Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis

Langerhans cell histiocytosis is a rare group of proliferative disorders. Beside cutaneous involvement, other internal organs can be affected. The treatment of cutaneous lesions is difficult and relies on topical corticosteroids, carmustine, nitrogen mustard, and photochemotherapy. Systemic steroids and vinblastine are used for recalcitrant skin lesions. However, some cases fail to respond. An 18-month old boy presented a CD1a+, S100a+ Langerhans cell histocytosis with cutaneous and severe scalp involvement. Topical corticosteroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and vinblastine improved the truncal involvement but had no effect on the scalp lesions. Methylaminolevulinate (MAL) based photodynamic therapy (PDT) resulted in a significant regression of the scalp lesions. Control histology revealed an almost complete clearance of the tumor infiltrate. Clinical follow-up after six months showed no recurrence

Measurement of high-p_T Single Electrons from Heavy-Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The momentum distribution of electrons from decays of heavy flavor (charm and beauty) for midrapidity |y| < 0.35 in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider (RHIC) over the transverse momentum range 0.3 < p_T < 9 GeV/c. Two independent methods have been used to determine the heavy flavor yields, and the results are in good agreement with each other. A fixed-order-plus-next-to-leading-log pQCD calculation agrees with the data within the theoretical and experimental uncertainties, with the data/theory ratio of 1.72 +/- 0.02^stat +/- 0.19^sys for 0.3 < p_T < 9 GeV/c. The total charm production cross section at this energy has also been deduced to be sigma_(c c^bar) = 567 +/- 57^stat +/- 224^sys micro barns.Comment: 375 authors from 57 institutions, 6 pages, 3 figures. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases

The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4, were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17, the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain

Bilateral Multi-Electrode Neurophysiological Recordings Coupled to Local Pharmacology in Awake Songbirds

Here we describe a protocol for bilateral multielectrode neurophysiological recordings during intracerebral pharmacological manipulations in awake songbirds. This protocol encompasses fitting adult animals with head-posts and recording chambers, and acclimating them to periods of restraint. The adaptation period is followed by bilateral penetrations of multiple electrodes to obtain acute, sensory-driven neurophysiological responses before versus during the application of pharmacological agents of interest. These local manipulations are achieved by simultaneous and restricted drug infusions carried out independently for each hemisphere. We have used this protocol to elucidate how neurotransmitter and neuroendocrine systems shape the auditory and perceptual processing of natural, learned communication signals. However, this protocol can be used to explore the neurochemical basis of sensory processing in other small vertebrates. Representative results and troubleshooting of key steps of this protocol are presented. Following the animal\u27s recovery from head-post and recording chamber implantation surgery, the length of the procedure is 2 d

NF-kappaB mediates the survival of human bronchial epithelial cells exposed to cigarette smoke extract

Background: We have previously reported that low concentrations of cigarette smoke extract induce DNA damage without leading to apoptosis or necrosis in human bronchial epithelial cells (HBECs), and that IL-6/STAT3 signaling contributes to the cell survival. Since NF-kappa B is also involved in regulating apoptosis and cell survival, the current study was designed to investigate the role of NF-kappa B in mediating cell survival in response to cigarette smoke exposure in HBECs. Methods: Both the pharmacologic inhibitor of NF-kappa B, curcumin, and RNA interference targeting p65 were used to block NF-kappa B signaling in HBECs. Apoptosis and cell survival were then assessed by various methods including COMET assay, LIVE/DEAD Cytotoxicity/Viability assay and colony formation assay. Results: Cigarette smoke extract (CSE) caused DNA damage and cell cycle arrest in S phase without leading to apoptosis in HBECs as evidenced by TUNEL assay, COMET assay and DNA content assay. CSE stimulated NF-kappa B -DNA binding activity and up-regulated Bcl-XL protein in HBECs. Inhibition of NF-kappa B by the pharmacologic inhibitor curcumin (20 mu M) or suppression of p65 by siRNA resulted in a significant increase in cell death in response to cigarette smoke exposure. Furthermore, cells lacking p65 were incapable of forming cellular colonies when these cells were exposed to CSE, while they behaved normally in the regular culture medium. Conclusion: The current study demonstrates that CSE activates NF-kappa B and up-regulates Bcl-XL through NF-kappa B activation in HBECs, and that CSE induces cell death in cells lacking p65. These results suggest that activation of NF-kappa B regulates cell survival following DNA damage by cigarette smoke in human bronchial epithelial cells.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000260432600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Respiratory SystemSCI(E)28ARTICLEnull

3D superimposition of craniofacial imaging—The utility of multicentre collaborations

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149360/1/ocr12281.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149360/2/ocr12281_am.pd

Mapping of the Disease Locus and Identification of ADAMTS10 As a Candidate Gene in a Canine Model of Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine chromosome 20. The Beagle POAG locus is syntenic to a previously mapped human quantitative trait locus for intraocular pressure on human chromosome 19. Sequence capture and next-generation sequencing of the entire canine POAG locus revealed a total of 2,692 SNPs segregating with disease. Of the disease-segregating SNPs, 54 were within exons, 8 of which result in amino acid substitutions. The strongest candidate variant causes a glycine to arginine substitution in a highly conserved region of the metalloproteinase ADAMTS10. Western blotting revealed ADAMTS10 protein is preferentially expressed in the trabecular meshwork, supporting an effect of the variant specific to aqueous humor outflow. The Gly661Arg variant in ADAMTS10 found in the POAG Beagles suggests that altered processing of extracellular matrix and/or defects in microfibril structure or function may be involved in raising intraocular pressure, offering specific biochemical targets for future research and treatment strategies