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West Jerusalem, Israel

Flori E.,San Gallicano Dermatologic Institute IRCCS | Mastrofrancesco A.,San Gallicano Dermatologic Institute IRCCS | Kovacs D.,San Gallicano Dermatologic Institute IRCCS | Ramot Y.,Hadassah University | And 7 more authors.
Pigment Cell and Melanoma Research | Year: 2011

Given the importance of the tanning response in protecting human skin from the harmful effects of UV radiation, one important research priority is to identify novel molecules that are capable of promoting pigmentation and/or antioxidant defence. Parrodienes share some structural features with carotenoids and retinoids, stimulate cell antioxidant defence and counteract senescence-like phenotype in fibroblasts. We selected the parrodiene-derivative 2,4,6-octatrienoic acid (Octa) to study its impact on key parameters of melanogenesis and antioxidant defence in organ-cultured human skin and in normal human melanocytes. Octa promoted melanogenesis by up-regulating tyrosinase and microphthalmia-associated transcription factor expression. This correlated with an increase of melanin content in both human epidermis in situ and cultured human epidermal melanocytes. Moreover, Octa increased the biological antioxidant potential content and the expression and activity of catalase. Activation of peroxisome proliferator-activated receptor (PPAR)-γ was necessary to evoke these effects. These data strongly encourage the systematic study of Octa as a novel candidate promoter of human skin photoprotection. © 2011 John Wiley & Sons A/S. Source

Guerrero-Preston R.,Johns Hopkins University | Guerrero-Preston R.,University of Puerto Rico at San Juan | Goldman L.R.,Johns Hopkins University | Brebi-Mieville P.,Johns Hopkins University | And 13 more authors.
Epigenetics | Year: 2010

Environmental exposures in utero may alter the epigenome, thus impacting chromosomal stability and gene expression. We hypothesized that in utero exposures to maternal smoking and perfluoroalkyl compounds (PFCs) are associated with global DNA hypomethylation in umbilical cord serum. Our objective was to determine if global DNA methylation could be used as a biomarker of in utero exposures to maternal smoking and PFCs. Using an ELISA-based method, global DNA methylation was quantified in umbilical cord serum from 30 newborns with high (>10 ng/ml, mean 123.8 ng/ml), low (range 1-10 ng/ml, mean 1.6 ng/ml) and very low (<1 ng/ml, mean 0.06 ng/ml) cord serum cotinine levels. Y chromosome analysis was performed to rule out maternal DNA cross-contamination. Cord serum global DNA methylation showed an inverse dose response to serum cotinine levels (p < 0.001). Global DNA methylation levels in cord blood were the lowest among newborns with smoking mothers (mean = 15.04%; 95% CI, 8.4, 21.7) when compared to babies of mothers who were second-hand smokers (21.1%; 95% CI, 16.6, 25.5) and non-smokers (mean = 29.2%; 95% CI, 20.1, 38.1). Global DNA methylation was inversely correlated with serum PFOA (r = -0.35, p = 0.06) but not PFOS levels. Serum Y chromosome analyses did not detect maternal DNA cross-contamination. This study supports the use of global DNA methylation status as a biomarker of in utero exposure to cigarette smoke and PFCs. © 2010 Landes Bioscience. Source

Hurley K.,Sloan Kettering Cancer Center | Hurley K.,Private Practice | Rubin L.R.,The New School | Werner-Lin A.,New York University | And 7 more authors.
Cancer | Year: 2012

