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[PMID]: 26002980
[Au] Autor:McCully ML; Collins PJ; Hughes TR; Thomas CP; Billen J; O'Donnell VB; Moser B
[Ad] Address:Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, United Kingdom; and....
[Ti] Title:Skin Metabolites Define a New Paradigm in the Localization of Skin Tropic Memory T Cells.
[So] Source:J Immunol;195(1):96-104, 2015 Jul 1.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The localization of memory T cells to human skin is essential for long-term immune surveillance and the maintenance of barrier integrity. The expression of CCR8 during naive T cell activation is controlled by skin-specific factors derived from epidermal keratinocytes and not by resident dendritic cells. In this study, we show that the CCR8-inducing factors are heat stable and protease resistant and include the vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 and PGE2. The effect of either metabolite alone on CCR8 expression was weak, whereas their combination resulted in robust CCR8 expression. Elevation of intracellular cAMP was essential because PGE2 could be substituted with the adenylyl cyclase agonist forskolin, and CCR8 expression was sensitive to protein kinase A inhibition. For effective induction, exposure of naive T cells to these epidermal factors needed to occur either prior to or during T cell activation even though CCR8 was only detected 4-5 d later in proliferating T cells. The importance of tissue environments in maintaining cellular immune surveillance networks within distinct healthy tissues provides a paradigm shift in adaptive immunity. Epidermal-derived vitamin D3 metabolites and PGs provide an essential cue for the localization of CCR8(+) immune surveillance T cells within healthy human skin.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1402961

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[PMID]: 25830923
[Au] Autor:Akiyama T; Nguyen T; Curtis E; Nishida K; Devireddy J; Delahanty J; Carstens MI; Carstens E
[Ad] Address:aDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA bDepartment of Dermatology, Department of Anatomy and Cell Biology, and Temple Itch Center, Temple University, Philadelphia, PA, USA.
[Ti] Title:A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch.
[So] Source:Pain;156(7):1240-6, 2015 Jul.
[Is] ISSN:1872-6623
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We investigated roles for spinal neurons expressing the neurokinin-1 receptor (NK1R) and/or gastrin-releasing peptide receptor (GRPR) in a mouse model of ovalbumin (OVA)-induced chronic atopic dermatitis. Mice receiving repeated topical application of OVA exhibited atopic-like skin lesions and behavioral signs of chronic itch including spontaneous scratching, touch-evoked scratching (alloknesis), and enhancement of chloroquine-evoked scratching (hyperknesis). Substance P-saporin (SP-SAP) and bombesin-saporin (BB-SAP) were intrathecally injected into OVA-sensitized mice to neurotoxically ablate NK1R- or GRPR-expressing spinal neurons, respectively. SP-SAP diminished the expression of NK1R in the superficial spinal dorsal horn and significantly attenuated all behavioral signs of chronic itch. BB-SAP reduced the spinal dorsal horn expression of GRPR and significantly attenuated hyperknesis, with no effect on spontaneous scratching or alloknesis. To investigate whether NK1R-expressing spinal neurons project in ascending somatosensory pathways, we performed a double-label study. The retrograde tracer, Fluorogold (FG), was injected into either the somatosensory thalamus or lateral parabrachial nucleus. In the upper cervical (C1-2) spinal cord, most neurons retrogradely labeled with FG were located in the dorsomedial aspect of the superficial dorsal horn. Of FG-labeled spinal neurons, 89% to 94% were double labeled for NK1R. These results indicate that NK1R-expressing spinal neurons play a major role in the expression of symptoms of chronic itch and give rise to ascending somatosensory projections. Gastrin-releasing peptide receptor-expressing spinal neurons contribute to hyperknesis but not to alloknesis or ongoing itch. NK1R-expressing spinal neurons represent a potential target to treat chronic itch.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1097/j.pain.0000000000000172

