re alloy samples after stress-rupture testing. (orig.) [de
Rawlings, N G; Simko, E; Bebchuk, T; Caldwell, S J; Singh, B
2003-07-01
Melanomas are common neoplasms of dogs and arise from pigment-producing cells called melanocytes or melanoblasts. Melanomas of skin are often easily cured by surgical excision, but those of oral mucosa are aggressive, metastasize to the regional lymph nodes and lungs, and respond poorly to conventional therapy. Tumor growth is sustained by proliferation of microvessels via a process called angiogenesis. Integrin alpha(v)beta3 is expressed in proliferating but not in quiescent microvessels suggesting a role in angiogenesis. Vascular endothelial growth factor (VEGF) manifests its mitogenic and angiogenic effects mainly via VEGF receptor-2 (VEGFR-2/Flk-1). We conducted this immunocytochemical study to investigate the expression of integrin alpha(v)beta3 and VEGFR-2 in archival and fresh samples from cases of canine melanomas. Results show that integrin alpha(v)beta3 was expressed in 72% and 88% of cutaneous and oral melanomas, respectively, and the expression was restricted to and immediately around the melanocytes and endothelial cells. VEGFR-2 staining of selected cases of melanoma revealed that its expression overlapped with the alpha(v)beta3 integrin. Dual immuno-gold electron microscopy confirmed co-localization of integrin alpha(v)beta3 and VEGFR-2 in melanocytes and endothelial cells. These data demonstrate expression and co-localization of integrin alpha(v)beta3 and VEGFR-2 in cutaneous and oral melanomas of dogs.
Self-Terminating, Oxidative Radical Cyclizations
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Uta Wille
2004-05-01
Full Text Available The recently discovered novel concept of self-terminating, oxidative radical cyclizations, through which alkynes can be converted into carbonyl compounds under very mild reaction conditions using O-centered inorganic and organic radicals as oxidants, is described
Directory of Open Access Journals (Sweden)
Judit Váradi
Full Text Available Alpha-melanocyte-stimulating hormone (α-MSH is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines.
Epitaxial growth of rhenium with sputtering
Energy Technology Data Exchange (ETDEWEB)
Oh, Seongshik [National Institute of Standards and Technology, Boulder, CO 80305 (United States) and Department of Physics, University of Illinois, Urbana, IL 61801 (United States)]. E-mail: soh@boulder.nist.gov; Hite, Dustin A. [National Institute of Standards and Technology, Boulder, CO 80305 (United States); Cicak, K. [National Institute of Standards and Technology, Boulder, CO 80305 (United States); Osborn, Kevin D. [National Institute of Standards and Technology, Boulder, CO 80305 (United States); Simmonds, Raymond W. [National Institute of Standards and Technology, Boulder, CO 80305 (United States); McDermott, Robert [University of California, Santa Barbara, CA 93106 (United States); Cooper, Ken B. [University of California, Santa Barbara, CA 93106 (United States); Steffen, Matthias [University of California, Santa Barbara, CA 93106 (United States); Martinis, John M. [University of California, Santa Barbara, CA 93106 (United States); Pappas, David P. [National Institute of Standards and Technology, Boulder, CO 80305 (United States)
2006-02-21
We have grown epitaxial Rhenium (Re) (0001) films on {alpha}-Al{sub 2}O{sub 3} (0001) substrates using sputter deposition in an ultra high vacuum system. We find that better epitaxy is achieved with DC rather than with RF sputtering. With DC sputtering, epitaxy is obtained with the substrate temperatures above 700 deg. C and deposition rates below 0.1 nm/s. The epitaxial Re films are typically composed of terraced hexagonal islands with screw dislocations, and island size gets larger with high temperature post-deposition annealing. The growth starts in a three dimensional mode but transforms into two dimensional mode as the film gets thicker. With a thin ({approx}2 nm) seed layer deposited at room temperature and annealed at a high temperature, the initial three dimensional growth can be suppressed. This results in larger islands when a thick film is grown at 850 deg. C on the seed layer. We also find that when a room temperature deposited Re film is annealed to higher temperatures, epitaxial features start to show up above {approx}600 deg. C, but the film tends to be disordered.
Bornemann, Holger; Wentrup, Curt
2005-07-22
The energy surface connecting oxazinium olates 9, several possible conformers of ketenes 10 and 11, and the final cyclization products 12, 13 and 14, as well as the isomeric 1,3-oxazine-6-ones 15, ring opening of the latter to N-acylimidoylketenes 16, and subsequent rearrangement of 16 to oxoketenimines 17, azetinones 18, and the cyclization products 19 and 20 are evaluated computationally at the B3LYP/6-31G and B3LYP/6-311+G//B3LYP/6-31G levels. The cyclizations of ketenes to oxazinium olates 9 and oxazines 15 have the characteristics of pseudopericyclic reactions. Plots of the energy vs internal reaction coordinate for the cyclization of transoid acylketenes such as 10 to 9 (via TS1) and 16 to 15 (via TS7) feature two inflection points and indicate that the part of the energy surface above the lower inflection points describe internal rotation of the acyl function in the ketene moiety, and the part below this point describes the cyclization of the cisoid ketene to the planar mesoionic oxazinium olate 9 or oxazinone 15. The 1,3-shifts of the OR group that interconvert ketenes 16 and ketenimines 17 via four-membered cyclic transition states TS8 behave similarly, the first portion (from the ketenimine side) of the activation barrier being due largely to internal rotation of substituents, and the top part being due to the 1,3-shift proper.
Electrodialysis separation of rhenium from silicon
International Nuclear Information System (INIS)
Prasolova, O.D.; Borisova, L.V.; Ermakov, A.N.
1989-01-01
A method of separation of ruthenium from silicon by electrodialysis with heterogenuos ion-exchange membranes is developed. The effeciency of purification of rhenium from silicon depending on the number of dialyzer chambers, temperature and pH value of the dialyzate is studed. It is found that an addditional fourth chamber between the middle and anolytic ones causes the purification coefficient increase 50 times. It is necessary to cool the dialyzate in order to reduce silicon migration into the anolyte and reverse diffusion of perrhenate-ion from the anolyte into the dialyzate. The optimal pH value of diaizate is 5.5-6. The method developed has been used for separating rhenium from industrial solution of lead production with complex composition
The slaty mutation affects the morphology and maturation of melanosomes in the mouse melanocytes.
Hirobe, Tomohisa; Abe, Hiroyuki
2006-10-01
The slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome tautomerase in melanocytes and to reduce the melanin content in skin, hairs and eyes. Although the melanosomes in slaty melanocytes are reported to be eumelanosome-like, detailed melanosome biogenesis is not well studied. To address this point, melanosomes in neonatal epidermal melanocytes from wild-type (Dct+/Dct+) mice at the slaty locus as well as its congenic mouse mutant (Dct(slt)/Dct(slt)) in serum-free primary culture were observed under the electron microscope. Wild-type melanocytes possessed exclusively elliptical melanosomes with internal longitudinal structures, whereas in mutant melanocytes, numerous spherical melanosomes with globular depositions of pigment and elliptical melanosomes as well as mixed type of the two melanosomes were observed. Mature stage IV melanosomes were greatly decreased in mutant melanocytes, whereas immature stage III melanosomes were more numerous than in wild-type melanocytes. These results suggest that the slaty mutation affects the morphology and maturation of melanosomes in mouse melanocytes.
Neurotized congenital melanocytic nevus resembling a pigmented neurofibroma
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Nidhi Singh
2015-01-01
Full Text Available Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF are close mimics and pose a clinicopathological challenge. We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss the differential diagnosis and its clinical, histopathological and immunohistochemistry features which may aid in differentiation. We highlight the difficulties faced in differentiating neurotized congenital melanocytic nevus from pigmented neurofibroma.
Giant Congenital Melanocytic Nevus
DEFF Research Database (Denmark)
Rasmussen, Bo Sonnich; Henriksen, Trine Foged; Kølle, Stig-Frederik Trojahn
2015-01-01
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...
Cyclization of the N-Terminal X-Asn-Gly Motif during Sample Preparation for Bottom-Up Proteomics
DEFF Research Database (Denmark)
Zhang, Xumin; Højrup, Peter
2010-01-01
We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N-terminal ......We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N......-terminal cyclizations, cyclization of N-terminal glutamine and S-carbamoylmethylcysteine, it is dependent on pH instead of [NH(4)(+)]. The data set from our recent study on large-scale N(α)-modified peptides revealed a sequence requirement for the cyclization event similar to the well-known deamidation of Asn to iso...
Solt, M W; Wahlberg, J S; Myers, A T
1969-01-01
Rhenium in molybdenite is separated from molybdenum by distillation of rhenium heptoxide from a perchloric-sulphuric acid mixture. It is concentrated by precipitation of the sulphide and then determined by X-ray fluorescence. From 3 to 1000 microg of rhenium can be measured with a precision generally within 2%. The procedure tolerates larger amounts of molybdenum than the usual colorimetric methods.
Solt, M.W.; Wahlberg, J.S.; Myers, A.T.
1969-01-01
Rhenium in molybdenite is separated from molybdenum by distillation of rhenium heptoxide from a perchloric-sulphuric acid mixture. It is concentrated by precipitation of the sulphide and then determined by X-ray fluorescence. From 3 to 1000 ??g of rhenium can be measured with a precision generally within 2%. The procedure tolerates larger amounts of molybdenum than the usual colorimetric methods. ?? 1969.
Lott, Jason P; Boudreau, Denise M; Barnhill, Ray L; Weinstock, Martin A; Knopp, Eleanor; Piepkorn, Michael W; Elder, David E; Knezevich, Steven R; Baer, Andrew; Tosteson, Anna N A; Elmore, Joann G
2018-01-01
Population-based information on the distribution of histologic diagnoses associated with skin biopsies is unknown. Electronic medical records (EMRs) enable automated extraction of pathology report data to improve our epidemiologic understanding of skin biopsy outcomes, specifically those of melanocytic origin. To determine population-based frequencies and distribution of histologically confirmed melanocytic lesions. A natural language processing (NLP)-based analysis of EMR pathology reports of adult patients who underwent skin biopsies at a large integrated health care delivery system in the US Pacific Northwest from January 1, 2007, through December 31, 2012. Skin biopsy procedure. The primary outcome was histopathologic diagnosis, obtained using an NLP-based system to process EMR pathology reports. We determined the percentage of diagnoses classified as melanocytic vs nonmelanocytic lesions. Diagnoses classified as melanocytic were further subclassified using the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) reporting schema into the following categories: class I (nevi and other benign proliferations such as mildly dysplastic lesions typically requiring no further treatment), class II (moderately dysplastic and other low-risk lesions that may merit narrow reexcision with skin biopsies, performed on 47 529 patients, were examined. Nearly 1 in 4 skin biopsies were of melanocytic lesions (23%; n = 18 715), which were distributed according to MPATH-Dx categories as follows: class I, 83.1% (n = 15 558); class II, 8.3% (n = 1548); class III, 4.5% (n = 842); class IV, 2.2% (n = 405); and class V, 1.9% (n = 362). Approximately one-quarter of skin biopsies resulted in diagnoses of melanocytic proliferations. These data provide the first population-based estimates across the spectrum of melanocytic lesions ranging from benign through dysplastic to malignant. These results may serve as a foundation for future
You, Yu-Wei; Kong, Xiang-Shan; Wu, Xuebang; Liu, C. S.; Fang, Q. F.; Chen, J. L.; Luo, G.-N.
2017-08-01
The formation of transmutation solute-rich precipitates has been reported to seriously degrade the mechanical properties of tungsten in a fusion environment. However, the underlying mechanisms controlling the formation of the precipitates are still unknown. In this study, first-principles calculations are therefore performed to systemically determine the stable structures and binding energies of solute clusters in tungsten consisting of tantalum, rhenium and osmium atoms as well as irradiation-induced vacancies. These clusters are known to act as precursors for the formation of precipitates. We find that osmium can easily segregate to form clusters even in defect-free tungsten alloys, whereas extremely high tantalum and rhenium concentrations are required for the formation of clusters. Vacancies greatly facilitate the clustering of rhenium and osmium, while tantalum is an exception. The binding energies of vacancy-osmium clusters are found to be much higher than those of vacancy-tantalum and vacancy-rhenium clusters. Osmium is observed to strongly promote the formation of vacancy-rhenium clusters, while tantalum can suppress the formation of vacancy-rhenium and vacancy-osmium clusters. The local strain and electronic structure are analyzed to reveal the underlying mechanisms governing the cluster formation. Employing the law of mass action, we predict the evolution of the relative concentration of vacancy-rhenium clusters. This work presents a microscopic picture describing the nucleation and growth of solute clusters in tungsten alloys in a fusion reactor environment, and thereby explains recent experimental phenomena.
Schoene, Christopher; Bennett, S. Paul; Howarth, Mark
2016-01-01
Enzymes catalyze reactions with exceptional selectivity and rate acceleration but are often limited by instability. Towards a generic route to thermo-resilience, we established the SpyRing approach, cyclizing enzymes by sandwiching between SpyTag and SpyCatcher (peptide and protein partners which lock together via a spontaneous isopeptide bond). Here we first investigated the basis for this resilience, comparing alternative reactive peptide/protein pairs we engineered from Gram-positive bacteria. Both SnoopRing and PilinRing cyclization gave dramatic enzyme resilience, but SpyRing cyclization was the best. Differential scanning calorimetry for each ring showed that cyclization did not inhibit unfolding of the inserted β-lactamase. Cyclization conferred resilience even at 100 °C, where the cyclizing domains themselves were unfolded. Phytases hydrolyze phytic acid and improve dietary absorption of phosphate and essential metal ions, important for agriculture and with potential against human malnutrition. SpyRing phytase (PhyC) resisted aggregation and retained catalytic activity even following heating at 100 °C. In addition, SpyRing cyclization made it possible to purify phytase simply by heating the cell lysate, to drive aggregation of non-cyclized proteins. Cyclization via domains forming spontaneous isopeptide bonds is a general strategy to generate resilient enzymes and may extend the range of conditions for isolation and application of enzymes. PMID:26861173
Effect of rhenium addition on tungsten fuzz formation in helium plasmas
Khan, A.; De Temmerman, G.; Morgan, T. W.; M. B. Ward,
2016-01-01
The effect of the addition of rhenium to tungsten on the formation of a nanostructure referred to as ‘fuzz’ when exposed to helium plasmas at fusion relevant ion fluxes was investigated in the Magnum and Pilot PSI devices at the FOM Institute DIFFER. The effect rhenium had on fuzz growth was seen to
Cyclization strategies of meditopes: affinity and diffraction studies of meditope–Fab complexes
International Nuclear Information System (INIS)
Bzymek, Krzysztof P.; Ma, Yuelong; Avery, Kendra A.; Horne, David A.; Williams, John C.
2016-01-01
An overview of cyclization strategies of a Fab-binding peptide to maximize affinity. Recently, a unique binding site for a cyclic 12-residue peptide was discovered within a cavity formed by the light and heavy chains of the cetuximab Fab domain. In order to better understand the interactions that drive this unique complex, a number of variants including the residues within the meditope peptide and the antibody, as well as the cyclization region of the meditope peptide, were created. Here, multiple crystal structures of meditope peptides incorporating different cyclization strategies bound to the central cavity of the cetuximab Fab domain are presented. The affinity of each cyclic derivative for the Fab was determined by surface plasmon resonance and correlated to structural differences. Overall, it was observed that the disulfide bond used to cyclize the peptide favorably packs against a hydrophobic ‘pocket’ and that amidation and acetylation of the original disulfide meditope increased the overall affinity ∼2.3-fold. Conversely, replacing the terminal cysteines with serines and thus creating a linear peptide reduced the affinity over 50-fold, with much of this difference being reflected in a decrease in the on-rate. Other cyclization methods, including the formation of a lactam, reduced the affinity but not to the extent of the linear peptide. Collectively, the structural and kinetic data presented here indicate that small perturbations introduced by different cyclization strategies can significantly affect the affinity of the meditope–Fab complex
Cyclization strategies of meditopes: affinity and diffraction studies of meditope–Fab complexes
Energy Technology Data Exchange (ETDEWEB)
Bzymek, Krzysztof P.; Ma, Yuelong; Avery, Kendra A.; Horne, David A.; Williams, John C., E-mail: jcwilliams@coh.org [Beckman Research Institute of City of Hope, 1710 Flower Street, Duarte, CA 91010 (United States)
2016-05-23
An overview of cyclization strategies of a Fab-binding peptide to maximize affinity. Recently, a unique binding site for a cyclic 12-residue peptide was discovered within a cavity formed by the light and heavy chains of the cetuximab Fab domain. In order to better understand the interactions that drive this unique complex, a number of variants including the residues within the meditope peptide and the antibody, as well as the cyclization region of the meditope peptide, were created. Here, multiple crystal structures of meditope peptides incorporating different cyclization strategies bound to the central cavity of the cetuximab Fab domain are presented. The affinity of each cyclic derivative for the Fab was determined by surface plasmon resonance and correlated to structural differences. Overall, it was observed that the disulfide bond used to cyclize the peptide favorably packs against a hydrophobic ‘pocket’ and that amidation and acetylation of the original disulfide meditope increased the overall affinity ∼2.3-fold. Conversely, replacing the terminal cysteines with serines and thus creating a linear peptide reduced the affinity over 50-fold, with much of this difference being reflected in a decrease in the on-rate. Other cyclization methods, including the formation of a lactam, reduced the affinity but not to the extent of the linear peptide. Collectively, the structural and kinetic data presented here indicate that small perturbations introduced by different cyclization strategies can significantly affect the affinity of the meditope–Fab complex.
The relationship between Na+/H+ exchanger expression and tyrosinase activity in human melanocytes
International Nuclear Information System (INIS)
Smith, Dustin R.; Spaulding, Deborah T.; Glenn, Hayden M.; Fuller, Bryan B.
2004-01-01
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
Adini, Irit; Adini, Avner; Bazinet, Lauren; Watnick, Randolph S; Bielenberg, Diane R; D'Amato, Robert J
2015-02-01
The incidence of certain angiogenesis-dependent diseases is higher in Caucasians than in African Americans. Angiogenesis is amplified in wound healing and cornea models in albino C57 mice compared with black C57 mice. Moreover, mouse and human melanocytes with low pigmentation stimulate endothelial cell (EC) proliferation and migration in vitro more than melanocytes with high pigmentation. This effect is due, in part, to the secretion of an angiogenic protein called fibromodulin (FMOD) from lowly pigmented melanocytes. Herein, we expand upon the mechanism contributing to increased angiogenesis in lighter skin and report that monocyte chemotactic protein-1 (MCP-1) is secreted by nonpigmented mouse melanocytes by 5- to 10-fold more than pigmented melanocytes. MCP-1 protein stimulates EC proliferation and migration in vitro and angiogenesis in vivo. Mechanistic studies determine that FMOD is upstream of MCP-1 and promotes its secretion from both melanocytes and activated ECs via stimulation of NF-κB activity. Mice injected with FMOD-neutralizing antibodies show 2.3-fold decreased levels of circulating MCP-1. Human studies confirmed that, on average, Caucasians have 2-fold higher serum levels of MCP-1 than African Americans. Taken together, this study implicates the FMOD/MCP-1 pathway in the regulation of angiogenesis by local melanocytes and suggests that melanogenic activity may protect against aberrant angiogenic diseases. © FASEB.
Electrodeposition of rhenium-tin nanowires
International Nuclear Information System (INIS)
Naor-Pomerantz, Adi; Eliaz, Noam; Gileadi, Eliezer
2011-01-01
Highlights: → Rhenium-tin nanowires were formed electrochemically, without using a template. → The nanowires consisted of a crystalline-Sn-core/amorphous-Re-shell structure. → The effects of bath composition and operating conditions were investigated. → A mechanism is suggested for the formation of the core/shell structure. → The nanowires may be attractive for a variety of applications. - Abstract: Rhenium (Re) is a refractory metal which exhibits an extraordinary combination of properties. Thus, nanowires and other nanostructures of Re-alloys may possess unique properties resulting from both Re chemistry and the nanometer scale, and become attractive for a variety of applications, such as in catalysis, photovoltaic cells, and microelectronics. Rhenium-tin coatings, consisting of nanowires with a core/shell structure, were electrodeposited on copper substrates under galvanostatic or potentiostatic conditions. The effects of bath composition and operating conditions were investigated, and the chemistry and structure of the coatings were studied by a variety of analytical tools. A Re-content as high as 77 at.% or a Faradaic efficiency as high as 46% were attained. Ranges of Sn-to-Re in the plating bath, applied current density and applied potential, within which the nanowires could be formed, were determined. A mechanism was suggested, according to which Sn nanowires were first grown on top of Sn micro-particles, and then the Sn nanowires reduced the perrhenate chemically, thus forming a core made of crystalline Sn-rich phase, and a shell made of amorphous Re-rich phase. The absence of mutual solubility of Re and Sn may be the driving force for this phase separation.
Neutron activation determination of rhenium in shales shales and molybdenites
International Nuclear Information System (INIS)
Zajtsev, E.I.; Radinovich, B.S.
1977-01-01
Described is the technique for neutron activation determination of rhenium in shales and molybdenites with its radiochemical extraction separation by methyl-ethyl ketone. The sensitivity of the analysis is 5x10 -7 %. Experimental checking of the developed technique in reference to the analysis of shales and molybdenites was carried out. Estimated is the possibility of application of X-ray gamma-spectrometer to instrumental determination of rhenium in molybdenites
Boyce, Jonathan H.
2014-01-01
We report a stereodivergent, asymmetric total synthesis of (−)-clusianone in six steps from commercial materials. We implement a challenging cationic cyclization forging a bond between two sterically encumbered quaternary carbons. Mechanistic studies point to the unique ability of formic acid to bring about successful cyclization to the clusianone framework. PMID:24916169
Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes
International Nuclear Information System (INIS)
Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa
2014-01-01
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 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
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.
Synthesis and study of rhenium (5) complexes with benzimidazole and rubeanic acid
Energy Technology Data Exchange (ETDEWEB)
Basitova, S M; Yurina, R D; Kotegov, K V; Amindzhanov, A A
1986-01-01
Mixed rhenium (5) oxohalide complex compounds with benzimidazole and rubeanic acid are synthesized. Composition of the compounds obtained is established by IR spectroscpy thermal and chemical analyses. It is shown that rhenium (5) chloride compound stability to pyrolysis is rather lower than that of the corresponding bromide derivatives.
Synthesis and study of rhenium (5) complexes with benzimidazole and rubeanic acid
International Nuclear Information System (INIS)
Basitova, S.M.; Yurina, R.D.; Kotegov, K.V.; Amindzhanov, A.A.
1986-01-01
Mixed rhenium (5) oxohalide complex compounds with benzimidazole and rubeanic acid are synthesized. Composition of the compounds obtained is established by IR spectroscpy thermal and chemical analyses. It is shown that rhenium (5) chloride compound stability to pyrolysis is rather lower than that of the corresponding bromide derivatives
Nazarov cyclization initiated by peracid oxidation: the total synthesis of (+/-)-rocaglamide.
Malona, John A; Cariou, Kevin; Frontier, Alison J
2009-06-10
The total syntheses of aglafolin, rocagloic acid, and rocaglamide using Nazarov cyclization are described. Generation of the necessary oxyallyl cation intermediate was accomplished via peracid oxidation of an allenol ether to generate an unusual oxycarbenium ion species that undergoes cyclization. The synthesis is efficient, highly diastereoselective, and strategically distinct from previous syntheses of rocaglamide.
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.
Taherzadeh, S; Sharma, S; Chhajlani, V; Gantz, I; Rajora, N; Demitri, M T; Kelly, L; Zhao, H; Ichiyama, T; Catania, A; Lipton, J M
1999-05-01
The hypothesis that macrophages contain an autocrine circuit based on melanocortin [ACTH and alpha-melanocyte-stimulating hormone (alpha-MSH)] peptides has major implications for neuroimmunomodulation research and inflammation therapy. To test this hypothesis, cells of the THP-1 human monocyte/macrophage line were stimulated with lipopolysaccharide (LPS) in the presence and absence of alpha-MSH. The inflammatory cytokine tumor necrosis factor (TNF)-alpha was inhibited in relation to alpha-MSH concentration. Similar inhibitory effects on TNF-alpha were observed with ACTH peptides that contain the alpha-MSH amino acid sequence and act on melanocortin receptors. Nuclease protection assays indicated that expression of the human melanocortin-1 receptor subtype (hMC-1R) occurs in THP-1 cells; Southern blots of RT-PCR product revealed that additional subtypes, hMC-3R and hMC-5R, also occur. Incubation of resting macrophages with antibody to hMC-1R increased TNF-alpha concentration; the antibody also markedly reduced the inhibitory influence of alpha-MSH on TNF-alpha in macrophages treated with LPS. These results in cells known to produce alpha-MSH at rest and to increase secretion of the peptide when challenged are consistent with an endogenous regulatory circuit based on melanocortin peptides and their receptors. Targeting of this neuroimmunomodulatory circuit in inflammatory diseases in which myelomonocytic cells are prominent should be beneficial.
Oxidative cyclization of prodigiosin by an alkylglycerol monooxygenase-like enzyme
DEFF Research Database (Denmark)
de Rond, Tristan; Stow, Parker; Eigl, Ian
2017-01-01
Prodiginines, which are tripyrrole alkaloids displaying a wide array of bioactivities, occur as linear and cyclic congeners. Identification of an unclustered biosynthetic gene led to the discovery of the enzyme responsible for catalyzing the regiospecific C–H activation and cyclization of prodigi...... of prodigiosin to cycloprodigiosin in Pseudoalteromonas rubra. This enzyme is related to alkylglycerol monooxygenase and unrelated to RedG, the Rieske oxygenase that produces cyclized prodiginines in Streptomyces, implying convergent evolution....
Rhenium Mechanical Properties and Joining Technology
Reed, Brian D.; Biaglow, James A.
1996-01-01
Iridium-coated rhenium (Ir/Re) provides thermal margin for high performance and long life radiation cooled rockets. Two issues that have arisen in the development of flight Ir/Re engines are the sparsity of rhenium (Re) mechanical property data (particularly at high temperatures) required for engineering design, and the inability to directly electron beam weld Re chambers to C103 nozzle skirts. To address these issues, a Re mechanical property database is being established and techniques for creating Re/C103 transition joints are being investigated. This paper discusses the tensile testing results of powder metallurgy Re samples at temperatures from 1370 to 2090 C. Also discussed is the evaluation of Re/C103 transition pieces joined by both, explosive and diffusion bonding. Finally, the evaluation of full size Re transition pieces, joined by inertia welding, as well as explosive and diffusion bonding, is detailed.
Yang, Liu; Lu, Jian-wei; An, Jing; Jiang, Xuan
2006-12-01
To observe the effect of Tribulus terrestris extract on melanocyte stimulating hormone (MSH) expression in C57BL/6J mouse hair follicles, and investigate the role of Tribulus terrestris extract in activation, proliferation, epidermal migration of dormant hair follicle melanocytes. The aqueous extract of Tribulus terrestris was administered orally in specific pathogen-free C57BL/6J mouse at the daily dose equivalent to 1 g/1 kg in adult human, and the expression and distribution of MSH in the mouse hair follicles was observed with immunohistochemistry. The positivity rate of MSH expression in the hair follicle melanocytes was 75% in mice treated with the extract, significantly higher than the rate of only 18.75% in the control group (PTribulus terrestris can significantly increase MSH expression in the hair follicle melanocytes by activating tyrosinase activity and promoting melanocyte proliferation, melanine synthesis, and epidermal migration of dormant melanocytes.
Blokx, Willeke Am M.; van Dijk, Marcory C. R. F.; Ruiter, Dirk J.
This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect
Blokx, W.A.M.; Dijk, M.C.R.F. van; Ruiter, D.J.
2010-01-01
This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect
Schoene, C; Bennett, S P; Howarth, M
2016-01-01
Enzymes often have marginal stability, with unfolding typically leading to irreversible denaturation. This sensitivity is a major barrier, both for de novo enzyme development and for expanding enzyme impact beyond the laboratory. Seeking an approach to enhance resilience to denaturation that could be applied to a range of different enzymes, we developed SpyRing cyclization. SpyRings contain genetically encoded SpyTag (13 amino acids) on the N-terminus and SpyCatcher (12kDa) on the C-terminus of the enzyme, so that the Spy partners spontaneously react together through an irreversible isopeptide bond. SpyRing cyclization gave major increases in thermal resilience, including on a model for enzyme evolution, β-lactamase, and an industrially important enzyme in agriculture and nutrition, phytase. We outline the SpyRing rationale, including comparison of SpyRing cyclization to other cyclization strategies. The cloning strategy is presented for the simple insertion of enzyme genes for recombinant expression. We discuss structure-based approaches to select suitable enzyme cyclization targets. Approaches to evaluate the cyclization reaction and its effect on enzyme resilience are described. We also highlight the use of differential scanning calorimetry to understand how SpyRing cyclization promotes enzyme refolding. Efficiently searching sequence space will continue to be important for enzyme improvement, but the SpyRing platform may be a valuable rational adjunct for conferring resilience. © 2016 Elsevier Inc. All rights reserved.
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.
Mechanistic Study of Oxygen Atom Transfer Catalyzed by Rhenium Compounds
Energy Technology Data Exchange (ETDEWEB)
Shan, Xiaopeng [Iowa State Univ., Ames, IA (United States)
2003-01-01
Two ionic and one neutral methyl(oxo)rhenium(V) compounds were synthesized and structurally characterized. They were compared in reactivity towards the ligands triphenylphosphane, pyridines, pyridine N-oxides. Assistance from Broensted bases was found on ligand displacement of ionic rhenium compounds as well as nucleophile assistance on oxidation of all compounds. From the kinetic data, crystal structures, and an analysis of the intermediates, a structural formula of PicH+3- and mechanisms of ligand displacement and oxidation were proposed.
Bilateral diffuse uveal melanocytic proliferation
DEFF Research Database (Denmark)
Klemp, Kristian; Kiilgaard, Jens Folke; Heegaard, Steffen
2017-01-01
cataract formation and uveal melanocytic tumours. The awareness and documentation of BDUMP has increased during the past decade, and the increasing amount of data collected demonstrates the effect of treatment with plasmapheresis and the value of diagnostic tools in BDUMP such as genetic and immunologic...
Lymph node scintigraphy with sup(99m)Tc-rhenium colloid
International Nuclear Information System (INIS)
Mitsuhata, Naoki; Suyama, Bunzo; Matsumura, Yosuke; Ohmori, Hiroyuki
1981-01-01
Lymph node scintigraphy with sup(99m)Tc-rhenium colloid in evaluation of nodal involvement by urological malignancy were performed on twelve cases (4 bladder cancer, 3 prostatic cancer, 2 penile cancer and 3 testicular tumor). These cases had been examined the extent of disease on the basis of findings at pedal lymphangiography, urography, computed tomography or laparotomy. sup(99m)Tc-rhenium colloid in a volume of 0.2 ml (2 mCi) was injected into the first interdigital webs of each foot without local anesthesia. In one case of penile cancer radioactive colloid was directly injected into the glans penis and prepuce including tumor area. Our clinical experience reported here reveals that lymph node scintigraphy with sup(99m)Tc-rhenium colloid can provide a useful method of investigating the lymphatic system. This technique is reproducible and can be performed in poor risk patients or pediatric patients readily and safely. (author)
FISH analysis for diagnostic evaluation of challenging melanocytic lesions.
Zimmermann, A K; Hirschmann, A; Pfeiffer, D; Paredes, B E; Diebold, J
2010-09-01
The differential diagnosis of malignant melanomas and atypical melanocytic nevi is still a diagnostic challenge. The currently accepted morphologic criteria show substantial interobserver variability, likewise immunohistochemical studies are often not able to discriminate these lesions reliably. Techniques that support diagnostic accuracy are of the greatest importance considering the growing incidence of malignant melanomas and their increase in younger patients. In this study we analyzed the feasibility of fluorescence in situ hybridization (FISH) analysis for the discrimination of malignant and benign melanocytic tumors. A panel of DNA probes was used to detect chromosomal aberrations of chromosomes 6 and 11. On a series of 5 clearly malignant and benign melanocytic tumors we confirmed the applicability of the test. Then we focused on examination of ambiguous melanocytic lesions, where atypical cells are often difficult to relocalize in the 4',6-Diamidino-2-phenylindol (DAPI)-fluorescence stain. FISH analyses were conducted on destained H&E-stained slides. By comparison of the DAPI-image with photos taken from the H&E stain, unambiguous assignment of the FISH results to the conspicuous groups of cells was possible. The results of FISH analysis were consistent with the conventional diagnosis in 11 of 14 small ambiguous lesions. Of the remaining 3 cases, 2 showed FISH-results close to the cut-off level. Comparison of FISH results on thin and thick sections revealed that the cut-off values have to be adapted for 2 microm destained sections. In conclusion, FISH analysis is a useful and applicable tool for assessment of even smallest melanocytic neoplasms, although there will remain unclear cases that cannot be solved even after additional FISH evaluation.
International Nuclear Information System (INIS)
Schrebler, R.; Cury, P.; Suarez, C.; Munoz, E.; Vera, F.; Cordova, R.; Gomez, H.; Ramos-Barrado, J.R.; Leinen, D.; Dalchiele, E.A.
2005-01-01
Rhenium thin films were prepared by electrodeposition from an aqueous solution containing 0.1 M Na 2 SO 4 +H 2 SO 4 , pH 2 in presence of y mM HReO 4 . As substrates polycrystalline gold (y=0.75 mM HReO 4 ) and monocrystalline n-Si(100) (y=40 mM HReO 4 ) were used. The electrochemical growth of rhenium was studied by cyclic voltammetry and electrochemical quartz microbalance on gold electrodes. The results found in the potential region before the hydrogen evolution reaction (her) showed that ReO 3 , ReO 2 and Re 2 O 3 with different hydration grades can be formed. In the potential region where the her is occurring, either on gold or n-Si(100) the electrodeposition of metallic rhenium takes place. On both substrates, rhenium films were formed by electrolysis at constant potential and X-ray photoelectron spectroscopy technique was used to characterise these deposits. It was concluded that the electrodeposited films were of metallic rhenium and only the uppermost atomic layer contained rhenium oxide species
High-temperature extraction of rhenium from sulfuric acid solutions with trialkylamines
International Nuclear Information System (INIS)
Gladyhev, V.P.; Andreeva, N.N.; Kim, E.M.; Kovaleva, S.V.
1985-01-01
This paper attempts to determine the possibility of conducting high-temperature extraction of rhenium from sulfuric acid solutions with trialkylamines (TAA) using higher hydrocarbon-paraffin mixtures as the diluent of the extraction system. Substitution of kerosene by paraffin in the extraction system would permit decreasing the danger of fire and explosions during he extraction process. In extracting rhenium from industrial solutions with a melt of higher paraffins containing TAA and alcohols, the extraction system can be continously heated in heat exchangers through which washing sulfuric acid passes and then goes to the extractor. This permits utilizing the heat and decreases the temperature of the solutions for extraction to the optimum temperatures. Extraction of rhenium with a melt of trioctylamine in paraffin obeys the same mechanisms as high-temperature extraction of ruthenium (IV) by amines in kerosene and aromatic hydrocarbons
DeFazio, Jennifer; Zalaudek, Iris; Busam, Klaus J.; Cota, Carlo; Marghoob, Ashfaq
2012-01-01
Clinical observations and an expanding knowledge of cell-to-cell communication have led us to speculate that the finding of a melanocytic nevus in conjunction with a seborrheic keratosis is more than a coincidental collision of two lesions. Here we present five cases demonstrating dermoscopic features of both melanocytic lesions and seborrheic keratoses with corresponding histology. Four cases demonstrate dermoscopic features of a melanocytic nevus and seborrheic keratosis, and the final case a melanoma arising in association with a seborrheic keratosis. PMID:23785597
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.
International Nuclear Information System (INIS)
Chantarawong, Wipa; Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki; Pradermwong, Kantimanee; Shibahara, Shigeki
2014-01-01
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
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...
Directory of Open Access Journals (Sweden)
J. V. Suponko
2010-06-01
Full Text Available Enzymes’ level in rat’s hepatocytes under Guerin's carcinoma T8 development as well as after injection of rhenium compounds and cis-platin has been studied. It has been determined that the decrease of enzymatic activity to the level of the animals of control group was observed at the simultaneous injection of cis-platin and cluster rhenium compounds in nanoliposomal and water-soluble forms. That confirms possible hepatoprotective properties of the rhenium compounds. It has been shown that hepatoprotective properties of rhenium cluster compounds mostly don’t depend on the form of their injection and are detected regardless of anticancer properties. Rhenium-platinum system with β-alanine ligand in aqueous solution, has been found. Its injection is accompanied by the hepatoprotective effect.
Reductive coupling of carbon monoxide in a rhenium carbonyl complex with pendant Lewis acids.
Miller, Alexander J M; Labinger, Jay A; Bercaw, John E
2008-09-10
Phosphinoborane ligands impart unique reactivity to a rhenium carbonyl cation relative to simple phosphine complexes. Addition of either triethylborohydride or a platinum hydride (that can be formed from H2) forms a rhenium boroxycarbene. This carbene, which crystallizes as a dimer, disproportionates over a period of days to afford the starting cation and a structurally unprecedented boroxy(boroxymethyl)carbene, in which a new C-C bond has been formed between two reduced CO ligands. This product of C-C bond formation can be independently synthesized by addition of 2 equiv of hydride to the rhenium carbonyl cation.
Aberrant expression of HMB-45 in traumatized melanocytic nevi.
Leleux, Todd M; Prieto, Victor G; Diwan, A Hafeez
2012-09-01
Assessment of histologic and immunohistochemical maturation (with HMB-45 and anti-Ki-67) may be helpful in differentiating benign melanocytic nevi (BMN) from malignant melanoma. Recently, we reported loss of maturation and aberrant immunohistochemical findings in melanocytic nevi after liquid nitrogen cryotherapy (Adeniran et al, J Am Acad Dermatol 2009;61:341-5). Herein we report a similar phenomenon identified in traumatized melanocytic nevi (TMN). We sought to evaluate the histologic and immunohistochemical findings in early and late stages of traumatized nevi. Twenty-four cases of TMN were retrieved from the pathology archives. These were then assessed by two pathologists (T.L. and A.H.D.) using HMB-45 and MIB-1 (for Ki-67) antibodies. TMN showed some of the following findings: epidermal changes (parakeratosis, ulceration, serum crust, flattening of the epidermis) and dermal changes including fibrosis and the presence of melanophages. In some cases, there was architectural disorder of the overlying melanocytes, with crowding in the basal layer, but without significant pagetoid spread. Occasionally, the dermal scar contained larger, more epithelioid-appearing melanocytes than those beneath the scar. Fifty-four percent of TMN lacked obvious immunohistochemical maturation with HMB-45, since nevus cells within the scar or directly beneath it were strongly labeled. None of the TMN showed appreciable labeling for Ki-67. The exact clinical duration between trauma and biopsy could not be determined. Loss of maturation with HMB-45 in TMN can be a diagnostic pitfall in challenging cases. Concurrent evaluation of MIB-1 expression, along with the characteristic histologic features of trauma, should allow the correct diagnosis to be reached. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Automated Estimation of Melanocytic Skin Tumor Thickness by Ultrasonic Radiofrequency Data.
Andrekute, Kristina; Valiukeviciene, Skaidra; Raisutis, Renaldas; Linkeviciute, Gintare; Makstiene, Jurgita; Kliunkiene, Renata
2016-05-01
High-frequency (>20-MHz) ultrasound (US) is a noninvasive preoperative tool for assessment of melanocytic skin tumor thickness. Ultrasonic melanocytic skin tumor thickness estimation is not always easy and is related to the experience of the clinician. In this article, we present an automated thickness measurement method based on time-frequency analysis of US radiofrequency signals. The study was performed on 52 thin (≤1-mm) melanocytic skin tumors (46 melanocytic nevi and 6 melanomas). Radiofrequency signals were obtained with a single-element focused transducer (fundamental frequency, 22 MHz; bandwidth, 12-28 MHz). The radiofrequency data were analyzed in the time-frequency domain to make the tumor boundaries more noticeable. The thicknesses of the tumors were evaluated by 3 different metrics: histologically measured Breslow thickness, manually measured US thickness, and automatically measured US thickness. The results showed a higher correlation coefficient between the automatically measured US thickness and Breslow thickness (r= 0.83; Pmeasured US thickness (r = 0.68; P measurement algorithm was 96.55%, and the specificity was 78.26% compared with histologic measurement. The sensitivity of the manually measured US thickness was 75.86%, and the specificity was 73.91%. The efficient automated tumor thickness measurement method developed could be used as a tool for preoperative assessment of melanocytic skin tumor thickness. © 2016 by the American Institute of Ultrasound in Medicine.
Use of cluster rhenium substances with alkyl ligands for inhibition of the Guerin carcinoma Growth
Directory of Open Access Journals (Sweden)
O. S. Voronkova
2007-04-01
Full Text Available Quantity and quality of erythrocytes, blood haemoglobin concentration, glucose levels in the erythrocytes and plasma, content of TBA-active products in blood plasma of rats were studied during development of the Guerin carcinoma, introduction of cis-platinum and cluster rhenium substances with organic ligands. It was shown that rhenium substances had essential antioxidant effects and changed the dynamic of tumour growth. The conclusion on perspectiveness of further investigations of rhenium substances with cluster fragment and organic ligands in experiments in vivo with changed redox-status of an organism was drawn.
PPARalpha/gamma expression and activity in mouse and human melanocytes and melanoma cells.