BACKGROUND: Studies have shown that BRCA1/2 mutation carriers are interested in learning about reproductive options such as preimplantation genetic diagnosis (PGD) to prevent passing their risk onto their children. However, attitudes vary widely, and the procedure raises complex ethical and psychosocial issues. This complexity, plus the highly technical nature of PGD, makes it difficult to integrate PGD information into genetic counseling sessions that already cover probabilistic, emotionally charged risk information. METHODS: A total of 33 carriers of the BRCA1/2 mutation who were of reproductive age and had previously undergone genetic counseling viewed a tutorial regarding PGD and were interviewed concerning their attitudes toward PGD and preferences about how to include PGD information in genetic counseling. RESULTS: The majority of participants preferred to be briefly informed of the availability of PGD information, and to receive written materials regarding PGD, but with the option of deferring detailed discussion if they already believed themselves to be overloaded or perceived that PGD was not immediately relevant to their risk management and/or childbearing plans. For some individuals, the stress of testing temporarily interfered with information processing, producing states of cognitive avoidance ("in a fog," or "tuning out"). Some preferred to discuss PGD with a physician with whom they had an ongoing relationship (eg, obstetrician/gynecologist, primary care provider, or oncologist). CONCLUSIONS: Providers offering cancer genetic testing may consider indicating the availability of PGD information to their patients, while attending to the patients' level of interest and ability to absorb information. Research is needed to link patient responses to information overload with psychosocial outcomes (eg, distress, and quality of decision-making). Continuing medical education is needed to support providers in facilitating informed decisions regarding PGD. © 2012 American Cancer Society. Source

Elishmereni M.,Hebrew University of Jerusalem | Bachelet I.,Hebrew University of Jerusalem | Ben-Efraim A.H.N.,Hebrew University of Jerusalem | Mankuta D.,Hadassah University | Levi-Schaffer F.,Hebrew University of Jerusalem
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2013

Background Mast cells (MCs) and eosinophils (Eos), the key effector cells in allergy, are abundantly co-localized particularly in the late and chronic stages of allergic inflammation. Recent evidence has outlined a specialized 'allergic effector unit' in which MCs and Eos communicate via both soluble mediators and physical contact. However, the functional impact of this bi-directional crosstalk on the cells' effector activities has not yet been revealed. We aimed to investigate whether MC/eosinophil interactions can influence the immediate and late activation phenotypes of these cells. Methods Human and murine MCs and Eos were co-cultured under various conditions for 1-2 h or 1-3 days, and in selected experiments cell-cell contact was blocked. Cell migration and mediator release were examined, and flow cytometry was applied to stain intracellular signaling molecules and surface receptors. Results Eosinophils enhanced basal MCs mediator release and co-stimulated IgE-activated MCs through physical contact involving CD48-2B4 interactions. Reciprocally, resting and IgE-stimulated MCs led to eosinophil migration and activation through a paracrine-dependent mechanism. Increased phosphorylation of activation-associated signaling molecules, and enhanced release of tumor necrosis factor α, was observed in long-term co-cultures. Eosinophils also showed enhanced expression of intercellular adhesion molecule 1, which depended on direct contact with MCs. Conclusions Our findings reveal a new role for MC/eosinophil interplay in augmenting short- and long-term activation in both cells, in a combined physical/paracrine manner. This enhanced functional activity may thus critically contribute to the perpetuation of the inflammatory response in allergic conditions. © 2012 John Wiley & Sons A/S. Source

Cohen J.E.,Hadassah University | Gomori J.M.,Hadassah University | Leker R.R.,Hadassah University | Ben-Hur T.,Hadassah University | And 2 more authors.
Neurological Research | Year: 2010

Background and Purpose: Internal carotid artery dissections (ICADs) with occlusion present with a high morbidity and mortality. No specific medical treatment has proven to be effective in this setting. In selected cases of ICAD with occlusion, stent-assisted angioplasty has been shown to be effective in restoring the perfusion. Spontaneous ICAD causing occlusion successfully recanalized with multiple telescoped stents extending intracranially has only been reported exceptionally. Methods: We report cases of symptomatic acute carotid occlusion after spontaneous dissection extending from the cervical to the petrocavernous ICA segments. Imaging studies revealed the presence of an extensive penumbra area in every case. Patients were treated by means of multiple stents deployed in a telescoped fashion with the aid of a delayed double-contrast road map. Results: Post-procedural angiography demonstrated restitution of the carotid lumen with no signs of residual dissection or intracranial emboli. The patients improved rapidly, showing no residual neurological deficit after a week. At follow-up, patients are clinically asymptomatic and the vessel is patent with no radiological signs of myointimal hyperplasia. Conclusions: The successful angiographic and clinical results observed in our cases of extraintracranial stenting of a long carotid dissection causing occlusion contribute to the literature of carotid dissection treated with multiple stents. © 2010 W. S. Maney & Son Ltd. Source

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