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Irvine, CA, United States

Warren R.V.,Beckman Laser Institute
International Journal of Obesity | Year: 2016

Background:Changes in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, diffuse optical spectroscopic imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties.Methods:Ten overweight or obese adults were assessed during 3 months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed-effects models and were also used to form 3D surface images.Results:Subjects lost a mean of 11.7±3.4% of starting weight, while significant changes in A (+0.23±0.04 mm-1, adj. P<0.001),b (−0.17±0.04, adj. P<0.001), tissue water fraction (+7.2±1.1%, adj. P<0.001) and deoxyhemoglobin (1.1±0.3 μM, adj. P<0.001) were observed using mixed-effect model analysis.Discussion:Optical scattering signals reveal alterations in tissue structure that possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.International Journal of Obesity advance online publication, 19 April 2016; doi:10.1038/ijo.2016.43. © 2016 Macmillan Publishers Limited

Mihm Jr. M.C.,Harvard University | Nelson J.S.,Beckman Laser Institute
Journal of Cutaneous Pathology | Year: 2010

Recent advances in the understanding of the metastatic phenomenon in cancer have led to the description of a metastatic niche. This concept describes a site prepared for the tumor cells in areas frequently associated with metastasis for the individual tumor studied. This niche is a "soil" that allows for the tumor cell or "seed" to lodge and grow. Certain aspects of the biology of infantile hemangioma cells suggest a relationship to the placenta as a possible site of origin for the hemangioma precursor cells. In this article, a relationship between the placenta, with or without a chorangioma and the hemangioma sites of localization, is hypothesized. The placenta is suggested as the site of humoral factors that prepare a niche similar to the function of malignant tumor cells. If the hypothesis proves to be valid, clues for possible treatment are outlined. © 2010 John Wiley & Sons A/S.

Meloty-Kapella L.,University of California at Los Angeles | Shergill B.,University of California at Irvine | Kuon J.,University of California at Los Angeles | Botvinick E.,University of California at Irvine | And 2 more authors.
Developmental Cell | Year: 2012

Notch signaling induced by cell surface ligands is critical to development and maintenance of many eukaryotic organisms. Notch and its ligands are integral membrane proteins that facilitate direct cell-cell interactions to activate Notch proteolysis and release the intracellular domain that directs Notch-specific cellular responses. Genetic studies suggest that Notch ligands require endocytosis, ubiquitylation, and epsin endocytic adaptors to activate signaling, but the exact role of ligand endocytosis remains unresolved. Here we characterize a molecularly distinct mode of clathrin-mediated endocytosis requiring ligand ubiquitylation, epsins, and actin for ligand cells to activate signaling in Notch cells. Using a cell-bead optical tweezers system, we obtained evidence for cell-mediated mechanical force dependent on this distinct mode of ligand endocytosis. We propose that the mechanical pulling force produced by endocytosis of Notch-bound ligand drives conformational changes in Notch that permit activating proteolysis.

Madsen S.J.,University of Nevada, Las Vegas | Hirschberg H.,Beckman Laser Institute
Journal of Biophotonics | Year: 2010

The blood-brain barrier (BBB) poses a significant impediment for the delivery of therapeutic drugs into the brain. This is particularly problematic for the treatment of malignant gliomas which are characterized by diffuse infiltration of tumor cells into normal brain where they are protected by a patent BBB. Selective disruption of the BBB, followed by administration of anti-cancer agents, represents a promising approach for the elimination of infiltrating glioma cells. A summary of the techniques (focused ultrasound, photodynamic therapy and photochemical internalization) for site-specific opening of the BBB will be discussed in this review. Each approach is capable of causing localized and transient opening of the BBB with minimal damage to surrounding normal brain as evidenced from magnetic resonance images and histology. © 2010 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ortiz A.E.,Harvard University | Nelson J.S.,Beckman Laser Institute
Facial Plastic Surgery | Year: 2012

Background and ObjectivesPort-wine stains (PWSs) are capillary vascular malformations that are commonly resistant to treatment. Currently, the pulsed dye laser (PDL) is the treatment of choice. Multiple treatments are required and complete blanching after laser irradiation is rarely achieved. We review current therapeutic modalities for PWSs and recent developments for enhanced clearance. Study Design/Materials and MethodsRelevant literature was reviewed including PDL modifications for improved efficacy, alternative laser devices for treatment-resistant PWSs, and the addition of agents to modulate the wound-healing response after laser irradiation. ResultsAlthough PDL is the treatment of choice for PWSs, increased understanding of interactions between PWSs and PDL has led to improvements in therapeutic outcome in terms of lesion blanching. ConclusionsPreliminary evidence of combination therapy using antiangiogenic agents after laser irradiation appears promising and could lead to the development of a new standard of care for PWSs. Copyright © 2012 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

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