Eastham, Linda L; Mills, Caroline N; Niles, Richard M
2008-06-01
We examined the expression of PPARs and the effects of PPARalpha and PPARgamma agonists on growth of mouse and human melanocytes and melanoma cells. PPARalpha,beta, and PPARgamma mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARalpha mRNA levels were determined by QuantiGene assay. PPARalpha and PPARgamma protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter gene assay, while knockdown of PPARalpha expression was achieved by transient transfection of siRNA. Both mouse and human melanoma cells produced more PPARalpha and PPARgamma protein compared to melanocytes. PPARalpha mRNA levels were elevated in human melanoma cells, but not in mouse melanoma cells relative to melanocytes. Silencing of PPARalpha in human melanoma cells did not alter cell proliferation or morphology. PPARgamma-selective agonists inhibited the growth of both mouse and human melanoma cells, while PPARalpha-selective agonists had limited effects. Increased expression of PPARalpha in melanoma relative to melanocytes may be a common occurrence, however its biologic significance remains to be determined. PPARgamma agonists may be useful for arresting the growth of some melanomas.
Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract.
Tseng, Diane; Kim, Julie; Warrick, Andrea; Nelson, Dylan; Pukay, Marina; Beadling, Carol; Heinrich, Michael; Selim, Maria Angelica; Corless, Christopher L; Nelson, Kelly
2014-08-01
The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood. We aim to characterize the frequency of mutations of the following genes: BRAF, NRAS, KIT, GNA11, and GNAQ in female genital tract melanomas. We also characterize the frequency of BRAF mutations in female genital tract melanomas compared with melanocytic nevi. Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi. Of the 25 female genital tract melanoma specimens queried, KIT mutations were detected in 4 (16.0%), NRAS mutations in 4 (16.0%), and BRAF mutations in 2 (8.0%) samples. Two of the tumors with KIT mutations harbored double mutations in the same exon. No GNAQ or GNA11 mutations were identified among 11 melanomas screened. BRAF V600E mutations were detected in 7 of 7 benign melanocytic genital nevi (100%) and 3 of 4 atypical genital nevi (75%). Our study is limited by the small sample size of this rare subset of melanomas. KIT, NRAS, and BRAF mutations are found in a subset of female genital tract melanomas. Screening for oncogenic mutations is important for developing and applying clinical therapies for melanomas of the female genital tract. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
A study of scandia and rhenium doped tungsten matrix dispenser cathode
Wang, Jinshu; Li, Lili; Liu, Wei; Wang, Yanchun; Zhao, Lei; Zhou, Meiling
2007-10-01
Scandia and rhenium doped tungsten powders were prepared by solid-liquid doping combined with two-step reduction method. The experimental results show that scandia was distributed evenly on the surface of tungsten particles. The addition of scandia and rhenium could decrease the particle size of doped tungsten, for example, the tungsten powders doped with Sc 2O 3 and Re had the average size of about 50 nm in diameter. By using this kind of powder, scandia and rhenium doped tungsten matrix with the sub-micrometer sized tungsten grains was obtained. This kind of matrix exhibited good anti-bombardment insensitivity at high temperature. The emission property result showed that high space charge limited current densities of more than 60 A/cm 2 at 900 °C could be obtained for this cathode. A Ba-Sc-O multilayer about 100 nm in thickness formed at the surface of cathode after activation led to the high emission property.
Characterization of rhenium compounds obtained by electrochemical synthesis after aging process
Energy Technology Data Exchange (ETDEWEB)
Vargas-Uscategui, Alejandro, E-mail: avargasuscat@ing.uchile.cl [Departamento de Ingeniería de Minas, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Tupper Av. 2069, Santiago (Chile); Mosquera, Edgar [Laboratorio de Materiales a Nanoescala, Departamento de Ciencia de los Materiales, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Tupper Av. 2069, Santiago (Chile); López-Encarnación, Juan M. [Department of Mathematics-Physics and Department of Chemistry, University of Puerto Rico at Cayey, 205 Ave. Antonio R. Barceló, Cayey, PR 00736, USA. (Puerto Rico); Chornik, Boris [Departamento de Física, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Blanco Encalada Av. 2008, Santiago (Chile); Katiyar, Ram S. [Department of Physics and Institute for Functional Nanomaterials, University of Puerto Rico San Juan, San Juan, PR 00931-3343 (United States); Cifuentes, Luis [Departamento de Ingeniería de Minas, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Tupper Av. 2069, Santiago (Chile)
2014-12-15
The proper identification of the molecular nature of the aged rhenium compound obtained by means of electrodeposition from an alkaline aqueous electrolyte was determined. Chemical, structural and vibrational experimental characterization of the aged Re compound showed agreement with quantum-computations, thereby allowing the unambiguous identification of the Re compound as H(ReO{sub 4})H{sub 2}O. - Graphical abstract: Rhenium oxides were electrodeposited on a copper surface and after environmental aging was formed the H(ReO{sub 4})H{sub 2}O compound. The characterization of the synthesized material was made through the comparison of experimental evidence with quantum mechanical computations carried out by means of density functional theory (DFT). - Highlights: • Aged rhenium compound obtained by means of electrodeposition was studied. • The study was made by combining experimental and DFT-computational information. • The aged electrodeposited material is consistent with the H(ReO{sub 4})H{sub 2}O compound.
Evaluation of oxide dispersion strengthened (ODS) molybdenum and molybdenum-rhenium alloys
International Nuclear Information System (INIS)
Mueller, A.J.; Bianco, R.; Buckman, R.W. Jr.
1999-01-01
Oxide dispersion strengthened (ODS) molybdenum alloys being developed for high temperature applications possess excellent high temperature strength and creep resistance. In addition they exhibit a ductile-to-brittle transition temperature (DBIT) in the worked and stress-relieved condition under longitudinal tensile load well below room temperature. However, in the recrystallized condition, the DBTT maybe near or above room temperature, depending on the volume fraction of oxide dispersion and the amount of prior work. Dilute rhenium additions (7 and 14 wt.%) to ODS molybdenum were evaluated to determine their effect on low temperature ductility. The addition of 7 wt.% rhenium to the ODS molybdenum did not significantly enhance the mechanical properties. However, the addition of 14 wt.% rhenium to the ODS molybdenum resulted in a DBTT well below room temperature in both the stress-relieved and recrystallized condition. Additionally, the tensile strength of ODS Mo-14Re is greater than the base ODS molybdenum at 1,000 to 1,250 C
International Nuclear Information System (INIS)
Koeppel, B.J.; Subhash, G.
1999-01-01
The plastic response of two kinds of rhenium processed via powder metallurgy (PM) and chemical vapor deposition (CVD) were investigated under uniaxial compression over a range of strain rates. The PM rhenium, further cold rolled to 50 and 80 pct of the original thickness, was also investigated to assess the influence of cold work on the plastic behavior. A strong basal texture was detected in all the preceding materials as a result of processing and cold work. Both CVD and PM rhenium exhibited an increase in yield strength and flow stress with increasing strain rate. In PM rhenium, cold work resulted in an increase in hardness and yield strength and a decrease in the work hardening rate. The deformed microstructures revealed extensive twinning in CVD rhenium. At large strains, inhomogeneous deformation mode in the form of classical cup and cone fracture was noticed
Nanograined Net-Shaped Fabrication of Rhenium Components by EB-PVD
International Nuclear Information System (INIS)
Singh, Jogender; Wolfe, Douglas E.
2004-01-01
Cost-effective net-shaped forming components have brought considerable interest into DoD, NASA and DoE. Electron beam physical vapor deposition (EB-PVD) offers flexibility in forming net-shaped components with tailored microstructure and chemistry. High purity rhenium (Re) components including rhenium-coated graphite balls, Re- plates and tubes have been successfully manufactured by EB-PVD. EB-PVD Re components exhibited sub-micron and nano-sized grains with high hardness and strength as compared to CVD. It is estimated that the cost of Re components manufactured by EB-PVD would be less than the current CVD and powder-HIP Technologies
Anodic Cyclization Reactions and the Mechanistic Strategies That Enable Optimization.
Feng, Ruozhu; Smith, Jake A; Moeller, Kevin D
2017-09-19
Oxidation reactions are powerful tools for synthesis because they allow us to reverse the polarity of electron-rich functional groups, generate highly reactive intermediates, and increase the functionality of molecules. For this reason, oxidation reactions have been and continue to be the subject of intense study. Central to these efforts is the development of mechanism-based strategies that allow us to think about the reactive intermediates that are frequently central to the success of the reactions and the mechanistic pathways that those intermediates trigger. For example, consider oxidative cyclization reactions that are triggered by the removal of an electron from an electron-rich olefin and lead to cyclic products that are functionalized for further elaboration. For these reactions to be successful, the radical cation intermediate must first be generated using conditions that limit its polymerization and then channeled down a productive desired pathway. Following the cyclization, a second oxidation step is necessary for product formation, after which the resulting cation must be quenched in a controlled fashion to avoid undesired elimination reactions. Problems can arise at any one or all of these steps, a fact that frequently complicates reaction optimization and can discourage the development of new transformations. Fortunately, anodic electrochemistry offers an outstanding opportunity to systematically probe the mechanism of oxidative cyclization reactions. The use of electrochemical methods allows for the generation of radical cations under neutral conditions in an environment that helps prevent polymerization of the intermediate. Once the intermediates have been generated, a series of "telltale indicators" can be used to diagnose which step in an oxidative cyclization is problematic for less successful transformation. A set of potential solutions to address each type of problem encountered has been developed. For example, problems with the initial
International Nuclear Information System (INIS)
Kasikov, A.G.; Petrova, A.M.
2007-01-01
It is established that extraction ability of octanols as regards to rhenium(VII) and sulfuric acid depends on the structure of alcohol, but if in passage from octanol-1 to octanol-3 as regard to rhenium(VII) it rises, then for H 2 SO 4 it falls. Dependence of the distribution function of rhenium from the concentration of the acid has maximums at 4-7 mol l 1- that the most distinctly it becomes apparent for secondary alcohols. Decreasing the extraction ability of octyl alcohols with the growth of H 2 SO 4 concentration more than 7 mol l 1- is connected with the change of extractant composition and forms of rhenium(VII) being in the solution [ru
Treatment of liver cancer with Rhenium-188 Lipiodol: Colombian experience
International Nuclear Information System (INIS)
Bernal, P.; Osorio, M.; Mendoza, M.; Esguerra, R.; Ucros, G.; Gutierrez, C.; Velez, O.; Cerquera, A.M.; Padhy, A.K.
2002-01-01
Aim:Trans-arterial Radio-conjugate therapy plays an important role in the palliative treatment of inoperable liver cancer. It also helps in reduction of the tumor to an operable state from an inoperable one. As a part of an IAEA sponsored coordinated research project, a new radiopharmaceutical, Rhenium-188 Lipiodol has been developed. The aim of this study was to establish the safety of the radiopharmaceutical and to find out the efficacy of treatment. Materials and Methods: Eight patients suffering from various forms of liver cancer (Hepatocellular carcinoma-4, Metastases from carcinoma of colon-3 and Carcinoid- 1) were treated with Rhenium -188 Lipiodol. Seven out of the eight patients were classified as ECOG- 1 and one as ECOG- 3. Labelling of Rhenium-188 with Lipiodol was carried out according to a protocol developed under the CRP and standardized in our service. Rhenium-188 Lipiodol was administered through the trans-arterial route by either selective (75%) or ultra selective (25%) hepatic arteriography. Administered therapeutic doses ranged between 170 MBq and 4181 MBq. Dosimetric evaluations were made using the IAEA developed dosimetry spreadsheet. All patients were followed up (1-5 months, average = 2 months) after treatment by clinical examination, liver function tests, haematological examinations and CT scans of liver to determine the size of hepatic tumor. Results: Rhenium-188 Lipiodol treatment was well tolerated by all patients. No immediate systemic complications were noted in any of the patients within 72 hrs. following therapy. Only two patients had mild rise in temperature in the immediate post-therapy period, which subsided subsequently. One patient who was classified as Child B and ECOG 3, developed encephalopathy on the seventh day after treatment. He died of hepatic failure. Another one present depressive syndrome, didn't accept food and died Follow-up CT scans in all the surviving (6/8) patients revealed significant reduction of the tumours
Kim, Ji Young; Shin, Jae Yong; Kim, Miri; Hann, Seung-Kyung; Oh, Sang Ho
2012-02-01
Cytosolic NADP(+)-dependent ICDH (IDPc) has an antioxidant effect as a supplier of NADPH to the cytosol, which is needed for the production of glutathione. To evaluate the expression of IDPc in melanocytes and to elucidate its role as an antioxidant. The knock-down of IDPc expression in immortalized mouse melanocyte cell lines (melan-a) was performed using the short interfering RNA (siRNA)-targeted gene silencing method. After confirming the silencing of IDPc expression with mRNA and protein levels, viability, apoptosis and necrosis, as well as ROS production in IDPc-silenced melanocytes were monitored under conditions of oxidative stress and non-stress. Also, the ratio of oxidized glutathione to total glutathione was examined, and whether the addition of glutathione recovered cell viability, decreased by oxidant stress, was checked. The expression of IDPc in both primary human melanocytes and melan-a cells was confirmed by Western blot and RT-PCR. The silencing of IDPc expression by transfecting IDPc siRNA in melan-a cells was observed by Western blotting and real-time RT-PCR. IDPc knock-down cells showed significantly decreased cell viability and an increased number of cells under apoptosis and necrosis. IDPc siRNA-treated melanocytes demonstrated a higher intensity of DCFDA after the addition of H(2)O(2) compared with scrambled siRNA-treated melanocytes, and a lower ratio of reduced glutathione to oxidized glutathione were observed in IDPc siRNA transfected melanocytes. In addition, the addition of glutathione recovered cell viability, which was previously decreased after incubation with H(2)O(2). This study suggests that decreased IDPc expression renders melanocytes more vulnerable to oxidative stress, and IDPc plays an important antioxidant function in melanocytes. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Shi, Q; Zhang, W; Guo, S; Jian, Z; Li, S; Li, K; Ge, R; Dai, W; Wang, G; Gao, T; Li, C
2016-01-01
Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. PMID:26315342
High-definition optical coherence tomography imaging of melanocytic lesions
DEFF Research Database (Denmark)
Boone, Marc A L M; Norrenberg, Sarah; Jemec, Gregor B E
2014-01-01
and 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...... with 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...
Directory of Open Access Journals (Sweden)
K. O. Piletska
2017-03-01
Full Text Available Tricarbonyl rhenium(I complexes have a great potential like biomarkers. It is caused their biological stability, low toxicity, large Stokes shifts, and long luminescence lifetimes. Rhenium tricarbonyl complexes fac-[Re(CO3(N^N], where N^N is a ligand with low π* orbitals are excellent candidates as imaging dyes. The method of obtaining potential biomarkers based on tricarbonyl rhenium(I complex with a 4-methyl-2,2’-bipyridine-4’-carboxylate by the addition of biomolecules by peptide synthesis was developed. The new complex [Re(CO3MebpyCOOHBr] was synthesized, composition and structure of which were established by mass spectrometry, IR and NMR spectroscopy. A selective attachment of receptor peptide enkephalin to complex [Re(CO3(MebpyCOOHBr] was performed. The formation of a new compound and its structure has been confirmed by HPLC and mass spectral analysis. The method which has been developed allows to connect various peptides to rhenium(I complex in the solution.
Structure and x-ray density of electrochemically deposited rhenium films
International Nuclear Information System (INIS)
Petrovich, V.A.; Fedenkov, A.L.; Shepurev, S.Yu.
1988-01-01
The electrodeposition of rhenium was carried out at a constant cathode-current density and room temperature. The backing was grade KEF-0.02 single-crystal silicon. The absorption coefficient μ of the film was determined for the K α radiation of the copper line. The investigation enabled us to conclude that electrochemically deposited rhenium films can be used as a material for the masking coatings of x-ray patterns, since the absorption coefficients of the x-ray radiation of the resultant films are superior to the similar parameters of traditionally employed materials, and surpass these materials in terms of corrosion resistance and simplicity of production
International Nuclear Information System (INIS)
Riftanio Natapratama Hidayat; Maria Christina Prihatiningsih; Duyeh Setiawan
2015-01-01
Determination of the distribution coefficient (K d ) of the rhenium and tungsten conducted for the purpose of knowing the value of K d of the two elements. K d value determination is applied to the process of separation rhenium-188 from target of tungsten-188 for the purposes purification of radioisotopes that are made to meet the radionuclide and radiochemical purity. The K d value determination using solvent extraction with methyl ethyl ketone (MEK). Prior to the determination of K d values, determined beforehand the optimum conditions of extraction process based on the effect of agitation time, the volume of MEK, and the pH of the solution. Confirmation the results of the extraction was conducted using UV-Vis spectrophotometer with a complexing KSCN under acidic conditions and reductant SnCl 2 . The results showed that the optimum condition extraction process to feed each of 10 ppm is when the agitation for 10 minutes, the volume of MEK in 20 ml, and the pH below 5. Obtained the maximum recovery of rhenium are drawn to the organic phase as much as 9.545 ppm. However, the condition of the extraction process does not affect the migration of tungsten to the organic phase. Then the maximum K d values obtained at 2.7566 rhenium and tungsten maximum K d is 0.0873. Optimum conditions of extraction process can be further tested on radioactive rhenium and tungsten as an alternative to the separation of radioisotopes. (author)
Synthesis, reactivity, and properties of N-fused porphyrin rhenium(I) tricarbonyl complexes.
Toganoh, Motoki; Ikeda, Shinya; Furuta, Hiroyuki
2007-11-12
The thermal reactions of N-fused tetraarylporphyrins or N-confused tetraarylporphyrins with Re2(CO)10 gave the rhenium(I) tricarbonyl complexes bearing N-fused porphyrinato ligands (4) in moderate to good yields. The rhenium complexes 4 are characterized by mass, IR, 1H, and 13C NMR spectroscopy, and the structures of tetraphenylporphynato complex 4a and its nitro derivative 15 are determined by X-ray single crystal analysis. The rhenium complexes 4 show excellent stability against heat, light, acids, bases, and oxidants. The aromatic substitution reactions of 4 proceed without a loss of the center metal to give the nitro (15), formyl (16), benzoyl (17), and cyano derivatives (19), regioselectively. In the electrochemical measurements for 4, one reversible oxidation wave and two reversible reduction waves are observed. Their redox potentials imply narrow HOMO-LUMO band gaps of 4 and are consistent with their electronic absorption spectra, in which the absorption edges exceed 1000 nm. Theoretical study reveals that the HOMO and LUMO of the rhenium complexes are exclusively composed of the N-fused porphyrin skeleton. Protonation of 4 takes place at the 21-position regioselectively, reflecting the high coefficient of the C21 atom in the HOMO orbital. The skeletal rearrangement reaction from N-confused porphyrin Re(I) complex (8) to N-fused porphyrin Re(I) complex (4) is suggested from the mechanistic study as well as DFT calculations.
Dagnino, Lina; Crawford, Melissa
2018-03-27
In this article, we provide a method to isolate primary epidermal melanocytes from reporter mice, which also allow targeted gene inactivation. The mice from which these cells are isolated are bred into a Rosa26 mT/mG reporter background, which results in GFP expression in the targeted melanocytic cell population. These cells are isolated and cultured to >95% purity. The cells can be used for gene expression studies, clonogenic experiments, and biological assays, such as capacity for migration. Melanocytes are slow moving cells, and we also provide a method to measure motility using individual cell tracking and data analysis.
Melanocytic nevi and non-neoplastic hyperpigmentations.
Clemente, C
2017-06-01
This is the first of three chapters that will be progressively published on Pathologica as updating activity of the Italian Study Group of Dermatopathology (GISD), Italian Society of Pathology and Cytology (SIAPeC IAP). The first chapter concerns non-neoplastic hyperpigmented skin lesions and nevi, the second will address the topics of dysplastic nevus, borderline and low malignant potential melanocytic proliferations and the third melanoma in its variants and differential diagnoses with a supplement on the immunohistochemistry and molecular support to diagnostic and prognostic definition of nevi and melanomas. Although we believe that great advances were made in the application of ancillary genetic, immunohistochemical and molecular techniques, for the diagnosis and biological characterization of melanocytic tumors the morphology still remains the gold standard. These chapters are not intended as substitutes or even claim to be compared to the numerous and valuable texts that are also recently published, but they want to present, concisely and quickly available, all of those traits that we believe essential to the histopathological evaluation of a melanocytic lesion. No morphological parameter is exclusive and individually sufficient to make the correct diagnosis of nevus or melanoma but to reach a final conclusive and appropriate interpretation a set of morphological characters must be evaluated and compared. I was lucky enough to be able to examine several thousand cases and to draw lessons from each of these increasing my diagnostic experience. I had a great lesson by my teacher and good friend Prof. Martin C. Mihm Jr of Boston, dermato-pathologist with undisputed international reputation, who, with great passion, patience and friendship, transferred me much of his experience and knowledge and for which I always thank him. Special thanks I would like to address Dr. Agostino Crupi, dermatologist, skin-oncologist and brilliant dermatoscopist who taught me how the
Extraction of rhenium(VII) by phosphorylated podands
International Nuclear Information System (INIS)
Turanov, A.N.; Karandashev, V.K.; Baulin, V.E.
2006-01-01
Interphase distribution of ReO 4 - between aqueous solutions of H 2 SO 4 and solutions of phosphoryl-containing podands in organic solvents is studied. Stoichiometry of the complexes extracted is determined. Effect of extractant structure and nature of organic solvent on efficiency of rhenium extraction into organic phase is determined [ru
Coat-sleeve type giant congenital melanocytic nevus with intraoral blue nevus: A rare case report
Directory of Open Access Journals (Sweden)
Lata M Kale
2017-01-01
Full Text Available Congenital melanocytic nevi (CMN are visible hyperpigmented (melanocytic, benign, tumor like proliferations in the skin resulting from faulty development of pigment cell precursors in the embryo, and are composed of an abnormal mixture of skin elements. Giant congenital melanocytic nevus (GCMN is usually defined as a melanocytic lesion present at birth that will reach a larger size in adulthood. GCMN is a rare variety of CMN which is characterized by its size (diameter ≥20 cm and the potential for malignant transformation. It is infrequently associated with other findings, which makes the clinical picture complex. In this case, we report a rare association of GCMN with intraoral blue nevus in a 24-year-old male patient.
Manoharan, Ramasamy; Jeganmohan, Masilamani
2015-09-21
A regioselective synthesis of substituted pyrroloquinolinones via a ruthenium-catalyzed oxidative cyclization of substituted N-carbamoyl indolines with alkynes is described. The cyclization reaction was compatible with various symmetrical and unsymmetrical alkynes including substituted propiolates. Later, we performed the aromatization of pyrroloquinolinones into indole derivatives in the presence of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ).
Chromatographic separation of rhenium in alumina-methanol/sulfuric acid system
International Nuclear Information System (INIS)
Oguma, Koichi
1983-01-01
The adsorption behavior of a number of metals on alumina was surveyed in a methanol-(0.005 -- 0.5) M H 2 SO 4 (3 : 1 v/v) developing solvent by thin-layer chromatography. Over the acid concentration range tested, Re(VII) does not favor the alumina phase to any great extent while the most other metals are strongly adsorbed on alumina. These findings allowed to establish a column chromatographic technique for selective separation of rhenium in a methanol-0.05 M H 2 SO 4 (3 : 1 v/v) eluent. The separation technique thus established was applied to molybdenite analysis for rhenium. About 100-mg powdered sample containing ca. 100 ppm rhenium was decomposed with HNO 3 and then evaporated nearly to dryness. The residue was dissolved in NH 4 OH and the excess NH 4 OH was expelled by evaporation to dryness. The residue was dissolved in 2.5-ml 0.5 M H 2 SO 4 and 10-ml water, the insoluble materials filtered off, and the filtrate diluted to exactly 25 ml with water. A 10-ml aliquot of this solution was mixed with 30-ml methanol and the mixture was passed through a column (diameter 15 mm, bed height 30 mm) containing 5 g of alumina. The column was then washed with 20 ml of a methanol-0.05 M H 2 SO 4 (3 : 1 v/v) mixture. Rhenium was recovered from the loaded solution and the subsequent washings, and was determined spectrophotometrically with Methylene Blue as a chromogenic reagent. The values obtained from four samples of molybdenite are in good agreement with those obtained by neutron activation analysis. The relative standard deviation (n = 4; calculated from the range) was between 2.0 and 5.2 %. (author)
Amna, Touseef; Park, Kyoung Mi; Cho, In-Kyung; Choi, Tae Jeong; Lee, Seung Soo; Seo, Kang-Seok; Hwang, Inho
2012-07-01
The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH), nitric oxide (NO) and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (pmuzzle melanocytes. On the contrary, L-cysteine greatly (pmuzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes.
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Dipti Dutta
2015-01-01
Full Text Available Oral melanocytic nevi are localized developmental tissue malformations of nevus cells in the oral mucosa. Relatively rare in occurrence compared to their dermal counterparts, considerable debate exists in the literature related to their origin, development and maturation, and their relationship to oral melanocytes.We report two cases of oral melanocytic nevi with classical clinical presentation. The histopathology was consistent with the known patterns of oral melanocytic nevi. Special stains such as Masson Fontana, further substantiated the observation. S-100 and HMB-45 were applied to immunohistochemically elaborate the cell population. Interestingly two distinct cell populations were detected in the lesions. "Type A" cells in the center of the lesion were S-100 positive, indicating a neural origin and immaturity in development, while peripheral "type B" cells stained positive with HMB-45, indicating melanocytic origin and mature development.
Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W
1999-02-01
The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.
Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts
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Mostafa Kiamehr
2013-06-01
Full Text Available The cyclization of cyclohexane-1,3-diones with various substituted pyridinium salts afforded functionalized 8-oxa-10-aza-tricyclo[7.3.1.02,7]trideca-2(7,11-dienes. The reaction proceeds by regioselective attack of the central carbon atom of the 1,3-dicarbonyl unit to 4-position of the pyridinium salt and subsequent cyclization by base-assisted proton migration and nucleophilic addition of the oxygen atom to the 2-position, as was elucidated by DFT computations. Fairly extensive screening of bases and additives revealed that the presence of potassium cations is essential for formation of the product.
Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence.
Jaworek-Korjakowska, Joanna; Kłeczek, Paweł
2016-01-01
Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD) systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision.
Proline-catalysed asymmetric ketol cyclizations: The template ...
Indian Academy of Sciences (India)
Unknown
Abstract. A modified template mechanism based on modelling studies of energy minimised complexes is presented for the asymmetric proline-catalysed cyclization of triketones 1, 2 and 3 to the 2S,3S-ketols. 1a, 2a and 3a respectively. The template model involves a three-point contact as favoured in enzyme– substrate ...
Manga, Prashiela; Bis, Sabina; Knoll, Kristen; Perez, Beremis; Orlow, Seth J
2010-10-01
Accumulation of proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), comprising three signaling pathways initiated by Ire1, Perk and Atf6 respectively. Unfolded protein response activation was compared in chemically stressed murine wildtype melanocytes and mutant melanocytes that retain tyrosinase in the ER. Thapsigargin, an ER stressor, activated all pathways in wildtype melanocytes, triggering Caspase 12-mediated apoptosis at toxic doses. Albino melanocytes expressing mutant tyrosinase showed evidence of ER stress with increased Ire1 expression, but the downstream effector, Xbp1, was not activated even following thapsigargin treatment. Attenuation of Ire1 signaling was recapitulated in wildtype melanocytes treated with thapsigargin for 8 days, with diminished Xbp1 activation observed after 4 days. Atf6 was also activated in albino melanocytes, with no response to thapsigargin, while the Perk pathway was not activated and thapsigargin treatment elicited robust expression of the downstream effector CCAAT-enhancer-binding protein homologous protein. Thus, melanocytes adapt to ER stress by attenuating two UPR pathways.
Topography of Protein Kinase C βII in Benign and Malignant Melanocytic Lesions.
Krasagakis, Konstanin; Tsentelierou, Eleftheria; Chlouverakis, Gregory; Stathopoulos, Efstathios N
2017-09-01
Protein kinase C βII promotes melanogenesis and affects proliferation of melanocytic cells but is frequently absent or decreased in melanoma cells in vitro. To investigate PKC-βII expression and spatial distribution within a lesion in various benign and malignant melanocytic proliferations. Expression of PKC-βII was semiquantitatively assessed in the various existing compartments (intraepidermal [not nested], junctional [nested], and dermal) of benign (n = 43) and malignant (n = 28) melanocytic lesions by immunohistochemistry. Melanocytes in the basal layer of normal skin or in lentigo simplex stained strongly for PKC-βII. Common nevi lacked completely PKC-βII. All other lesions expressed variably PKC-βII, with cutaneous melanoma metastases displaying the lowest rate of positivity (14%). In the topographical analysis within a lesion, PKC-βII expression was largely retained in the intraepidermal and junctional part of all other lesions (dysplastic nevus, lentigo maligna, and melanoma). Reduced expression of PKC-βII was found in the dermal component of benign and malignant lesions ( P = .041 vs intraepidermal). PKC-βII expression in the various compartments did not differ significantly between benign and malignant lesions. The current study revealed a significant correlation between PKC-βII expression and spatial localization of melanocytes, with the lowest expression found in the dermal compartment and the highest in the epidermal compartment.
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Vinogradov-Zhabrov O.N.
2003-01-01
Full Text Available Processes involved in the electrodeposition of rhenium from chloride melts have been studied over the temperature interval from 680 to 970 0C at a cathodic current density of 5 to 250 mA/cm2. It has been found that rhenium is deposited in the form of continuous layers. In addition to that the growth of deposits as separate single-crystal needles has also been noticed. Continuous layers had axial growth textures. The crystallographic direction of the textures is due to electrolysis conditions, such as concentration of oxygen-containing impurities, temperature, melt composition and cathodic current density. When the concentration of oxygen-containing impurities in the melt decreased, electrolysis temperature increased, the average radius of the supporting electrolyte cations became smaller, or cathodic current density diminished, the direction of the growth textures was changing as follows: (1010 →(1120 →(101L →(0001 →(0001needles. The microhardness of the deposits in this series is 900 to 250 kg/mm2. The growth of deposits on textured rhenium substrates and single crystals having different orientations, including bent substrates, was studied. It has been found that the epitaxial growth is virtually unlimited in depth if the orientation of the substrate coincides with the growth texture under given conditions. If the substrate orientation deviated from the growth texture, the epitaxial growth was nearly absent. Kinetic parameters were measured using the galvanostatic method. The exchange current density was determined over the interval of (0.01-0.1 A/cm2 depending on the concentration of oxygen-containing impurities, cation composition, type of the surface and its condition. The parameter α⋅Z, which was estimated by two methods, was equal to 2.1-3.1. The diffusion coefficient of rhenium ions has been found to be 2.8 ⋅10 −5 cm2/s at 790 0C and 3.5 ⋅10 −5 cm2/s at 840 0C. Galvanoplastic production of rhenium products, such as
Chain elongation and cyclization in type III PKS DpgA.
Wu, Hai-Chen; Li, Yi-San; Liu, Yu-Chen; Lyu, Syue-Yi; Wu, Chang-Jer; Li, Tsung-Lin
2012-04-16
Chain elongation and cyclization of precursors of dihydroxyphenylacetyl-CoA (DPA-CoA) catalyzed by the bacterial type III polyketide synthase DpgA were studied. Two labile intermediates, di- and tri-ketidyl-CoA (DK- and TK-CoA), were proposed and chemically synthesized. In the presence of DpgABD, each of these with [(13)C(3)]malonyl-CoA (MA-CoA) was able to form partially (13)C-enriched DPA-CoA. By NMR and MS analysis, the distribution of (13)C atoms in the partially (13)C-enriched DPA-CoA shed light on how the polyketide chain elongates and cyclizes in the DpgA-catalyzed reaction. Polyketone intermediates elongate in a manner different from that which had been believed: two molecules of DK-CoA, or one DK-CoA plus one acetoacetyl-CoA (AA-CoA), but not two molecules of AA-CoA can form one molecule of DPA-CoA. As a result, polyketidyl-CoA serves as both the starter and extender, whereas polyketone-CoA without the terminal carboxyl group can only act as an extender. The terminal carboxyl group is crucial for the cyclization that likely takes place on CoA. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Bergman cyclization in polymer chemistry and material science.
Xiao, Yuli; Hu, Aiguo
2011-11-01
Bergman cyclization of enediynes, regarded as a promising strategy for anticancer drugs, now finds its own niche in the area of polymer chemistry and material science. The highly reactive aromatic diradicals generated from Bergman cyclization can undergo polymerization acting as either monomers or initiators of other vinyl monomers. The former, namely homopolymerization, leads to polyphenylenes and polynaphthalenes with excellent thermal stability, good solubility, and processability. The many remarkable properties of these aromatic polymers have further endowed them to be manufactured into carbon-rich materials, e.g., glassy carbons and carbon nanotubes. Whereas used as initiators, enediynes provide a novel resource for high molecular weight polymers with narrow polydispersities. The aromatic diradicals are also useful for introducing oligomers or polymers onto pristine carbonous nanomaterials, such as carbon nano-onions and carbon nanotubes, to improve their dispersibility in organic solvents and polymer solutions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Touseef Amna
2012-07-01
Full Text Available The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH, nitric oxide (NO and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (p<0.05 the amount of total melanin in black and brindle whereas eumelanin production in brown Hanwoo muzzle melanocytes. On the contrary, L-cysteine greatly (p<0.05 depressed the eumelanin production in black color but increased in brown. Simultaneously, up regulation of Tyr by nitric oxide and α-MSH and down regulation of Tyr, Tyrp-2 and MC1R genes by L-cysteine were observed in muzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes.
Energy Technology Data Exchange (ETDEWEB)
Nahama, F.
1996-11-30
The aim of this work is to study the influence of the acid-basic properties of rhenium oxide supported on alumina catalyst on the catalytic performance in olefin metathesis. The literature data indicate that the environment of the active site does possess acid properties. However, the nature of the acid sites is still matter of debate. Concerning the Re O{sub x} - Al{sub 2}O{sub 3} interactions, we have shown that perrhenate ions are electrostatically absorbed on alumina. The uptake of rhenium is favoured at acidic pH (below 4), and the absorbed rhenium is in equilibrium with rhenium in solution. The results of rhenium extraction by water strongly suggest that the surface compounds of the calcined Re{sub 2}O{sub 7}/Al{sub 2}O{sub 3} materials is aluminium perrhenate. Characterization of surface acidity of the catalyst by infrared spectroscopy reveals that the initiation of the metathesis reaction is governed essentially by Lewis acidity. This strongly supports the role of Lewis acidity, which is exalted by the increase of the rhenium content and the calcination temperature. Finally, we point out by ammonia adsorption-thermodesorption a band at 1320 cm{sup -1} characteristic of the Lewis acidity of aluminium perrhenate. This result is a second indication of the presence of aluminium perrhenate on the Re{sub 2}O{sub 7}/Al{sub 2}O{sub 3} catalyst surface. (author)
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Ichiro Yajima
Full Text Available BACKGROUND: Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA, a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2 and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes.
Puig, Isabel; Champeval, Delphine; Kumasaka, Mayuko; Belloir, Elodie; Bonaventure, Jacky; Mark, Manuel; Yamamoto, Hiroaki; Taketo, Mark M.; Choquet, Philippe; Etchevers, Heather C.; Beermann, Friedrich; Delmas, Véronique; Monassier, Laurent; Larue, Lionel
2013-01-01
Background Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA), a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2) and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes. PMID:23382837
International Nuclear Information System (INIS)
Drobot, D.V.; Belyaev, A.V.; Kutvitskij, V.A.; Rysev, A.P.
1999-01-01
A procedure to prepare rhenium-containing glass-like specimens on the basis of bismuth and boron oxides is proposed. The glasses produced are studied by X-ray fluorescent analysis and routine spectrometric thiocyanate analysis. The results make it possible to determine rhenium in oxide mixtures in the range of its content 0.01 - 10% with S r = 0.03 [ru
Development and validation of a simple method for the extraction of human skin melanocytes.
Wang, Yinjuan; Tissot, Marion; Rolin, Gwenaël; Muret, Patrice; Robin, Sophie; Berthon, Jean-Yves; He, Li; Humbert, Philippe; Viennet, Céline
2018-03-21
Primary melanocytes in culture are useful models for studying epidermal pigmentation and efficacy of melanogenic compounds, or developing advanced therapy medicinal products. Cell extraction is an inevitable and critical step in the establishment of cell cultures. Many enzymatic methods for extracting and growing cells derived from human skin, such as melanocytes, are described in literature. They are usually based on two enzymatic steps, Trypsin in combination with Dispase, in order to separate dermis from epidermis and subsequently to provide a suspension of epidermal cells. The objective of this work was to develop and validate an extraction method of human skin melanocytes being simple, effective and applicable to smaller skin samples, and avoiding animal reagents. TrypLE™ product was tested on very limited size of human skin, equivalent of multiple 3-mm punch biopsies, and was compared to Trypsin/Dispase enzymes. Functionality of extracted cells was evaluated by analysis of viability, morphology and melanin production. In comparison with Trypsin/Dispase incubation method, the main advantages of TrypLE™ incubation method were the easier of separation between dermis and epidermis and the higher population of melanocytes after extraction. Both protocols preserved morphological and biological characteristics of melanocytes. The minimum size of skin sample that allowed the extraction of functional cells was 6 × 3-mm punch biopsies (e.g., 42 mm 2 ) whatever the method used. In conclusion, this new procedure based on TrypLE™ incubation would be suitable for establishment of optimal primary melanocytes cultures for clinical applications and research.
Vehapoğlu, Aysel; Türkmen, Serdar; Terzioğlu, Şule
2016-03-05
The hypothalamus plays a crucial role in the regulation of feeding behavior. The anorexigenic neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) and the orexigenic neuropeptide agouti-related protein (AgRP) are among the major peptides produced in the hypothalamus. This study investigated the plasma concentrations of α-MSH and AgRP in underweight and obese children and their healthy peers. The associations between α-MSH and AgRP levels and anthropometric and nutritional markers of malnutrition and obesity were also assessed. Healthy sex-matched subjects aged 2 to 12 years were divided into 3 groups, as underweight (n=57), obese (n=61), and of normal weight (n=57). Plasma fasting concentrations of α-MSH and AgRP were measured by enzyme-linked immunosorbent assay. The differences between the three groups as to the relationships between plasma concentrations of α-MSH and AgRP and anthropometric data, serum biochemical parameters and homeostatic model assessment of insulin resistance were evaluated. Obese children had significantly lower α-MSH levels than underweight (1194±865 vs. 1904±1312 ng/mL, p=0.006) and normal weight (1194±865 vs. 1762±1463 ng/mL, p=0.036) children; there were no significant differences in the α-MSH levels between the underweight and normal weight children (p=0.811). Also, no significant differences were observed between the underweight and obese children regarding the AgRP levels (742±352 vs. 828±417 ng/mL, p=0.125). We found a significant positive correlation between plasma α-MSH and AgRP levels across the entire sample. This study is the first to demonstrate body weight-related differences in α-MSH and AgRP levels in children. Circulating plasma α-MSH levels in obese children were markedly lower than those of underweight and normal-weight children. This suggests that α-MSH could play a role in appetite regulation.
Melanocytes and melanin represent a first line of innate immunity against Candida albicans.
Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna
2014-07-01
Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Melanoma and melanocytic nevi in decorative tattoos: three case reports.
Varga, Erika; Korom, Irma; Varga, János; Kohán, József; Kemény, Lajos; Oláh, Judit
2011-12-01
In response to the demands of style and fashion, the number of decorative tattoos has been increasing worldwide. This has been paralleled by a rising incidence of melanocytic proliferations, including melanoma. The coincidence of various dermatological diseases and skin tumors with tattoos has been documented with some frequency, but reports of melanoma associated with tattoos are exceedingly rare. To date, only 13 cases have been documented in the English language literature. The possibility of an association between melanocytic proliferations and tattoos remains an area for further study. This report presents two cases of melanocytic nevi and one of melanoma occurring in association with a decorative tattoos. At present, the pathogenesis of melanoma developing in a tattoo is unknown. Mere coincidence cannot be ruled out. However, trauma, ultraviolet light exposure, a photoallergic effect, or an inflammatory reaction may promote malignant transformation. Clinicians and histopathologists should be aware of the clinical and pathological features if they are to make a correct diagnosis. Copyright © 2011 John Wiley & Sons A/S.
Elassiuty, Yasser E.; Klarquist, Jared; Speiser, Jodi; Yousef, Randa M.; El Refaee, Abdelaziz A.; Hunter, Nahla S.; Shaker, Olfat G.; Gundeti, Mohan; Nieuweboer-Krobotova, Ludmila; Caroline Le Poole, I.
2011-01-01
To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP.
A Study on the Trapping Characteristics of Rhenium Oxide Using Ca(OH)_2
International Nuclear Information System (INIS)
Lee, Tae-Kyo; Eun, Hee-Chul; Choi, Jung-Hoon; Lee, Ki-Rak; Han, Seung-Youb; Park, Hwan-Seo
2017-01-01
The objective of this study was to obtain basic data for trapping gaseous technetium (Tc) oxide generated from the voloxidation process in spent nuclear fuel pyroprocessing. Rhenium (Re) and Ca(OH)_2 were used as surrogates for the technetium and a trapping material, respectively. The trapping characteristics of rhenium oxide were investigated with changing temperatures and molar ratios of calcium (Ca) over rhenium, and the thermal behaviors of the trapping products were observed. The products following after the trapping test were identified as Ca(ReO_4)_2 and Ca_5Re_2O_1_2. The conversion to Ca_5Re_2O_1_2 was preferred with increasing temperatures, and the trapping products were completely converted into Ca5Re2O12 under conditions exceeding 800 ℃, or when maintained at 750 ℃ for 4 hr. The trapping efficiency at a molar ratio of 2.5 (Ca:Re=5:2) was significantly superior to that at the molar ratio of 2.
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)
alpha-MSH in systemic inflammation. Central and peripheral actions.
Catania, A; Delgado, R; Airaghi, L; Cutuli, M; Garofalo, L; Carlin, A; Demitri, M T; Lipton, J M
1999-10-20
Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on alpha-melanocyte stimulating hormone (alpha-MSH). Increases in circulating TNF-alpha and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central alpha-MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central alpha-MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation. In addition to its central influences, alpha-MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. alpha-MSH reduces chemotaxis of human neutrophils and production of TNF-alpha, neopterin, and NO by monocytes. In research on septic patients, alpha-MSH inhibited release of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.
International Nuclear Information System (INIS)
Svedberg, R.C.; Bowen, W.W.; Buckman, R.W. Jr.
1980-04-01
Chemical Vapor Deposit (CVD) rhenium was selected as the muffle material for an 1800 0 C high thermal efficiency fuel processing furnace. The muffle is exposed to high vacuum on the heater/insulation/instrumentation side and to a flowing argon-8 V/0 hydrogen gas mixture at one atmosphere pressure on the load volume side. During operation, the muffle cycles from room temperature to 1800 0 C and back to room temperature once every 24 hours. Operational life is dependent on resistance to thermal fatigue during the high temperature exposure. For a prototypical furnace, the muffle is approximately 13 cm I.D. and 40 cm in length. A small (about one-half size) rhenium closed end tube overcoated with tungsten was used to evaluate the concept. The fabrication and testing of the composite tungsten-rhenium tube and prototypic rhenium muffle is described
Directory of Open Access Journals (Sweden)
Melissa Crawford
2017-08-01
Full Text Available Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, and melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations. This is due, in part, to differences in the conditions used to isolate, purify and culture these cells in individual studies. By breeding ROSAmT/mG and Tyr::CreERT2 mice, we generated animals in which melanocytic lineage cells are identified through expression of green fluorescent protein. We also used defined conditions to systematically investigate the proliferation and migration responses of primary melanocytes on various extracellular matrix (ECM substrates. Under our culture conditions, mouse melanocytes exhibit doubling times in the range of 10 days, and retain exponential proliferative capacity for 50-60 days. In culture, these melanocytes showed distinct responses to different ECM substrates. Specifically, laminin-332 promoted cell spreading, formation of dendrites, random motility and directional migration. In contrast, low or intermediate concentrations of collagen I promoted adhesion and acquisition of a bipolar morphology, and interfered with melanocyte forward movements. Our systematic evaluation of primary melanocyte responses emphasizes the importance of clearly defining culture conditions for these cells. This, in turn, is essential for the interpretation of melanocyte responses to extracellular cues and to understand the molecular basis of disorders involving the melanocytic cell lineage.
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.
Influence of ligand structure on anticancer and antioxidant properties of rhenium cluster compounds
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I. V. Leus
2009-11-01
Full Text Available Under the model growth of T8 Guerin’s carcinoma in rats we studied the anticancer activity of the system rhenium-platinum, which includes cis-dicarboxylates of rhenium (III with different alkyl ligands, erythrocytes number and its morphological structure, erythrocytic stability, blood haemoglobin concentration, catalase activity and concentration of TBA-active products in the rats blood plasma. The renium-platinum system had considerable antioxidat effect and prevented the growth of tumour, that was maximal for a compound with the pivalate ligand.
Epimerization-free C-terminal peptide activation, elongation and cyclization
Popović, S.
2015-01-01
C-terminal peptide activation and cyclization reactions are generally accompanied with epimerization (partial loss of C‐terminal stereointegrity). Therefore, the focus of this thesis was to develop epimerization-free methods for C-terminal peptide activation to enable C-terminal peptide elongation
Aqueous humor tyrosinase activity is indicative of iris melanocyte toxicity.
Mahanty, Sarmistha; Kawali, Ankush A; Dakappa, Shruthi Shirur; Mahendradas, Padmamalini; Kurian, Mathew; Kharbanda, Varun; Shetty, Rohit; Setty, Subba Rao Gangi
2017-09-01
Antibiotics such as fluoroquinolones (FQLs) are commonly used to treat ocular infections but are also known to cause dermal melanocyte toxicity. The release of dispersed pigments from the iris into the aqueous humor has been considered a possible ocular side effect of the systemic administration of FQLs such as Moxifloxacin, and this condition is known as bilateral acute iris transillumination (BAIT). Bilateral acute depigmentation of iris (BADI) is a similar condition, with iris pigment released into the aqueous, but it has not been reported as a side effect of FQL. Iris pigments are synthesized by the melanogenic enzyme tyrosinase (TYR) and can be detected but not quantified by using slit-lamp biomicroscopy. The correlation between dispersed pigments in the aqueous and the extent of melanocyte toxicity due to topical antibiotics in vivo is not well studied. Here, we aimed to study the effect of topical FQLs on iris tissue, the pigment release in the aqueous humor and the development of clinically evident iris atrophic changes. We evaluated this process by measuring the activity of TYR in the aqueous humor of 82 healthy eyes undergoing cataract surgery following topical application of FQLs such as Moxifloxacin (27 eyes, preservative-free) or Ciprofloxacin (29 eyes, with preservative) or the application of non-FQL Tobramycin (26 eyes, with preservative) as a control. In addition, the patients were questioned and examined for ocular side effects in pre- and post-operative periods. Our data showed a significantly higher mean TYR activity in the aqueous humor of Ciprofloxacin-treated eyes compared to Moxifloxacin- (preservative free, p iris melanocytes. However, the reduced TYR activity in the aqueous of Moxifloxacin-treated eyes was possibly due to the presence of a higher drug concentration, which inhibits TYR activity. Consistently, immunoblotting analysis of the aqueous humor from both Ciprofloxacin- and Moxifloxacin-treated eyes showed the presence of soluble
Garcia, Maria Fernanda; Zhang, Xiuli; Gallazzi, Fabio; Fernandez, Marcelo; Moreno, Maria; Gambini, Juan Pablo; Porcal, Williams; Cabral, Pablo; Quinn, Thomas P
2015-01-01
Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with (99m) via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with (99m)Tc using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that (99m)Tc- HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than (99m)Tc-HYNIC-cyc-MSH/EDDA at early time points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize tumors, underscoring the potential utility of (99m)Tc labeled lactam cyclized MSH molecules as melanoma imaging agents.
Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence
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Joanna Jaworek-Korjakowska
2016-01-01
Full Text Available Background. Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. Method. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. Results. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. Conclusions. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision.
Progressive Increase in Telomerase Activity From Benign Melanocytic Conditions to Malignant Melanoma
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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.
Crawford, Melissa; Leclerc, Valerie; Dagnino, Lina
2017-08-15
Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, and melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations. This is due, in part, to differences in the conditions used to isolate, purify and culture these cells in individual studies. By breeding ROSA mT/mG and Tyr::CreER T2 mice, we generated animals in which melanocytic lineage cells are identified through expression of green fluorescent protein. We also used defined conditions to systematically investigate the proliferation and migration responses of primary melanocytes on various extracellular matrix (ECM) substrates. Under our culture conditions, mouse melanocytes exhibit doubling times in the range of 10 days, and retain exponential proliferative capacity for 50-60 days. In culture, these melanocytes showed distinct responses to different ECM substrates. Specifically, laminin-332 promoted cell spreading, formation of dendrites, random motility and directional migration. In contrast, low or intermediate concentrations of collagen I promoted adhesion and acquisition of a bipolar morphology, and interfered with melanocyte forward movements. Our systematic evaluation of primary melanocyte responses emphasizes the importance of clearly defining culture conditions for these cells. This, in turn, is essential for the interpretation of melanocyte responses to extracellular cues and to understand the molecular basis of disorders involving the melanocytic cell lineage. © 2017. Published by The Company of Biologists Ltd.
International Nuclear Information System (INIS)
Kuznetsov, V.V.; Samorukova, O.L.
1978-01-01
The method has been proposed of determining rhenium (7) microamounts by spectrophotometric titration in the medium water-dimethyl-sulphoxide with the reagent nitrochromazo. The method is based on the formation of ionic pairs K + ReO 4 - in water-organic solvents. The results of rhenium determination are satisfactory in a wide concentration range up to 0.3 mkg in 15 ml which makes the method proposed close in sensitivity to photometric methods and much better in reproducibility
Reductive Coupling of Carbon Monoxide in a Rhenium Carbonyl Complex with Pendant Lewis Acids
Miller, Alexander J. M.; Labinger, Jay A.; Bercaw, John E.
2008-01-01
Phosphinoborane ligands impart unique reactivity to a rhenium carbonyl cation relative to simple phosphine complexes. Addition of either triethylborohydride or a platinum hydride (that can be formed from H2) forms a rhenium boroxycarbene. This carbene, which crystallizes as a dimer, disproportionates over a period of days to afford the starting cation and a structurally unprecedented boroxy(boroxymethyl)carbene, in which a new C−C bond has been formed between two reduced CO ligands. This prod...
Tungsten - rhenium alloys wire: overview of thermomechanical processing and properties data
International Nuclear Information System (INIS)
Bryskin, B.
2001-01-01
The scope of this study encompasses the compositional modifications of the tungsten-rhenium dual system (W-3/5 Re up to W-27 Re) as well as some of the tungsten-molybdenum-rhenium ternary system. The alloys of interest are considered with a specific representation of powder metallurgy route based on doped or undoped tungsten vs. vacuum melted materials. This paper constitutes an in-depth review of structural and mechanical properties and systematic compilation of challenges necessary to provide the quality consistency of severely drawn filaments. The issue of thermomechanical processing trends is addressed as an important part of W-Re fabrication technology to achieve further improvement in design properties of rod and wire. (author)
International Nuclear Information System (INIS)
Ishikawa, Takehiko; Paradis, Paul-Francois; Yoda, Shinichi
2004-01-01
Surface tension and viscosity of liquid rhenium, which have hardly been measured due to the extremely high melting temperature of rhenium, were measured using an electrostatic levitation method combined with the oscillation drop technique. Sample position instability problems caused by the photon pressure of the heating lasers and by sample evaporation were solved by modifying the electrodes design. Good sample stability allowed the measurements of the surface tension and the viscosity over wide temperature ranges including the undercooled states. Over the 2800-3600 K interval, the surface tension of rhenium was measured as σ(T)=2.71x10 3 -0.23(T-T m ), where T m is the melting temperature, 3453 K. At T m , the datum agrees well with the literature values. Similarly, on the same temperature range, the viscosity was determined as η(T)=0.08 exp[1.33x10 5 /(RT)] (mPa s)
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)
Image enhancement of optical images for binary system of melanocytes and keratinocytes
Takanezawa, S.; Baba, A.; Sako, Y.; Ozaki, Y.; Date, A.; Toyama, K.; Morita, S.
2013-05-01
Automatic determination of the cell shapes of large numbers of melanocytes based on optical images of human skin models have been largely unsuccessful (the complexities introduced by dendrites and the melanin pigmentation over the keratinocytes to give unclear outlines). Here, we present an image enhancement procedure for enhancing the contrast of images with removing the non-uniformity of background. The brightness is normalized also for the non-uniform population density of melanocytes.
Beberok, Artur; Wrześniok, Dorota; Otręba, Michał; Miliński, Maciej; Rok, Jakub; Buszman, Ewa
2015-03-01
Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.
Arowojolu, Omotayo A; Orlow, Seth J; Elbuluk, Nada; Manga, Prashiela
2017-07-01
Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
International Nuclear Information System (INIS)
Webb, Jonathan A.; Charit, Indrajit
2011-01-01
Highlights: → The addition of rhenium to the tungsten matrix within W-UO 2 and W-UN CERMET materials can help reduce the risk of submersion criticality accidents while increasing the strength and ductility of tungsten based nuclear fuel elements. → The addition of rhenium up to 30 at.% to simple geometries containing W-UO 2 mixtures can increase the critical mass by 65 kg. → The addition of rhenium up to 30 at.% to simple geometries containing W-UN mixtures can increase the critical mass by 22 kg. → The addition of rhenium by up to 30 at.% to simple geometries containing W-UO 2 mixtures can reduce the change in reactivity change due to water submersion by $5.07. → The addition of rhenium by up to 30 at.% to simple geometries containing W-UN mixtures can reduce the change in reactivity due to water submersion by $3.24. - Abstract: The critical mass and dimensions of simple geometries containing highly enriched uranium dioxide (UO 2 ) and uranium mononitride (UN) encapsulated in tungsten-rhenium alloys are determined using MCNP5 criticality calculations. Spheres as well as cylinders with length to radius ratios of 1.82 are computationally built to consist of 60 vol.% fuel and 40 vol.% metal matrix. Within the geometries, the uranium is enriched to 93 wt.% uranium-235 and the rhenium content within the metal alloy was modeled over the range of 0-30 at.%. The spheres containing UO 2 were determined to have a critical radius of 18.29-19.11 cm and a critical mass ranging from 366 kg to 424 kg. The cylinders containing UO 2 were found to have a critical radius ranging from 17.07 cm to 17.84 cm with a corresponding critical mass of 406-471 kg. Spheres engrained with UN were determined to have a critical radius ranging from 14.82 cm to 15.19 cm and a critical mass between 222 kg and 242 kg. Cylinders which were engrained with UN were determined to have a critical radius ranging from 13.81 cm to 14.15 cm and a corresponding critical mass of 245-267 kg. The critical
Confocal laser scanning microscopy in vivo for diagnosing melanocytic skin neoplasms
Directory of Open Access Journals (Sweden)
A. A. Kubanova
2014-01-01
Full Text Available The authors discuss the use of confocal laser scanning microscopy in vivo (CLSM for diagnosing melanocytic skin neoplasms and its value for early diagnostics of melanoma. CLSM is an innovation noninvasive visual examination method for real-time multiple and painless examinations of the patient’s skin without injuring the skin integument. The method ensures early diagnostics of skin melanomas with high sensitivity and specificity, which makes it possible to use CLSM for screening melanocytic skin neoplasms for the sake of the early onset of treatment to save patient life and health.
Photochemical Aryl Radical Cyclizations to Give (E-3-Ylideneoxindoles
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Michael Gurry
2014-09-01
Full Text Available (E-3-Ylideneoxindoles are prepared in methanol in reasonable to good yields, as adducts of photochemical 5-exo-trig of aryl radicals, in contrast to previously reported analogous radical cyclizations initiated by tris(trimethylsilylsilane and azo-initiators that gave reduced oxindole adducts.
MC1R and the response of melanocytes to ultraviolet radiation
International Nuclear Information System (INIS)
Rouzaud, Francois; Kadekaro, Ana Luisa; Abdel-Malek, Zalfa A.; Hearing, Vincent J.
2005-01-01
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 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
McCloy, John S; Riley, Brian J; Goel, Ashutosh; Liezers, Martin; Schweiger, Michael J; Rodriguez, Carmen P; Hrma, Pavel; Kim, Dong-Sang; Lukens, Wayne W; Kruger, Albert A
2012-11-20
The immobilization of technetium-99 ((99)Tc) in a suitable host matrix has proven to be a challenging task for researchers in the nuclear waste community around the world. In this context, the present work reports on the solubility and retention of rhenium, a nonradioactive surrogate for (99)Tc, in a sodium borosilicate glass. Glasses containing target Re concentrations from 0 to 10,000 ppm [by mass, added as KReO(4) (Re(7+))] were synthesized in vacuum-sealed quartz ampules to minimize the loss of Re from volatilization during melting at 1000 °C. The rhenium was found as Re(7+) in all of the glasses as observed by X-ray absorption near-edge structure. The solubility of Re in borosilicate glasses was determined to be ~3000 ppm (by mass) using inductively coupled plasma optical emission spectroscopy. At higher rhenium concentrations, additional rhenium was retained in the glasses as crystalline inclusions of alkali perrhenates detected with X-ray diffraction. Since (99)Tc concentrations in a glass waste form are predicted to be wastes, assuming Tc as Tc(7+) and similarities between Re(7+) and Tc(7+) behavior in this glass system.
Energy Technology Data Exchange (ETDEWEB)
Khan, Aneeqa, E-mail: aneeqa.khan-3@postgrad.manchester.ac.uk [School of Mechanical, Aerospace and Civil Engineering, The University of Manchester, M13 9PL (United Kingdom); Elliman, Robert; Corr, Cormac [Research School of Physics and Engineering, The Australian National University, Canberra, ACT 2601 (Australia); Lim, Joven J.H.; Forrest, Andrew [School of Materials, The University of Manchester, M13 9PL (United Kingdom); Mummery, Paul [School of Mechanical, Aerospace and Civil Engineering, The University of Manchester, M13 9PL (United Kingdom); Evans, Llion M. [Culham Centre for Fusion Energy, Culham Science Centre, Abingdon, Oxon, OX14 3DB (United Kingdom)
2016-08-15
As-received and annealed tungsten samples were irradiated at a temperature of 400 °C with Re and W ions to peak concentrations of 1600 appm (atomic parts per million) and damage levels of 40 dpa (displacements per atom). Mechanical properties were investigated using nanoindentation, and the orientation and depth dependence of irradiation damage was investigated using Electron Back Scatter Diffraction (EBSD). Following irradiation there was a 13% increase in hardness in the as received sheet and a 23% increase in the annealed material for both tungsten and rhenium irradiation. The difference between the tungsten and rhenium irradiated samples was negligible, suggesting that for the concentrations and damage levels employed, the presence of rhenium does not have a significant effect on the hardening mechanism. Energy dependent EBSD of annealed samples provided information about the depth distribution of the radiation damage in individual tungsten grains and confirmed that the radiation damage is orientation dependant.
Digital Repository Service at National Institute of Oceanography (India)
Parvatkar, P.T.; Majik, M.S.
and 15 can be synthesized from a common intermediate 16 via reductive cyclization reaction. The key intermediate 16 in turn can be obtained by Wittig reaction of (2-nitrobenzyl)triphenylphosphonium bromide with isatin. Hence compound 16 could... be considered as an advance intermediate for preparation of alkaloids in present work. N N 1 N H N 11 N H N 15NH O O2NN H O O + PPh3 NO2 + Br- 16 17 18 N N13 Wittig reaction reductive cyclization N-Methylation N-Methylation reductive cyclization Scheme 1...
UVA phototransduction drives early melanin synthesis in human melanocytes.
Wicks, Nadine L; Chan, Jason W; Najera, Julia A; Ciriello, Jonathan M; Oancea, Elena
2011-11-22
Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (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 (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin. Copyright © 2011 Elsevier Ltd. All rights reserved.
Marušić, Zlatko; Buljan, Marija; Busam, Klaus J
2015-06-01
Multiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms. We report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1-associated cancer susceptibility syndrome. The neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up. We report two new cases of melanoma arising in a BAP1-deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1-deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.
Adini, Irit; Ghosh, Kaustabh; Adini, Avner; Chi, Zai-Long; Yoshimura, Takeru; Benny, Ofra; Connor, Kip M; Rogers, Michael S; Bazinet, Lauren; Birsner, Amy E; Bielenberg, Diane R; D'Amato, Robert J
2014-01-01
Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in African-Americans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays. Additionally, FMOD enhanced vascular sprouting during normal retinal development. Deletion of Fmod in albino mice resulted in a marked reduction in the amount of neovascularization induced by retinal vein occlusion, corneal growth factor pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for epidemiological differences between light-skinned individuals of mixed European descent and African-Americans. Furthermore, inhibition of FMOD in humans has potential as a therapeutic strategy for treating angiogenesis-dependent diseases.
International Nuclear Information System (INIS)
Boyle, G.M.; Pedley, J.; Martyn, A.C.; Fraser, L.M.; Banducci, K.J.; Parsons, P.G.; Breit, S.N.
2003-01-01
Melanoma is a highly aggressive cancer resulting from the abnormal proliferation and spread of specialised pigment cells in the skin, known as melanocytes. Extensive epidemiological and molecular evidence suggests that a major risk factor for melanoma formation is exposure to non-ionising radiation in the form of solar ultra-violet (UV) light. However, the exact role of solar UV in the development of melanoma is unclear. To elucidate the molecular events that occur in melanocytes following solar UV exposure and determine how they lead to melanoma development, cDNA microarray analysis was used to analyse the gene expression profile of normal melanocytes, melanocytes exposed to simulated solar UV and melanoma cells. The development of cDNA microarray technology has allowed gene expression profiling at the mRNA level to be conducted for many thousands of genes simultaneously by hybridising an array of known sequences with labelled cDNA reverse transcribed form the sample RNA. Gene expression analysis was performed for over 13,000 genes. More than 500 genes were identified as differentially expressed in melanocytes following a single UV exposure, although overall there was a general suppression of transcription. Genes that were up-regulated included oncogenes and cytoskeletal genes; in contrast, genes encoding protein tyrosine kinases and apoptosis effectors were down-regulated. Many of the genes identified as being differentially expressed represent novel UV-regulated targets. Repeated exposure to solar UV resulted in the elevation in expression of a novel member of the transforming growth factor-b (TGF-b) superfamily, the Macrophage Inhibitory Cytokine-1 (MIC-1). Our results have shown that MIC-1 is up-regulated by solar UV in melanocytes, and is highly expressed (>3 fold) in a number of metastatic melanoma cell lines (31/61) in comparison to primary melanocytes. Furthermore functional, dimerised MIC-1 was found to be secreted by melanocytes, and secreted levels were
Double reductive cyclization: A facile synthesis of the indoloquinoline alkaloid cryptotackieine
Digital Repository Service at National Institute of Oceanography (India)
Parvatkar, P.T.; Parameswaran, P.S.; Tilve, S.G.
A new synthesis of the indoloquinoline alkaloid cryptotackieine, isolated from Cryptolepis sanguinolenta, is described which involves a Perkin reaction, a tandem double reduction-double cyclization reaction followed by regioselective methylation...
Energy Technology Data Exchange (ETDEWEB)
Craft, A.E., E-mail: aaron.craft@inl.gov [Center for Space Nuclear Research (CSNR), INL, Idaho Falls, ID (United States); O’Brien, R.C., E-mail: Robert.OBrien@inl.gov [Center for Space Nuclear Research (CSNR), INL, Idaho Falls, ID (United States); Howe, S.D., E-mail: Steven.Howe@inl.gov [Center for Space Nuclear Research (CSNR), INL, Idaho Falls, ID (United States); King, J.C., E-mail: kingjc@mines.edu [Nuclear Science and Engineering Program, Metallurgical and Materials Engineering Department, Colorado School of Mines, Golden, CO 80401 (United States)
2014-07-01
Highlights: • Criticality safety studies consider a generic space nuclear reactor in reentry scenarios. • Describes the submersion criticality behavior for a reactor fueled with a tungsten cermet fuel. • Study considers effects of varying fuel content, geometry, and other conditions. - Abstract: Nuclear thermal rockets are the preferred propulsion technology for a manned mission to Mars, and tungsten–uranium oxide cermet fuels could provide significant performance and cost advantages for nuclear thermal rockets. A nuclear reactor intended for use in space must remain subcritical before and during launch, and must remain subcritical in launch abort scenarios where the reactor falls back to Earth and becomes submerged in terrestrial materials (including seawater, wet sand, or dry sand). Submersion increases reflection of neutrons and also thermalizes the neutron spectrum, which typically increases the reactivity of the core. This effect is typically very significant for compact, fast-spectrum reactors. This paper provides a submersion criticality safety analysis for a representative tungsten/uranium oxide fueled reactor with a range of fuel compositions. Each submersion case considers both the rhenium content in the matrix alloy and the uranium oxide volume fraction in the cermet. The inclusion of rhenium significantly improves the submersion criticality safety of the reactor. While increased uranium oxide content increases the reactivity of the core, it does not significantly affect the submersion behavior of the reactor. There is no significant difference in submersion behavior between reactors with rhenium distributed within the cermet matrix and reactors with a rhenium clad in the coolant channels. The combination of the flooding of the coolant channels in submersion scenarios and the presence of a significant amount of spectral shift absorbers (i.e. high rhenium concentration) further decreases reactivity for short reactor cores compared to longer cores.
Separation of tungsten and rhenium on alumina
Directory of Open Access Journals (Sweden)
MILOVAN SM. STOILJKOVIC
2004-09-01
Full Text Available The conditions for the efficient separation of tungsten(VI and rhenium (VII on alumina were established. The distribution coefficients Kd for tungstate and perrhenate anions, as well as the separation factors a (a = KdWO42-/Kd ReO4- were determined using hydrochloric or nitric acid as the aqueous media. A solution of sodium chloride in the pH range 26 was also examined. Under all the tested experimental conditions, alumina is a much better adsorbent for tungsten than for rhenium. The obtained results indicated that the best separation of these two elements is achieved when 0.01 0.1 mol dm-3 HCl or 1.0 mol dm-3 HNO3 are used as the aqueous media. If NaCl is used as the aqueous phase, the best separation is achieved with 0.20 mol dm-3 NaCl, pH 46. Under these experimental conditions, the breakthrough and saturation capacities of alumina for tungsten at pH 4 are 17 and 26 mg W/g Al2O3, respectively. With increasing pH, these values decrease. Thus, at pH 6 they are only 4 and 13 mg W/g Al2O3, respectively.
Energy Technology Data Exchange (ETDEWEB)
Figueroa-Villar, J. Daniel; Oliveira, Sandra C.G. de, E-mail: figueroa@ime.eb.br [Grupo de Quimica Medicinal, Departamento de Quimica, Instituto Militar de Engenharia, Rio de Janeiro, RJ (Brazil)
2011-09-15
The thermal cyclization reaction of o-halobenzylidene barbiturates was developed as an efficient and simple method for the preparation of oxadeazaflavines. The use of solid state reaction conditions with microwave irradiation afforded the products in 5 min with 47 to 98% yield. Experimental synthetic results and thermogravimetric reaction analyses agree with the molecular modeling mechanism simulation, indicating that this reaction occurs through an intramolecular hetero-Diels-Alder cyclization followed by fast re-aromatization. (author)
International Nuclear Information System (INIS)
Cario-Andre, M.
2000-11-01
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)
G2 accumulation and melanin overproduction in malignant melanocytes treated with a new nitrosourea.
Buchdahl, C; Papon, J; Communal, Y; Bourges, M; Madelmont, J C
1998-12-01
Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea), a new anticancer chloroethylnitrosourea (CENU) is being tested in a phase II clinical trial of disseminated melanoma. The antitumour effect of this drug is mainly due to DNA damage in malignant melanocytes. Recently, we have shown that this damage can induce apoptosis in some melanoma cell lines. In others, apoptosis is not clearly observed, although there is a strong cytostatic effect. In this paper, we have characterized the cytological effect of cystemustine on murine malignant melanocytes (B16 cell line) which are resistant to apoptosis induced by this CENU. The results show that 3 days after cystemustine treatment, these melanocytes had accumulated in phase G2 of the cell cycle. There was then a strong morphological modification during a long cytostatic phase up to 30 days after treatment. During this cytostatic phase, there was uncontrolled DNA synthesis and marked swelling. Also, tyrosinase activity, melanin content and the number of mature melanosomes were greatly increased. These results suggest that when malignant melanocytes are not able to undergo apoptosis after treatment with CENU, they accumulate in G2 and this is followed by enhancement of melanogenesis.
Directory of Open Access Journals (Sweden)
Guanghui Li
2016-11-01
Full Text Available Lead-rich molybdenite is a typical rhenium-bearing molybdenum resource in China, which has not been efficiently utilized due to its high contents of lead and gangue minerals. In this study, hydrochloric acid was used for preliminarily removing lead and calcite from a lead-rich molybdenite concentrate. Oxidative roasting-ammonia leaching was then carried out for separation of rhenium and extraction of molybdenum. The hydrochloric acid leaching experiments revealed that 93.6% Pb and 97.4% Ca were removed when the leaching was performed at 95 °C for 10 min with HCl concentration of 8 wt. % and liquid-solid ratio of 5 (mL/g. The results of direct oxidative roasting indicated that 89.3% rhenium was volatilized from the raw concentrate after roasting at 600 °C for 120 min in air. In contrast, the rhenium volatilization was enhanced distinctly to 98.0% after the acid-leached concentrate (leaching residue was roasted at 550 °C for 100 min. By the subsequent ammonia leaching, 91.5% molybdenum was leached out from the calcine produced from oxidative roasting of the acid-leached concentrate, while only 79.3% Mo was leached from the calcine produced by roasting molybdenite concentrate without pretreatment.
Directory of Open Access Journals (Sweden)
Mostafa Hosseinzadeh
2014-06-01
Full Text Available The extraction of rhenium from molybdenite roasting dust leach solution was performed using a mixer-settler extractor by tributyl phosphate (TBP diluted in kerosene as the extractant. In the single-stage extraction experiments, effect of the aqueous to organic phase ratios, Qa/Qo, and the number of extraction stages, N, on the rhenium extraction was studied. It was found that using the phase ratio of 1:1 in a two-stage extraction, 87.5% depletion of rhenium was obtained. The comparison of experimental results with the continuous co-current extraction showed a good agreement. The effect of internal recycle of organic phase was investigated in the phase ratio of 1:1 by changing the flow rate ratio of recycle-to-fresh organic phase, Qro/Qfo. The optimum performance was achieved in the phase ratio, Qro/Qfo, equal to 3:7. It was found that improvement in the performance of the mixer-settler for the rhenium-TBP system can be obtained in the phase ratio of 1:1when Qro/Qfo = 3:7.
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.
International Nuclear Information System (INIS)
Miyata, Maiko; Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko; Sugiura, Kazumitsu; Furukawa, Koichi; Furukawa, Keiko
2014-01-01
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
Wańkowicz-Kalińska, Anna; van den Wijngaard, René M. J. G. J.; Tigges, Bert J.; Westerhof, Wiete; Ogg, Graham S.; Cerundolo, Vincenzo; Storkus, Walter J.; Das, Pranab K.
2003-01-01
Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. High frequencies of melanocyte-reactive cytotoxic T cells in the peripheral blood of vitiligo patients and the observed correlation between perilesional T-cell infiltration and melanocyte loss in situ suggest the
Energy Technology Data Exchange (ETDEWEB)
Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Dannoon, Shorouk F.; Noll, Samantha M. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Ruthengael, Varyanna C. [Research Service, Harry S Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: JurissonS@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: LewisMic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)
2011-05-15
Introduction: To probe the interplay between radiotracer stability and somatostatin receptor affinity, Tyr{sup 3}-octreotate and six variations of its peptide sequence, for which the Re-cyclized products were previously reported, were radiolabeled with {sup 99m}Tc and investigated for their in vitro stability. Methods: Radiolabeling of the peptides was effected by ligand exchange from {sup 99m}Tc-glucoheptonate, and the desired products were purified by radio-RP-HPLC. The in vitro stability in phosphate buffered saline, mouse serum and cysteine solutions at physiological temperature and pH for all seven {sup 99m}Tc-cyclized peptides was determined by radio-RP-HPLC and radio-TLC. Normal CF-1 mouse biodistribution studies were performed for three of the {sup 99m}Tc-cyclized peptides. Results: Based on the fully characterized Re-cyclized peptide analogues, four {sup 99m}Tc-coordination motifs were proposed for the {sup 99m}Tc-cyclized peptides. Technetium-99m-cyclized Tyr{sup 3}-octreotate derivatives with N{sub 2}S{sub 2} metal coordination modes and large metal ring sizes were susceptible to oxidation and loss of {sup 99m}Tc in the form of {sup 99m}TcO{sub 4}{sup -}, as evidenced by their instability in the various solutions under physiological conditions (15-58% intact at 24 h). As anticipated, the addition of a third cysteine to the sequence stabilized the {sup 99m}Tc metal coordination, and peptides with NS{sub 3} coordination modes remained >85% intact out to 24 h. No significant differences were observed in the biodistribution studies performed with three peptides of varying stabilities. Conclusions: Improvements in stability were not sufficient to outweigh the low somatostatin receptor affinity for the peptides in this study. Further improvements in the peptide sequence and/or metal coordination are needed to result in a radiodiagnostic/radiotherapeutic pair for targeting the somatostatin receptor.
Photodecarboxylative Cyclizations of ω-Phthalimido-para-phenoxy Carboxylates
Energy Technology Data Exchange (ETDEWEB)
Kim, Ae Rhan; Lee, Younsik; Yoo, Dong Jin [Chonbuk National Univ., Jeonju (Korea, Republic of); Cho, Hyunseung [Seonam Univ., Namwon (Korea, Republic of)
2012-10-15
The chemistry of electronically-excited phthalimides is dictated by electron and/or hydrogen transfer reactions. The photochemistry of phthalimides has been intensively studied, and numerous synthetically useful transformations with high chemical and quantum yields have been developed. 3 Among the synthetic applications, intra- and intermolecular photodecarboxylation (PDC) of ω-phthalimidoalkyl carboxylates has been developed by Griesbeck and coworkers as a versatile pathway to medium- and large-ring heterocycles. Model reactions were further realized on macro- and micro-scales. We recently described PDC cyclizations of ω-phthalimidoalkynoates to produce macrocyclic alkynes with ring-sizes up to 17. In recent study, we expanded the portfolio of this reaction and investigated the photochemistry of related aryl-linked phthalimides in Scheme 1. Based on these approaches, we demonstrated that ω-phthalimido-ortho/meta-phenoxy carboxylates undergo efficient PDC cyclizations. While the yields of ω-phthalimido-ortho-phenoxy carboxylates steadily decreased with increasing chain-length and the maximum yield of the 6-membered product was obtained in 75%, the yields of meta-phenoxy carboxylates steadily increased with increasing chain-length and the extended 16-membered product was subsequently obtained in 48% yield.
SOCl 2 catalyzed cyclization of chalcones: Synthesis and spectral ...
African Journals Online (AJOL)
Some aryl-aryl 1H pyrazoles have been synthesised by cyclization of aryl chalcones and hydrazine hydrate in the presence of SOCl2. The yields of the pyrazoles are more than 85%. These pyrazoles are characterized by their physical constants and spectral data. The infrared, NMR spectral group frequencies of these ...
Directory of Open Access Journals (Sweden)
Stephanie H. Shirley
2012-01-01
Full Text Available Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete proinflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce proinflammatory mediators and that Slug is important in this process. Microarray studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of proinflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.
A Study on the Trapping Characteristics of Rhenium Oxide Using Ca(OH){sub 2}
Energy Technology Data Exchange (ETDEWEB)
Lee, Tae-Kyo; Eun, Hee-Chul; Choi, Jung-Hoon; Lee, Ki-Rak; Han, Seung-Youb; Park, Hwan-Seo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)
2017-01-15
The objective of this study was to obtain basic data for trapping gaseous technetium (Tc) oxide generated from the voloxidation process in spent nuclear fuel pyroprocessing. Rhenium (Re) and Ca(OH){sub 2} were used as surrogates for the technetium and a trapping material, respectively. The trapping characteristics of rhenium oxide were investigated with changing temperatures and molar ratios of calcium (Ca) over rhenium, and the thermal behaviors of the trapping products were observed. The products following after the trapping test were identified as Ca(ReO{sub 4}){sub 2} and Ca{sub 5}Re{sub 2}O{sub 12}. The conversion to Ca{sub 5}Re{sub 2}O{sub 12} was preferred with increasing temperatures, and the trapping products were completely converted into Ca5Re2O12 under conditions exceeding 800 ℃, or when maintained at 750 ℃ for 4 hr. The trapping efficiency at a molar ratio of 2.5 (Ca:Re=5:2) was significantly superior to that at the molar ratio of 2.
Soong, Joanne; Chen, Yulin; Shustef, Elina M; Scott, Glynis A
2012-04-01
Semaphorins are secreted and membrane-bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilin receptors. We recently reported that Plexin B1, the Semaphorin 4D (Sema4D) receptor, is a tumor-suppressor protein for melanoma, which functions, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report, we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation, and that it stimulates proliferation and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, partly through downregulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand, hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Sema4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met-dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly downregulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF-dependent effects on melanocytes, including melanocyte migration.
A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives
Directory of Open Access Journals (Sweden)
Debabrata Samanta
2014-12-01
Full Text Available A versatile synthetic procedure is described to prepare the benzimidazole-fused 1,2,4-thiadiazoles 2a–c via a methanesulfonyl chloride initiated multistep cyclization involving the intramolecular reaction of an in-situ generated carbodiimide with a thiourea unit. The structure of the intricate heterocycle 2a was confirmed by single-crystal X-ray analysis and its mechanism of formation supported by DFT computations.
Depletion of brain alpha-MSH alters prostaglandin and interleukin fever in rats.
Martin, S M; Malkinson, T J; Veale, W L; Pittman, Q J
1990-09-03
Alpha-melanocyte stimulating hormone (alpha-MSH), a putative endogenous antipyretic agent, is synthesized largely within neurons in the arcuate nucleus. To test the hypothesis that destruction of this area would increase the febrile response, male Wistar rats, treated as neonates with intraperitoneal injections of monosodium glutamate (MSG) or saline, were given intracerebroventricular (i.c.v.) injections of prostaglandin E1 (20 ng; 200 ng) or purified interleukin-1 (20 U) and body temperature was monitored. The fevers displayed by the MSG-treated animals were significantly greater (P less than 0.05) than those of the controls for the lower dose of PGE1 at 10-30 min and for IL-1 at 3-6 h after the injections. MSG-treated rats showed significant reduction (P less than 0.01) in alpha-MSH content of the medial basal hypothalamus and lateral septum when compared to saline controls. Body temperature response of non-febrile animals to high ambient temperature was not affected by the MSG treatment. These data support the hypothesis that alpha-MSH is an endogenous antipyretic in the rat.
Popović, Mara; Dolenc-Strazar, Zvezdana; Anzic, Jozica; Luzar, Bostjan
2004-10-01
Blue nevus is an uncommon pigmented tumor of dermal melanocytes that has traditionally been classified into common and cellular variant. It is usually a skin tumor in adults but can become apparent in early childhood or even be present at birth. Malignant blue nevus is a rare melanocytic tumor of the skin arising from a preexisting cellular blue nevus. We report a multinodular blue nevus of the left ear in an 11-year-old girl who also had 2 intracranial melanocytic lesions. Differential diagnosis between metastases from malignant blue nevus and neurocutaneous melanosis is discussed.
Molecular effects of 1-naphthyl-methylcarbamate and solar radiation exposures on human melanocytes.
Ferrucio, Bianca; Tiago, Manoela; Fannin, Richard D; Liu, Liwen; Gerrish, Kevin; Maria-Engler, Silvya Stuchi; Paules, Richard S; Barros, Silvia Berlanga de Moraes
2017-02-01
Carbaryl (1-naphthyl-methylcarbamate), a broad-spectrum insecticide, has recently been associated with the development of cutaneous melanoma in an epidemiological cohort study with U.S. farm workers also exposed to ultraviolet radiation, the main etiologic factor for skin carcinogenesis. We hypothesized that carbaryl exposure may increase deleterious effects of UV solar radiation on skin melanocytes. This study aimed to characterize human melanocytes after individual or combined exposure to carbaryl (100μM) and solar radiation (375mJ/cm 2 ). In a microarray analysis, carbaryl, but not solar radiation, induced an oxidative stress response, evidenced by the upregulation of antioxidant genes, such as Hemeoxygenase-1 (HMOX1), and downregulation of Microphtalmia-associated Transcription Factor (MITF), the main regulator of melanocytic activity; results were confirmed by qRT-PCR. Carbaryl and solar radiation induced a gene response suggestive of DNA damage and cell cycle alteration. The expression of CDKN1A, BRCA1/2 and MDM2 genes was notably more intense in the combined treatment group, in a synergistic manner. Flow cytometry assays demonstrated S-phase cell cycle arrest, reduced apoptosis levels and faster induction of cyclobutane pyrimidine dimers (CPD) lesions in carbaryl treated groups. Our data suggests that carbaryl is genotoxic to human melanocytes, especially when associated with solar radiation. Copyright © 2016 Elsevier B.V. All rights reserved.
Lindahl, Sarah E; Park, Hyunsoo; Pink, Maren; Zaleski, Jeffrey M
2013-03-13
Reaction of 2 equiv of 1,2-bis((diphenylphosphino)ethynyl)benzene (dppeb, 1) with Pt(cod)Cl2 followed by treatment with N2H4 yields the reduced Pt(0) metalloenediyne, Pt(dppeb)2, 2. This complex is stable to both air oxidation and metal-mediated Bergman cyclization under ambient conditions due to the nearly idealized tetrahedral geometry. Reaction of 2 with 1 equiv of I2 in the presence of excess 1,4-cyclohexadiene (1,4-CHD) radical trap rapidly and near-quantitatively generates the cis-Bergman-cyclized, diiodo product 3 ((31)P: δ = 41 ppm, J(Pt-P) = 3346 Hz) with concomitant loss of 1 equiv of uncyclized phosphine chelate ((31)P: δ = -33 ppm). In contrast, addition of 2 equiv of I2 in the absence of additional radical trap instantaneously forms a metastable Pt(dppeb)2(2+) intermediate species, 4, that is characterized by δ = 51 ppm in the (31)P NMR (J(Pt-P) = 3171 Hz) and ν(C≡C) = 2169 cm(-1) in the Raman profile, indicating that it is an uncyclized, bis-ligated complex. Over 24 h, 4 undergoes ligand exchange to form a neutral, square planar complex that spontaneously Bergman cyclizes at ambient temperature to give the crystalline product Pt(dppnap-I2)I2 (dppnap-I2 = (1,4-diiodonaphthalene-2,3-diyl)bis(diphenylphosphine)), 5, in 52% isolated yield. Computational analysis of the oxidation reaction proposes two plausible flattened tetrahedral structures for intermediate 4: one where the phosphine core has migrated to a trans-spanning chelate geometry, and a second, higher energy structure (3.3 kcal/mol) with two cis-chelating phosphine ligands (41° dihedral angle) via a restricted alkyne-terminal starting point. While the energies are disparate, the common theme in both structures is the elongated Pt-P bond lengths (>2.4 Å), indicating that nucleophilic ligand substitution by I(-) is on the reaction trajectory to the cyclized product 5. The efficiency of the redox-mediated Bergman cyclization reaction of this stable Pt(0) metalloenediyne prodrug and
Lee, John Hwan; Lee, Eun-Soo; Bae, Il-Hong; Hwang, Jeong-Ah; Kim, Se-Hwa; Kim, Dae-Yong; Park, Nok-Hyun; Rho, Ho Sik; Kim, Yong Jin; Oh, Seong-Geun; Lee, Chang Seok
2017-01-01
Excessive melanogenesis often causes unaesthetic hyperpigmentation. In a previous report, our group introduced a newly synthesized depigmentary agent, Melasolv™ (3,4,5-trimethoxycinnamate thymol ester). In this study, we demonstrated the significant whitening efficacy of Melasolv using various melanocytes and human skin equivalents as in vitro experimental systems. The depigmentary effect of Melasolv was tested in melan-a cells (immortalized normal murine melanocytes), α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 murine melanoma cells, primary normal human melanocytes (NHMs), and human skin equivalent (MelanoDerm). The whitening efficacy of Melasolv was further demonstrated by photography, time-lapse microscopy, Fontana-Masson (F&M) staining, and 2-photon microscopy. Melasolv significantly inhibited melanogenesis in the melan-a and α-MSH-stimulated B16 cells. In human systems, Melasolv also clearly showed a whitening effect in NHMs and human skin equivalent, reflecting a decrease in melanin content. F&M staining and 2-photon microscopy revealed that Melasolv suppressed melanin transfer into multiple epidermal layers from melanocytes as well as melanin synthesis in human skin equivalent. Our study showed that Melasolv clearly exerts a whitening effect on various melanocytes and human skin equivalent. These results suggest the possibility that Melasolv can be used as a depigmentary agent to treat pigmentary disorders as well as an active ingredient in cosmetics to increase whitening efficacy. © 2017 S. Karger AG, Basel.
Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi
2016-05-01
Tranexamic acid has an inhibitory action on ultraviolet (UV) B-induced melanocyte activation. This study examined the sex differences in the inhibitory action of tranexamic acid on UVB-induced melanocyte activation. We irradiated the eye and ear of male and female mice with UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp. We orally administered tranexamic acid (750 mg/kg/day) at 30 min before UVB exposure. Tranexamic acid inhibited the UVB-induced epidermal melanocyte activation, and the effect was more remarkable under UVB eye irradiation than under UVB ear irradiation. Furthermore, the melanocyte activity suppression effect was stronger in female mice than in male mice. Following the administration of tranexamic acid, the female displayed increased blood levels of β-endorphin and μ-opioid receptor and estradiol receptor β expression in comparison with the male. Furthermore, the effect of melanocyte activity suppression in the female mice was decreased by the administration of tamoxifen (antagonist of estrogen receptor) or naltrexone (antagonist of μ-opioid receptor). These results suggest that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
1,7-Cyclization of 1-diazo-2,4-pentadiene and its heteroanalogues: DFT study
Subbotina, Julia O.; Bakulev, V. A.; Herges, R.; Fabian, W. M. F.
1,7-Dipolar cyclizations of 1-diazo-2,4-pentadiene 1a and its heteroanalogues 1b,c and 4c were studied using density functional theory (DFT). Although the heteroanalogue 1c has an appropriate electronic structure to allow for pseudopericyclic cyclization, natural bond order (NBO) analysis has provided evidence for the electrocyclic ring closure. Magnetic criteria (anisotropy of the induced current density [ACID], nucleus-independent chemical shifts [NICS]) confirmed the pericyclic character of the located transition states 2a,c and 5c. The activation barriers for the cyclization of 1-diazo-2,4-pentadiene 1a and its aza analogues 1c, 4c are 3.3, 8.2, and 12.3 kcal/mol at the B3LYP/6-31G(d) level, respectively. The higher barrier of the 1c?3c and 4c?3c reactions compared with 1a?3a is in line with the Hammond postulate. The out-of-plane distorted geometry of the cyclic product is an additional factor arguing against a pseudopericyclic mechanism.
Directory of Open Access Journals (Sweden)
Hiroki Oguri
2012-06-01
Full Text Available By emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure–activity relationship (SAR studies were also undertaken.
Expression of monocarboxylate transporter 1 in oral and ocular canine melanocytic tumors.
Shimoyama, Y; Akihara, Y; Kirat, D; Iwano, H; Hirayama, K; Kagawa, Y; Ohmachi, T; Matsuda, K; Okamoto, M; Kadosawa, T; Yokota, H; Taniyama, H
2007-07-01
Solid tumors are composed of a heterogeneous population of cells surviving in various concentrations of oxygen. In a hypoxic environment, tumor cells generally up-regulate glycolysis and, therefore, generate more lactate that must be expelled from the cell through proton transporters to prevent intracellular acidosis. Monocarboxylate transporter 1 (MCT1) is a major proton transporter in mammalian cells that transports monocarboxylates, such as lactate and pyruvate, together with a proton across the plasma membrane. Melanocytic neoplasia occurs frequently in dogs, but the prognosis is highly site-dependent. In this study, 50 oral canine melanomas, which were subdivided into 3 histologic subtypes, and 17 ocular canine melanocytic neoplasms (14 melanocytomas and 3 melanomas) were used to examine and compare MCT1 expression. Immunohistochemistry using a polyclonal chicken anti-rat MCT1 antibody showed that most oral melanoma exhibited cell membrane staining, although there were no significant differences observed among the 3 histologic subtypes. In contrast, the majority of ocular melanocytic tumors were not immunoreactive. Additionally, we documented the presence of a 45-kDa band in cell membrane protein Western blots, and sequencing of a reverse transcriptase polymerase chain reaction band of expected size confirmed its identity as a partial canine MCT1 transcript in 3 oral tumors. Increased MCT1 expression in oral melanomas compared with ocular melanocytic tumors may reflect the very different biology between these tumors in dogs. These results are the first to document canine MCT1 expression in canine tumors and suggest that increased MCT1 expression may provide a potential therapeutic target for oral melanoma.
Smooth isoindolinone formation from isopropyl carbamates via Bischler-Napieralski-type cyclization.
Adachi, Satoshi; Onozuka, Masao; Yoshida, Yuko; Ide, Mitsuaki; Saikawa, Yoko; Nakata, Masaya
2014-01-17
Isopropyl carbamates derived from benzylamines provide isoindolinones by treatment with phosphorus pentoxide at room temperature. Utility of this Bischler-Napieralski-type cyclization and a new mechanism involving a carbamoyl cation for rationalization of this smooth conversion are discussed.
Lott, Jason P; Elmore, Joann G; Zhao, Ge A; Knezevich, Stevan R; Frederick, Paul D; Reisch, Lisa M; Chu, Emily Y; Cook, Martin G; Duncan, Lyn M; Elenitsas, Rosalie; Gerami, Pedram; Landman, Gilles; Lowe, Lori; Messina, Jane L; Mihm, Martin C; van den Oord, Joost J; Rabkin, Michael S; Schmidt, Birgitta; Shea, Christopher R; Yun, Sook Jung; Xu, George X; Piepkorn, Michael W; Elder, David E; Barnhill, Raymond L
2016-08-01
Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated. Most participants were board-certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71-0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91. This was a small sample size of experienced pathologists in a testing situation. Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Direct Synthesis of Medium-Bridged Twisted Amides via a Transannular Cyclization Strategy
Szostak, Michal; Aubé, Jeffrey
2009-01-01
The sequential RCM to construct a challenging medium-sized ring followed by a transannular cyclization across a medium-sized ring delivers previously unattainable twisted amides from simple acyclic precursors. PMID:19708701
sup(99m)Tc-sulfur-rhenium-colloid and 111In-indiumcitrate in the bone marrow scintigraphy
International Nuclear Information System (INIS)
Glaubitt, D.; Haberland, K.; Knoch, K.; Fejer, F.L.; Zachariah, S.; Staedtische Krankenanstalten Krefeld
1975-01-01
Bone marrow scintigraphy using 111 In-Indium-citrate and sup(99m)Tc-sulfur rhenium colloid was compared with each other in 6 male and 3 female patients. Our results in all patients were in favour of 111 In-citrate which caused a better delineation of morphological details than sup(99m)Tc-sulfur rhenium colloid did. In the first days after intravenous administration of 111 In-citrate, radioindium accumulated markedly in the pudendal region, this finding being more distinct in male patients than in female ones. On account of these results a considerable radiation dose has to be assumed in bone marrow scintigraphy using 111 In-citrate as long as the absorbed dose from 111 In has not been estimated under consideration of the radioindium accumulation in the pudendal region. 111 In-citrate should be applied in bone marrow scanning only exceptionally and sup(99m)Tc-sulfur rhenium colloid be preferred in the routine diagnostics of bone marrow. (orig.) [de
Grimes, Janet A; Matz, Brad M; Christopherson, Pete W; Koehler, Jey W; Cappelle, Kelsey K; Hlusko, Katelyn C; Smith, Annette
2017-07-01
Melanocytic neoplasms are common in dogs and frequently occur within the oral cavity or in haired skin. The behavior of melanocytic neoplasms is variable and depends on tumor location, size, and histopathologic features. This study compared cytopathology and histopathology of 32 lymph nodes from 27 dogs diagnosed with melanocytic neoplasms. Agreement between the original cytology report, cytology slide review, original histopathology report, and histopathology slide review was determined for each lymph node. A subset of lymph nodes was subjected to immunohistochemistry (Melan-A) and additional histochemical stains/techniques (Prussian blue, bleach) to assist in differentiation of melanocytes and melanophages. Agreement ranged from slight to fair for each of the variables evaluated with weighted kappa (κ w ) or kappa (κ) analysis (original cytology vs cytology review κ w = 0.24; original cytology vs original histopathology κ w = 0.007; original cytology vs histopathology review κ w = 0.23; cytology review vs original histopathology κ w = 0.008; cytology review vs histopathology review κ w = 0.006; and original histopathology vs histopathology review κ = 0.18). The diagnoses (metastatic, equivocal, or negative for metastasis) of the original report and slide review for both cytology and histopathology were not significantly correlated with survival in this population of patients. Overall, agreement between cytology and histopathology was poor even with a single clinical or anatomic pathologist performing slide review. Consensus between routine cytology and histopathology for staging of lymph nodes in patients with melanocytic neoplasms is poor and does not correlate with survival.
International Nuclear Information System (INIS)
Shirley, S. H.; Kusewitt, D. F.; Grimm, E. A.
2012-01-01
Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR) component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete pro inflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce pro inflammatory mediators and that Slug is important in this process. Micro array studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of pro inflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.
Catalytic enantioselective alkene aminohalogenation/cyclization involving atom transfer.
Bovino, Michael T; Chemler, Sherry R
2012-04-16
Problem solved: the title reaction was used for the synthesis of chiral 2-bromo, chloro, and iodomethyl indolines and 2-iodomethyl pyrrolidines. Stereocenter formation is believed to occur by enantioselective cis aminocupration and C-X bond formation is believed to occur by atom transfer. The ultility of the products as versatile synthetic intermediates was demonstrated, as was a radical cascade cyclization sequence. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
International Nuclear Information System (INIS)
Knapp, F. F. Jr.
2005-01-01
Full text: The increasing use of unsealed radioactive targeting agents for cancer treatment requires the routine availability of cost-effective radioisotopes. Rhenium-188 (Re-188; half-life 16.9 hours) is a high-energy beta-emitter (E max 2.12 MeV), readily available no- max carrier-added from the alumina-based tungsten-188 (half-life 69 days)/rhenium-188 generator system. Rhenium-188 also emits a 155 keV (15%) gamma photon, permitting gamma camera imaging for biodistribution and dosimetry evaluation. The versatile chemistry of rhenium allows attachment to a wide variety of targeting molecules for Re-188 applications in nuclear oncology for both palliative metastatic treatment and targeted tumor therapy - radionuclide synovectomy, and coronary restenosis therapy. The long parent half-life and consistent performance provide an indefinite generator shelf-life of several months with high Re-188 elution yields (75-85 %) and consistently low W-188 parent breakthrough ( -6 ). Simple post-elution concentration methods have been developed which provide very high specific volume solution of Re-188 for radiolabeling (> 700 mCi/mL saline/1 Ci generator). Over 60 physician-sponsored clinical trials are currently in progress worldwide with applications in nuclear medicine, nuclear oncology and interventional cardiology. A variety of Re-188-labeled therapeutic radiopharmaceuticals and devices are being developed for clinical trials currently in progress for treatment of both benign and metastatic oncological disorders. Palliation of metastatic bone pain with Re-188-HEDP - prepared from a simple 'kit' - has been demonstrated as a cost-effective alternative to similar agents. Recent studies have in fact demonstrated the enhancement of progression-free interval and survival time by repeated Re-188-HEDP injections to patients with metastatic disease from prostate cancer. The use of the Re-188-labeled antiNCA95 (CD66) antibody in conjunction with external beam irradiation is an
Synthesis of heterocyclic compounds through palladium-catalyzed C-H cyclization processes.
Inamoto, Kiyofumi
2013-01-01
Herein, we describe our development of synthetic methods for heterocyclic compounds based on the palladium-catalyzed carbon-hydrogen bond (C-H) functionalization/intramolecular carbon-heteroatom (nitrogen or sulfur) bond formation process. By this C-H cyclization method, we efficiently prepared various N-heterocycles, including indazoles, indoles, and 2-quinolinones, as well as S-heterocycles such as benzothiazoles and benzo[b]thiophenes. Yields are typically good to high and good functional-group tolerance is observed for each process, thereby indicating that the method provides a novel, highly applicable synthetic route to the abovementioned biologically important heterocyclic frameworks. As an application of this approach, an auto-tandem-type, one-pot process involving the oxidative Heck reaction and subsequent C-H cyclization using cinnamamides and arylboronic acids as starting materials in the presence of a palladium catalyst was also developed for the rapid construction of the 2-quinolinone nucleus.
International Nuclear Information System (INIS)
Sedlmaier, Angela; Wernert, Nicolas; Gallitzendörfer, Rainer; Abouzied, Mekky M; Gieselmann, Volkmar; Franken, Sebastian
2011-01-01
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
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.
Effect of deformation and annealing on mechanical properties of nickel-rhenium alloys
International Nuclear Information System (INIS)
Mashkova, V.M.
1978-01-01
Studied have been the mechanical properties of nickel-rhenium alloys, depending on the extent of deformation and heat treatment leading to softening. The mechanical properties of the alloys have been estimated by the results of the tensile tests of wire samples. The softening of the alloy at different temperatures is judged about by the variation in hardness. The results of the study indicate that the most abrupt reduction in the hardness of the cold-hardened metal occurs at 900-1,000 deg C and the hold-time of 1 min. Increase in the hold-time at such temperature almost does not reduce the hardness. It is established that in order to soften nickel-rhenium alloys in the process of the cold-deformation at brief annealings in the air the hold-time should not exceed 5 min at 800-900 deg C
Highvalent and organometallic technetium and rhenium compounds
International Nuclear Information System (INIS)
Oehlke, Elisabeth
2010-01-01
Diagnostic methods in nuclear medicine allow a detailed description of morphological organ structures and their function. The beta emitting isotope Tc-99 has optimal physical properties (140 keV gamma rays, half-life 6 h) and is therefore used for radiopharmaceuticals. The thesis is concerned with the search for new technetium complexes and their reproducible production. The (TcO3) core is of main interest. The second part of the thesis deals with organometallic technetium and rhenium complexes with carbonyl ligands and N-heterocyclic carbenes that show stability in aerobic aqueous solutions.
Heterocycles by Transition Metals Catalyzed Intramolecular Cyclization of Acetylene Compounds
International Nuclear Information System (INIS)
Vizer, S.A.; Yerzhanov, K.B.; Dedeshko, E.C.
2003-01-01
Review shows the new strategies in the synthesis of heterocycles, having nitrogen, oxygen and sulfur atoms, via transition metals catalyzed intramolecular cyclization of acetylenic compounds on the data published at the last 30 years, Unsaturated heterocyclic compounds (pyrroles and pyrroline, furans, dihydro furans and benzofurans, indoles and iso-indoles, isoquinolines and isoquinolinones, aurones, iso coumarins and oxazolinone, lactams and lactones with various substitutes in heterocycles) are formed by transition metals, those salts [PdCl 2 , Pd(OAc) 2 , HgCl 2 , Hg(OAc) 2 , Hg(OCOCF 3 ) 2 , AuCl 3 ·2H 2 O, NaAuCl 4 ·2H 2 O, CuI, CuCl], oxides (HgO) and complexes [Pd(OAc) 2 (PPh 3 )2, Pd(PPh 3 ) 4 , PdCl 2 (MeCN) 2 , Pd(OAc ) 2 /TPPTS] catalyzed intramolecular cyclization of acetylenic amines, amides, ethers, alcohols, acids, ketones and βdiketones. More complex hetero polycyclic systems typical for natural alkaloids can to obtain similar. Proposed mechanisms of pyrroles, isoquinolines, iso indoles and indoles, benzofurans and iso coumarins, thiazolopyrimidinones formation are considered. (author)
Giant Congenital Melanocytic Nevus (GCMN - A New Hope for Targeted Therapy?
Directory of Open Access Journals (Sweden)
Georgi Tchernev
2017-07-01
Full Text Available We present a 6-month-old male patient, who was consulted with dermatologist by his parents, because of a pigmented lesion, present since birth, covering almost the all skin of the back and buttocks. A sharply bordered, unequally coloured congenital pigmented nevus, measuring approximately 21 cm in diameter was observed in the whole body skin examination. The lesion was affecting the lower 2/3 of the skin of the back and the top half of the gluteus area, extending to the lateral part of the tors, forward the abdomen and the upper lateral part of the hips, composed by multiple darker-pigmented nests and several lighter areas, with single depigmented zones, hairy surface, irregularly infiltrated on palpation. Congenital melanocytic nevi are presented in approximately 1% of newborns, while giant congenital melanocytic nevi (GCMN are the most uncommon subtype of them; with occurrence rate 1 in 50,000 births. They affect 2% of a total body surface or presenting in a diameter larger than 20 cm in older children. Although not common, the possible malignant transformation remains one of the most important considerations related to them, as the related lifetime risk of melanoma is 4% to 10%. Treatment recommendations include non-surgical methods as dermabrasion only within the first two weeks of life, for prevention the possible melanocytic deeper migration, while serial surgical excisions or tissue expanders could be useful treatment tool even in later stages. Nevertheless, cosmetic result is not always satisfactory, and the risk of malignant changes remains, in cases of previous melanocytic migration in deeper layer. Recent article suggests the potential role in the treatment of GCMN with NRAS inhibitor trametinib, approved for treatment of advanced melanoma, associated with underlying NRAS mutations. Although promising, the drug could be useful in paediatric patients, only with associated NRAS gene mutation. It is still unclear whether it could be
Asymmetry and irregularity border as discrimination factor between melanocytic lesions
Sbrissa, David; Pratavieira, Sebastião.; Salvio, Ana Gabriela; Kurachi, Cristina; Bagnato, Vanderlei Salvadori; Costa, Luciano Da Fontoura; Travieso, Gonzalo
2015-06-01
Image processing tools have been widely used in systems supporting medical diagnosis. The use of mobile devices for the diagnosis of melanoma can assist doctors and improve their diagnosis of a melanocytic lesion. This study proposes a method of image analysis for melanoma discrimination from other types of melanocytic lesions, such as regular and atypical nevi. The process is based on extracting features related with asymmetry and border irregularity. It were collected 104 images, from medical database of two years. The images were obtained with standard digital cameras without lighting and scale control. Metrics relating to the characteristics of shape, asymmetry and curvature of the contour were extracted from segmented images. Linear Discriminant Analysis was performed for dimensionality reduction and data visualization. Segmentation results showed good efficiency in the process, with approximately 88:5% accuracy. Validation results presents sensibility and specificity 85% and 70% for melanoma detection, respectively.
International Nuclear Information System (INIS)
Wang Xiaolin; Fu Yibei; Liu Yinong; Xiong Zonghua; Hao Fanhua
1996-01-01
The extraction behaviour of rubidium and rhenium with 18-crown-6 (18C6) and benzo-15-crown-5 (B15C5) in nitrobenzene from picric acid or potassium hydroxide solution are studied and methods for separation and determination are developed. The molar ratio of 18C6 to Rb and B15C5 to Re in the extracted species is probably 2:1. Rubidium and rhenium in rock samples are satisfactorily determined by neutron activation method
Malignant melanoma arising in congenital melanocytic nevi: clinical and dermoscopic challenges
Directory of Open Access Journals (Sweden)
Fatma Pelin Cengiz
2017-01-01
Full Text Available Congenital melanocytic nevi (CMN are visible pigmented lesions in the skin that are present at birth. CMN are benign malformations resulting from defective development of melanocyte precursors in the embryo. Six MMs from six patients were analyzed by clinical and dermoscopic examination. Of the patients, 33.3% were female (N = 2 and 66.6% were male (N = 4. Of the MMs, four (66.6% were superficial spreading MM and two (33.3 % were in situ MM. A reticular pattern was present in the MMs of three patients (50%, a homogeneous pattern was present in the other patients (50% at the base of the MMs. Superficial spreading melanomas and in situ melanomas with atypical dots and globules and a blue-white veil were the most common dermoscopic features of MMs found in CMN.
Griewank, Klaus; Koelsche, Christian; van de Nes, Johannes A P; Schrimpf, Daniel; Gessi, Marco; Möller, Inga; Sucker, Antje; Scolyer, Richard A; Buckland, Michael E; Murali, Rajmohan; Pietsch, Torsten; von Deimling, Andreas; Schadendorf, Dirk
2018-06-11
In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria can be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis. Targeted next-generation-sequencing, array-based genome-wide methylation analysis and BAP1 immunohistochemistry was performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, incl. 47 primary tumors of the central nervous system, 16 uveal melanomas. 13 cutaneous melanoma metastasis and 2 blue nevus-like melanomas. Gene mutation, DNA-methylation and copy-number profiles were correlated with clinicopathological features. Combining mutation, copy-number and DNA-methylation profiles clearly distinguished cutaneous melanoma metastases from other melanocytic tumors. Primary leptomeningeal melanocytic tumors, uveal melanomas and blue nevus-like melanoma showed common DNA-methylation, copy-number alteration and gene mutation signatures. Notably, tumors demonstrating chromosome 3 monosomy and BAP1 alterations formed a homogeneous subset within this group. Integrated molecular profiling aids in distinguishing primary from metastatic melanocytic tumors of the central nervous system. Primary leptomeningeal melanocytic tumors, uveal melanoma and blue nevus-like melanoma share molecular similarity with chromosome 3 and BAP1 alterations markers of poor prognosis. Copyright ©2018, American Association for Cancer Research.
DEFF Research Database (Denmark)
Fenger, M; Hilsted, L
1988-01-01
The effect of ascorbic acid depletion on the amidation of alphamelanocyte stimulating hormone (alpha MSH) was studied in vivo in guinea pig pituitary. After four weeks, the concentration of ascorbic acid was 1.20 +/- 0.11 mumol/g tissue (mean +/- SD) in the pituitary and 0.34 +/- 0.07 mumol......-39) immunoreactivity was observed in the depleted guinea pigs. Gel chromatography and reversed-phase high-performance luquid chromatography showed that the alpha MSH and ACTH (1-14) immunoreactivity was of low molecular weight and partly mono- or diacetylated. Depletion of ascorbic acid had no influence on the degree...... of acetylation of alpha MSH and ACTH (1-14). It is concluded that depletion of ascorbic acid reduces the in vivo amidation of ACTH (1-14) in the guinea pig pituitary....
Duan, Yeqing; Liu, Yuxia; Bi, Siwei; Ling, Baoping; Jiang, Yuan-Ye; Liu, Peng
2016-10-07
Gold-catalyzed cyclization of 2-alkynyl-N-propargylanilines provides a step-economic method for the construction of three-dimensional indolines. In this article, the M06 functional of density functional theory was employed to gain deeper insights into the reaction mechanism and the associated intriguing experimental observations. The reaction was found to first undergo Au(I)-induced cyclization to form an indole intermediate, 1,3-propargyl migration, and substitution with the substrate 2-alkynyl-N-propargylaniline (R1) to generate the intermediate product P1, an allene species. Subsequently, Au(I)-catalyzed conversion of P1 into the final product P2, an indoline compound, occurs first through direct cyclization rather than via the previously proposed four-membered carbocycle intermediate. Thereafter, water-assisted oxygen heterocycle formation and proton transfer generate the final product. The calculated activation free energies indicate that P1 formation is 5.9 times slower than P2 formation, in accordance with the fact that P1 formation is rate-limiting. Futhermore, the intriguing experimental phenomenon that P2 can be accessed only after almost all the substrate R1 converts to P1 although P1 formation is rate-limiting was rationalized by employing an energetic span model. We found the initial facile cyclization to form a highly stable indole intermediate in the formation of P1 is the key to the intriguing experimental phenomenon.
Femtosecond Fluorescence and Intersystem Crossing in Rhenium(I) Carbonyl-Bipyridine Complexes
Czech Academy of Sciences Publication Activity Database
Cannizzo, A.; Blanco-Rodríguez, A. M.; Nahhas, A. E.; Šebera, Jakub; Záliš, Stanislav; Vlček, Antonín; Chergui, M.
2008-01-01
Roč. 130, č. 28 (2008), s. 8967-8974 ISSN 0002-7863 R&D Projects: GA MŠk 1P05OC068 Institutional research plan: CEZ:AV0Z40400503 Keywords : rhenium(I) * carbonyl-bipyridine * intersystem crossing Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 8.091, year: 2008
Molecular Engineering of Technetium and Rhenium Based Radiopharmaceuticals
International Nuclear Information System (INIS)
Zubieta, J.
2003-01-01
The research was based on the observation that despite the extraordinarily rich coordination chemistry of technetium and rhenium and several notable successes in reagent design, the extensive investigations by numerous research groups on a variety of N 2 S 2 and N 3 S donor type ligands and on HYNIC have revealed that the chemistries of these ligands with Tc and Re are rather complex, giving rise to considerable difficulties in the development of reliable procedures for the development of radiopharmaceutical reagents
Rhenium(V) complexing with benzimidazole in acidic media
International Nuclear Information System (INIS)
Zakaeva, R.Sh.; Gagieva, S.Ch.; Kaloev, N.I.; Bukov, N.N.; Panyushkin, V.T.
2003-01-01
Coordination compounds of rhenium(V) with 1H-benzimidazole (L) separated from acid media: (HL) 2 [ReOX 5 ](H 2 O) n and [ReOL x X y (H 2 O) z ](H 2 O) n (HL and L - protonated and deprotonated forms of benzimidazole; X = Cl - , Br - ) were studied by the methods of IR spectroscopy, 1 H NMR spectroscopy and thermal gravimetric analysis. Methods of ligand coordination in the complexes are discussed on the basis of data obtained [ru
International Nuclear Information System (INIS)
Wilkins, S.C.; Sepold, L.K.
1985-01-01
The thermocouples described in this report are zircaloy/tantalum-sheathed and molybdenum/rhenium alloy-sheathed instruments intended for fuel rod cladding and fuel centerline temperature measurements, respectively. Both types incorporate beryllium oxide insulation and tungsten/rhenium alloy thermoelements. These thermocouples, operated at temperatures of 2000 0 C and above, were developed for use in the internationally sponsored Severe Fuel Damage test series in the Power Burst Facility. The fabrication steps for both thermocouple types are described in detail. A laser-welding attachment technique for the cladding-type thermocouple is presented, and experience with alternate materials for cladding and fuel therocouples is discussed
Cyclization of lapachol induced by thallium salts
International Nuclear Information System (INIS)
Ribeiro, Carlos Magno R.; Souza, Pablo P. de; Ferreira, Leticia L.D.M.; Pinto, Lia A.; Almeida, Leonardo S. de; Jesus, Janaina G. de
2008-01-01
This work describes the cyclization of lapachol (1) induced by thallium triacetate (TTA) and thallium trinitrate (TTN) in several solvents using magnetic stirring and under microwave irradiation. α-Xyloidone (2) - dehydro-a-lapachone - was obtained as the main product in these reactions in 20 - 75% yield. However, rhinacanthin-A (4) was isolated as main product in a 40% yield, using TTA and acetic anhydride:water (1:1) as solvent, and dehydroiso- a-lapachone (3) in 21% yield, using TTA and dichloromethane as solvent. The reaction time decreased drastically under microwave conditions, but the yields of these reactions were not the expected. (author)
Toosi, Siavash; Orlow, Seth J.; Manga, Prashiela
2012-01-01
Vitiligo is characterized by depigmented skin patches due to loss of epidermal melanocytes. Oxidative stress may play a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol (4-TBP) and monobenzyl ether of hydroquinone (MBEH), known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box binding protein 1 (XBP1), are increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators interleukin-6 (IL6) and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while over-expression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity. PMID:22696056
Toosi, Siavash; Orlow, Seth J; Manga, Prashiela
2012-11-01
Vitiligo is characterized by depigmented skin patches caused by loss of epidermal melanocytes. Oxidative stress may have a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study, we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol and monobenzyl ether of hydroquinone, known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box-binding protein 1 (XBP1), is increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators IL6 and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while overexpression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity.
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.
Energy Technology Data Exchange (ETDEWEB)
Gwon, Sung Hyuk; Kim, Sunggon [Kyonggi Univ., Suwon (Korea, Republic of)
2012-04-15
We described the cascade Michael.cyclization reaction of o-hydroxycinnamaldehydes with diethyl α-bromomalonate promoted by potassium carbonate. The reactions provided functionalized 2,3-dihydrobenzofurans in good yields for a variety of o-hydroxyaromatic α,β-unsaturated aldehydes. Current work focuses on expanding the scope of this reaction to other substrates such as sulfur yields, and on developing an efficient catalytic asymmetric variant. 2,3-Dihydrobenzofurans are found in numerous biologically active natural products and synthetic compounds. These are an attractive type of oxygenated compound because their basic core skeleton is present in neolignans, pterocarpans, and synthetic drugs used in the treatment of pulmonary hypertension, atherosclerotic peripheral arterial disease, and central nervous system trauma and ischemia. Owing to the importance of their structures, numerous synthetic methods for 2,3-dihydrobenzofurans have been developed, primarily: radical cyclizations, Lewis acid promoted reactions, anionic cyclizations, and transition-metal catalyzed processes. However, these methods cannot be generalized as much as is desirable, and they yielded poor chemo- and/or stereoselectivities. Hence, the development of an efficient enantioselective synthetic method for obtaining 2,3-dihydrobenzofuran scaffolds attracted our attention.
International Nuclear Information System (INIS)
Gwon, Sung Hyuk; Kim, Sunggon
2012-01-01
We described the cascade Michael.cyclization reaction of o-hydroxycinnamaldehydes with diethyl α-bromomalonate promoted by potassium carbonate. The reactions provided functionalized 2,3-dihydrobenzofurans in good yields for a variety of o-hydroxyaromatic α,β-unsaturated aldehydes. Current work focuses on expanding the scope of this reaction to other substrates such as sulfur yields, and on developing an efficient catalytic asymmetric variant. 2,3-Dihydrobenzofurans are found in numerous biologically active natural products and synthetic compounds. These are an attractive type of oxygenated compound because their basic core skeleton is present in neolignans, pterocarpans, and synthetic drugs used in the treatment of pulmonary hypertension, atherosclerotic peripheral arterial disease, and central nervous system trauma and ischemia. Owing to the importance of their structures, numerous synthetic methods for 2,3-dihydrobenzofurans have been developed, primarily: radical cyclizations, Lewis acid promoted reactions, anionic cyclizations, and transition-metal catalyzed processes. However, these methods cannot be generalized as much as is desirable, and they yielded poor chemo- and/or stereoselectivities. Hence, the development of an efficient enantioselective synthetic method for obtaining 2,3-dihydrobenzofuran scaffolds attracted our attention
Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung
2016-01-01
The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.
Directory of Open Access Journals (Sweden)
Hyunjung Choi
Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.
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...
Madankumar, Reshmi; Gumaste, Priyanka V; Martires, Kathryn; Schaffer, Panta R; Choudhary, Sonal; Falto-Aizpurua, Leyre; Arora, Harleen; Kallis, Penelope J; Patel, Shailee; Damanpour, Shadi; Sanchez, Margaret I; Yin, Natalie; Chan, Aegean; Sanchez, Miguel; Polsky, David; Kanavy, Holly; Grichnik, James M; Stein, Jennifer A
2016-04-01
Acral lentiginous melanoma has increased mortality compared with other melanoma subtypes and disproportionately affects ethnic minorities. Acral melanocytic lesions have not been well studied in diverse populations of the United States. We sought to assess the prevalence, awareness, and dermoscopic patterns of acral melanocytic lesions in skin-of-color and non-Hispanic white patients. We prospectively examined the palms and soles of 1052 patients presenting to dermatology clinics in New York, NY, and Miami, FL, from October 2013 to April 2015. Acral melanocytic lesions were observed in 36% of our cohort. Skin-of-color patients were more likely to have acral melanocytic lesions than non-Hispanic white patients (P < .01). Acral melanocytic lesions correlated with increased mole counts, particularly on non-Hispanic white patients. The majority of lesions demonstrated benign dermoscopic patterns. We observed 2 lesions with the parallel ridge pattern in our cohort, both found to be atypical nevi on biopsy specimen. Patients often lacked awareness of the presence of their lesions. Interobserver variability in assessing dermoscopic patterns is a limitation. Melanocytic lesions of the palms and soles are common, particularly in a cohort of multiple ethnicities from the United States. Dermoscopy of acral lesions is an important clinical tool for diagnosis and management of these lesions. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
A case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome.
Chen, Y; Zhang, Y; Wang, L; Yang, X
2017-01-01
To date, cervical carcinoma complicated with Cushing's syndrome were all diagnosed as small cell carcinoma histo- logically, but not adenosquamous carcinoma. Here the authors present the diagnosis, management, and prognosis of a case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome. A 28-year-old woman was admitted with the chief complaint of post-coital bleeding for one month. Gynecological examination revealed a nodular yellowish-pigmented vegetation (6x5 cm) on the cervix. Laboratory findings proved the diagnosis of Cushing's syndrome. Histopathological diagnosis showed the adenosquamous carcinoma with melanoma differentiation. Immunohistochemical stainings for melanoma A and anti- adrenocorticotropic hormone (ACTH) were positive in the majority of the tumor cells, which indicated that this melanocytic cervical carcinoma lesion was the source of ectopic ACTH production resulting in Cushing's syndrome. This is a unique case of a rare type of cervical carcinoma.
Rhenium(V) complexes with sulfur-containing amino acids
International Nuclear Information System (INIS)
Gagieva, S.Ch.; Tautieva, M.A.; Tsaloev, A.T.; Galimov, Yu.B.; Gagieva, L.Ch.; Belyaeva, T.N.
2007-01-01
Rhenium(V) complexes with 2-amino-4-(methylthio)butanoic acid (methionine, Met) and 2-amino-3-sulfopropionic acid (cysteine, Cys) have been synthesized. Depending on the initial reagent ratio, the resulting complexes contain one or two ligand molecules. On heating the compounds with one amino acid molecule, two hydrogen halide molecules are removed at 128-132 deg C to form a molecular complex. The composition, structure, and thermal stability of the complexes have been studied by elemental analysis, conductometry, IR spectroscopy, NMR, and mass spectrometry [ru
An Intramolecular Heck reaction that Prefers a 5-endo- to a 6-exo-trig Cyclization Pathway
DEFF Research Database (Denmark)
Vital, Paulo; Norrby, Per-Ola; Tanner, David Ackland
2006-01-01
A regioselective aromatic Claisen rearrangement was used to prepare 17a, the precursor of triflate 17e. The intramolecular Heck reaction of 17e is promoted only by bidentate phosphine ligands, giving exclusively and in excellent yield 20, the product of a 5-endo-trig cyclization, despite the poss......A regioselective aromatic Claisen rearrangement was used to prepare 17a, the precursor of triflate 17e. The intramolecular Heck reaction of 17e is promoted only by bidentate phosphine ligands, giving exclusively and in excellent yield 20, the product of a 5-endo-trig cyclization, despite...
THERMIONIC EMISSION ENHANCEMENT FROM CESIUM COATED RHENIUM IN ELECTRIC FIELDS
Energy Technology Data Exchange (ETDEWEB)
de Steese, J. G.; Zollweg, R. J.
1963-04-15
The plasma-anode technique was used to observe anomalously high thermionic emission from a rhenium surface with small cesium coverage, where the work function of the composite surface is greater than the ionization potential of cesium. Data suggest that emission enhancement is caused by increased cesium coverage because of cesiumion trapping near the emitter surface under the influence of an ion-rich sheath. (auth)
Poorman, Kelsey; Borst, Luke; Moroff, Scott; Roy, Siddharth; Labelle, Philippe; Motsinger-Reif, Alison; Breen, Matthew
2014-01-01
Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address t...
77 FR 18831 - Government-Owned Inventions; Availability for Licensing
2012-03-28
... Technology: Inflammatory processes associated with the over-production of tumor necrosis-alpha (TNF-[alpha... treat insulin resistance. Insulin resistance is associated with reduced gene expression and production... and at low levels in normal melanocytes. MART-1 is a melanocyte differentiation antigen found on the...
Czech Academy of Sciences Publication Activity Database
Holan, Martin; Pohl, Radek; Císarová, I.; Jahn, Ullrich
2012-01-01
Roč. 106, - (2012), s1298-s1298 ISSN 0009-2770. [EuCheMS Chemistry Congress /4./. 26.08.2012-30.08.2012, Prague] Institutional research plan: CEZ:AV0Z40550506 Keywords : cyclization * diastereoselectivity * Michael addiction * radical reactions * domino reactions Subject RIV: CC - Organic Chemistry
Czech Academy of Sciences Publication Activity Database
Holan, Martin; Pohl, Radek; Císařová, I.; Klepetářová, Blanka; Jones, P. G.; Jahn, Ullrich
2015-01-01
Roč. 21, č. 27 (2015), s. 9877-9888 ISSN 0947-6539 R&D Projects: GA ČR GA13-40188S Institutional support: RVO:61388963 Keywords : cyclization * domino reactions * electron transfer * Michael addition * radical reactions Subject RIV: CC - Organic Chemistry Impact factor: 5.771, year: 2015
Flook, Adam M.; Yang, Jianquan; Miao, Yubin
2013-01-01
The purpose of this study was to examine the melanoma targeting and imaging properties of two new 99mTc-labeled Arg-X-Asp-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg11)CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg11)CCMSH peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg11)CCMSH and RVD-Lys-(Arg11)CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH displayed high melanoma uptake. 99mTc-RTD-Lys-(Arg11)CCMSH exhibited the peak tumor uptake of 18.77 ± 5.13% ID/g at 2 h post-injection, whereas 99mTc-RVD-Lys-(Arg11)CCMSH reached the peak tumor uptake of 19.63 ± 4.68% ID/g at 4 h post-injection. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h post-injection. The renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h post-injection, respectively. The melanoma lesions were clearly visualized by SPECT/CT using either 99mTc-RTD-Lys-(Arg11)CCMSH or 99mTc-RVD-Lys-(Arg11)CCMSH as an imaging probe at 2 h post-injection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH. However, high renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH need to be reduced to facilitate their future applications. PMID:23885640
Intracranial melanocytic meningeal tumours and melanosis oculi: case report and literature review
International Nuclear Information System (INIS)
Doglietto, Francesco; Colosimo, Cesare; Lauriola, Libero; Balducci, Mario; De Bonis, Pasquale; Montano, Nicola; Zadeh, Gelareh; Maira, Giulio; Pallini, Roberto
2012-01-01
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
Lattice strains in gold and rhenium under nonhydrostatic compression to 37 GPa
International Nuclear Information System (INIS)
Duffy, Thomas S.; Shen, Guoyin; Heinz, Dion L.; Shu, Jinfu; Ma, Yanzhang; Mao, Ho-Kwang; Hemley, Russell J.; Singh, Anil K.
1999-01-01
Using energy-dispersive x-ray diffraction techniques together with the theory describing lattice strains under nonhydrostatic compression, the behavior of a layered sample of gold and rhenium has been studied at pressures of 14-37 GPa. For gold, the uniaxial stress component t is consistent with earlier studies and can be described by t=0.06+0.015P where P is the pressure in GPa. The estimated single-crystal elastic moduli are in reasonable agreement with trends based on extrapolated low-pressure data. The degree of elastic anisotropy increases as α, the parameter which characterizes stress-strain continuity across grain boundaries, is reduced from 1.0 to 0.5. For rhenium, the apparent equation of state has been shown to be strongly influenced by nonhydrostatic compression, as evidenced by its dependence on the angle ψ between the diffracting plane normal and the stress axis. The bulk modulus obtained by inversion of nonhydrostatic compression data can differ by nearly a factor of 2 at angles of 0 degree sign and 90 degree sign . On the other hand, by a proper choice of ψ, d spacings corresponding to quasihydrostatic compression can be obtained from data obtained under highly nonhydrostatic conditions. The uniaxial stress in rhenium over the pressure range from 14-37 GPa can be described by t=2.5+0.09P. The large discrepancy between x-ray elastic moduli and ultrasonic data and theoretical calculations indicates that additional factors such as texturing or orientation dependence of t need to be incorporated to more fully describe the strain distribution in hexagonal-close-packed metals. (c) 1999 The American Physical Society
Recent Advances in Substrate-Controlled Asymmetric Cyclization for Natural Product Synthesis
Directory of Open Access Journals (Sweden)
Jeyun Jo
2017-06-01
Full Text Available Asymmetric synthesis of naturally occurring diverse ring systems is an ongoing and challenging research topic. A large variety of remarkable reactions utilizing chiral substrates, auxiliaries, reagents, and catalysts have been intensively investigated. This review specifically describes recent advances in successful asymmetric cyclization reactions to generate cyclic architectures of various natural products in a substrate-controlled manner.
Collet, Jurriën W.; Ackermans, Kelly; Lambregts, Jeffrey; Maes, Bert U.W.; Orru, Romano V.A.; Ruijter, Eelco
2018-01-01
We developed a one-pot, two-stage synthetic route to substituted 4-aminoquinolines involving an imidoylative Sonogashira coupling followed by acid-mediated cyclization. This three-component reaction affords pharmaceutically valuable 4-aminoquinolines in a one-pot procedure from readily available
International Nuclear Information System (INIS)
Wedding, Jason L.; Harris, Hugh H.; Bader, Christie A.; Plush, Sally E.; Mak, Rachel
2016-01-01
Optical fluorescence microscopy was used in conjunction with X-ray fluorescence microscopy to monitor the stability and intracellular distribution of the luminescent rhenium(I) complex fac-[Re(CO) 3 (phen)L], where phen = 1,10-phenathroline and L = 5-(4-iodophenyl)tetrazolato, in 22Rv1 cells. The rhenium complex showed no signs of ancillary ligand dissociation, a conclusion based on data obtained via X-ray fluorescence imaging aligning iodine and rhenium distributions. A diffuse reticular localisation was detected for the complex, in the nuclear/perinuclear region of cells, by either optical or X-ray fluorescence techniques. Furthermore, X-ray fluorescence also showed that the Re-I complex disrupted the homeostasis of some biologically relevant elements, such as chlorine, potassium and zinc.
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. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Hydroxyl-substituted ladder polyethers via selective tandem epoxidation/cyclization sequence.
Czabaniuk, Lara C; Jamison, Timothy F
2015-02-20
A new and highly selective method for the synthesis of hydroxyl-substituted tetrahydropyrans is described. This method utilizes titanium(IV) isopropoxide and diethyl tartrate to perform a diastereoselective epoxidation followed by in situ epoxide activation and highly selective endo-cyclization to form the desired tetrahydropyran ring. The HIJ ring fragment of the marine ladder polyether yessotoxin was synthesized using this two-stage tactic that proceeds with high efficiency and excellent regioselectivity.
Behandling og håndtering af kongenitte melanocytære naevi
DEFF Research Database (Denmark)
Bahn, Kamille-Amalie; Hædersdal, Merete; Schmidt, Grethe
2016-01-01
Congenital melanocytic naevi (CMN) appear in approximately 2.6% of Caucasians. There is a major demand for treatment but no vital indication. Laser therapy, curettage and excision are available treatment modalities, but there is no ideal treatment with documented long-term effect and without side...
Giant melanocytic nevus with malignant melanoma: a rare disorder in a black African child.
Katibi, Oludolapo Sherifat; Ogunbiyi, Adebola; Brown, Biobele Jotham; Adeyemi, Oyedeji Oladele
2014-10-01
Giant congenital melanocytic nevus (GCMN) is rare in babies of African descent. Unfortunately, it has an increased potential for malignant transformation. A 3-year-old female child presented with a 6-month history of multiple nodules on an existing giant congenital melanocytic nevus and swelling in the right axilla of four weeks duration. Skin biopsy of the nodular skin lesions was in keeping with a metastatic malignant melanoma (Clark stage 4). She completed a full course of chemotherapy but subsequently died four months after presentation. Patients with large GCMN should be counseled and followed up appropriately to improve and prolong life. © 2014 The International Society of Dermatology.
International Nuclear Information System (INIS)
Delijewski, Marcin; Wrześniok, Dorota; Beberok, Artur; Rok, Jakub; Otręba, Michał; Buszman, Ewa
2016-01-01
Nicotine is a main compound of tobacco plants and may affect more than a billion people all over the world that are permanently exposed to nicotine from cigarettes, various forms of smoking cessation therapies, electronic cigarettes or second-hand smoke. It is known that nicotine forms complexes with melanin what may lead to accumulation of this alkaloid in tissues of living organisms containing the pigment. This may affect the viability of cells and process of melanin biosynthesis that takes place in melanocytes. Although UV radiation is known to be a particular inductor of melanin biosynthesis, its simultaneous effect with nicotine on this process as well as the viability of human cells containing melanin have not been assessed so far. The aim of this study was to examine the simultaneous impact of nicotine and UV radiation on viability and melanogenesis in cultured normal human melanocytes dark (HEMn-DP) and light (HEMn-LP) pigmented. Nicotine together with UV radiation induced concentration-dependent loss in melanocytes viability. The higher cell loss was observed in dark pigmented melanocytes in comparison to light pigmented cells. Simultaneous exposure of cells to nicotine and UV radiation also caused changes in melanization process in both tested cell lines. The data suggest that simultaneous exposure of melanocytes to nicotine and UV radiation up-regulates melanogenesis and affects cell viability. Observed processes are more pronounced in dark pigmented cells. - Highlights: • Nicotine and UVA induced concentration-dependent loss in melanocytes viability. • Nicotine and UVA modulated melanization process in melanocytes. • Changes in viability and melanization were more pronounced in dark pigmented cells.
Energy Technology Data Exchange (ETDEWEB)
Delijewski, Marcin; Wrześniok, Dorota; Beberok, Artur; Rok, Jakub; Otręba, Michał; Buszman, Ewa, E-mail: ebuszman@sum.edu.pl
2016-11-15
Nicotine is a main compound of tobacco plants and may affect more than a billion people all over the world that are permanently exposed to nicotine from cigarettes, various forms of smoking cessation therapies, electronic cigarettes or second-hand smoke. It is known that nicotine forms complexes with melanin what may lead to accumulation of this alkaloid in tissues of living organisms containing the pigment. This may affect the viability of cells and process of melanin biosynthesis that takes place in melanocytes. Although UV radiation is known to be a particular inductor of melanin biosynthesis, its simultaneous effect with nicotine on this process as well as the viability of human cells containing melanin have not been assessed so far. The aim of this study was to examine the simultaneous impact of nicotine and UV radiation on viability and melanogenesis in cultured normal human melanocytes dark (HEMn-DP) and light (HEMn-LP) pigmented. Nicotine together with UV radiation induced concentration-dependent loss in melanocytes viability. The higher cell loss was observed in dark pigmented melanocytes in comparison to light pigmented cells. Simultaneous exposure of cells to nicotine and UV radiation also caused changes in melanization process in both tested cell lines. The data suggest that simultaneous exposure of melanocytes to nicotine and UV radiation up-regulates melanogenesis and affects cell viability. Observed processes are more pronounced in dark pigmented cells. - Highlights: • Nicotine and UVA induced concentration-dependent loss in melanocytes viability. • Nicotine and UVA modulated melanization process in melanocytes. • Changes in viability and melanization were more pronounced in dark pigmented cells.
International Nuclear Information System (INIS)
Pal'chevskaya, T.A.; Bogutskaya, L.V.; Belousov, V.M.
1988-01-01
The effect of conditions of rhenium heptasulfide synthesis by thiosulfate method on its physicochemical and catalytic properties during hydrogenation of nitrobenzene and m-nitrobenzoic acid has been studied. It is shown that the maximum yield of m-aminobenzoic acid can be attained on insoluble sulfide rhenium contacts, containing excessive amount of sulfur (3.5 %). Under certain conditions of catalyst synthesis particles of Re 2 S 7 soluble in dimethylformamide are formed, which possess selectivity towards amine
Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes
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Tianzhi Chen
2016-09-01
Full Text Available To investigate whether ocular albinism type 1 (OA1 is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR, immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes’ pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor (MITF, tyrosinase (TYR, tyrosinase-related protein 1 (TRP1 and premelanosome protein (PMEL. However, the tyrosinase-related protein 2 (TRP2 level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1. Therefore, we propose that OA1 may
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Zalfa A. Abdel-Malek
2016-08-01
Full Text Available The membrane bound melanocortin 1 receptor (MC1R, and the endothelin B receptor (ENDBR are two G-protein coupled receptors that play important roles in constitutive regulation of melanocytes and their response to ultraviolet radiation (UVR, the main etiological factor for melanoma. The human MC1R is a Gs protein-coupled receptor, which is activated by its agonists α-melanocyte stimulating hormone (α-melanocortin; α-MSH and adrenocorticotropic hormone (ACTH. The ENDBR is a Gq coupled-receptor, which is activated by Endothelin (ET-3 during embryonic development, and ET-1 postnatally. Pigmentation and the DNA repair capacity are two major factors that determine the risk for melanoma. Activation of the MC1R by its agonists stimulates the synthesis of eumelanin, the dark brown photoprotective pigment. In vitro studies showed that α-MSH and ET-1 interact synergistically in the presence of basic fibroblast growth factor (bFGF to stimulate human melanocyte proliferation and melanogenesis, and to inhibit UVR-induced apoptosis. An important function of the MC1R is reduction of oxidative stress and activation of DNA repair pathways. The human MC1R is highly polymorphic, and MC1R variants, particularly those that cause loss of function of the expressed receptor, are associated with increased melanoma risk independently of pigmentation. These variants compromise the DNA repair and antioxidant capacities of human melanocytes. Recently, activation of ENDBR by ET-1 was reported to reduce the induction and enhance the repair of UVR-induced DNA photoproducts. We conclude that α-MSH and ET-1 and their cognate receptors MC1R and ENDBR reduce the risk for melanoma by maintaining genomic stability of melanocytes via modulating the DNA damage response to solar UVR. Elucidating the response of melanocytes to UVR should improve our understanding of the process of melanomagenesis, and lead to effective melanoma chemoprevention, as well as therapeutic strategies.
Schmidt, C O; Bouwmeester, H J; Bülow, N; König, W A
1999-04-15
The leaves of the composite Solidago canadensis (goldenrod) were shown to contain (-)-alpha-gurjunene synthase activity. This sesquiterpene is likely to be the precursor for cyclocolorenone, a sesquiterpene ketone present in high amounts in S. canadensis leaves. (-)-alpha-Gurjunene synthase was purified to apparent homogeneity (741-fold) by anion-exchange chromatography (on several matrices), dye ligand chromatography, hydroxylapatite chromatography, and gel filtration. Chromatography on a gel filtration matrix indicated a native molecular mass of 48 kDa, and SDS-PAGE showed the enzyme to be composed of one subunit with a denatured mass of 60 kDa. Its maximum activity was observed at pH 7.8 in the presence of 10 mM Mg2+ and the KM value for the substrate farnesyl diphosphate was 5.5 microM. Over a range of purification steps (-)-alpha-gurjunene and (+)-gamma-gurjunene synthase activities copurified. In addition, the product ratio of the enzyme activity under several different assay conditions was always 91% (-)-alpha-gurjunene and 9% (+)-gamma-gurjunene. This suggests that the formation of these two structurally related products is catalyzed by one enzyme. For further confirmation, we carried out a number of mechanistic studies with (-)-alpha-gurjunene synthase, in which an enzyme preparation was incubated with deuterated substrate analogues. Based on mass spectrometry analysis of the products formed, a cyclization mechanism was postulated which makes it plausible that the synthase catalyzes the formation of both sesquiterpenes. Copyright 1999 Academic Press.
(Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes
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
Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation
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Hastings, Courtney; Pluth, Michael; Bergman, Robert; Raymond, Kenneth
2010-03-29
A primary goal in the design and synthesis of molecular hosts has been the selective recognition and binding of a variety of guests using non-covalent interactions. Supramolecular catalysis, which is the application of such hosts towards catalysis, has much in common with many enzymatic reactions, chiefly the use of both spatially appropriate binding pockets and precisely oriented functional groups to recognize and activate specific substrate molecules. Although there are now many examples which demonstrate how selective encapsulation in a host cavity can enhance the reactivity of a bound guest, all have failed to reach the degree of increased reactivity typical of enzymes. We now report the catalysis of the Nazarov cyclization by a self-assembled coordination cage, a carbon-carbon bond-forming reaction which proceeds under mild, aqueous conditions. The acceleration in this system is over a million-fold, and represents the first example of supramolecular catalysis that achieves the level of rate enhancement comparable to that observed in several enzymes. We explain the unprecedented degree of rate increase as due to the combination of (a) preorganization of the encapsulated substrate molecule, (b) stabilization of the transition state of the cyclization by constrictive binding, and (c) increase in the basicity of the complexed alcohol functionality.
Larson, Allison R; Dresser, Karen A; Zhan, Qian; Lezcano, Cecilia; Woda, Bruce A; Yosufi, Benafsha; Thompson, John F; Scolyer, Richard A; Mihm, Martin C; Shi, Yujiang G; Murphy, George F; Lian, Christine Guo
2014-07-01
DNA methylation is the most well-studied epigenetic modification in cancer biology. 5-hydroxymethylcytosine is an epigenetic mark that can be converted from 5-methylcytosine by the ten-eleven translocation gene family. We recently reported the loss of 5-hydroxymethylcytosine in melanoma compared with benign nevi and suggested that loss of this epigenetic marker is correlated with tumor virulence based on its association with a worse prognosis. In this study, we further characterize the immunoreactivity patterns of 5-hydroxymethylcytosine in the full spectrum of melanocytic lesions to further validate the potential practical application of this epigenetic marker. One hundred and seventy-five cases were evaluated: 18 benign nevi, 20 dysplastic nevi (10 low-grade and 10 high-grade lesions), 10 atypical Spitz nevi, 20 borderline tumors, 5 melanomas arising within nevi, and 102 primary melanomas. Progressive loss of 5-hydroxymethylcytosine from benign dermal nevi to high-grade dysplastic nevi to borderline melanocytic neoplasms to melanoma was observed. In addition, an analysis of the relationship of nuclear diameter with 5-hydroxymethylcytosine staining intensity within lesional cells revealed a significant correlation between larger nuclear diameter and decreased levels of 5-hydroxymethylcytosine. Furthermore, borderline lesions uniquely exhibited a diverse spectrum of staining of each individual case. This study further substantiates the association of 5-hydroxymethylcytosine loss with dysplastic cytomorphologic features and tumor progression and supports the classification of borderline lesions as a biologically distinct category of melanocytic lesions.
International Nuclear Information System (INIS)
Liu Guozheng; Liu Boli
1995-01-01
Some bond length regularities in MO 6 , MO-4, MX 5 α and MX 4 αβ moieties of technetium and rhenium compounds are summarized and rationalized by cavity model. The chemical properties of technetium and rhenium are so similar that their corresponding complexes have almost the same configuration and M-X bond lengths when they are in cavity-controlled state. Technetium and Rhenium combine preferably with N, O, F, S, Cl and Br when they are in higher oxidation states (>3), but preferably with P, Se etc. when they are in lower oxidation states ( 4 αβ is approximately constant; (2) the average M-X bond length of MX 6 varies moderately with the oxidation state of M; (3) the bond length of M-X trans to M-α in MX 5 α has a linear relationship with the angle
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.; Abdel-Malek, Zalfa 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 that expression of 2 red hair variants abolished the response to α-melanocortin and its photoprotective effects, evidenced by lack of functional coupling of the receptor, and absence of reduction in ultraviolet radiation-induced hydrogen peroxide generation or enhancement of repair of DNA photoproducts, respectively. These variants had different heterozygous effects on receptor function. Microarray data confirmed the observed differences in responses of melanocytes with functional vs. nonfunctional receptor to α-melanocortin and ultraviolet radiation, and identified DNA repair and antioxidant genes that are modulated by α-melanocortin. Our findings highlight the molecular mechanisms by which the melanocortin 1 receptor genotype controls genomic stability of and the mutagenic effect of ultraviolet radiation on human melanocytes.—Kadekaro, A. L., Leachman, S., Kavanagh, R. J., Swope, V., Cassidy, P., Supp, D., Sartor, M., Schwemberger, S., Babcock, G., Wakamatsu, K., Ito, S., Koshoffer, A., Boissy, R. E., Manga, P., Sturm, R. A., Abdel-Malek, Z. A. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. PMID:20519635
Neutron activation determination of rhenium in mineral raw materials of complex composition
International Nuclear Information System (INIS)
Shiryaeva, M.B.; Lyubimova, L.N.; Salmin, Yu.P.; Ryumina, K.N.; Tatarkin, M.A.
1984-01-01
The method of neutron-activation rhenium determination in mineral raw material of complex composition is developed, according to which easily hydrolized elements: scandium, iron, lanthanum, ytterbium, protactinium, hafnium and partially ruthenium and osmium are isolated in the form of hydroxides after smelting of a sample, which has been previously irradiated in nuclear reactor (thermal neutron flux 1.2x10 13 n/cm 2 xs for 22 hr) with sodium peroxide and leaching of the melt by water. To separate Re from other interfering elements extraction of perrhenate-ion by methylethylketone from alkali solution is used. Interfering effect of gold is eliminated by its extraction with TBP 30% solution in toluence or benzene from 1 M HNO 3 . Activity of rhenium preparations, singled out from samples of comparison, is measured, using multichannel γ-spectrometer with Ge(Li)-coaxial detector of high resolution (approximately 2.0-2.2 keV over the line 122 keV 5+ Co). Relative standard deviation in Re content range 5x10 -7 -5x10 -2 % does not exceed 0.3
Lee, Seon Hwa; Kyung, Hyunsook; Yokota, Ryo; Goto, Takaaki; Oe, Tomoyuki
2015-01-20
The hydroxyl radical-mediated oxidation of peptides and proteins constitutes a large group of post-translational modifications that can result in structural and functional changes. These oxidations can lead to hydroxylation, sulfoxidation, or carbonylation of certain amino acid residues and cleavage of peptide bonds. In addition, hydroxyl radicals can convert the N-terminus of peptides to an α-ketoamide via abstraction of the N-terminal α-hydrogen and hydrolysis of the ketimine intermediate. In the present study, we identified N-terminal cyclization as a novel modification mediated by a hydroxyl radical. The reaction of angiotensin (Ang) II (DRVYIHPF) and the hydroxyl radical generated by the Cu(II)/ascorbic acid (AA) system or UV/hydrogen peroxide system produced N-terminal cyclized-Ang II (Ang C) and pyruvamide-Ang II (Ang P, CH3COCONH-RVYIHPF). The structure of Ang C was confirmed by mass spectrometry and comparison to an authentic standard. The subsequent incubation of isolated Ang P in the presence of Cu(II)/AA revealed that Ang P was the direct precursor of Ang C. The proposed mechanism involves the formation of a nitrogen-centered (aminyl) radical, which cyclizes to form a five-membered ring containing the alkoxy radical. The subsequent β-scission reaction of the alkoxyl radical results in the cleavage of the terminal CH3CO group. The initial aminyl radical can be stabilized by chelation to the Cu(II) ions. The affinity of Ang C toward the Ang II type 1 receptor was significantly lower than that of Ang II or Ang P. Ang C was not further metabolized by aminopeptidase A, which converts Ang II to Ang III. Hydroxyl radical-mediated N-terminal cyclization was also observed in other Ang peptides containing N-terminal alanine, arginine, valine, and amyloid β 1-11 (DAEFRHDSGYE).
DMEM enhances tyrosinase activity in B16 mouse melanoma cells and human melanocytes
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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.
Liquid kit for preparation of 188rhenium-etidronate
International Nuclear Information System (INIS)
Marczewski, Barbara; Dias, Carla Roberta; Moraes, Vanessa; Osso Junior, Joao Alberto
2005-01-01
The aim of this study was the preparation of a liquid kit for radiolabeling of 188 Re-HEDP (hydroxyethylidene diphosphonate). 188 Re was obtained from alumina based 188 W/ 188 Re generators. This paper reports the efficacy of a cold kit stored for more than two weeks, determined by the dependence of the radiolabeling yields of 188 Re-HEDP on the incubation time, reducing agent concentration, the effects of concentration of ligand, the p H of the reaction and the temperature. The cold kits showed a good stability when carrie-free rhenium-188 was added in the reaction mixture. (author)
Directory of Open Access Journals (Sweden)
Mao Lin
2014-01-01
Full Text Available Reduced or defective melanin skin pigmentation may cause many hypopigmentation disorders and increase the risk of damage to the skin triggered by UV irradiation. Ginsenosides Rb1 and Rg1 have many molecular targets including the cAMP-response element-binding protein (CREB, which is involved in melanogenesis. This study aimed to investigate the effects of ginsenosides Rb1 and Rg1 on melanogenesis in human melanocytes and their related mechanisms. The effects of Rb1 and Rg1 on cell viability, tyrosinase activity, cellular melanin content and protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF, and activation of CREB in melanocytes were assessed. Results showed that Rb1 or Rg1 significantly increased cellular melanin content and tyrosinase activity in a dose-dependent manner. By contrast, the cell viability of melanocytes remained unchanged. After exposure to Rb1 or Rg1, the protein levels of tyrosinase, MITF, and phosphorylated CREB were significantly increased. Furthermore, pretreatment with the selective PKA inhibitor H-89 significantly blocked the Rb1- or Rg1-induced increase of melanin content. These findings indicated that Rb1 and Rg1 increased melanogenesis and tyrosinase activity in human melanocytes, which was associated with activation of PKA/CREB/MITF signaling. The effects and mechanisms of Rb1 or Rg1 on skin pigmentation deserve further study.
Robles, Francisco E; Deb, Sanghamitra; Fischer, Martin C; Warren, Warren S; Selim, Maria Angelica
2017-04-01
Melanomas of the female genital tract present a unique clinical challenge. Not only are these lesions in an anatomically sensitive area, but also they tend to be multifocal and have high recurrence rates. Furthermore, several benign melanocytic proliferations resemble early-stage melanoma clinically and/or histopathologically. Thus, there is a significant need for additional tools that can help correctly diagnose and stage these lesions. Here, we quantitatively and nondestructively analyze the chemical composition of melanin in excised pigmented lesions of the female genital tract using pump-probe microscopy, a high-resolution optical imaging technique that is sensitive to many biochemical properties of melanin. Thirty-one thin (~5 μm) tissue sections previously excised from female genital tract melanocytic lesions were imaged with pump-probe microscopy and analyzed. We find significant quantitative differences in melanin type and structure between melanoma and nonmalignant melanocytic proliferations. Our analysis also suggests a link between the molecular signatures of melanins and lesion-specific genetic mutations. Finally, significant differences are found between metastatic and nonmetastatic melanomas. The limitations of this work include the fact that molecular information is restricted to melanin pigment and the sample size is relatively small. Pump-probe microscopy provides unique information regarding the biochemical composition of genital tract melanocytic lesions, which can be used to improve the diagnosis and staging of vulvar melanomas.
Cermets based on rhenium and rare earth element oxides
International Nuclear Information System (INIS)
Varfolomeev, M.B.; Velichko, A.V.; Zajtseva, L.L.; Shishkov, N.V.
1977-01-01
The reduction of perrhenates of rare earth elements and of yttrium by hydrogen and the subsequent sintering have yielded cermets based on rhenium and rare earth element oxides inherent in which are more disperse and homogeneous structures than those of the ''molecular'' rare earth element-Tc cermets. The dispersity of cermets increases in the rare earth elements series from La to Lu. The microhardness of the Re phase in cermets is 490 kgf/mm 2 ; the total microhardness of a cermet is substantially higher
Golshahi, Azadeh; Bornfeld, Norbert; Weinitz, Silke; Kellner, Ulrich
2016-01-01
To investigate the advantage of near-infrared autofluorescence (787 nm) for the detection of melanocytic lesions in a patient with bilateral diffuse uveal melanocytic proliferation in association with esophageal carcinoma complicated by most likely unilateral choroidal metastasis. In this retrospective case report, a 55-year-old woman referred for the evaluation of sudden visual loss underwent normal ophthalmological evaluation and, in addition, was examined with near-infrared reflectance, near-infrared autofluorescence, fundus autofluorescence (Heidelberg Retina Angiograph II [HRA2; Heidelberg Engineering]), spectral domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering), and multifocal electroretinography (RetiScan; Roland Consult). The patient had been diagnosed with esophageal carcinoma 3 months before the onset of visual symptoms. The visual acuity was 20/40 in the right eye and 20/20 in the left eye. Bilateral patchy melanocytic proliferation was detected on ophthalmoscopy. The extent of lesions was best detected with near-infrared reflectance and near-infrared autofluorescence, whereas fundus autofluorescence and spectral domain optical coherence tomography did not reveal alterations of the outer retina or retinal pigment epithelium in this early stage of bilateral diffuse uveal melanocytic proliferation. The right eye showed in addition to the findings on the left eye choroidal folds in the fovea and an elevated lesion inferotemporal of the fovea suspicious of a choroidal metastasis. In the B-scan ultrasonography, a homogenous lesion was seen. Spectral domain optical coherence tomography demonstrated a mild accumulation of subretinal fluid adjacent to and over the choroidal metastasis. Transretinal biopsy of this elevated lesion revealed a low differentiated carcinoma of squamous epithelium, compatible with choroidal metastasis of the esophageal carcinoma. The choroidal metastasis increased within 3 months after the first visit. The
Todorovic, Aleksandar; Holder, Jerry Ryan; Bauzo, Rayna M; Scott, Joseph Walker; Kavanagh, Renny; Abdel-Malek, Zalfa; Haskell-Luevano, Carrie
2005-05-05
The melanocortin system is involved in the regulation of a diverse number of physiologically important pathways including pigmentation, feeding behavior, weight and energy homeostasis, inflammation, and sexual function. All the endogenous melanocortin agonist ligands possess the conserved His-Phe-Arg-Trp tetrapeptide sequence that is postulated to be important for melanocortin receptor molecular recognition and stimulation. Previous studies by our laboratory resulted in the discovery that increasing alkyl chain length at the N-terminal "capping" region of the His-dPhe-Arg-Trp-NH(2) tetrapeptide resulted in a 100-fold increased melanocortin receptor agonist potency. This study was undertaken to systematically evaluate the pharmacological effects of increasing N-capping alkyl chain length of the CH(3)(CH(2))(n)CO-His-dPhe-Arg-Trp-NH(2) (n = 6-16) tetrapeptide template. Twelve analogues were synthesized and pharmacologically characterized at the mouse melanocortin receptors MC1R and MC3R-MC5R and human melanocytes known to express the MC1R. These peptides demonstrated melanocortin receptor selectivity profiles different from those of previously published tetrapeptides. The most notable results of enhanced ligand potency (20- to 200-fold) and receptor selectivity were observed at the MC1R. Tetrapeptides that possessed greater than nine alkyl groups were superior to alpha-MSH in terms of the stimulation of human melanocyte tyrosinase activity. Additionally, the n-pentadecanoyl derivative had a residual effect on tyrosinase activity that existed for at least 4 days after the peptide was removed from the human melanocyte culture medium. These data demonstrate the utility, potency, and residual effect of melanocortin tetrapeptides by adding N-terminal fatty acid moieties.
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Pedro Almendros
2011-09-01
Full Text Available The last decade has witnessed dramatic growth in the number of reactions catalyzed by gold complexes because of their powerful soft Lewis acid nature. In particular, the gold-catalyzed activation of propargylic compounds has progressively emerged in recent years. Some of these gold-catalyzed reactions in alkynes have been optimized and show significant utility in organic synthesis. Thus, apart from significant methodology work, in the meantime gold-catalyzed cyclizations in alkynol derivatives have become an efficient tool in total synthesis. However, there is a lack of specific review articles covering the joined importance of both gold salts and alkynol-based compounds for the synthesis of natural products and derivatives. The aim of this Review is to survey the chemistry of alkynol derivatives under gold-catalyzed cyclization conditions and its utility in total synthesis, concentrating on the advances that have been made in the last decade, and in particular in the last quinquennium.
Kimeswenger, Susanne; Schwarz, Agatha; Födinger, Dagmar; Müller, Susanne; Pehamberger, Hubert; Schwarz, Thomas; Jantschitsch, Christian
2016-06-01
The link between solar radiation and melanoma is still elusive. Although infrared radiation (IR) accounts for over 50% of terrestrial solar energy, its influence on human skin is not well explored. There is increasing evidence that IR influences the expression patterns of several molecules independently of heat. A previous in vivo study revealed that pretreatment with IR might promote the development of UVR-induced non-epithelial skin cancer and possibly of melanoma in mice. To expand on this, the aim of the present study was to evaluate the impact of IR on UVR-induced apoptosis and DNA repair in normal human epidermal melanocytes. The balance between these two effects is a key factor of malignant transformation. Human melanocytes were exposed to physiologic doses of IR and UVR. Compared to cells irradiated with UVR only, simultaneous exposure to IR significantly reduced the apoptotic rate. However, IR did not influence the repair of UVR-induced DNA damage. IR partly reversed the pro-apoptotic effects of UVR via modification of the expression and activity of proteins mainly of the extrinsic apoptotic pathway. In conclusion, IR enhances the survival of melanocytes carrying UVR-induced DNA damage and thereby might contribute to melanomagenesis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Venneker, G. T.; Vodegel, R. M.; Okada, N.; Westerhof, W.; Bos, J. D.; Asghar, S. S.
1998-01-01
Complement regulatory molecules, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, protect body cells from autologous complement. They have wide tissue distribution but nothing is known about the expression of these molecules on human melanocytes. Since melanocytes are lysed
Side Chain Cyclized Aromatic Amino Acids
DEFF Research Database (Denmark)
Van der Poorten, Olivier; Knuhtsen, Astrid; Sejer Pedersen, Daniel
2016-01-01
Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute...... the peptide pharmacophore is equally important. Control of χ-space utilizes conformationally constrained amino acids that favor, disfavor, or exclude the gauche (-), the gauche (+), or the trans conformation. In this review we focus on cyclic aromatic amino acids in which the side chain is connected...... to the peptide backbone to provide control of χ(1)- and χ(2)-space. The manifold applications for cyclized analogues of the aromatic amino acids Phe, Tyr, Trp, and His within peptide medicinal chemistry are showcased herein with examples of enzyme inhibitors and ligands for G protein-coupled receptors....
Tarafder, Abul K; Bolasco, Giulia; Correia, Maria S; Pereira, Francisco J C; Iannone, Lucio; Hume, Alistair N; Kirkpatrick, Niall; Picardo, Mauro; Torrisi, Maria R; Rodrigues, Inês P; Ramalho, José S; Futter, Clare E; Barral, Duarte C; Seabra, Miguel C
2014-04-01
The transfer of melanin from melanocytes to keratinocytes is a crucial process underlying maintenance of skin pigmentation and photoprotection against UV damage. Here, we present evidence supporting coupled exocytosis of the melanin core, or melanocore, by melanocytes and subsequent endocytosis by keratinocytes as a predominant mechanism of melanin transfer. Electron microscopy analysis of human skin samples revealed three lines of evidence supporting this: (1) the presence of melanocores in the extracellular space; (2) within keratinocytes, melanin was surrounded by a single membrane; and (3) this membrane lacked the melanosomal membrane protein tyrosinase-related protein 1 (TYRP1). Moreover, co-culture of melanocytes and keratinocytes suggests that melanin exocytosis is specifically induced by keratinocytes. Furthermore, depletion of Rab11b, but not Rab27a, caused a marked decrease in both keratinocyte-stimulated melanin exocytosis and transfer to keratinocytes. Thus, we propose that the predominant mechanism of melanin transfer is keratinocyte-induced exocytosis, mediated by Rab11b through remodeling of the melanosome membrane, followed by subsequent endocytosis by keratinocytes.
Energy Technology Data Exchange (ETDEWEB)
Berenger, N.; Lebtahi, R.; Piketty, M.L.; Merienne, L.; Turak, B.; Bok, R.; Askienazy, S. (Hopital Sainte-Anne, 75 - Paris (France)); Munari, C. (Centre Hospitalier Universitaire, 38 - Grenoble (France))
1993-01-01
Forty-three patients with craniopharyngioma cysts were treated by intracystic injection of 186-rhenium. Leakage of colloid isotope into the CSF spaces during the ''test'' or ''therapeutic'' injection was detected by scintigraphic follow-up (15 cases/58 intracystic injections). In fact the physical characteristics of [sup 186]Re are well adapted to the requirements of treatment and, with the gamma emission, also allows early detection of leakage, avoiding irradiation of neighbouring structures. Follow-up studies revealed that craniopharyngioma cysts were effectively treated, with cessation of fluid formation, progressive shrinkage of the cysts leading to total disappearance in 14 cases (10-156 months, mean 52.5) and a considerable decrease in 13 cases (5-53 months, mean 23).
Blood Supply--Susceptible Formation of Melanin Pigment in Hair Bulb Melanocytes of Mice
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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.
Li, Nan; Xie, Yaoming; King, R Bruce; Schaefer, Henry F
2010-11-04
Rhenium carbonyl hydride chemistry dates back to the 1959 synthesis of HRe(CO)₅ by Hieber and Braun. The binuclear H₂Re₂(CO)₈ was subsequently synthesized as a stable compound with a central Re₂(μ-H)₂ unit analogous to the B₂(μ-H)₂ unit in diborane. The complete series of HRe(CO)(n) (n = 5, 4, 3) and H₂Re₂(CO)(n) (n = 9, 8, 7, 6) derivatives have now been investigated by density functional theory. In contrast to the corresponding manganese derivatives, all of the triplet rhenium structures are found to lie at relatively high energies compared with the corresponding singlet structures consistent with the higher ligand field splitting of rhenium relative to manganese. The lowest energy HRe(CO)₅ structure is the expected octahedral structure. Low-energy structures for HRe(CO)(n) (n = 4, 3) are singlet structures derived from the octahedral HRe(CO)₅ structure by removal of one or two carbonyl groups. For H₂Re₂(CO)₉ a structure HRe₂(CO)₉(μ-H), with one terminal and one bridging hydrogen atom, lies within 3 kcal/mol of the structure Re₂(CO)₉(η²-H₂), similar to that of Re₂(CO)₁₀. For H₂Re₂(CO)(n) (n = 8, 7, 6) the only low-energy structures are doubly bridged singlet Re₂(μ-H)₂(CO)(n) structures. Higher energy dihydrogen complex structures are also found.
UVB-Stimulated TNFα Release from Human Melanocyte and Melanoma Cells Is Mediated by p38 MAPK
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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.
Complexes of technetium, rhenium, and rhodium with sexidentate Schiff-base ligands
International Nuclear Information System (INIS)
Hunter, G.; Kilcullen, N.
1989-01-01
The monocationic technetium (IV) and rhenium (IV) complexes with the sexidentate Schiff-base ligands tris[2-(2'-hydroxybenzylideneethyl)]amine and its substituted derivatives have been prepared and their electrochemical properties studied. The variable-temperature 90.6 MHz 13 C-{ 1 H} n.m.r. spectrum of the rhodium (III) complex of tris[2-(2-hydroxy-5'-isopropylbenzylideneethyl)-amine] has been observed, indicating fluxionality at temperatures above 218 K. (author)
Thiersch, Markus; Lange, Christina; Joly, Sandrine; Heynen, Severin; Le, Yun Zheng; Samardzija, Marijana; Grimm, Christian
2009-06-01
Hypoxic preconditioning stabilizes hypoxia-inducible factor (HIF) 1 alpha in the retina and protects photoreceptors against light-induced cell death. HIF-1 alpha is one of the major transcription factors responding to low oxygen tension and can differentially regulate a large number of target genes. To analyse whether photoreceptor-specific expression of HIF-1 alpha is essential to protect photoreceptors by hypoxic preconditioning, we knocked down expression of HIF-1 alpha specifically in photoreceptor cells, using the cyclization recombinase (Cre)-lox system. The Cre-mediated knockdown caused a 20-fold reduced expression of Hif-1 alpha in the photoreceptor cell layer. In the total retina, RNA expression was reduced by 65%, and hypoxic preconditioning led to only a small increase in HIF-1 alpha protein levels. Accordingly, HIF-1 target gene expression after hypoxia was significantly diminished. Retinas of Hif-1 alpha knockdown animals did not show any pathological alterations, and tolerated hypoxic exposure in a comparable way to wild-type retinas. Importantly, the strong neuroprotective effect of hypoxic preconditioning against light-induced photoreceptor degeneration persisted in knockdown mice, suggesting that hypoxia-mediated survival of light exposure does not depend on an autocrine action of HIF-1 alpha in photoreceptor cells. Hypoxia-mediated stabilization of HIF-2 alpha and phosphorylation of signal transducer and activator of transcription 3 (STAT 3) were not affected in the retinas of Hif-1 alpha knockdown mice. Thus, these factors are candidates for regulating the resistance of photoreceptors to light damage after hypoxic preconditioning, along with several potentially neuroprotective genes that were similarly induced in hypoxic knockdown and control mice.
Gold(I-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles
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Mathieu Morin
2013-11-01
Full Text Available Gold(I complexes have emerged as powerful and useful catalysts for the formation of new C–C, C–O and C–N bonds. Taking advantage of the specificity of [IPrAuNCMe][SbF6] complexes to favor the 5-exo-dig cyclization over the 6-endo-dig pathway, we report a high yielding and efficient method to generate substituted polyaromatic heterocycles under remarkably mild reaction conditions.
Analysis of the Nuclear Structure of Rhenium-186 Using Neutron-Induced Reactions
2015-03-26
5 1.5 Methods ... radioisotope power source for use on the battlefield. 1 Re-Os Cosmochronometer. The isotope 187Re has a half-life in its ground state of 4.35⇥ 1010 years [2...187Os in meteorites permits one to date the nucleosynthesis of rhenium and osmium by high neutron flux events such as supernovae. The Re-Os radioactive
Glud, Martin; Klausen, Mikkel; Gniadecki, Robert; Rossing, Maria; Hastrup, Nina; Nielsen, Finn C; Drzewiecki, Krzysztof T
2009-05-01
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 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-PCR. In conclusion, FFPE specimens of melanocytic lesions are suitable as a source for miRNA microarray profiling.
Spontaneous regression of a congenital melanocytic nevus
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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.
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Alessandra eZulian
2014-11-01
Full Text Available Ullrich congenital muscular dystrophy and Bethlem myopathy are caused by mutations in collagen VI genes, which encode an extracellular matrix protein; yet mitochondria play a major role in disease pathogenesis through a short circuit caused by inappropriate opening of the permeability transition pore, a high conductance channel which causes a shortage in ATP production. We find that melanocytes do not produce collagen VI yet they bind it at the cell surface, suggesting that this protein may play a trophic role and that its absence may cause lesions similar to those seen in skeletal muscle. We show that mitochondria in melanocytes of Ullrich congenital muscular dystrophy and Bethlem myooathy patients display increased size, reduced matrix density and disrupted cristae, findings that suggest a functional impairment. In keeping with this hypothesis, mitochondria (i underwent anomalous depolarization after inhibition of the F-ATP synthase with oligomycin, and (ii displayed decreased respiratory reserve capacity. The non-immunosuppressive cyclophilin inhibitor NIM811 prevented mitochondrial depolarization in response to oligomycin in melanocytes from both Ullrich congenital muscular dystrophy and Bethlem myopathy patients, and partially restored the respiratory reserve of melanocytes from one Bethlem myopathy patient. These results match our recent findings on melanocytes from patients affected by Duchenne muscular dystrophy (Pellegrini et al., 2013 Melanocytes--a novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy. J Cell Physiol 228, 1323-1331, and suggest that skin biopsies may represent a minimally invasive tool to investigate mitochondrial dysfunction and to evaluate drug efficacy in collagen VI-related myopathies and possibly in other muscle wasting conditions like aging sarcopenia.
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Keith A Hultman
2007-01-01
Full Text Available The retention of particular genes after the whole genome duplication in zebrafish has given insights into how genes may evolve through partitioning of ancestral functions. We examine the partitioning of expression patterns and functions of two zebrafish kit ligands, kit ligand a (kitla and kit ligand b (kitlb, and discuss their possible coevolution with the duplicated zebrafish kit receptors (kita and kitb. In situ hybridizations show that kitla mRNA is expressed in the trunk adjacent to the notochord in the middle of each somite during stages of melanocyte migration and later expressed in the skin, when the receptor is required for melanocyte survival. kitla is also expressed in other regions complementary to kita receptor expression, including the pineal gland, tail bud, and ear. In contrast, kitlb mRNA is expressed in brain ventricles, ear, and cardinal vein plexus, in regions generally not complementary to either zebrafish kit receptor ortholog. However, like kitla, kitlb is expressed in the skin during stages consistent with melanocyte survival. Thus, it appears that kita and kitla have maintained congruent expression patterns, while kitb and kitlb have evolved divergent expression patterns. We demonstrate the interaction of kita and kitla by morpholino knockdown analysis. kitla morphants, but not kitlb morphants, phenocopy the null allele of kita, with defects for both melanocyte migration and survival. Furthermore, kitla morpholino, but not kitlb morpholino, interacts genetically with a sensitized allele of kita, confirming that kitla is the functional ligand to kita. Last, we examine kitla overexpression in embryos, which results in hyperpigmentation caused by an increase in the number and size of melanocytes. This hyperpigmentation is dependent on kita function. We conclude that following genome duplication, kita and kitla have maintained their receptor-ligand relationship, coevolved complementary expression patterns, and that
Li, Yawen; Ma, Lixin; Gaddam, Vikram; Gallazzi, Fabio; Hennkens, Heather M; Harmata, Michael; Lewis, Michael R; Deakyne, Carol A; Jurisson, Silvia S
2016-02-01
Radiolabeled proteolytic degradation-resistant somatostatin analogues have been of long-standing interest as cancer imaging and radiotherapy agents for targeting somatostatin receptor-positive tumors. Our interest in developing (186)Re- and (188)Re-based therapeutic radiopharmaceuticals led to investigation of a new Re(V)-cyclized octreotide analogue, Re(V)-cyclized, thiolated-DPhe(1)-Cys(2)-Tyr(3)-DTrp(4)-Lys(5)-Thr(6)-Cys(7)-Thr(OH)(8) (Re-SDPhe-TATE) using both experimental and quantum chemical methods. The metal is directly coordinated to SDPhe-TATE through cyclization of the peptide around the [ReO](3+) core. Upon complexation, four isomers were observed; the isolated/semi-isolated isomers exhibited different somatostatin receptor (sstr) binding affinities, 0.13 to 1.5 μM, in rat pancreatic tumor cells. Two-dimensional NMR experiments and electronic structure calculations were employed to elucidate the structural differences among the different isomers. According to NMR studies, the metal is coordinated to three thiolates and the backbone amide of Cys(2) in isomers 1 and 4, whereas the metal is coordinated to three thiolates and the backbone amide of Tyr(3) in isomer 2. Quantum chemical methods clarified the stereochemistry of Re-SDPhe-TATE and the possible peptide arrangements around the [ReO](3+) core. The re-cyclization reaction was translated to the (99m)Tc radiotracer level with four isomers observed on complexation with comparable HPLC retention times as the Re-SDPhe-TATE isomers. About 85% total (99m)Tc labeling yield was achieved by ligand exchange from (99m)Tc-glucoheptonate at 60 °C for an hour. About 100% and 51% of (99m)Tc(V)-cyclized SDPhe-TATE remained intact in phosphate buffered saline and 1 mM cysteine solution under physiological conditions at 6 h, respectively.
International Nuclear Information System (INIS)
Elmets, Craig A.; Yusuf, Nabiha; Hamza, Sate; Iranikakh, Nasser; Smith, Jeffrey; Volk, Andrea L.; Skelton, Henry; Smith, Kathy
2004-01-01
Melanocytic nevi are a common dermatological problem for which there are few in vivo models. It has been postulated that environmental factors contribute to their development. Experiments were therefore conducted to determine whether application of dimethylbenz[a]anthracene (DMBA) to the skin of mice would result in the development of melanocytic nevi. One hundred microliters of a 0.1%, 0.5%, or 1.0% solution of DMBA was applied to the dorsal skin of C3H/HeN mice. The mice were then observed for the appearance of pigmented lesions. Histological examination revealed perifollicular accumulations of nevus cells, which were S-100-protein and HMB-45-positive, confirming their melanocytic origin. Pigmented lesions did not occur in animals treated with vehicle alone. Dose response studies revealed both greater numbers of nevi and lesions with larger diameters as the dose of DMBA was increased from 0.1% to 0.5%. In no instance was an invasive melanoma observed even after 40 weeks. The fact that melanocytic nevi can be produced by topical application of DMBA suggests that xenobiotics may play a previously unrecognized role in the development of this common benign neoplasm. Because this is one of the only animal models for melanocytic nevi, further examination of this model may facilitate identification of the molecular and biochemical mechanisms that lead to the development of pigmented nevi and the factors that promote their evolution into invasive melanomas
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Joshi Sandeep S
2009-11-01
Full Text Available Abstract Background Hypoxia inducible factor-1 alpha (HIF-1α protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP, vertical growth phase (VGP and metastatic (MET melanomas. Results HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part of the oxygen-dependent regulation domain in WM1366 and WM9 melanoma cells. Over-expression of HIF-1α and its splice variant in the RGP cell line SbCl2 resulted in a small increase in soft agar colony formation and a large increase in matrigel invasion relative to control transfected cells. Knockdown of HIF-1α expression by siRNA in the MET WM9 melanoma cell line resulted in a large decrease in both soft agar colony formation and matrigel invasion relative to cells treated with non-specific siRNA. There is a high level of ERK1/2 phosphorylation in WM9 cells, indicating an activated Ras-Raf-MEK-ERK1/2 MAPK pathway. Treatment of WM9 cells with 30 μM U0126 MEK inhibitor, decreased ERK1/2 phosphorylation and resulted in a decrease in HIF-1α expression. However, a 24 h treatment with 10 μM U0126 totally eliminated Erk1/2 phosphorylation, but did not change HIF-1alpha levels. Furthermore, siRNA knockdown of MEK siRNA did not change HIF-1alpha levels. Conclusion We speculate that metabolic products of U0126 decrease HIF-1alpha expression through "off target" effects. Overall our data suggest that increased HIF-1α expression under normoxic conditions contributes to some of the malignant phenotypes exhibited by human melanoma cells. The expanded role of HIF-1α in melanoma biology increases
Ando, Hideya; Niki, Yoko; Ito, Masaaki; Akiyama, Kaoru; Matsui, Mary S; Yarosh, Daniel B; Ichihashi, Masamitsu
2012-04-01
Recent studies have described the role of shedding vesicles as physiological conveyers of intracellular components between neighboring cells. Here we report that melanosomes are one example of shedding vesicle cargo, but are processed by a previously unreported mechanism. Pigment globules were observed to be connected to the filopodia of melanocyte dendrites, which have previously been shown to be conduits for melanosomes. Pigment globules containing multiple melanosomes were released from various areas of the dendrites of normal human melanocytes derived from darkly pigmented skin. The globules were then captured by the microvilli of normal human keratinocytes, also derived from darkly pigmented skin, which incorporated them in a protease-activated receptor-2 (PAR-2)-dependent manner. After the pigment globules were ingested by the keratinocytes, the membrane that surrounded each melanosome cluster was gradually degraded, and the individual melanosomes then spread into the cytosol and were distributed primarily in the perinuclear area of each keratinocyte. These results suggest a melanosome transfer pathway wherein melanosomes are transferred from melanocytes to keratinocytes via the shedding vesicle system. This packaging system generates pigment globules containing multiple melanosomes in a unique manner.
Wang, Jing; Fang, Pengfei; Chase, Peter; Tshori, Sagi; Razin, Ehud; Spicer, Timothy P; Scampavia, Louis; Hodder, Peter; Guo, Min
2017-01-01
Microphthalmia transcription factor (MITF) is a master transcription factor expressed in melanocytes, essential for melanocyte survival, differentiation, and pigment formation, and is a key oncogenic factor in melanoma initiation, migration, and treatment resistance. Although identified as an important therapeutic target for melanoma, clinical inhibitors directly targeting the MITF protein are not available. Based on the functional state of MITF, we have designed an MITF dimerization-based AlphaScreen (MIDAS) assay that sensitively and specifically mirrors the dimerization of MITF in vitro. This assay is further exploited for identification of the MITF dimer disruptor for high-throughput screening. A pilot screen against a library of 1280 pharmacologically active compounds indicates that the MIDAS assay performance exhibits exceptional results with a Z' factor of 0.81 and a signal-to-background (S/B) ratio of 3.92 while identifying initial hit compounds that yield an ability to disrupt MITF-DNA interaction. The results presented demonstrate that the MIDAS assay is ready to screen large chemical libraries in order to discover novel modulators of MITF for potential melanoma treatment.
Green chemistry: solvent- and metal-free Prins cyclization. Application to sequential reactions.
Clarisse, Damien; Pelotier, Béatrice; Piva, Olivier; Fache, Fabienne
2012-01-04
Prins cyclization between a homoallylic alcohol and an aldehyde, promoted by trimethylsilyl halide, afforded 4-halo-tetrahydropyrans with good to excellent yields. Thanks to the absence of the solvent and metal, the THP thus obtained have been implicated without purification in several other reactions, in a sequential way, affording in particular new indole derivatives. This journal is © The Royal Society of Chemistry 2012
Beyer, Astrid; Reucher, Christine M M; Bolm, Carsten
2011-06-03
A new protocol for intramolecular N-arylations of ureas to form benzimidazol-2-ones has been developed. The cyclization reaction occurs in the presence of KOH and DMSO at close to ambient temperature. Under these conditions the yields are high and a wide range of functional groups are tolerated.
Melanin-concentrating hormone and its receptor are expressed and functional in human skin.
Hoogduijn, Martin J; Ancans, Janis; Suzuki, Itaru; Estdale, Siân; Thody, Anthony J
2002-08-23
In this study, we have demonstrated the presence of melanin-concentrating hormone (MCH) and melanin-concentrating hormone receptor (MCHR1) transcripts in human skin. Sequence analysis confirmed that the transcripts of both genes were identical to those previously found in human brain. In culture, endothelial cells showed pro-MCH expression whereas no signal was found in keratinocytes, melanocytes, and fibroblasts. MCHR1 expression was restricted to melanocytes and melanoma cells. Stimulation of cultured human melanocytes with MCH reduced the alpha-MSH-induced increase in cAMP production. Furthermore, the melanogenic actions of alpha-MSH were inhibited by MCH. We propose that the MCH/MCHR1 signalling system is present in human skin and may have a role with the melanocortins in regulating the melanocyte.
Boros, Audrey L; Handlers, Janice P; Melrose, Raymond J
2014-10-01
The concept of pseudomelanocytic nests has been recently described in the dermatology literature. To our knowledge, this entity has yet to be published in the oral pathology literature. We report 2 cases with features of pseudomelanocytic nests. In both instances, nests of cells suspicious for melanocytes were observed. Interpretation of melan-A was negative. Both cases showed strong and diffuse immunoreactivity of the nested cells to CD68. This immunohistochemical staining pattern is most consistent with a melanophage identity. Pseudomelanocytic nests are a recently described entity that represents a potential diagnostic pitfall. Distinguishing pseudomelanocytic nests from an authentic atypical melanocytic proliferation can be challenging and is important for appropriate patient management. Clinicopathologic correlation with cautious interpretation of immunohistochemistry may be necessary to arrive at the correct diagnosis. These cases represent the first reports of pseudomelanocytic nests in the oral pathology literature. Copyright © 2014 Elsevier Inc. All rights reserved.
Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won
2014-08-01
Alpha-melanocyte stimulating hormone (α-MSH) is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of α-MSH located in the spinal cord in the regulation of the blood glucose level were investigated in d-glucose-fed and immobilization stress (IMO) mouse models. We found in the present study that intrathecal (i.t.) injection with α-MSH alone did not affect the blood glucose level. However, i.t. administration with α-MSH reduced the blood glucose level in d-glucose-fed model. The plasma insulin level was increased in d-glucose-fed model and was further increased by α-MSH, whereas α-MSH did not affect plasma corticosterone level in d-glucose-fed model. In addition, i.t. administration with glucagon alone enhanced blood glucose level and, i.t. injection with glucagon also increased the blood glucose level in d-glucose-fed model. In contrasted to results observed in d-glucose-fed model, i.t. treatment with α-MSH caused enhancement of the blood glucose level in IMO model. The plasma insulin level was increased in IMO model. The increased plasma insulin level by IMO was reduced by i.t. treatment with α-MSH, whereas i.t. pretreatment with α-MSH did not affect plasma corticosterone level in IMO model. Taken together, although spinally located α-MSH itself does not alter the blood glucose level, our results suggest that the activation of α-MSH system located in the spinal cord play important modulatory roles for the reduction of the blood glucose level in d-glucose fed model whereas α-MSH is responsible for the up-regulation of the blood glucose level in IMO model. The enhancement of insulin release may be responsible for modulatory action of α-MSH in down-regulation of the blood glucose in d-glucose fed model whereas reduction of insulin release may be responsible for modulatory action of α-MSH in up-regulation of the blood glucose in IMO model. Copyright © 2014 Elsevier Ltd. All rights reserved.
Gu, Haidong; Wang, Congyang
2015-06-07
A dehydrogenative olefination of C(sp(3))-H bonds is disclosed here, by merging rhenium catalysis with an alanine-derived hypervalent iodine(III) reagent. Thus, cyclic and acyclic ethers, toluene derivatives, cycloalkanes, and nitriles are all successfully alkenylated in a regio- and stereoselective manner.
Warf, M Bryan; Flake, Darl D; Adams, Doug; Gutin, Alexander; Kolquist, Kathryn A; Wenstrup, Richard J; Roa, Benjamin B
2015-01-01
These studies were to validate the analytical performance of a gene expression signature that differentiates melanoma and nevi, using RNA expression from 14 signature genes and nine normalization genes that generates a melanoma diagnostic score (MDS). Formalin-fixed paraffin-embedded melanocytic lesions were evaluated in these studies. The overall SD of the assay was determined to be 0.69 MDS units. Individual amplicons within the signature had an average amplification efficiency of 92% and a SD less than 0.5 CT. The MDS was reproducible across a 2000-fold dilution range of input RNA. Melanin, an inhibitor of PCR, does not interfere with the signature. These studies indicate this signature is robust and reproducible and is analytically validated on formalin-fixed paraffin-embedded melanocytic lesions.
New extraction chromatographic material for rhenium separation
International Nuclear Information System (INIS)
Lucanikova, M.; Czech Technical University, Prague; Kucera, J.; Czech Technical University, Prague; Sebesta, F.
2008-01-01
Three types of the extraction chromatographic materials, composed from Aliquat R 336 deposited in the polyacrylonitrile (PAN) beads and prepared by different procedures, were compared for extraction of rhenium. The best properties were exhibited when the solid extractant was prepared by impregnation of the ready-made PAN beads. Solid extractant prepared by direct coagulation of the beads from the suspension of Aliquat R 336 in solution of PAN in nitric acid differs only by lower capacity in dynamic conditions. Material prepared from the PAN solution in dimethylsulfoxide was the worst because Aliquat R 336 was washed out from the beads during coagulation of the polymer and the extraction capacity was low. As it is shown, the first two solid extractants are fully comparable with the commercial TEVA Resin. (author)
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.
International Nuclear Information System (INIS)
Gagieva, S.Ch.; Gutnova, N.A.; Tsaloev, A.T.; Khubulov, A.B.; Arutyunyants, A.A.; Galimov, Yu.B.
2003-01-01
Rhenium (V) complexing with mono- and bis-benzoylthiosemicarbazones is studied in dependence on hydrohalic acids concentration changes. It is determined that in media with high concentration of hydrohalic acids (6 mol/l HCl, 7 mol/l HBr) in dependence on reaction conditions stable complexes with bi- and tridentate coordination of thiosemicarbazone are formed. In the case of hydrohalic acid concentration decreasing stable binuclear and oxohydroxycomplexes are formed. Composition and structure of the compounds obtained are determined by the methods of element analysis, IR spectroscopy, conductometry. Thermal investigations of the compounds obtained are done [ru
Kobiela, K.; Smolina, I.; Dziedzic, R.; Szymczyk, P.; Kurzynowski, T.; Chlebus, E.
2016-12-01
The paper presents the results of the process development of laser surface modification of commercially pure titanium with rhenium. The criterion of the successful/optimal process is the repetitive geometry of the surface, characterized by predictable and repetitive chemical composition over its entire surface as well as special mechanical properties (hardness and wear resistance). The analysis of surface geometry concluded measurements of laser penetration depth and heat affected zone (HAZ), the width of a single track as well as width of a clad. The diode laser installed on the industrial robot carried out the laser treatment. This solution made possible the continuous supply of powder to the substrate during the process. The aim of an investigation is find out the possibility of improving the tribological characteristics of the surface due to the rhenium alloying. The verification of the surface properties (tribological) concluded geometry measurements, microstructure observation, hardness tests and evaluation of wear resistance.
Abundance of the benign melanocytic universe: Dermoscopic-histopathological correlation in nevi.
Woltsche, Nora; Schmid-Zalaudek, Karin; Deinlein, Teresa; Rammel, Katrin; Hofmann-Wellenhof, Rainer; Zalaudek, Iris
2017-05-01
The broad universe of "melanocytic nevi" includes a variety of different subtypes, which can be classified either due to their morphology, epidemiology, genetic alterations or risk for developing melanoma. Regarding morphology, on the one hand macroscopic/clinical and on the other hand histopathological appearance were used to subdivide in the past, often resulting in confusion and poor interobserver agreement, while nowadays dermoscopy presents the clinician's precious bridge between naked-eye examination and histopathological diagnostics, allowing prediction of the lesions' histopathology, follow up and monitoring over time without need of excision. The non-invasive dermoscopic examination relies on the assessment of colors, patterns and the distribution of both within a cutaneous lesion. Until today, the correspondence of certain dermoscopic colors and patterns to certain histopathological correlates has been reported for a huge amount of different cutaneous lesions. Moreover, the correspondence of certain dermoscopic features to certain body sites, age groups and pigmentary traits, but also to specific genetic alterations in lesions, has been broadly investigated. Dermoscopy has led us to a new understanding of melanocytic nevi's biology and evolution and, last but not least, to a new classification system, which we want to present herein. © 2017 Japanese Dermatological Association.
Zeng, Wei; Wu, Wanqing; Jiang, Huanfeng; Huang, Liangbin; Sun, Yadong; Chen, Zhengwang; Li, Xianwei
2013-07-28
Regioselective synthesis of polysubstituted benzofurans using a copper catalyst and molecular oxygen from phenols and alkynes in a one-pot procedure has been reported. The transformation consists of a sequential nucleophilic addition of phenols to alkynes and oxidative cyclization. A wide variety of phenols and alkynes can be used in the same manner.
Rhenium-186 direct labelling HIgG
International Nuclear Information System (INIS)
Lungu, V.; Mihailescu, G.; Dumitrescu, G.
2001-01-01
The aim of this study is to develop and improve existing radiolabelling techniques of peptides and monoclonal antibodies with 186 Re for achievement of potential agents for cancer targeted radiotherapy. There were selected methods and techniques for the direct labelling of intact HIgG by studding chemical and radiochemical processes of -S-S- bridges prereduction, reduction of 186 ReO 4 - and coupling reaction of rhenium with HIgG. The -S-S- bridges prereduction of HIgG to sulfhydryls was effected using different reducing agents: ascorbic acid, 2,3 dimercaptopropanol, cysteine, active hydrogen. The prereduction reactions are controlled by masic ratios of HIgG/reduction agent, pH, temperature and time of incubation. A pH=4.5 and a 24 hours incubation time are in the advantage of the prereduction yield. The labelling with 186 Re of prereduced HIgG with ascorbic acid or active hydrogen and 37 deg. C incubation in 22 hours releases 92% radiochemical purity. (author)
Liquid kit for preparation of {sup 188}rhenium-etidronate
Energy Technology Data Exchange (ETDEWEB)
Marczewski, Barbara; Dias, Carla Roberta; Moraes, Vanessa; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), SP (Brazil). Centro de Radiofarmacia]. E-mail: baszot@gmail.com
2005-10-15
The aim of this study was the preparation of a liquid kit for radiolabeling of {sup 188} Re-HEDP (hydroxyethylidene diphosphonate). {sup 188} Re was obtained from alumina based {sup 188} W/{sup 188} Re generators. This paper reports the efficacy of a cold kit stored for more than two weeks, determined by the dependence of the radiolabeling yields of {sup 188} Re-HEDP on the incubation time, reducing agent concentration, the effects of concentration of ligand, the p H of the reaction and the temperature. The cold kits showed a good stability when carrie-free rhenium-188 was added in the reaction mixture. (author)
International Nuclear Information System (INIS)
Korenyako, G.I.; Belousov, V.M.
1985-01-01
A study was made on kinetics of nitrobenzene hydrogenation to phenylhydroxylamine in dimethylformamide solutions of rhenium thiocomplexes. The mechanism of hydrogenation was suggested. Formation of hydride catalyst complex represents the first stage of the process. Kinetic equation derived on the basis of suggested mechanism corresponds satisfactorily with experimental results. Thermodynamic parameters of separate process stages calculated on the basis of equilibrium constant values testify as well to the benefit of suggested mechanism
International Nuclear Information System (INIS)
Kim, Cheolwoong; Seo, Seung Woo; Lee, Yona; Kim, Sunggon
2014-01-01
We have developed the synthetic methodology of enantioenriched benzindoloquinolizidines based on the organocatalytic enantioselective conjugate addition-cyclization cascade reaction of o-N-(3-indoleacetyl)amino-cinnamaldehydes with malonates followed by an acid-catalyzed intramolecular Pictet-Spengler type cyclization. The asymmetric reaction using diphenylprolinol TMS ether as an organocatalyst produces the desired products with good to excellent yields and high enantioselectivities (up to 98% ee). The evaluation of the applications of this synthetic methodology for generating enantioenriched benzindolo-quinolizidines and studies on the biological activity of these compounds against human prostate cancer in particular are now in progress. Results of these studies will be presented in due course. Many new types of chemical reactions have been developed to facilitate easier synthesis of complex compounds. Among the strategies, domino reactions, which have been utilized for the efficient and stereoselective construction of complex molecules from simple precursors in a single process, are widely used due to their high synthetic efficiency by reducing both the number of synthetic operation required and the quantities of chemicals and solvents used
Formamidine sulfinic acid as reducing agent in technetium-99m rhenium sulfide labelling
Energy Technology Data Exchange (ETDEWEB)
Neves, M; Patricio, L [Laboratorio Nacional de Engenharia e Technologia Industrial, Sacavem (Portugal). Dept. de Radioisotopes; Ferronha, H [Laboratorio Nacional de Investigacao Veterinaria, Lisboa (Portugal)
1989-08-01
Labelling kinetic studies, radiochemical characterization and particle size evaluation of {sup 99m}Tc rhenium sulfide colloid using formamidine sulfinic acid as reducing agent are described. Comparison with the same colloid which makes use of Sn-sodium pyrophosphate complex as reducing agent showed higher labelling yields, simplification of labelling procedure and a longer shelf life when formamidine sulfinic acid was used. (author) 15 refs.; 7 figs.
Constitutive activation of the ERK pathway in melanoma and skin melanocytes in Grey horses.
Jiang, Lin; Campagne, Cécile; Sundström, Elisabeth; Sousa, Pedro; Imran, Saima; Seltenhammer, Monika; Pielberg, Gerli; Olsson, Mats J; Egidy, Giorgia; Andersson, Leif; Golovko, Anna
2014-11-21
Constitutive activation of the ERK pathway, occurring in the vast majority of melanocytic neoplasms, has a pivotal role in melanoma development. Different mechanisms underlie this activation in different tumour settings. The Grey phenotype in horses, caused by a 4.6 kb duplication in intron 6 of Syntaxin 17 (STX17), is associated with a very high incidence of cutaneous melanoma, but the molecular mechanism behind the melanomagenesis remains unknown. Here, we investigated the involvement of the ERK pathway in melanoma development in Grey horses. Grey horse melanoma tumours, cell lines and normal skin melanocytes were analyzed with help of indirect immunofluorescence and immunoblotting for the expression of phospho-ERK1/2 in comparison to that in non-grey horse and human counterparts. The mutational status of BRAF, RAS, GNAQ, GNA11 and KIT genes in Grey horse melanomas was determined by direct sequencing. The effect of RAS, RAF and PI3K/AKT pathways on the activation of the ERK signaling in Grey horse melanoma cells was investigated with help of specific inhibitors and immunoblotting. Individual roles of RAF and RAS kinases on the ERK activation were examined using si-RNA based approach and immunoblotting. We found that the ERK pathway is constitutively activated in Grey horse melanoma tumours and cell lines in the absence of somatic activating mutations in BRAF, RAS, GNAQ, GNA11 and KIT genes or alterations in the expression of the main components of the pathway. The pathway is mitogenic and is mediated by BRAF, CRAF and KRAS kinases. Importantly, we found high activation of the ERK pathway also in epidermal melanocytes, suggesting a general predisposition to melanomagenesis in these horses. These findings demonstrate that the presence of the intronic 4.6 kb duplication in STX17 is strongly associated with constitutive activation of the ERK pathway in melanocytic cells in Grey horses in the absence of somatic mutations commonly linked to the activation of this
Klar, Agnes S; Biedermann, Thomas; Michalak, Katarzyna; Michalczyk, Teresa; Meuli-Simmen, Claudia; Scherberich, Arnaud; Meuli, Martin; Reichmann, Ernst
2017-12-01
There is accumulating evidence that interactions between epidermal melanocytes and stromal cells play an important role in the regulation of skin pigmentation. In this study we established a pigmented dermo-epidermal skin model, melDESS, of human origin to investigate the effects of distinct stromal cells on melanogenesis. melDESS is a complex, clinically relevant skin equivalent composed of an epidermis containing both melanocytes and keratinocytes. Its dermal compartment consists either of adipose tissue-derived stromal cells, dermal fibroblasts (Fbs), or a mixture of both cell types. These skin substitutes were transplanted for 5 weeks on the backs of immuno-incompetent rats and analyzed. Gene expression and Western blot analyses showed a significantly higher expression of transforming growth factor-β1 by adipose tissue-derived stromal cells compared with dermal Fbs. In addition, we showed that melanocytes responded to the increased levels of transforming growth factor-β1 by down-regulating the expression of key melanogenic enzymes such as tyrosinase. This caused decreased melanin synthesis and, consequently, greatly reduced pigmentation of melDESS. The conclusions are of utmost clinical relevance, namely that adipose tissue-derived stromal cells derived from the hypodermis fail to appropriately interact with epidermal melanocytes, thus preventing the sustainable restoration of the patient's native skin color in bioengineered skin grafts. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Directory of Open Access Journals (Sweden)
Yu-Mi Kim
2017-10-01
Full Text Available This study evaluated frequency-dependent effects of extremely low frequency electromagnetic fields (ELF-EMFs on melanogenesis by melanocytes in vitro. Melanocytes were exposed to 2 mT EMFs at 30–75 Hz for 3 days before melanogenesis was examined. Exposure to ELF-EMFs at 50 and 60 Hz induced melanogenic maturation without cell damage, without changing cell proliferation and mitochondrial activity. Melanin content and tyrosinase activity of cells exposed to 50 Hz were higher than in controls, and mRNA expression of tyrosinase-related protein-2 was elevated relative to controls at 50 Hz. Phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB levels were higher than controls in cells exposed to ELF-EMFs at 50–75 Hz. Immunohistochemical staining showed that melanocyte-specific markers (HMB45, Melan-A were strongly expressed in cells exposed to EMFs at 50 and 60 Hz compared to controls. Thus, exposure to ELF-EMFs at 50 Hz could stimulate melanogenesis in melanocytes, through activation of p-CREB and p-p38 and inhibition of phosphorylated extracellular signal-regulated protein kinase and phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase. The results may form the basis of an appropriate anti-gray hair treatment or be applied in a therapeutic device for inducing repigmentation in the skin of vitiligo patients.
A rare case of unilateral diffuse melanocytic proliferation
Directory of Open Access Journals (Sweden)
Guruprasad Ayachit
2018-01-01
Full Text Available A 67-year-old woman presented with metamorphopsia in the right eye. Leopard mottling was seen temporal to the fovea oculus dexter with corresponding hyper- and hypo-autofluorescent lesions on fundus autofluorescence. Spectral domain-optical coherence tomography revealed hyperreflective dots in the retinal pigment epithelium and choroid with subretinal fluid (SRF. Intravitreal bevacizumab was administered with which SRF resolved, albeit with increase in the areas of mottling. The patient was diagnosed to have metastatic ductal carcinoma of the right breast. It is important to bear in mind that the well-known entity of bilateral diffuse uveal melanocytic proliferation can rarely present unilaterally.
Wang, Shanshan; Dong, Cheng; Yu, Lian; Guo, Cheng; Jiang, Kezhi
2016-01-15
In the tandem mass spectrometry of protonated N-(3-phenyl-2H-chromen-2-ylidene)benzenesulfonamides, the precursor ions have been observed to undergo gas-phase dissociation via two competing channels: (a) the predominant channel involves migration of the sulfonyl cation to the phenyl C atom and the subsequent loss of benzenesulfinic acid along with cyclization reaction, and (b) the minor one involves dissociation of the precursor ion to give an ion/neutral complex of [sulfonyl cation/imine], followed by decomposition to afford sulfonyl cation or the INC-mediated electron transfer to give an imine radical cation. The proposed reaction channels have been supported by theoretical calculations and D-labeling experiments. The gas-phase cyclization reaction originating from the N- to C-sulfonyl cation transfer has been first reported to the best of our knowledge. For the substituted sulfonamides, the presence of electron-donating groups (R(2) -) at the C-ring effectively facilitates the reaction channel of cyclization reaction, whereas that of electron-withdrawing groups inhibits this pathway. Copyright © 2015 John Wiley & Sons, Ltd.
Energy Technology Data Exchange (ETDEWEB)
Wen, Jiangwei [The; Center; Shi, Wenyan [The; Zhang, Fan [The; Liu, Dong [The; Tang, Shan [The; Wang, Huamin [The; Lin, Xiao-Min [Center; Lei, Aiwen [The
2017-05-25
An,electrooxidative direct arylsulfonlylation of yones sulfintc acids via a radical tandem cyclization strategy has been developed for the construction of sulfonated ilicIenones:under oxidant, free conditions. This method provides a simple and efficient approach to prepare various sulfonylindenones in good to,excellent:Tyidds,, demonstrating the tremendous prospect of utilizing electrocatalysis in oxidative coupling, Notably, this reaction could Be easily scaled up with good, efficiency.
Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.
Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet; Kelsh, Robert N; Hansen, Lars; Levesque, Mitchell P; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L; Rosenberg, Thomas
2013-03-07
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 albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an 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 substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
International Nuclear Information System (INIS)
Knapp, F.F. Jr.; Beets, A.L.; Mirzadeh, S.; Guhlke, S.
1998-01-01
In this paper we describe the first application of our simple and inexpensive post-elution tandem cation/anion exchange column system which is based on generator elution with salts of weak acids such as ammonium acetate instead of saline solution to provide very high specific volume solutions of technetium-99m and rhenium-188 from clinical-scale molybdenum-99/technetium-99m generator prepared from low specific activity (n,y) molybdenum-99, and tungsten-188/rhenium-188 generators, respectively. Initial passage of the bolus through a strong cation exchange cartridge converts the ammonium acetate to acetic acid which is essentially not ionized at the acidic pH, allowing specific subsequent amine-type (QMA SepPak TM ) anion exchange cartridge column trapping of the microscopic levels of the pertechnetate or perrhenate. Subsequent elution of the anion cartridge with a small volume ( 500 mCi/mL) from the alumina-based tungsten-188/rhenium-188 generator. (author)
Ding, Qiuping; Wang, Zhiyong; Wu, Jie
2009-01-16
Tandem electrophilic cyclization-[3+2] cycloaddition-rearrangement reactions of 2-alkynylbenzaldoximes, DMAD, and bromine are described, which afford the unexpected isoquinoline-based azomethine ylides in good to excellent yields. The products could be further elaborated via palladium-catalyzed cross-coupling reactions to generate highly functionalized isoquinoline-based stable azomethine ylides.
Ivanova, Krassimira; Zadeh, Nahid Hamidi; Block, Ingrid; Das, Pranab K.; Gerzer, Rupert
2004-01-01
Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non-metastatic and metastatic
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
in an 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...
Gao, Yang; Huang, Yubing; Wu, Wanqing; Huang, Kefan; Jiang, Huanfeng
2014-08-07
An efficient Pd-catalyzed oxidative cyclization reaction for the synthesis of functionalized indolines by direct C-H activation of acetanilide has been developed. The norbornylpalladium species formed via direct ortho C-H activation of acetanilides is supposed to be a key intermediate in this transformation.
Nie, Jing; Zhu, Hong-Wei; Cui, Han-Feng; Hua, Ming-Qing; Ma, Jun-An
2007-08-02
A new catalytic stereoselective tandem transformation via Nazarov cyclization/electrophilic fluorination has been accomplished. This sequence is efficiently catalyzed by a Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity (trans/cis up to 49/1). Three examples of catalytic enantioselective tandem transformation are presented.
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.
International Nuclear Information System (INIS)
Dasgupta, Amrita; Katdare, Meena
2015-01-01
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
Mammalian melanocytes and radiations
International Nuclear Information System (INIS)
Hirobe, Tomohisa
2008-01-01
Melanocytes (M) decide the skin and hair color through the synthesis of melanine pigment, which is transported via their melanosome to keratinocytes (K) for body color expression in animals. This paper describes mainly author's studies of M concerning effects of ultraviolet (UV), ionizing radiation and heavy ion (carbon ion) beam on their development and differentiation together with its mechanism. In vitro, studies of UV effect on proliferation and differentiation of M and melanoblast (MB) have been greatly advanced since their culturing in serum-free media became possible using cells from author's black-mouse (C57BL/10JHir strain): Their mixed culture with K firstly revealed that their proliferation and differentiation were enhanced by UV irradiation. The important K's factor to regulate M/MB cells was identified to be GMCSF (granulocyte-macrophage colony-stimulating factor). In vivo studies of the skin color of the black-mouse before and after birth were performed using radiations like 60 Co gamma ray and high linear energy transfer (LET) carbon ion beam and have revealed that abnormal proliferation and differentiation of M/MB, which were expressed as white spot formation, death and mal-differentiation of M/MB, were induced dose-, LET- and developmental stage-dependently. (R.T.)
Kim, Minjeong; Baek, Heung Soo; Lee, Miri; Park, Hyeonji; Shin, Song Seok; Choi, Dal Woong; Lim, Kyung-Min
2016-04-01
Rhododenol or rhododendrol (RD, 4-(4-hydroxyphenyl)-2-butanol) occurs naturally in many plants along with raspberry ketone (RK, 4-(4-hydroxyphenyl)-2-butanone), a ketone derivative, which include Nikko maple tree (Acer nikoense) and white birch (Betula platyphylla). De-pigmenting activity of RD was discovered and it was used as a brightening ingredient for the skin whitening cosmetics. Recently, cosmetics containing RD were withdrawn from the market because a number of consumers developed leukoderma, inflammation and erythema on their face, neck and hands. Here, we explored the mechanism underlying the toxicity of RD and RK against melanocytes using B16F10 murine melanoma cells and human primary epidermal melanocytes. Treatment with RD or RK resulted in the decreased cell viability in a dose-dependent manner which appeared from cell growth arrest. Consistently, ROS generation was significantly increased by RD or RK as determined by DCF-enhanced fluorescence. An antioxidant enzyme, glutathione peroxidase was depleted as well. In line with ROS generation, oxidative damages and the arrest of normal cell proliferation, GADD genes (Growth Arrest and DNA Damage) that include GADD45 and GADD153, were significantly up-regulated. Prevention of ROS generation with an anti-oxidant, N-acetylcysteine (NAC) significantly rescued RD and RK-suppressed melanocyte proliferation. Consistently, up-regulation of GADD45 and GADD153 was significantly attenuated by NAC, suggesting that increased ROS and the resultant growth arrest of melanocytes may contribute to RD and RK-induced leukoderma. Copyright © 2016 Elsevier Ltd. All rights reserved.
Thermal decomposition of rhenium (5) complexes with 1,2,4-triazole
International Nuclear Information System (INIS)
Amindzhanov, A.A.; Gagieva, S.Ch.; Kotegov, K.V.
1991-01-01
Processes of thermal decomposition of rhenium (5) complexes with 1,2,4-triazole were studied. Thermolysis products were identified on the basis of data of the element analysis, IR spectra, conductometry and other methods. It is ascertained that at the first stage of thermolysis of hydroxyl-containing monomer complexes removal of water molecules occurs, and at the second one - dimerization process with formation of Re-O-Re group. It is shown that the nature of halide ion practically does not affect the temperature of the start of intensive thermal decomposition of the complexes
The analysis of mechanism of rhenium-coated tools' wear-resistance rising
Directory of Open Access Journals (Sweden)
Daniel Petrosyan
2017-06-01
Full Text Available It is proposed to obtain wear-resistant layers on the hard-alloy materials by thermochemical treatment. In the different field of production – mechanical engineering, metallurgy and military technologies, with machine parts demanding high wearproof and corrosion-proof machinery parts on the surfaces of syntheses of diamonds, with metal surface thermal-diffusion with rhenium, to receive diffusion wearing layers for the first time. A method for thermochemical treatment of hard alloy plates has been investigated, allowing to raise the wear-resistance of cutting and mining tools.
Grevelink, JM; vanLeeuwen, RL; Anderson, RR; Byers, HR
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
Oxidation of iridium coating on rhenium coated graphite at elevated temperature in stagnated air
International Nuclear Information System (INIS)
Huang, Yongle; Bai, Shuxin; Zhang, Hong; Ye, Yicong
2015-01-01
Highlights: • Continuous and dense Ir coatings were prepared on graphite by electrodepostion. • The purification of the as-prepared Ir coating was higher than about 99.98%. • The Ir/Re/C specimen kept integrity without significant failures after oxidation. • The average oxidation rate of the Ir coating was about 0.219 mg/(cm 2 min). • Penetrating holes at gains boundaries resulted in the failure of the Ir coating. - Abstract: Continuous and dense iridium coatings were prepared on the rhenium coated graphite specimens by electrodeposition. The iridium/rhenium coated graphite (Ir/Re/C) specimens were oxidized at elevated temperatures in stagnated air for 3600 s. The purification of the as-prepared Ir coating was higher than about 99.98% with the main impurity elements Si, Al, Fe and Ru. After oxidation, the Ir/Re/C specimens kept integrity without significant failures and the average oxidation rate was about 0.219 mg/(cm 2 min). Pores were found at the grain boundaries and concentrated to penetrating holes with the growth of Ir grains, which resulted in disastrous failures of the Ir coating
Oxidation of iridium coating on rhenium coated graphite at elevated temperature in stagnated air
Energy Technology Data Exchange (ETDEWEB)
Huang, Yongle; Bai, Shuxin, E-mail: NUDT_MSE_501@163.com; Zhang, Hong; Ye, Yicong
2015-02-15
Highlights: • Continuous and dense Ir coatings were prepared on graphite by electrodepostion. • The purification of the as-prepared Ir coating was higher than about 99.98%. • The Ir/Re/C specimen kept integrity without significant failures after oxidation. • The average oxidation rate of the Ir coating was about 0.219 mg/(cm{sup 2} min). • Penetrating holes at gains boundaries resulted in the failure of the Ir coating. - Abstract: Continuous and dense iridium coatings were prepared on the rhenium coated graphite specimens by electrodeposition. The iridium/rhenium coated graphite (Ir/Re/C) specimens were oxidized at elevated temperatures in stagnated air for 3600 s. The purification of the as-prepared Ir coating was higher than about 99.98% with the main impurity elements Si, Al, Fe and Ru. After oxidation, the Ir/Re/C specimens kept integrity without significant failures and the average oxidation rate was about 0.219 mg/(cm{sup 2} min). Pores were found at the grain boundaries and concentrated to penetrating holes with the growth of Ir grains, which resulted in disastrous failures of the Ir coating.
International Nuclear Information System (INIS)
Porst, Jan-Patrick
2011-01-01
This thesis describes the development of metallic magnetic calorimeters (MMCs) for high resolution spectroscopy. MMCs are energy dispersive particle detectors based on the calorimetric principle which are typically operated at temperatures below 100 mK. The detectors make use of a paramagnetic temperature sensor to transform the temperature rise upon the absorption of a particle in the detector into a measurable magnetic flux change in a dc-SQUID. The application of MMCs for neutrino mass measurements and their advantages with respect to other approaches are discussed. In view of this application the development of an MMC optimized for β-endpoint spectroscopy on 187 rhenium is presented. A fully micro-fabricated X-ray detector is characterized and performs close to design values. Furthermore, a new technique to more efficiently couple rhenium absorbers mechanically and thermally to the sensor was developed and successfully tested. By employing a metallic contact, signal rise times faster than 5 μs could be observed with superconducting rhenium absorbers. In addition to the single pixel detectors, an alternative approach of reading out multiple pixels was developed in this work, too. Here, the individual absorbers have a different thermal coupling to only one temperature sensor resulting in a distribution of different pulse shapes. Straightforward position discrimination by means of rise time analysis is demonstrated for a four pixel MMC and a thermal model of the detector is provided. Unprecedented so far, an energy resolution of less than ΔE FWHM <5 eV for 5.9 keV X-rays was achieved across all absorbers. (orig.)
International Nuclear Information System (INIS)
Arkowska, A.; Wojciechowski, W.
1979-01-01
Two rhenium compounds have been synthesized: compound 1 with cysteine HS-CH 2 -CH-NH 2 -COOH and compound 2 with homocysteine HS-CH 2 -CH 2 -CH-NH 2 -COOH. On the basis of spectroscopic measurements (IR, far IR, Raman, VIS and UV spectra) and magnetic susceptibility measurements their probable electronic and molecular structures have been determined. (author)
International Nuclear Information System (INIS)
Knapp, F.R. Jr.; Beets, A.L.; Mirzadeh, S.; Guhlke, S.; Univ. of Bonn
1998-03-01
In this paper the authors describe the first application of a simple and inexpensive post elution tandem cation-anion exchange column system which is based on generator elution with salts of weak acids such as ammonium acetate instead of saline solution to provide very high specific volume solutions of technetium-99m and rhenium-188 from clinical scale molybdenum-99/technetium-99m generator prepared from low specific activity (n,y) molybdenum-99, and tungsten-188/rhenium-188 generators, respectively. Initial passage of the bolus through a strong cation exchange cartridge converts the ammonium acetate to acetic acid which is essentially not ionized at the acidic pH, allowing specific subsequent amine type (QMA SepPak trademark) anion exchange cartridge column trapping of the microscopic levels of the pertechnetate or perrhenate. Subsequent elution of the anion cartridge with a small volume ( 500 mCi/mL) from the alumina-based tungsten-188/rhenium-188 generator
Rhenium (5) and molybdenum (5) complexes with 4',4''(5'')-ditretbutyldibenzo-24-crown-8
International Nuclear Information System (INIS)
Ashurova, N.Kh.; Yakubov, K.G.; Basitova, S.M.; Tashmukhamedova, A.K.; Sajfullina, N.Zh.
1989-01-01
Rhenium and molybdenum complexes in +5 oxidation degree with 4',4''(5'')-ditretbutyldibenzo-24-crown-8 (L) are synthesized with 75-95 % yield. Composition and structure of compounds produced are investigated using element analysis, conductometry, IR spectroscopy, thermogravimetry methods. Oxidation degree of complexer metal is determined. It is ascertained that the compound composition corresponds to the MOLX 3 formula, where M-Re, Mo; X-Cl - , Br -
Xiang, Shi-Kai; Tan, Wen; Zhang, Dong-Xue; Tian, Xian-Li; Feng, Chun; Wang, Bi-Qin; Zhao, Ke-Qing; Hu, Ping; Yang, Hua
2013-11-14
The synthesis of benzimidazoles by intermolecular cyclization reaction of 2-iodoanilines with nitriles has been developed. These reactions proceeded without the aid of any transition metals or ligands and just using KOBu(t) as the base. A variety of substituted benzimidazole derivatives can be synthesized by the approach.
Chalcogenhalide cluster rhenium- and molybdenum complexes
International Nuclear Information System (INIS)
Fedin, V.P.; Gubin, S.P.; Mishchenko, A.V.; Fedorov, V.E.
1984-01-01
The interaction of rhenium- and molybdenum chalcogenhalides with n-donor ligands (L) is studied. At heating Re 3 X 2 Hal 5 complexes up to 100 deg in DMSO in the L presence obtained are the complexes of the 1-6 composition Re 3 X 2 Hal 5 -x Lx DMSO (X=Se, Hal=Cl, L=Et 3 N(1); X=Se, Hal=Cl, L=Bipy(2); X=Se, Hal=Br, L=Et 3 N(3); X=Se, Hal=Br, L=Bipy(4); X=Te, Hal=Br, L=Et 3 N(5); X=Te, Hal=Br, L=(Me 2 NCH 2 ) 2 (6). In the course of boiling of Mo 3 S 7 Hal 4 with PPh 3 in MeCN the Mo 3 S 7 Hal 4 2PPh 3 complexes (Hal=Cl(7); Br(8)) are obtained. For 1 through 8 complexes the chemical analysis data and IR spectra are given. For 4 and 8 complexes the molecular mass is measured. A possible method of obtaining molecular trinuclear clusters from polymer clusters is discussed
Directory of Open Access Journals (Sweden)
Sheng Liu
2015-08-01
Full Text Available An ascorbic acid-promoted and metal-free tandem room temperature cyclization of N-arylacrylamides with 4-nitrobenzenediazonium generated in situ was developed. This reaction proceeds smoothly through a radical mechanism and provides an environmentally friendly alternative approach to biologically active 3-alkyl-3-benzyloxindoles, avoiding the use of excess oxidants and light irradiation.
Development of the Vinylogous Pictet-Spengler Cyclization and Total Synthesis of (±)-Lundurine A.
Nash, Aaron; Qi, Xiangbing; Maity, Pradip; Owens, Kyle; Tambar, Uttam K
2018-04-16
A novel vinylogous Pictet-Spengler cyclization has been developed for the generation of indole-annulated medium-sized rings. The method enables the synthesis of tetrahydroazocinoindoles with a fully substituted carbon center, a prevalent structural motif in many biologically active alkaloids. The strategy has been applied to the total synthesis of (±)-lundurine A. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Czech Academy of Sciences Publication Activity Database
Storch, Jan; Čermák, Jan; Karban, Jindřich
2007-01-01
Roč. 48, č. 38 (2007), s. 6814-6816 ISSN 0040-4039 R&D Projects: GA MŠk(CZ) LC06070 Institutional research plan: CEZ:AV0Z40720504 Keywords : aromate * cyclization * cycloizomerization Subject RIV: CC - Organic Chemistry Impact factor: 2.615, year: 2007
Zhu, Cansheng; Yuan, Xiaoying; Li, Dongguang; Gu, Weijie; Ma, Huimin; Xie, Xin; Gao, Tianwen
2012-01-01
Background Melanosomes are specialized membrane-surrounded organelles, which are involved in the synthesis, storage and transport of melanin. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB), a melanosome-specific structural protein, shares significant amino acid sequence homology with Pmel-17. Proteomic analysis demonstrated that GPNMB is present in all stages (I-IV) of melanosomes. However, little is known about the role of GPNMB in melanosomes. Methodology/Principal Findings Using real-time quantitative PCR, Western blotting and immunofluorescence analysis, we demonstrated that the expression of GPNMB in PIG1 melanocytes was up-regulated by ultraviolet B (UVB) radiation. Transmission electron microscopy analysis showed that the total number of melanosomes in PIG1 melanocytes was sharply reduced by GPNMB-siRNA transfection. Simultaneously, the expression levels of tyrosinase (Tyr), tyrosinase related protein 1 (Trp1), Pmel17/gp100 and ocular albinism type 1 protein (OA1) were all significantly attenuated. But the expression of microphthalmia-associated transcription factor (MITF) was up-regulated. Intriguingly, in GPNMB silenced PIG1 melanocytes, UVB radiation sharply reduced MITF expression. Conclusion Our present work revealed that the GPNMB was critical for the formation of melanosomes. And GPNMB expression down-regulation attenuated melanosome formation in a MITF-independent fashion. PMID:22912767
Convenient synthesis of bis(alkoxy)rhenium(VII) complexes
Energy Technology Data Exchange (ETDEWEB)
Zhu, Z.; Al-Ajlouni, A.M.; Espenson, J.H. [Iowa State Univ., Ames, IA (United States)
1996-02-28
The study of high-oxidation-state organorhenium compounds has been a field of continuing activity, thanks to the success of methylrhenium trioxide (CH{sub 3}ReO{sub 3} or MTO) in catalytic processes. This catalyst is effective in oxidations, olefin metathesis, the olefination of aldehydes, and the preparation of other compounds with three-membered rings. The syntheses of some rhenium compounds derived form MTO have been reported. Epoxide formation is a key reaction, and it bears directly on these findings reported here. Re(VII) complexes containing a chelated bis(diolate) ligand can be synthesized by refluxing MTO with 2,3-dimethyl-2,3-diol. Here, the authors report a more convenient method for this preparation. A different series of related compounds consists of chelated bis(diolates) of the Cp*Re-oxo series, Cp*ReO-(diolate).
Energy Technology Data Exchange (ETDEWEB)
Porst, Jan-Patrick
2011-02-01
This thesis describes the development of metallic magnetic calorimeters (MMCs) for high resolution spectroscopy. MMCs are energy dispersive particle detectors based on the calorimetric principle which are typically operated at temperatures below 100 mK. The detectors make use of a paramagnetic temperature sensor to transform the temperature rise upon the absorption of a particle in the detector into a measurable magnetic flux change in a dc-SQUID. The application of MMCs for neutrino mass measurements and their advantages with respect to other approaches are discussed. In view of this application the development of an MMC optimized for {beta}-endpoint spectroscopy on {sup 187}rhenium is presented. A fully micro-fabricated X-ray detector is characterized and performs close to design values. Furthermore, a new technique to more efficiently couple rhenium absorbers mechanically and thermally to the sensor was developed and successfully tested. By employing a metallic contact, signal rise times faster than 5 {mu}s could be observed with superconducting rhenium absorbers. In addition to the single pixel detectors, an alternative approach of reading out multiple pixels was developed in this work, too. Here, the individual absorbers have a different thermal coupling to only one temperature sensor resulting in a distribution of different pulse shapes. Straightforward position discrimination by means of rise time analysis is demonstrated for a four pixel MMC and a thermal model of the detector is provided. Unprecedented so far, an energy resolution of less than {delta}E{sub FWHM}<5 eV for 5.9 keV X-rays was achieved across all absorbers. (orig.)
International Nuclear Information System (INIS)
Miao Yubin; Fisher, Darrell R.; Quinn, Thomas P.
2006-01-01
Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys 3,4,1 , D-Phe 7 , Arg 11 ]α-melanocyte stimulating hormone 3-13 {DOTA-Re(Arg 11 )CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu 2 , Arg 11 )CCMSH was designed, synthesized and labeled with 9 Y and 177 Lu. Pharmacokinetics of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH exhibited significantly (P 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH were 28.16% and 28.81% of those of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH displayed higher tumor-to-kidney uptake ratios than 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was 2.28 and 1.69 times of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. The 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )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 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma
Energy Technology Data Exchange (ETDEWEB)
AA KRUGER; A GOEL; CP RODRIGUEZ; JS MCCLOY; MJ SCHWEIGER; WW LUKENS; JR, BJ RILEY; D KIM; M LIEZERS; P HRMA
2012-08-13
The immobilization of 99Tc in a suitable host matrix has proved a challenging task for researchers in the nuclear waste community around the world. At the Hanford site in Washington State in the U.S., the total amount of 99Tc in low-activity waste (LAW) is {approx} 1,300 kg and the current strategy is to immobilize the 99Tc in borosilicate glass with vitrification. In this context, the present article reports on the solubility and retention of rhenium, a nonradioactive surrogate for 99Tc, in a LAW sodium borosilicate glass. Due to the radioactive nature of technetium, rhenium was chosen as a simulant because of previously established similarities in ionic radii and other chemical aspects. The glasses containing target Re concentrations varying from 0 to10,000 ppm by mass were synthesized in vacuum-sealed quartz ampoules to minimize the loss of Re by volatilization during melting at 1000 DC. The rhenium was found to be present predominantly as Re7 + in all the glasses as observed by X-ray absorption near-edge structure (XANES). The solubility of Re in borosilicate glasses was determined to be {approx}3,000 ppm (by mass) using inductively coupled plasma-optical emission spectroscopy (ICP-OES). At higher rhenium concentrations, some additional material was retained in the glasses in the form of alkali perrhenate crystalline inclusions detected by X-ray diffraction (XRD) and laser ablation-ICP mass spectrometry (LA-ICP-MS). Assuming justifiably substantial similarities between Re7 + and Tc 7+ behavior in this glass system, these results implied that the processing and immobilization of 99Tc from radioactive wastes should not be limited by the solubility of 99Tc in borosilicate LAW glasses.
Seet, Katrina Y T; Nieminen, Timo A; Zvyagin, Andrei V
2009-01-01
The cell nucleus is the dominant optical scatterer in the cell. Neoplastic cells are characterized by cell nucleus polymorphism and polychromism-i.e., the nuclei exhibits an increase in the distribution of both size and refractive index. The relative size parameter, and its distribution, is proportional to the product of the nucleus size and its relative refractive index and is a useful discriminant between normal and abnormal (cancerous) cells. We demonstrate a recently introduced holographic technique, digital Fourier microscopy (DFM), to provide a sensitive measure of this relative size parameter. Fourier holograms were recorded and optical scatter of individual scatterers were extracted and modeled with Mie theory to determine the relative size parameter. The relative size parameter of individual melanocyte cell nuclei were found to be 16.5+/-0.2, which gives a cell nucleus refractive index of 1.38+/-0.01 and is in good agreement with previously reported data. The relative size parameters of individual malignant melanocyte cell nuclei are expected to be greater than 16.5.
Boyce, Jonathan H.
Polycyclic polyprenylated acylphloroglucinols (PPAPs) are structurally complex natural products with promising biological activities. These compounds have interesting anticancer and anti-HIV properties as well as other biological activities making them highly attractive synthetic targets. We report a stereodivergent, asymmetric total synthesis of (-)-clusianone in six steps from commercial materials. We have implemented a challenging cationic cyclization forging a bond between two sterically encumbered quaternary carbon atoms. Mechanistic studies point to the unique ability of formic acid to mediate the cyclization forming the clusianone framework. We also present a biosynthesis-inspired, diversity-oriented synthesis approach for rapid construction of PPAP analogs via palladium-catalyzed dearomative conjunctive allylic alkylation (DCAA). These efficient palladium-catalyzed protocols construct the [3.3.1]-bicyclic PPAP core in a single step from their stable aromatic precursors. The first syntheses of 13,14-didehydroxyisogarcinol and garcimultiflorone A stereoisomers are reported in six steps from a commercially available phloroglucinol. Lewis acid-controlled, diastereoselective cationic oxycyclizations enabled asymmetric syntheses of (-)-6-epi-13,14-didehydroxyisogarcinol and (+)-30-epi-13,14-didehydroxyisogarcinol. A similar strategy enabled production of the meso-derived isomers (+/-)-6,30- epi-13,14-didehydroxyisogarcinol and (+/-)-6,30-epi -garcmultiflorone A. A convenient strategy for gram scale synthesis of these stereoisomers was developed utilizing diastereomer separation at a later stage in the synthesis that minimized the number of necessary synthetic operations to access all possible stereoisomers. Finally, we report cationic rearrangements of dearomatized acylphloroglucinols leading to the formation of unprecedented PPAP scaffolds. A novel type A [3.3.1]-bicyclic PPAP was produced as a major product and the structure confirmed by X-ray crystallographic
Czech Academy of Sciences Publication Activity Database
Kafka, František; Pohl, Radek; Císařová, I.; Mackman, R.; Bahador, G.; Jahn, Ullrich
2016-01-01
Roč. 2016, č. 22 (2016), s. 3862-3871 ISSN 1434-193X R&D Projects: GA ČR GA13-40188S Grant - others:COST(XE) CM1201 Institutional support: RVO:61388963 Keywords : tandem reactions * nitrogen heterocycles * Michael addition * radical reactions * cyclization * enolates Subject RIV: CC - Organic Chemistry Impact factor: 2.834, year: 2016
The direct oxidative diene cyclization and related reactions in natural product synthesis
Directory of Open Access Journals (Sweden)
Juliane Adrian
2016-09-01
Full Text Available The direct oxidative cyclization of 1,5-dienes is a valuable synthetic method for the (diastereoselective preparation of substituted tetrahydrofurans. Closely related reactions start from 5,6-dihydroxy or 5-hydroxyalkenes to generate similar products in a mechanistically analogous manner. After a brief overview on the history of this group of transformations and a survey on mechanistic and stereochemical aspects, this review article provides a summary on applications in natural product synthesis. Moreover, current limitations and future directions in this area of chemistry are discussed.
Rhenium Alloys as Ductile Substrates for Diamond Thin-Film Electrodes.
Halpern, Jeffrey M; Martin, Heidi B
2014-02-01
Molybdenum-rhenium (Mo/Re) and tungsten-rhenium (W/Re) alloys were investigated as substrates for thin-film, polycrystalline boron-doped diamond electrodes. Traditional, carbide-forming metal substrates adhere strongly to diamond but lose their ductility during exposure to the high-temperature (1000°C) diamond, chemical vapor deposition environment. Boron-doped semi-metallic diamond was selectively deposited for up to 20 hours on one end of Mo/Re (47.5/52.5 wt.%) and W/Re (75/25 wt.%) alloy wires. Conformal diamond films on the alloys displayed grain sizes and Raman signatures similar to films grown on tungsten; in all cases, the morphology and Raman spectra were consistent with well-faceted, microcrystalline diamond with minimal sp 2 carbon content. Cyclic voltammograms of dopamine in phosphate-buffered saline (PBS) showed the wide window and low baseline current of high-quality diamond electrodes. In addition, the films showed consistently well-defined, dopamine electrochemical redox activity. The Mo/Re substrate regions that were uncoated but still exposed to the diamond-growth environment remained substantially more flexible than tungsten in a bend-to-fracture rotation test, bending to the test maximum of 90° and not fracturing. The W/Re substrates fractured after a 27° bend, and the tungsten fractured after a 21° bend. Brittle, transgranular cleavage fracture surfaces were observed for tungsten and W/Re. A tension-induced fracture of the Mo/Re after the prior bend test showed a dimple fracture with a visible ductile core. Overall, the Mo/Re and W/Re alloys were suitable substrates for diamond growth. The Mo/Re alloy remained significantly more ductile than traditional tungsten substrates after diamond growth, and thus may be an attractive metal substrate for more ductile, thin-film diamond electrodes.
Arck, Petra Clara; Overall, Rupert; Spatz, Katharina; Liezman, Christiane; Handjiski, Bori; Klapp, Burghard F; Birch-Machin, Mark A; Peters, Eva Milena Johanne
2006-07-01
Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.
Premalignant quiescent melanocytic nevi do not express the MHC class I chain-related protein A
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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.
Directory of Open Access Journals (Sweden)
Douglas Blackiston
2011-01-01
Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl. Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT. These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior.
DEFF Research Database (Denmark)
Ascic, Erhad; Jensen, Jakob Feldthusen; Nielsen, Thomas Eiland
2011-01-01
Tandem bicycle: In the title reaction double bonds created during ring-closing metathesis isomerize to generate reactive iminium intermediates that undergo intramolecular cyclization reactions with tethered heteroatom and carbon nucleophiles. In this way, a series of biologically interesting hete...... heterocyclic compounds can be made, including a known precursor for the total synthesis of the antiparasitic natural product harmicine....
Directory of Open Access Journals (Sweden)
Visalini Muthusamy
2011-01-01
Full Text Available UV-induced inflammation and reactive oxygen species formation are involved in the development of melanoma. Natural products like 5β-scymnol and CO2-supercritical fluid extract (CO2-SFE of mussel oil contain anti-inflammatory and antioxidant properties that may aid in reducing the deleterious effects of UV radiation. Therefore, their effect on the release of the proinflammatory cytokine, tumour necrosis factor-α (TNF-α, from UVB-irradiated human melanocytic cells was examined. Human epidermal melanocytes (HEM and MM96L melanoma cells were exposed to UVB radiation and IL-1α. Cell viability and TNF-α levels were determined 24 hours after-irradiation while p38 mitogen-activated protein kinase (MAPK activation was observed at 15 min after-irradiation. When α-tocopherol, CO2-SFE mussel oil, and 5β-scymnol were added to the UVB-irradiated HEM cells treated with IL-1α, TNF-α levels fell by 53%, 65%, and 76%, respectively, while no inhibition was evident in MM96L cells. This effect was not due to inhibition of the intracellular p38 MAPK signalling pathway. These compounds may be useful in preventing inflammation-induced damage to normal melanocytes.
Poorman, Kelsey; Borst, Luke; Moroff, Scott; Roy, Siddharth; Labelle, Philippe; Motsinger-Reif, Alison; Breen, Matthew
2015-06-01
Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3-17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.
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Amit Kumar
2013-10-01
Full Text Available An Ugi four-component reaction of propargylamine with 3-formylindole and various acids and isonitriles produces adducts which are subjected to a cationic gold-catalyzed diastereoselective domino cyclization to furnish diversely substituted spiroindolines. All the reactions run via an exo-dig attack in the hydroarylation step followed by an intramolecular diastereoselective trapping of the imminium ion. The whole sequence is atom economic and the application of a multicomponent reaction assures diversity.
Liang, Zhongwei; Xu, Song; Tian, Wenyan; Zhang, Ronghua
2015-01-01
A novel and simple strategy for the efficient synthesis of the corresponding tetrahydroquinolines from N,N-dimethylanilines and maleimides using visible light in an air atmosphere in the presence of Eosin Y as a photocatalyst has been developed. The metal-free protocol involves aerobic oxidative cyclization via sp(3) C-H bond functionalization process to afford good yields in a one-pot procedure under mild conditions.
Alkene-glycol interconversion with technetium and rhenium oxo complexes
International Nuclear Information System (INIS)
Pearlstein, R.M.; Davison, Alan
1988-01-01
The trioxotechnetium(VII) complexes TcO 3 Cl(AA) (AA = phen, bpy, 5-NO 2 -phen, 3,4,7,8-Me 4 -phen) cleanly oxidize olefins (C 2 R 4 ) in solution at 22 0 C, forming in high yields the corresponding oxotechnetium(V) diolate complexes, TcOCl(OCR 2 CR 2 O)(AA). The complexes have been characterized by 1 H NMR, IR, elemental analysis, and fast atom bombardment mass spectrometry. The free diols isolated by hydrolysis of these diolate complexes with HCl were shown by capillary gas chromatography to represent syn addition of the two hydroxyl groups across the double bond. The related rhenium complex, ReOCl(OCH 2 CH 2 O)(phen) undergoes the reverse reaction when thermalized, releasing ethylene and producing ReO 3 Cl(phen). (author)
Altered expression of versican and hyaluronan in melanocytic tumors of dogs.
Docampo, María-José; Rabanal, Rosa M; Miquel-Serra, Laia; Hernández, Daniel; Domenzain, Clelia; Bassols, Anna
2007-12-01
To analyze the expression of versican and hyaluronan in melanocytomas and malignant melanomas of dogs, to correlate their expression with expression of the hyaluronan receptor CD44, and to identify enzymes responsible for the synthesis and degradation of hyaluronan in canine dermal fibroblasts and canine melanoma cell lines. 35 biopsy specimens from melanocytic tumors of dogs, canine primary dermal fibroblasts, and 3 canine melanoma cell lines. Versican, hyaluronan, and CD44 were detected in tumor samples by use of histochemical or immunohistochemical methods. Expression of hyaluronan-metabolizing enzymes was analyzed with a reverse transcriptase-PCR assay. Versican was found only in some hair follicles and around some blood vessels in normal canine skin, whereas hyaluronan was primarily found within the dermis. Hyaluronan was found in connective tissue of the oral mucosa. Versican and, to a lesser extent, hyaluronan were significantly overexpressed in malignant melanomas, compared with expression in melanocytomas. No significant difference was found between malignant tumors from oral or cutaneous origin. The expression of both molecules was correlated, but hyaluronan had a more extensive distribution than versican. Versican and hyaluronan were mainly associated with tumor stroma. Canine fibroblasts and melanoma cell lines expressed hyaluronan synthase 2 and 3 (but not 1) and hyaluronidase 1 and 2. Versican may be useful as a diagnostic marker for melanocytic tumors in dogs. Knowledge of the enzymes involved in hyaluronan metabolism could reveal new potential therapeutic targets.
Jo, Seo-Hyeon; Park, Hyung-Youl; Kang, Dong-Ho; Shim, Jaewoo; Jeon, Jaeho; Choi, Seunghyuk; Kim, Minwoo; Park, Yongkook; Lee, Jaehyeong; Song, Young Jae; Lee, Sungjoo; Park, Jin-Hong
2016-08-01
The effects of triphenylphosphine and (3-aminopropyl)triethoxysilane on a rhenium diselenide (ReSe2 ) photodetector are systematically studied by comparing with conventional MoS2 devices. This study demonstrates a very high performance ReSe2 photodetector with high photoresponsivity (1.18 × 10(6) A W(-1) ), fast photoswitching speed (rising/decaying time: 58/263 ms), and broad photodetection range (possible above 1064 nm). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Zhongwei Liang
2015-04-01
Full Text Available A novel and simple strategy for the efficient synthesis of the corresponding tetrahydroquinolines from N,N-dimethylanilines and maleimides using visible light in an air atmosphere in the presence of Eosin Y as a photocatalyst has been developed. The metal-free protocol involves aerobic oxidative cyclization via sp3 C–H bond functionalization process to afford good yields in a one-pot procedure under mild conditions.
Czech Academy of Sciences Publication Activity Database
Amatov, Tynchtyk; Gebauer, Martin; Pohl, Radek; Císařová, I.; Jahn, Ullrich
2016-01-01
Roč. 50, Suppl 1 (2016), S6-S17 ISSN 1071-5762 Grant - others:COST(XE) CM1201 Institutional support: RVO:61388963 Keywords : alkaloids * diketopiperazines * radical cyclizations * single electron transfer * oxidation Subject RIV: CC - Organic Chemistry Impact factor: 3.188, year: 2016 http://www.tandfonline.com/doi/full/10.1080/10715762.2016.1223295
Energy Technology Data Exchange (ETDEWEB)
NONE
1998-03-01
Production of the radioactive rhenium isotopes {sup 186}Re and {sup 188}Re, and synthesis of their labeled compounds have been studied together with the biodistributions of the compounds. This work was carried out by the Working Group on Radioactive Rhenium, consisting of researchers of JAERI and some universities, in the Subcommittee for Production and Radiolabeling under the Consultative Committee of Research on Radioisotopes. For {sup 186}Re, production methods by the {sup 185}Re(n,{gamma}){sup 186}Re reaction in a reactor and by the {sup 186}W(p,n){sup 186}Re reaction with an accelerator, which can produce nocarrier-added {sup 186}Re, have been established. For {sup 188}Re, a production method by the double neutron capture reaction of {sup 186}W, which produces a {sup 188}W/{sup 188}Re generator, has been established. For labeling of bisphosphonate, DMSA, DTPA, DADS, aminomethylenephosphonate and some monoclonal antibodies with the radioactive rhenium isotopes, the optimum conditions, including pH, the amounts of reagents and so on, have been determined for each compound. The biodistributions of each of the labeled compounds in mice have been also obtained. (author)
Choi, Hyunjung; Kim, Mina; Ahn, Song Ih; Cho, Eun-Gyung; Lee, Tae Ryong; Shin, Jennifer H
2014-03-01
The elasticity of the cellular microenvironment is a key regulator of cellular physiology in many cell types. To investigate the effects of substrate stiffness on the pigmentation process, we cultured normal human melanocytes (NHM) and MNT1 melanoma cells on laminin-coated polydimethylsiloxane (PDMS) substrates of different stiffness. The dendricity of NHM and MNT1 cells was reduced as the substrate stiffness decreased, and the degree of melanosome transfer from NHM or MNT1 cells to normal human keratinocytes was decreased on softer substrates with the reduced dendricity. Gene and protein expressions of MITF, tyrosinase, TRP2, and gp100/PMEL17 exhibited a consistent decreasing trend with the decreasing stiffness. Because the stiffness sensing is mediated by focal adhesion complex through integrin receptors, we checked laminin specific integrin alpha 6 and p-FAK for MNT1 cells to observe that the substrate adhesion was weakened as the substrate stiffness decreased. Weaker adhesion on a softer substrate was accompanied by dynamic shape changes in MNT1 cells with higher speed and larger scattering. Dendritic MNT1 cells cultured on a stiffer substrate exhibited lower migration with smaller root mean squared displacement. These results demonstrate the possibility that skin pigmentation can be influenced by mechanical properties of the cellular microenvironment and can increase when the skin becomes stiff. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L
2015-10-01
The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.
Synthesis, molecular structure and magnetic properties of a rhenium(IV) compound with catechol
Cuevas, A.; Geis, L.; Pintos, V.; Chiozzone, R.; Sanchíz, J.; Hummert, M.; Schumann, H.; Kremer, C.
2009-03-01
A novel Re(IV) complex containing catechol as ligand has been prepared and characterized. The crystal structure of (HNEt 3)(NBu 4)[ReCl 4(cat)]·H 2cat was determined. The rhenium ion presents a distorted octahedral geometry, being bonded to a bidentate catecholate group and four chloride anions. The magnetic properties of the complex were studied, a /2 D/ (the energy gap between ±3/2 and ±1/2 Kramers doublets) value of 190(10) cm -1. This is the largest /2 D/ value reported for Re(IV) up to now.
International Nuclear Information System (INIS)
Goehler, Thomas
2016-01-01
In the present work, design criteria and property models for the creep strength optimization of rhenium-free nickel based single crystal Superalloys are investigated. The study focuses on a typical load condition of 1050 C and 150 MPa, which is representative for flight engine applications. Thereby the key aspect is to link chemical composition, manufacturing processes, microstructure formation and mechanistic understanding of dislocation creep through a computational materials engineering approach. Beside the positive effect of rhenium on solid solution hardening, a second mechanism in which rhenium increases high temperature creep strength is identified. It indirectly stabilizes precipitation hardening by reducing the coarsening kinetics of γ'-rafting. Five 1st and 2nd generation technical Superalloys show a comparable microstructure evolution for up to 2 % plastic elongation, while creep times differ by a factor of five. The application of a microstructure sensitive creep model shows that these coarsening processes can activate γ-cutting and thus lead to an increasing creep rate. Based on these calculations a threshold value of φ γ/γ' > 2,5 at 150 MPa is estimated. This ratio of matrix channel to raft thickness has been proofed for multiple positions by microstructure analysis of interrupted creep tests. The mechanism described previously can be decelerated by the enrichment of the γ-matrix with slow diffusing elements. The same principle also increases the solid solution strength of the γ-matrix. Therefore, the present work delivers an additional mechanistic explanation why creep properties of single phase nickel based alloys can be transferred to two phase technical Superalloys with rafted γ'-structure. Following, the best way to substitute both rhenium fundamental properties, namely a slow diffusion coefficient and a small solubility in g', has been investigated by means of CALPHAD-modeling. Only molybdenum and especially tungsten
The Influence of Cobalt and Rhenium on the Behaviour of MCrAlY Coatings
Täck, Ulrike
2009-01-01
Superalloys are widely applied as materials for components in the hot section of gas turbines. As superalloys have a limited oxidation life, the application of a coating is vital. The most commonly applied coatings in stationary gas turbines are MCrAlY coatings. Since the turbine components are exposed to high cyclic thermal stresses, MCrAlY coatings must also show a high thermal fatigue resistance. In this thesis, the effect of Cobalt and Rhenium on microstructure, oxidation and thermal fati...
Xu, Guangyang; Zhu, Chenghao; Gu, Weijin; Li, Jian; Sun, Jiangtao
2015-01-12
An unprecedented gold-catalyzed ligand-controlled cross-coupling of diazo compounds by sequential selective denitrogenation and cyclization affords N-substituted pyrazoles in a position-switchable mode. This novel transformation features selective decomposition of one diazo moiety and simultaneous preservation of the other one from two substrates. Notably, the choice of the ancillary ligand to the gold complex plays a pivotal role on the chemo- and regioselectivity of the reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Narea, J. Freddy; Muñoz, Aarón A.; Castro, Jorge; Muñoz, Rafael A.; Villalba, Caroleny E.; Martinez, María. F.; Bravo, Kelly D.
2013-11-01
Human skin has been studied in numerous investigations, given the interest in knowing information about physiology, morphology and chemical composition. These parameters can be determined using non invasively optical techniques in vivo, such as the diffuse reflectance spectroscopy. The human skin color is determined by many factors, but primarily by the amount and distribution of the pigment melanin. The melanin is produced by the melanocytes in the basal layer of the epidermis. This research characterize the spectral response of the human skin using the coefficients of Fourier series expansion. Simulating the radiative transfer equation for the Monte Carlo method to vary the concentration of the melanocytes (fme) in a simplified model of human skin. It fits relating the Fourier series coefficient a0 with fme. Therefore it is possible to recover the skin biophysical parameter.
Fate of rhenium in the environment as a chemical analogue of technetium
International Nuclear Information System (INIS)
Tagami, Keiko; Uchida, Shigeo
2007-01-01
Concentrations of rhenium, a chemical analogue of Tc, were measured in various environmental samples by ICP-MS to obtain information values on long-lived 99 Tc mobility in the environment. From the results, it was assumed that Re was removed from the rock and soil by water due to weathering and transport to the sea through rivers. The element would be retained in seawater for a long time, i.e., 2 x 10 5 to 7.5 x 10 5 y. The reservoirs of Re in the sea would be seaweeds, and anoxic and suboxic sediments, especially slightly below the water-sediment interface. (author)
Hot rocket plume experiment - Survey and conceptual design. [of rhenium-iridium bipropellants
Millard, Jerry M.; Luan, Taylor W.; Dowdy, Mack W.
1992-01-01
Attention is given to a space-borne engine plume experiment study to fly an experiment which will both verify and quantify the reduced contamination from advanced rhenium-iridium earth-storable bipropellant rockets (hot rockets) and provide a correlation between high-fidelity, in-space measurements and theoretical plume and surface contamination models. The experiment conceptual design is based on survey results from plume and contamination technologists throughout the U.S. With respect to shuttle use, cursory investigations validate Hitchhiker availability and adaptability, adequate remote manipulator system (RMS) articulation and dynamic capability, acceptable RMS attachment capability, adequate power and telemetry capability, and adequate flight altitude and attitude/orbital capability.
Doubleday, Charles; Boguslav, Mayla; Howell, Caronae; Korotkin, Scott D; Shaked, David
2016-06-22
An unusual H/D kinetic isotope effect (KIE) is described, in which isotopic selectivity arises primarily from nonstatistical dynamics in the product. In DFT-based quasiclassical trajectories of Bergman cyclization of (Z)-3-hexen-1,5-diyne (1) at 470 K, the new CC bond retains its energy, and 28% of nascent p-benzyne recrosses back to the enediyne on a vibrational time scale. The competing process of intramolecular vibrational redistribution (IVR) in p-benzyne is too slow to prevent this. Deuteration increases the rate of IVR, which decreases the fraction of recrossing and increases the yield of statistical (trapable) p-benzyne, 2. Trapable yields for three isotopomers of 2 range from 72% to 86%. The resulting KIEs for Bergman cyclization differ substantially from KIEs predicted by transition state theory, which suggests that IVR in this reaction can be studied by conventional KIEs. Leakage of vibrational zero point energy (ZPE) into the reaction coordinate was probed by trajectories in which initial ZPE in the CH/CD stretching modes was reduced by 25%. This did not change the predicted KIEs.
Tosios, Konstantinos I; Prountzos, Nikolaos; Katsoulas, Nikolaos; Koutlas, Ioannis G; Sklavounou-Andrikopoulou, Alexandra
2012-03-01
Melanin pigment and melanocytes may be found in odontogenic cysts and tumors, particularly calcifying cystic odontogenic tumor (CCOT). In the present study we investigated the immunohistochemical expression of the Melan-A/Mart-1 and HMB-45 antigens in 13 Caucasians patients with CCOT. Melan-A/Mart-1- and HMB-45-positive melanocytes were not seen in any of the cases. Our findings are in agreement with the assumption that pigmentation in odontogenic lesions may be a racial phenomenon.
DEFF Research Database (Denmark)
Linderoth, Lars; Peters, Günther H.j.; Madsen, Robert
2009-01-01
Special delivery: Liposomal drug-delivery systems in which prodrugs are activated specifically by disease-associated enzymes have great potential for the treatment of severe diseases, such as cancer. A new type of phospholipid-based prodrug has the ability to form stable small unilamellar vesicle...... (see picture). Activation of the prodrug vesicles by the enzyme sPLA2 initiates a cyclization reaction, which leads to the release of the drug....
International Nuclear Information System (INIS)
Knapp, F.F.Jr.; Turner, J.H.; Jeong, J.-M.; Padhy, A.K.
2004-01-01
The ready availability of no-carrier-added Rhenium-188 from the Tungsten-188/Rhenium-188 generator represents an important source of a therapeutic radioisotope for a broad range of therapeutic applications in nuclear medicine, oncology, rheumatology and interventional cardiology. The International Atomic Energy Agency (IAEA) is coordinating a clinical trial involving the use of Rhenium188-Lipiodol for therapy of hepatocellular carcinoma. This report summarizes the experience of investigators at ten participating centres associated with the use and performance of the Tungsten-188/Rhenium-188 generators and the preparation and handling of the Re-188 HDD agent. This evaluation has demonstrated the cost effective provision of on-site therapeutic activities of Rhenium-188 and recommendations are made for further development of the next generator prototype in light of this international experience. The high bolus volumes (20-40 ml) of the ORNL generator requires post elution concentration of the Re-188 bolus by passage through the tandem silver cation/anion column system. The high back pressure often encountered during generator elution through the silver cation/anion concentrator system has been identified as a potential problem. The details of a method involving in house preparation of the silver cation columns were provided and implementation of this method for Re-188 bolus concentration is recommended. It is also recommended that ORNL investigators reassess the possibility of increasing Tungsten generator loading capacity and the use of higher specific activity Tungsten-188, with a view to reducing the generator bolus volume. The Re-188 HDD/Lipiodol conjugate?;ate is used in this IAEA trial for radioembolytic therapy of primary liver cancer, and methods for preparation of Re-188 HDD and its extraction into Lipiodol are discussed. Since Re-188 HDD binds to glass surfaces, the recovery yields are variable and can be as low as 40-45%. In an effort to maximize the
International Nuclear Information System (INIS)
Goncharov, V.B.; Fialko, E.F.; Shejnin, D.Eh.; Kikhtenko, A.V.
1997-01-01
Reactivity in a gaseous phase o rhenium (Re + ) and rhenium monocarbonyl (ReCO + ) in the reaction of CO oxidation in oxygen-containing reagents (NO, O 2 , H 2 O) is studied through the method of the ionic cyclotron resonance. It is shown that presence of carbonyl ligand essentially influences the ion reactivity. The effective channel of the metal monocarbonyl ions oxidation through molecular oxygen is found. Accounting for this stage makes of possible to explain the low-temperature activity of a number of oxide catalyzer Mo, W in the reaction of CO oxidation by molecular oxygen
Raman spectroscopic approach to monitor the in vitro cyclization of creatine → creatinine
Gangopadhyay, Debraj; Sharma, Poornima; Singh, Sachin Kumar; Singh, Pushkar; Tarcea, Nicolae; Deckert, Volker; Popp, Jürgen; Singh, Ranjan K.
2015-01-01
The creatine → creatinine cyclization, an important metabolic phenomenon has been initiated in vitro at acidic pH and studied through Raman spectroscopic and DFT approach. The equilibrium composition of neutral, zwitterionic and protonated microspecies of creatine has been monitored with time as the reaction proceeds. Time series Raman spectra show clear signature of creatinine formation at pH 3 after ∼240 min at room temperature and reaction is faster at higher temperature. The spectra at pH 1 and pH 5 do not show such signature up to 270 min implying faster reaction rate at pH 3.
Lebœuf, David; Theiste, Eric; Gandon, Vincent; Daifuku, Stephanie L; Neidig, Michael L; Frontier, Alison J
2013-04-08
The discovery and elucidation of a new Nazarov cyclization/Wagner-Meerwein rearrangement/oxidation sequence is described that constitutes an efficient strategy for the synthesis of 4-alkylidene cyclopentenones. DFT computations and EPR experiments were conducted to gain further mechanistic insight into the reaction pathways. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Petroselli, Gabriela; Mandal, Mridul Kanti; Chen, Lee Chuin; Ruiz, Gustavo T; Wolcan, Ezequiel; Hiraoka, Kenzo; Nonami, Hiroshi; Erra-Balsells, Rosa
2012-03-01
A group of rhenium (I) complexes including in their structure ligands such as CF(3)SO(3)-, CH(3)CO(2)-, CO, 2,2'-bipyridine, dipyridil[3,2-a:2'3'-c]phenazine, naphthalene-2-carboxylate, anthracene-9-carboxylate, pyrene-1-carboxylate and 1,10-phenanthroline have been studied for the first time by mass spectrometry. The probe electrospray ionization (PESI) is a technique based on electrospray ionization (ESI) that generates electrospray from the tip of a solid metal needle. In this work, mass spectra for organometallic complexes obtained by PESI were compared with those obtained by classical ESI and high flow rate electrospray ionization assisted by corona discharge (HF-ESI-CD), an ideal method to avoid decomposition of the complexes and to induce their oxidation to yield intact molecular cation radicals in gas state [M](+·) and to produce their reduction yielding the gas species [M](-·). It was found that both techniques showed in general the intact molecular ions of the organometallics studied and provided additional structure characteristic diagnostic fragments. As the rhenium complexes studied in the present work showed strong absorption in the UV-visible region, particularly at 355 nm, laser desorption ionization (LDI) mass spectrometry experiments could be conducted. Although intact molecular ions could be detected in a few cases, LDI mass spectra showed diagnostic fragments for characterization of the complexes structure. Furthermore, matrix-assisted laser desorption ionization (MALDI) mass spectra were obtained. Nor-harmane, a compound with basic character, was used as matrix, and the intact molecular ions were detected in two examples, in negative ion mode as the [M](-·) species. Results obtained with 2-[(2E)-3-(4-tert-buthylphenyl)-2-methylprop-2-enylidene] malononitrile (DCTB) as matrix are also described. LDI experiments provided more information about the rhenium complex structures than did the MALDI ones. Copyright © 2012 John Wiley & Sons, Ltd.
Rhenium(5) and molybdenum(5) complexes with 4',4(5)-divaleryldibenzo-18-crown-6
International Nuclear Information System (INIS)
Ashurova, N.Kh.; Yakubov, K.G.; Tashmukhamedova, A.K.; Basitova, S.M.
1993-01-01
Methods for synthesizing oxohalide complexes of rhenium and molybdenum with +5 oxidation degree with 4',4 (5) -divaleryldibenzo-18-crown-6 were developed. Content and composition of prepared compounds were investigated by the methods of element analysis, crystal optics, conductometry, IR spectroscopy in the near and far regions, thermogravimetry. Oxidation degree of the complex-forming metal was determined. It was established that composition of the compounds coressponded to the general formula MOLX · H 2 O, where M - Re, Mo; L -4',4 (5) -divaleryldibenzo-18-crown-6; X -Cl - , Br -
Mechanical properties of tungsten following rhenium ion and helium plasma exposure
Directory of Open Access Journals (Sweden)
C.S. Corr
2017-08-01
Full Text Available Mechanical properties of Tungsten (W samples irradiated with 2 MeV Rhenium (Re ions and helium (He plasma were investigated using nanoindentation. It was found that there was an increase in hardness for all samples following separate irradiation with both Re ion and He plasma. A slight increase in hardness was obtained for combined exposures. A comparable increase in hardness was observed for a pure He plasma with a sample temperature of 473 K and 1273 K. Optical interferometry was employed to compare surface modification of the samples. Grazing incidence small angle x-ray scattering confirmed He nano-bubble formation of approximately 1 nm diameter in the higher temperature sample, which was not observed with samples at the lower temperatures.
Rhenium Dichalcogenides: Layered Semiconductors with Two Vertical Orientations.
Hart, Lewis; Dale, Sara; Hoye, Sarah; Webb, James L; Wolverson, Daniel
2016-02-10
The rhenium and technetium diselenides and disulfides are van der Waals layered semiconductors in some respects similar to more well-known transition metal dichalcogenides (TMD) such as molybdenum sulfide. However, their symmetry is lower, consisting only of an inversion center, so that turning a layer upside-down (that is, applying a C2 rotation about an in-plane axis) is not a symmetry operation, but reverses the sign of the angle between the two nonequivalent in-plane crystallographic axes. A given layer thus can be placed on a substrate in two symmetrically nonequivalent (but energetically similar) ways. This has consequences for the exploitation of the anisotropic properties of these materials in TMD heterostructures and is expected to lead to a new source of domain structure in large-area layer growth. We produced few-layer ReS2 and ReSe2 samples with controlled "up" or "down" orientations by micromechanical cleavage and we show how polarized Raman microscopy can be used to distinguish these two orientations, thus establishing Raman as an essential tool for the characterization of large-area layers.
Directory of Open Access Journals (Sweden)
Nikolai V. Rostovskii
2015-03-01
Full Text Available Strained azirinium ylides derived from 2H-azirines and α-diazoketones under Rh(II-catalysis can undergo either irreversible ring opening across the N–C2 bond to 2-azabuta-1,3-dienes that further cyclize to 2H-1,4-oxazines or reversibly undergo a 1,5-cyclization to dihydroazireno[2,1-b]oxazoles. Dihydroazireno[2,1-b]oxazoles derived from 3-aryl-2H-azirines and 3-diazoacetylacetone or ethyl diazoacetoacetate are able to cycloadd to acetyl(methylketene generated from 3-diazoacetylacetone under Rh(II catalysis to give 4,6-dioxa-1-azabicyclo[3.2.1]oct-2-ene and/or 5,7-dioxa-1-azabicyclo[4.3.1]deca-3,8-diene-2-one derivatives. According to DFT calculations (B3LYP/6-31+G(d,p, the cycloaddition can involve two modes of nucleophilic attack of the dihydroazireno[2,1-b]oxazole intermediate on acetyl(methylketene followed by aziridine ring opening into atropoisomeric oxazolium betaines and cyclization. Azirinium ylides generated from 2,3-di- and 2,2,3-triaryl-substituted azirines give rise to only 2-azabuta-1,3-dienes and/or 2H-1,4-oxazines.
Townley, William A; Bragg, Thomas W H; Wright, Philip A; Cole, Richard P
2013-12-01
Periorbital congenital melanocytic naevi can be very disfiguring and difficult to treat effectively. Although surgical excision and reconstruction is the most widely accepted treatment strategy, we describe a case in which cutaneous lasers treatment followed by the application of cosmetic skin camouflage make-up provided an alternative solution delivering a good cosmetic improvement.
Superhard Rhenium/Tungsten Diboride Solid Solutions.
Lech, Andrew T; Turner, Christopher L; Lei, Jialin; Mohammadi, Reza; Tolbert, Sarah H; Kaner, Richard B
2016-11-02
Rhenium diboride (ReB 2 ), containing corrugated layers of covalently bonded boron, is a superhard metallic compound with a microhardness reaching as high as 40.5 GPa (under an applied load of 0.49 N). Tungsten diboride (WB 2 ), which takes a structural hybrid between that of ReB 2 and AlB 2 , where half of the boron layers are planar (as in AlB 2 ) and half are corrugated (as in ReB 2 ), has been shown not to be superhard. Here, we demonstrate that the ReB 2 -type structure can be maintained for solid solutions of tungsten in ReB 2 with tungsten content up to a surprisingly large limit of nearly 50 atom %. The lattice parameters for the solid solutions linearly increase along both the a- and c-axes with increasing tungsten content, as evaluated by powder X-ray and neutron diffraction. From micro- and nanoindentation hardness testing, all of the compositions within the range of 0-48 atom % W are superhard, and the bulk modulus of the 48 atom % solid solution is nearly identical to that of pure ReB 2 . These results further indicate that ReB 2 -structured compounds are superhard, as has been predicted from first-principles calculations, and may warrant further studies into additional solid solutions or ternary compounds taking this structure type.
Nandi, Ganesh Chandra; Singh, Maya Shankar
2016-07-15
Metal-free, p-toluenesulfonic acid (p-TSA)-mediated, straightforward propargylation of β-ketothioamides with aryl propargyl alcohol has been achieved at room temperature. In addition, the reaction also provided thiazole rings as byproducts. Furthermore, the propargylated thioamides undergo intramolecular 1,5-cyclization to afford fully substituted (hydro)thiophenes in the presence of base. Notably, the approach is pot, atom, and step economical (PASE).
Czech Academy of Sciences Publication Activity Database
Kučera, Jan; Byrne, A. R.; Mizera, Jiří; Lučaníková, M.; Řanda, Zdeněk
2006-01-01
Roč. 269, č. 2 (2006), s. 251-257 ISSN 0236-5731 R&D Projects: GA ČR(CZ) GA203/04/0943 Institutional research plan: CEZ:AV0Z10480505 Keywords : radiochemical neutron activation analysis * rhenium * biological and environmental samples Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.509, year: 2006
Poth, Aaron G; Colgrave, Michelle L; Philip, Reynold; Kerenga, Bomai; Daly, Norelle L; Anderson, Marilyn A; Craik, David J
2011-04-15
Cyclotides are plant proteins whose defining structural features are a head-to-tail cyclized backbone and three interlocking disulfide bonds, which in combination are known as a cyclic cystine knot. This unique structural motif confers cyclotides with exceptional resistance to proteolysis. Their endogenous function is thought to be as plant defense agents, associated with their insecticidal and larval growth-inhibitory properties. However, in addition, an array of pharmaceutically relevant biological activities has been ascribed to cyclotides, including anti-HIV, anthelmintic, uterotonic, and antimicrobial effects. So far, >150 cyclotides have been elucidated from members of the Rubiaceae, Violaceae, and Cucurbitaceae plant families, but their wider distribution among other plant families remains unclear. Clitoria ternatea (Butterfly pea) is a member of plant family Fabaceae and through its usage in traditional medicine to aid childbirth bears similarity to Oldenlandia affinis, from which many cyclotides have been isolated. Using a combination of nanospray and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) analyses, we examined seed extracts of C. ternatea and discovered cyclotides in the Fabaceae, the third-largest family of flowering plants. We characterized 12 novel cyclotides, thus expanding knowledge of cyclotide distribution and evolution within the plant kingdom. The discovery of cyclotides containing novel sequence motifs near the in planta cyclization site has provided new insights into cyclotide biosynthesis. In particular, MS analyses of the novel cyclotides from C. ternatea suggest that Asn to Asp variants at the cyclization site are more common than previously recognized. Moreover, this study provides impetus for the examination of other economically and agriculturally significant species within Fabaceae, now the largest plant family from which cyclotides have been described.
Resolution of vitiligo following excision of halo congenital melanocytic nevus: a rare case report.
Wang, Kai; Wang, Zhi; Huang, Weiqing
2016-05-01
Halo congenital melanocytic nevus (CMN) associated with vitiligo is rare, especially with regard to CMN excision. Only two reports of excision of halo CMN following repigmentation of vitiligo are found in the literature. We present a case of a girl with halo CMN and periorbital vitiligo. The halo CMN was excised and followed by spontaneous improvement of vitiligo. The result suggests excision of the inciting lesion may be a promising way to control vitiligo. © 2015 Wiley Periodicals, Inc.
Smit, N.P.M.; Vink, A.A.; Kolb, R.M.; Steenwinkel, M.J.S.T.; Berg, P.T.M. van den; Nieuwpoort, F. van; Roza, L.; Pavel, S.
2001-01-01
The goal of this investigation was to correlate the melanin content in human pigmentary cells with the generation of UVB-induced photoproducts and to examine the relationship between the melanin content and the removal of the photoproducts. Cultured melanocytes from light-skinned individuals
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.
Andrade, Gabriel A.; Pistner, Allen J.; Yap, Glenn P.A.; Lutterman, Daniel A.; Rosenthal, Joel
2013-01-01
Harnessing of solar energy to drive the reduction of carbon dioxide to fuels requires the development of efficient catalysts that absorb sunlight. In this work, we detail the synthesis, electrochemistry and photophysical properties of a set of homologous fac-ReI(CO)3 complexes containing either an ancillary phenyl (8) or BODIPY (12) substituent. These studies demonstrate that both the electronic properties of the rhenium center and BODIPY chromophore are maintained for these complexes. Photolysis studies demonstrate that both assemblies 8 and 12 are competent catalysts for the photochemical reduction of CO2 to CO in DMF using triethanolamine (TEOA) as a sacrificial reductant. Both compounds 8 and 12 display TOFs for photocatalytic CO production upon irradiation with light (λex ≥ 400 nm) of ~5 hr−1 with TON values of approximately 20. Although structural and photophysical measurements demonstrate that electronic coupling between the BODIPY and fac-ReI(CO)3 units is limited for complex 12, this work clearly shows that the photoactive BODIPY moiety is tolerated during catalysis and does not interfere with the observed photochemistry. When taken together, these results provide a clear roadmap for the development of advanced rhenium bipyridine complexes bearing ancillary BODIPY groups for the efficient photocatalytic reduction of CO2 using visible light. PMID:24015374
Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Chong-Morrison, Vanessa; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana
2018-04-06
A complex network of inflammatory genes is closely linked to somatic cell transformation and malignant disease. Immune cells and their associated molecules are responsible for detecting and eliminating cancer cells as they establish themselves as the precursors of a tumour. By the time a patient has a detectable solid tumour, cancer cells have escaped the initial immune response mechanisms. Here, we describe the development of a double binary zebrafish model that enables regulatory programming of the myeloid cells as they respond to oncogene-activated melanocytes to be explored, focussing on the initial phase when cells become the precursors of cancer. A hormone-inducible binary system allows for temporal control of expression of different Ras oncogenes ( NRas Q61K , HRas G12V and KRas G12V ) in melanocytes, leading to proliferation and changes in morphology of the melanocytes. This model was coupled to binary cell-specific biotagging models allowing in vivo biotinylation and subsequent isolation of macrophage or neutrophil nuclei for regulatory profiling of their active transcriptomes. Nuclear transcriptional profiling of neutrophils, performed as they respond to the earliest precursors of melanoma in vivo , revealed an intricate landscape of regulatory factors that may promote progression to melanoma, including Serpinb1l4, Fgf1, Fgf6, Cathepsin H, Galectin 1 and Galectin 3. The model presented here provides a powerful platform to study the myeloid response to the earliest precursors of melanoma. © 2018. Published by The Company of Biologists Ltd.
Rhenium and technetium complexes with phenylbis(2-pyridyl)phosphine and tris(2-pyridyl)phosphine
Energy Technology Data Exchange (ETDEWEB)
Saucedo A, S. A. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico); Hagenbach, A.; Abram, U., E-mail: ssaucedo@uaz.edu.m [Institut fur Chemie und Biochemie, Freie Universitat Berlin, Fabeckstr. 34-36, D-14195, Berlin (Germany)
2010-10-15
Reactions of common technetium and rhenium precursors with 2-pyridyl phosphines produce novel, air stable tricarbonyl and oxo complexes. (NEt{sub 4}){sub 2}[Re(CO){sub 3}Br{sub 3}] or (NEt{sub 4}){sub 2}[Tc(CO){sub 3}Cl{sub 3}] react with phenylbis(2-pyridyl)phosphine (PPhpy{sub 2}) or tris(2-pyridyl)phosphine (Ppy{sub 3}) under formation of neutral tricarbonyl complexes of the composition [M(CO){sub 3}X(L)] (M = Re, X = Br; M = Tc, X = Cl, L = PPhpy{sub 2} or Ppy{sub 3}), where the ligands coordinate only with two for their nitrogen atoms. Removal of the bromo ligands from (NEt{sub 4}){sub 2}[Re(CO){sub 3}(Br){sub 3}] with AgNO{sub 3}, to force a tripodal coordination, and the subsequent reaction with the Ppy{sub 3} results in the formation of the complex [Re(CO){sub 3}(NO{sub 3})(Ppy{sub 3}{sup -}N,N{sup '})] with a monodentate coordinated nitrato ligand. (NBu{sub 4})[ReOCl{sub 4}] reacts with PPhpy{sub 2} to give the asymmetric, oxo-bridged rhenium (V) dimer (NBu{sub 4})[Re{sub 2}O{sub 2}Cl{sub 5}({mu}-PPhpy{sub 2}{sup -}P,N,N,N{sup '})({mu}-O)], while a similar reaction with (ReOCl{sub 3}(PPh{sub 3}){sub 2}] in boiling Thf results in reduction of the metal and gives (ReCl{sub 3}(OPPhpy{sub 2})(PPh{sub 3})]. The products have been characterized spectroscopically and by X-ray structure analyses. (Author)
DEFF Research Database (Denmark)
Flagstad, Thomas; Azevedo, Carlos M. G.; Min, Geanna
2018-01-01
A new effective strategy for the synthesis of sp3‐rich small molecules for library production is presented. The key steps to generate complexity highlight Petasis 3‐component reaction followed by an intramolecular Diels‐Alder and cyclization to generate a densely enriched tricyclic or tetracyclic...
Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals
Directory of Open Access Journals (Sweden)
Thomas L. Mindt
2013-03-01
Full Text Available The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (biomolecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.
Sierralta, Walter D; Epuñan, María J; Reyes, José M; Valladares, Luis E; Pino, Ana M
2008-01-01
A stable cyclized 9-mer peptide (cP) containing the active site of alpha-alpha fetoprotein (alphaFP) has been shown to be effective for prevention of estrogen-stimulated tumor cell proliferation in culture or of xenographt growth in immunodeficient mice. cP does not block 17beta-estradiol (E2) binding to its receptors, but rather appears to interfere with intracellular processing of the signal that supports growth. To obtain insight on that mechanism we studied the effect of cP on the proliferation of MCF-7 cells in culture. Proliferation in the presence of 2 microM E2 is decreased up to 40% upon addition of 2 microg ml(-1) cP to the medium; the presence of cP did not increase cell death, cP reduced also the proliferation of estrogen-dependent ZR75-1 cells but had no effect on autonomous MDA-MB-231 cells, cP did not modify the number of binding sites for labeled E2 or affected cell death. We detected increased nuclear p21Cip1 immunoreactivity after cP treatment. Our results suggest that cP acts via p21Cip1 to slow the process of MCF-7 cells through the cycle.
The Melanocyte Fate in Neural Crest is Triggered by Myb Proteins through Activation of c-kit
Czech Academy of Sciences Publication Activity Database
Karafiát, Vít; Dvořáková, Marta; Pajer, Petr; Čermák, Vladimír; Dvořák, Michal
2007-01-01
Roč. 64, č. 21 (2007), s. 2975-2984 ISSN 1420-682X R&D Projects: GA MŠk(CZ) LC06061; GA ČR GA204/06/1728 Institutional research plan: CEZ:AV0Z50520514 Keywords : c-myb proto-oncogene * v-mybAMV oncogene * neural crest * cell fate determination * melanocytes * c-kit signal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.239, year: 2007
Catalytic transformation of functionalized carboxylic acids using multifunctional rhenium complexes.
Naruto, Masayuki; Agrawal, Santosh; Toda, Katsuaki; Saito, Susumu
2017-06-13
Carboxylic acids (CAs) are one of the most ubiquitous and important chemical feedstocks available from biorenewable resources, CO 2 , and the petrochemical industry. Unfortunately, chemoselective catalytic transformations of CH n CO 2 H (n = 1-3) groups into other functionalities remain a significant challenge. Herein, we report rhenium V complexes as extremely effective precatalysts for this purpose. Compared to previously reported heterogeneous and homogeneous catalysts derived from high- or low-valent metals, the present method involves a α-C-H bond functionalization, a hydrogenation, and a hydrogenolysis, which affords functionalized alcohols with a wide substrate scope and high chemoselectivity under relatively mild reaction conditions. The results represent an important step toward a paradigm shift from 'low-valent' to 'high-valent' metal complexes by exploring a new portfolio of selective functional group transformations of highly oxygenated organic substrates, as well as toward the exploitation of CAs as a valuable biorenewable feedstock.
Jurca, Titel; Chen, Wen-Ching; Michel, Sheila; Korobkov, Ilia; Ong, Tiow-Gan; Richeson, Darrin S
2013-03-25
The development of rhenium(I) chemistry has been restricted by the limited structural and electronic variability of the common pseudo-octahedral products fac-[ReX(CO)3L2] (L2 = α-diimine). We address this constraint by first preparing the bidentate bis(imino)pyridine complexes [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)3X] (X = Cl 2, Br 3), which were characterized by spectroscopic and X-ray crystallographic means, and then converting these species into tridentate pincer ligand compounds, [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)2X] (X = Cl 4, Br 5). This transformation was performed in the solid-state by controlled heating of 2 or 3 above 200 °C in a tube furnace under a flow of nitrogen gas, giving excellent yields (≥95 %). Compounds 4 and 5 define a new coordination environment for rhenium(I) carbonyl chemistry where the metal center is supported by a planar, tridentate pincer-coordinated bis(imino)pyridine ligand. The basic photophysical features of these compounds show significant elaboration in both number and intensity of the d-π* transitions observed in the UV/Vis spec tra relative to the bidentate starting materials, and these spectra were analyzed using time-dependent DFT computations. The redox nature of the bis(imino)pyridine ligand in compounds 2 and 4 was examined by electrochemical analysis, which showed two ligand reduction events and demonstrated that the ligand reduction shifts to a more positive potential when going from bidentate 2 to tridentate 4 (+160 mV for the first reduction step and +90 mV for the second). These observations indicate an increase in electrostatic stabilization of the reduced ligand in the tridentate conformation. Elaboration on this synthetic methodology documented its generality through the preparation of the pseudo-octahedral rhenium(I) triflate complex [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)2OTf] (7, 93 % yield). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Radial-velocity variations in Alpha Ori, Alpha Sco, and Alpha Her
International Nuclear Information System (INIS)
Smith, M.A.; Patten, B.M.; Goldberg, L.
1989-01-01
Radial-velocity observations of Alpha Ori, Alpha Sco A, and Alpha Her A are used to study radial-velocity periodicities in M supergiants. The data refer to several metallic lines in the H-alpha region and to H-alpha itself. It is shown that Alpha Ori and Alpha Sco A have cycle lengths of about 1 yr and semiamplitudes of 2 km/s. It is suggested that many semiregular red supergiant varibles such as Alpha Ori may be heading toward chaos. All three stars show short-term stochastic flucutations with an amplitude of 1-2 km/s. It is found that the long-term variability of H-alpha velocities may be a consequence of intermittent failed ejections. 58 refs
Czech Academy of Sciences Publication Activity Database
Jahn, Ullrich; Dinca, E.
2009-01-01
Roč. 15, č. 1 (2009), s. 58-62 ISSN 0947-6539 Grant - others:DFG(DE) Ja896/3-1 Institutional research plan: CEZ:AV0Z40550506 Keywords : cyclization * electron transfer * prostanoids * radical ions Subject RIV: CC - Organic Chemistry Impact factor: 5.382, year: 2009
Directory of Open Access Journals (Sweden)
Wood Scott A
2002-01-01
Full Text Available To understand the aqueous species important for transport of rhenium under supercritical conditions, we conducted a series of solubility experiments on the Re–ReO2 buffer assemblage and ReS2. In these experiments, pH was buffered by the K–feldspar–muscovite–quartz assemblage; in sulfur-free systems was buffered by the Re–ReO2 assemblage; and and in sulfur-containing systems were buffered by the magnetite–pyrite–pyrrhotite assemblage. Our experimental studies indicate that the species ReCl40 is dominant at 400°C in slightly acidic to near-neutral, and chloride-rich (total chloride concentrations ranging from 0.5 to 1.0 M environments, and ReCl3+ may predominate at 500°C in a solution with total chloride concentrations ranging from 0.5 to 1.5 M. The results also demonstrate that the solubility of ReS2 is about two orders of magnitude less than that of ReO2. This finding not only suggests that ReS2 (or a ReS2 component in molybdenite is the solubility-controlling phase in sulfur-containing, reducing environments but also implies that a mixing process involving an oxidized, rhenium-containing solution and a solution with reduced sulfur is one of the most effective mechanisms for deposition of rhenium. In analogy with Re, TcS2 may be the stable Tc-bearing phase in deep geological repositories of radioactive wastes.
Tracing oxidative weathering from the Andes to the lowland Amazon Basin using dissoved rhenium
Dellinger, M.; Hilton, R. G.; West, A. J.; Torres, M.; Burton, K. W.; Clark, K. E.; Baronas, J. J.
2016-12-01
Over long timescales (>105 yrs), the abundance of carbon dioxide (CO2) in the atmosphere is determined by the balance of the major carbon sources and sinks. Among the major carbon sources, the oxidation of organic carbon contained within sedimentary rocks ("petrogenic" carbon, or OCpetro) is thought to result in CO2 emission of similar magnitude to that released by volcanism. Rhenium (Re) has been proposed as a proxy for tracing OCpetro oxidation. Here we investigate the source, behavior and flux of dissolved and particulate rhenium (Re) in the Madre de Dios watershed (a major Andean tributary of the Amazon River) and the lowlands, aiming to characterize the behavior of Re in river water and quantify the flux of CO2 released by OCpetro oxidation. Measured Re concentrations in Andean rivers range from 0.07 to 1.55 ppt. In the Andes, Re concentration do not change significantly with water discharge, whereas in the lowlands, Re concentration decrease at high water discharge. Mass balance calculation show that more than 70% of the dissolved Re is sourced from the oxidation of OCpetro the Andes-floodplain system. We calculate dissolved Re flux over a hydrological year to estimate the rates of oxidative weathering, and the associated CO2 release from OCpetro. Rates are high in the Andean headwaters, consistent with estimates from other mountain rivers with similar rates of physical erosion. We find evidence that a significant amount of additional oxidation (Re flux) happens during floodplain transport. These results have important implications for improving our understanding of the source and processes controlling Re in rivers, and allowing us to quantify long-term OCpetro cycling in large river basins.
International Nuclear Information System (INIS)
Chen, Wei-Chieh; Venkatesan, Parthiban; Wu, Shu-Pao
2015-01-01
Highlights: • A BODIPY-based fluorescent probe for sensing HOCl was developed. • The probe utilizes the HOCl-promoted cyclization in response to the amount of HOCl. • The probe might have application in the investigation of HOCl in biological systems. - Abstract: A BODIPY-based fluorescent probe, HBP, was developed for the detection of hypochlorous acid based on the specific hypochlorous acid-promoted oxidative intramolecular cyclization of heterocyclic hydrazone in response to the amount of HOCl. The reaction is accompanied by a 41-fold increase in the fluorescent quantum yield (from 0.004 to 0.164). The fluorescence intensity of the reaction between HOCl and HBP is linear in the HOCl concentration range of 1–8 μM with a detection limit of 2.4 nM (S/N = 3). Confocal fluorescence microscopy imaging using RAW264.7 cells showed that the new probe HBP could be used as an effective fluorescent probe for detecting HOCl in living cells
Energy Technology Data Exchange (ETDEWEB)
Chen, Wei-Chieh; Venkatesan, Parthiban; Wu, Shu-Pao, E-mail: spwu@mail.nctu.edu.tw
2015-07-02
Highlights: • A BODIPY-based fluorescent probe for sensing HOCl was developed. • The probe utilizes the HOCl-promoted cyclization in response to the amount of HOCl. • The probe might have application in the investigation of HOCl in biological systems. - Abstract: A BODIPY-based fluorescent probe, HBP, was developed for the detection of hypochlorous acid based on the specific hypochlorous acid-promoted oxidative intramolecular cyclization of heterocyclic hydrazone in response to the amount of HOCl. The reaction is accompanied by a 41-fold increase in the fluorescent quantum yield (from 0.004 to 0.164). The fluorescence intensity of the reaction between HOCl and HBP is linear in the HOCl concentration range of 1–8 μM with a detection limit of 2.4 nM (S/N = 3). Confocal fluorescence microscopy imaging using RAW264.7 cells showed that the new probe HBP could be used as an effective fluorescent probe for detecting HOCl in living cells.
International Nuclear Information System (INIS)
Zailaie, Mohamad Z.
2005-01-01
Increased serum levels of certain immunologic markers including immunoglobulin G (IgG) anti-melanocyte/ vitiligo antibodies (V-IgG) and soluble interleukin-2 receptors (sIL-2R) are associated with augmented humoral and cellular immunity involved in melanocyte cytotoxicity during the active phase of non-segmental vitiligo. Recent reports have shown that, aspirin possesses a wide range of immunomodulatory and antioxidant properties. Therefore, the aim of the present study is to investigate the effect of long-term treatment of vitiligo patients with low-dose oral aspirin on serum V-IgG activity and sIL-2R concentration. The present study was carried out at the Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia between March and October 2003. Eighteen female and 14 male patients with a recent onset of non-segmental vitiligo were divided into 2 equal groups. One group received a daily single dose of oral aspirin (300 mg) and the second group received only placebo for a period of 12 weeks. Serum V-IgG activity and sIL-2R concentration were determined before and at the end of treatment period. The V-IgG activity was measured using cellular enzyme-linked immunosorbent assay (ELISA) following incubation of IgG antibodies with an adult cultured melanocytes. Serum sIL-2R concentration was measured using the highly sensitive quantitative sandwich ELISA utilizing a commercially available kit. As expected, the serum V-IgG activity and sIL-2R concentration of the active vitiligo patients (0.81 +/- 0.23 optical density (O.D.), 1428 +/- 510 pg/ml) were significantly increased compared with that of controls (0.27 +/- 0.1 O.D., 846 +/- 312 pg/ml; p<0.05, p<0.01). Aspirin-treated vitiligo patients showed significant decrease in serum V-IgG activity and sIL-2R concentration (0.32 +/- 0.08 O.D., 756 +/- 216 pg/ml) compared with that of placebo-treated patients (0.83 +/- 0.19 O.D., 1327 +/- 392 pg/ml; p<0.01). Low-dose oral aspirin treatment of
Sarma, Bani Kanta
2013-09-01
The redox regulation of protein tyrosine phosphatase 1B (PTP1B) via the unusual transformation of its sulfenic acid (PTP1B-SOH) to a cyclic sulfenyl amide intermediate is studied by using small molecule chemical models. These studies suggest that the sulfenic acids derived from the H2O2-mediated reactions o-amido thiophenols do not efficiently cyclize to sulfenyl amides and the sulfenic acids produced in situ can be trapped by using methyl iodide. Theoretical calculations suggest that the most stable conformer of such sulfenic acids are stabilized by nO → σ*S-OH orbital interactions, which force the -OH group to adopt a position trans to the S⋯O interaction, leading to an almost linear arrangement of the O⋯S-O moiety and this may be the reason for the slow cyclization of such sulfenic acids to their corresponding sulfenyl amides. On the other hand, additional substituents at the 6-position of o-amido phenylsulfenic acids that can induce steric environment and alter the electronic properties around the sulfenic acid moiety by S⋯N or S⋯O nonbonded interactions destabilize the sulfenic acids by inducing strain in the molecule. This may lead to efficient the cyclization of such sulfenic acids. This model study suggests that the amino acid residues in the close proximity of the sulfenic acid moiety in PTP1B may play an important role in the cyclization of PTP1B-SOH to produce the corresponding sulfenyl amide.
Ali, Sharique A; Naaz, Ishrat; Zaidi, Kamal Uddin; Ali, Ayesha S
2017-01-01
Skin pigmentation is a broadly appearing phenomenon in nature which plays an important task of determining the appearance and biology of all vertebrates including human beings. Skin color is a crucial attribute, determined by the synthesis of melanin pigment within melanocytes by the process of melanogenesis and is regulated by many extrinsic as well as intrinsic factors. Tyrosinase catalyzes the key step of melanogenesis, dysfunction of tyrosinase leads to reduce melanin production which results in severe clinical and aesthetical problems of hypopigmentation. Therefore, the regulation of melanin production is an important strategy in the treatment of abnormal skin pigmentation for cosmetic and medicinal purpose. The present review covers the various aspects of mammalian melanocyte biology which will help in the identification of key regulators of melanogenesis from pharmaceutical and pharmacological point of view. Further sections of the review focus on the dysfunctions of melanogenic pathways, which result in severe clinical and aesthetical problems of hypopigmentation. We have also attempted to highlight the ability of available scientifically validated plant extracts to naturally enhance melanin synthesis in order to cure hypopigmentation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Effect of rhenium and osmium on mechanical properties of a 9Cr-2W-0.25V-0.07Ta-0.1C steel
International Nuclear Information System (INIS)
Klueh, R.L.; Alexander, D.J.; Sokolov, M.A.
2000-01-01
The nuclear transmutation of tungsten to rhenium and osmium in a tungsten-containing steel irradiated in a fission or fusion reactor will change the chemical composition of the steel. To determine the possible consequences of such compositional changes on the mechanical properties, tensile and Charpy impact properties were measured on five 9Cr-2W-0.25V-0.07Ta-0.1C steels that contained different amounts of rhenium, osmium, and tungsten. The mechanical properties changes caused by these changes in composition were minor. Observations were also made on the effect of carbon concentration. The effect of carbon on tensile behavior was minor, but there was a large effect on Charpy properties. Several of the steels showed little effect of tempering temperature on the Charpy transition temperature, a behavior that was tentatively attributed to the low silicon and/or manganese concentration of the experimental steels
Absorption behavior of technetium and rhenium through plant roots
International Nuclear Information System (INIS)
Tagami, K.; Uchida, S.
2004-01-01
The absorption behavior of technetium (Tc) and rhenium (Re) through plant roots was studied using nutrient solution culture. Radish samples, grown in culture solutions for 20-30 days in a green house, were transferred into plastic vessels containing nutrient solutions contaminated with multi-tracer solutions including Tc-95m and Re-183. The plant samples were grown individually for 1-7 days under laboratory conditions. The activities of radionuclides in nutrient solutions and oven-dried plant parts (roots, fleshy roots and leaves) were measured with Ge detecting systems. The concentrations of Tc-95m and Re-183 in the nutrient solutions after harvesting the plants were almost the same as those in the initial solution. Possibly, the radionuclides were taken up with water through plant roots. The distributions of Tc and Re in the plants showed no differences, thus, soluble Tc and Re absorption by plant samples were the same. It is suggested that Re could be used as a geochemical tracer of Tc in the soil environment. (author)
A tungsten-rhenium interatomic potential for point defect studies
Setyawan, Wahyu; Gao, Ning; Kurtz, Richard J.
2018-05-01
A tungsten-rhenium (W-Re) classical interatomic potential is developed within the embedded atom method interaction framework. A force-matching method is employed to fit the potential to ab initio forces, energies, and stresses. Simulated annealing is combined with the conjugate gradient technique to search for an optimum potential from over 1000 initial trial sets. The potential is designed for studying point defects in W-Re systems. It gives good predictions of the formation energies of Re defects in W and the binding energies of W self-interstitial clusters with Re. The potential is further evaluated for describing the formation energy of structures in the σ and χ intermetallic phases. The predicted convex-hulls of formation energy are in excellent agreement with ab initio data. In pure Re, the potential can reproduce the formation energies of vacancies and self-interstitial defects sufficiently accurately and gives the correct ground state self-interstitial configuration. Furthermore, by including liquid structures in the fit, the potential yields a Re melting temperature (3130 K) that is close to the experimental value (3459 K).
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.
One-Pot Synthesis of Cyclopropane-Fused Cyclic Amidines: An Oxidative Carbanion Cyclization.
Veeranna, Kirana Devarahosahalli; Das, Kanak Kanti; Baskaran, Sundarababu
2017-12-18
A novel and efficient one-pot method has been developed for the synthesis of cyclopropane-fused bicyclic amidines on the basis of a CuBr 2 -mediated oxidative cyclization of carbanions. The usefulness of this unique multicomponent strategy has been demonstrated by the use of a wide variety of substrates to furnish novel cyclopropane-containing amidines with a quaternary center in very good yields. This ketenimine-based approach provides straightforward access to biologically active and pharmaceutically important 3-azabicyclo[n.1.0]alkane frameworks under mild conditions. The synthetic power of this methodology is exemplified in the concise synthesis of the pharmaceutically important antidepressant drug candidate GSK1360707 and key intermediates for the synthesis of amitifadine, bicifadine, and narlaprevir. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
DEFF Research Database (Denmark)
Sørensen, Flemming Brandt; Ottosen, P D
1991-01-01
The volume-weighted, mean nuclear volume (nuclear vv) may be estimated without any assumptions regarding nuclear shape using modern stereological techniques. As a part of an investigation concerning the prospects of nuclear vv for classification and malignancy grading of cutaneous melanocytic tum...
DeKorver, Kyle A.; Hsung, Richard P.; Lohse, Andrew G.; Zhang, Yu
2010-01-01
A fascinating mechanistic study of ynamido-palladium-π-allyl complexes is described that features isolation of a unique silyl-ketenimine via aza-Claisen rearrangement, which can be accompanied by an unusual thermal N-to-C 1,3-Ts shift in the formation of tertiary nitriles, and a novel cyclopentenimine formation via a palladium catalyzed aza-Rautenstrauch-type cyclization pathway. PMID:20337418
Davis, Owen A; Croft, Rosemary A; Bull, James A
2016-11-18
1,4-Dioxenes present interesting potential as synthetic intermediates and as unusual motifs for incorporation into biologically active compounds. Here, an efficient synthesis of functionalized 1,4-dioxenes is achieved in two steps. Using keto-diazo compounds, a ruthenium catalyzed O-H insertion with β-halohydrins followed by treatment with base results in cyclization with excellent selectivity, through O-alkylation of the keto-enolate. A variety of halohydrins and anion-stabilizing groups in the diazo-component are tolerated, affording novel functionalized dioxenes. Enantioenriched β-bromohydrins provide enantioenriched 1,4-dioxenes.
Hastrup, N; Hou-Jensen, K
1993-11-01
This study reviews a total of 1000 melanocytic lesions--two separate 500 consecutive sample groupings from 1980 and 1989, respectively--diagnosed in a private non-hospital-associated pathology practice. Lesions were classified as lentigo simplex, congenital nevus, "common" nevus, dysplastic nevus, blue nevus, Spitz's nevus or malignant melanoma. A comparison of the two periods reveals an increase in dysplastic nevi from one in 1980 to nine in 1989. The histologic changes in these nevi were compared to those of the other tumors. Pronounced cytologic atypia was seen in the melanocytes of a few "common" nevi, but more often in the dysplastic nevi and in all of the melanomas. Slight nuclear atypia was usual in "common" nevi and lentigines, and also fibroplasia, lymphocytic infiltration, vessel proliferation and pigment incontinence were seen in both "common" nevi and dysplastic nevi. It is concluded that no single histologic variable was specific for dysplastic nevi.
International Nuclear Information System (INIS)
Friedmann, P.S.; Wren, F.E.; Matthews, J.N.
1990-01-01
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
Mayo, Muhammad Shareef; Yu, Xiaoqiang; Zhou, Xiaoyu; Feng, Xiujuan; Yamamoto, Yoshinori; Bao, Ming
2014-02-07
Brønsted acid catalyzed cyclization reactions of 2-amino thiophenols/anilines with β-diketones under oxidant-, metal-, and radiation-free conditions are described. Various 2-substituted benzothiazoles/benzimidazoles are obtained in satisfactory to excellent yields. Different groups such as methyl, chloro, nitro, and methoxy linked on benzene rings were tolerated under the optimized reaction conditions.
Sinikumpu, Suvi-Päivikki; Huilaja, Laura; Jokelainen, Jari; Auvinen, Juha; Timonen, Markku; Tasanen, Kaisa
2017-02-08
Having multiple melanocytic naevi (sex, socioeconomic status (education) in childhood and adulthood, skin type and sunbathing habits. The prevalence of multiple melanocytic naevi was 11.6% (223/1,930). Higher education (odds ratio (OR) 2.11, 95% confidence interval (95% CI) 1.51-2.96), male sex (OR 1.48, 95% CI 1.07-2.06), sun-sensitive skin type (OR 2.09, 95% CI 1.34-3.27) and regular use of sunscreen (OR 2.03, 95% CI 1.23-3.37) were associated with increased risk of multiple naevi. Inflammatory skin diseases decreased (OR 0.49, 95 CI% 0.33-0.72) the risk of multiple naevi. In conclusion, several risk factors were found for multiple naevi among adults living in high latitudes, in Northern Finland.
Xu, Yongjin; Yin, Zhiping; Lin, Xinglong; Gan, Zubao; He, Yanyang; Gao, Lu; Song, Zhenlei
2015-04-17
A regioselective 1,4-hydroiodination of dienyl alcohols has been developed using trimethylsilyl iodide as Lewis acid and iodide source. A range of homoallylic alcohols containing a multisubstituted Z-alkene was synthesized with good to excellent configurational control. The approach was applied in sequential hydroiodination/Prins cyclization to afford multisubstituted tetrahydropyrans diastereoselectively.
International Nuclear Information System (INIS)
Luo, Hongyan; Setyawati, Ika; Rettig, S.J.; Orvig, C.
1995-01-01
The synthesis of several phosphine-based chelating compounds and chelates formed between these compounds and rhenium or technetium is discussed. Four categories of products result, (i) bis-(o-hydroxyphenyl) diphenylphosphine (PO) complexes, (ii) mono- (PO) complexes, (iii) bis-bis(o-hydroxyphenyl)-phenylphosphine (PO 2 ) complexes, and mixed-(PO) and (PO 2 ) complexes. Molecular structures of these compounds (including isomers) were probed by NMR, MS, and IR spectroscopies and by X-ray crystallography
Czech Academy of Sciences Publication Activity Database
Nahhas, A. E.; Consani, C.; Blanco-Rodríguez, A. M.; Lancaster, K. M.; Braem, O.; Cannizzo, A.; Towrie, M.; Clark, I. P.; Záliš, Stanislav; Chergui, M.; Vlček, Antonín
2011-01-01
Roč. 50, č. 7 (2011), s. 2932-2943 ISSN 0020-1669 R&D Projects: GA MŠk(CZ) ME10124; GA MŠk(CZ) LD11082 Institutional research plan: CEZ:AV0Z40400503 Keywords : rhenium * photosynthesis * diimine effects Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.601, year: 2011
Back, Christopher; Dearman, Bronwyn; Li, Amy; Neild, Tim; Greenwood, John E
2009-01-01
Randomized controlled trials in the literature investigating the efficacy of noncultured keratinocyte/melanocyte suspensions are scarce; however, the advocates of such techniques press the value of their application based largely on case studies and anecdote. Caucasian patients with burn hypopigmentation seldom request cosmetic revision making worthwhile clinical trials difficult so that informal case treatments with new therapies generate anecdotal results. A randomized, placebo-controlled trial was carried out to evaluate whether cosuspensions of noncultured skin cells are capable of (1) decreasing the time to reepithelialization and (2) reestablishing pigmentation in vitiligo leukoderma following epidermal/superficial dermal ablation (in the knowledge that a positive result would make the technique likely to be successful in burn hypopigmentation). Vitiligo is common and is socially more debilitating such that suitable trial subjects for new therapies from this pool are more forthcoming. This study demonstrated that suspensions of noncultured keratinocytes and melanocytes do not decrease the time to epithelialization of superficial partial thickness wounds compared with controls. It also suggested that the achievement, quality, and duration of any pigmentation were unpredictable and largely disappointing. Some pigmentation was recorded in placebo-treated areas indicating an effect of the method of epidermal ablation in these patients. These findings have mandated a complete review of the use of these techniques in burn care at the Royal Adelaide Hospital; they have been omitted from surgical protocols where the aim of use was to speed reepithelialization. Their infrequent use in burns hypopigmentation will continue contingent on the successful repigmentation of a test patch.
Directory of Open Access Journals (Sweden)
Daniela Mayumi Takano
2010-02-01
Full Text Available INTRODUÇÃO E OBJETIVOS: Acredita-se que a exposição solar possa alterar número, distribuição e morfologia dos melanócitos na pele humana, muitas vezes dificultando a interpretação de biópsias de pele, principalmente para o diagnóstico de lesões melanocíticas iniciais e para a avaliação precisa de margens de ressecção. O objetivo deste trabalho foi avaliar os melanócitos da pele humana em área exposta e não exposta ao sol. MÉTODOS: Realizada análise histológica de 60 fragmentos de biópsias de pele obtidas do antebraço (área fotoexposta e região glútea (área coberta de cadáveres do Serviço de Verificação de Óbitos de Recife-PE. A estatística foi realizada com o SPSS Windows versão 12.0. RESULTADOS: Observou-se um número bastante variável de melanócitos nos fragmentos de pele, com maior concentração destes na região do antebraço (área de maior fotoexposição (p INTRODUCTION AND OBJECTIVES: It is believed that sun exposure can change the number, distribution and morphology of melanocytes in human skin, which often hinders the interpretation of skin biopsies, mainly as to diagnosis of initial melanocytic lesions and accurate assessment of resection margins. Our objective was to evaluate melanocytes in sun-exposed and non-exposed skin. METHODS: It was conducted the histological analysis of 60 skin biopsy samples resected from cadaver forearm (sun-exposed skin and cadaver buttock (non-exposed skin from the Death Verification Service (Serviço de Verificação de Óbitos of Recife, state of Pernambuco. The statistical analysis was performed with SPSS Windows version 12.0. RESULTS: There was considerable variability in melanocyte density, with a higher concentration of these cells in sun-exposed areas (p < 0.001. There was also an irregular distribution of melanocytes along the epidermal basal layer, occasionally with cells arranged side by side. This confluence was identified with a higher frequency in sun
Rhenium-188: Availability from the W-188/Re-188 Generator and Status of Current Applications
International Nuclear Information System (INIS)
Pillai, M.R.A.; Dash, A.; Knapp, Russ F. Jr.
2012-01-01
Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting β-particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 KeV, 15.1%). The 188W/188Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) 188Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent 188W radionuclide have been a major impediment in the progress of application of 188Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade 188W/188Re generator. Since the specific activity of 188W used in the generator is relatively low (<5 Ci/g), the eluted 188ReO4- can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful 188ReO4-. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on 188Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability, and use of188Re including a discussion of why broader use of 188Re has not progressed as ecpected as a popular radionuclide for therapy.
International Nuclear Information System (INIS)
Kim, Ji Eun; Stones, Clare; Joseph, Wayne R; Leung, Euphemia; Finlay, Graeme J; Shelling, Andrew N; Phillips, Wayne A; Shepherd, Peter R; Baguley, Bruce C
2012-01-01
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
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.
Lytwak, Lauren A; Stanley, Julie M; Mejía, Michelle L; Holliday, Bradley J
2010-09-07
A bromo tricarbonyl rhenium(I) complex with a thiophene-functionalized bis(pyrazolyl) pyridine ligand (L), ReBr(L)(CO)(3) (1), has been synthesized and characterized by variable temperature and COSY 2-D (1)H NMR spectroscopy, single-crystal X-ray diffraction, and photophysical methods. Complex 1 is highly luminescent in both solution and solid-state, consistent with phosphorescence from an emissive (3)MLCT excited state with an additional contribution from a LC (3)(pi-->pi*) transition. The single-crystal X-ray diffraction structure of the title ligand is also reported.
International Nuclear Information System (INIS)
Pecking, A.; Le Mercier, N.; Gobin, R.; Bardy, A.; Najean, Y.
1978-01-01
We have studied for lymphatic scintigraphy a new radiopharmaceutical, sup(99m)Tc-labelled rhenium sulfocolloid. This preliminary study includes 20 adults patients with lymphomas and lymphoedemas. The principal advantage of this drug is its absence of toxicity and local pain, so that a rapid sub-cutaneous injection without local anesthesia is made possible. Good results have been obtained, as well in morphological studies of para-aortic and mammary lymph nodes as for kinetic studies of lymphatic flow in lymphoedemas. No liver and spleen uptake of radio-isotope was observed after foot injection [fr
Vummaleti, Sai V. C.; Falivene, Laura; Poater, Albert; Cavallo, Luigi
2014-01-01
We demonstrate that the experimentally observed switch in selectivity from 5-exo-dig to 6-endo-dig cyclization of an alkynyl substrate, promoted by Au I and AuIII complexes, is connected to a switch from thermodynamic to kinetic reaction control. The AuIII center pushes alkyne coordination toward a single Au-C(alkyne) σ-bond, conferring carbocationic character (and reactivity) to the distal alkyne C atom. © 2014 American Chemical Society.
Vummaleti, Sai V. C.
2014-05-02
We demonstrate that the experimentally observed switch in selectivity from 5-exo-dig to 6-endo-dig cyclization of an alkynyl substrate, promoted by Au I and AuIII complexes, is connected to a switch from thermodynamic to kinetic reaction control. The AuIII center pushes alkyne coordination toward a single Au-C(alkyne) σ-bond, conferring carbocationic character (and reactivity) to the distal alkyne C atom. © 2014 American Chemical Society.