  3 / 616118 MEDLINE  
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[PMID]: 26085885
[Au] Autor:Foahom Kamwa AD; Mateus C; Thanigasalam R; Boulay-Coletta I; Duchatelle V; Triller M; Robert C; Baumert H
[Ad] Address:Department of Urology, Hopital Saint Joseph, Paris, France; ; Department of Urology, Carémeau University Hospital, place du Professeur Debré, Nîmes, France....
[Ti] Title:Seminal vesicle metastasis of cutaneous malignant melanoma: An unusual and challenging presentation.
[So] Source:Can Urol Assoc J;9(3-4):E220-3, 2015 Mar-Apr.
[Is] ISSN:1911-6470
[Cp] Country of publication:Canada
[La] Language:eng
[Ab] Abstract:Malignant melanoma is a tumour, which usually involves skin melanocytes. Involvement of the male genitourinary (GU) system by melanoma is an uncommon and challenging diagnosis. We report the first case of seminal vesicle metastasis from a primary cutaneous melanoma in a 58-year-old man, with hemospermia as the only clinical sign. This case highlights the role of multiparametric magnetic resonance imaging, as a more sensitive assessment to early detect metastatic melanoma in the GU system. The patient underwent a robot-assisted laparoscopic bilateral seminal vesiculectomy, which had good functional and oncological results and is still in complete remission at the 1-year follow-up.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Da] Date of entry for processing:150618
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.5489/cuaj.2172

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[PMID]: 26085873
[Au] Autor:Goel A; Kumar M; Singh M
[Ad] Address:Department of Urology, King George Medical University, Lucknow, India;
[Ti] Title:Orandi flap for penile urethral stricture: Polishing the gold standard.
[So] Source:Can Urol Assoc J;9(3-4):E160-3, 2015 Mar-Apr.
[Is] ISSN:1911-6470
[Cp] Country of publication:Canada
[La] Language:eng
[Ab] Abstract:INTRODUCTION: We describe the combined use of the Orandi flap and the scrotal skin advancement flap to reduce complications for pendulous urethral stricture in men >40 years old. METHODS: Over the last 40 months, 10 men underwent urethroplasty for pendulous stricture by the modified Orandi urethroplasty. In this, additionally, a midline hairless scrotal skin flap of the size of the ventral skin defect on the pendulous portion was raised based on the dartos fascia. This flap was mobilized so that it reached the pendulous portion without tension and covered the penile defect. The catheter was removed after 4 weeks. Patients were followed every 3 months using uroflowmetry and the American Urological Association (AUA) symptom score. RESULTS: The mean age was 55.5. Of the 10 patients, the etiology was post-catheterization in 5 and idiopathic in the remaining 5. Three men also had stricture extending into the bulbous urethra (repaired using buccal graft). The mean additional time needed for the flap coverage was 36.2 minutes (range: 30-45). The median follow-up was 12 months (range: 3-40). The mean postoperative symptom score was 5.2 and the mean flow rate was 20.1 mL/sec. In 2 men, the meatus got retracted to the distal penile part (probably due to downward traction by scrotal skin). No patient complained of disfigurement. Two men reported recurrence (1 each in bulbous and penile urethra). The limitations are small number of patients and the observational nature of this study. CONCLUSIONS: The intermediate-term results show that the modified Orandi urethroplasty is an acceptable treatment option with acceptable cosmetic results.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Da] Date of entry for processing:150618
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.5489/cuaj.2455

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[PMID]: 26084469
[Au] Autor:Falginella L; Cipriani G; Monte C; Gregori R; Testolin R; Velasco R; Troggio M; Tartarini S
[Ad] Address:Department of Agriculture and Environmental Sciences, University of Udine, Via delle Scienze 208, 33100, Udine, Italy. luigi.falginella@uniud.it....
[Ti] Title:A major QTL controlling apple skin russeting maps on the linkage group 12 of 'Renetta Grigia di Torriana'.
[So] Source:BMC Plant Biol;15:150, 2015.
[Is] ISSN:1471-2229
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Russeting is a disorder developed by apple fruits that consists of cuticle cracking followed by the replacement of the epidermis by a corky layer that protects the fruit surface from water loss and pathogens. Although influenced by many environmental conditions and orchard management practices, russeting is under genetic control. The difficulty in classifying offspring and consequent variable segregation ratios have led several authors to conclude that more than one genetic determinant could be involved, although some evidence favours a major gene (Ru). RESULTS: In this study we report the mapping of a major genetic russeting determinant on linkage group 12 of apple as inferred from the phenotypic observation in a segregating progeny derived from 'Renetta Grigia di Torriana', the construction of a 20 K Illumina SNP chip based genetic map, and QTL analysis. Recombination analysis in two mapping populations restricted the region of interest to approximately 400 Kb. Of the 58 genes predicted from the Golden Delicious sequence, a putative ABCG family transporter has been identified. Within a small set of russeted cultivars tested with markers of the region, only six showed the same haplotype of 'Renetta Grigia di Torriana'. CONCLUSIONS: A major determinant (Ru_RGT) for russeting development putatively involved in cuticle organization is proposed as a candidate for controlling the trait. SNP and SSR markers tightly co-segregating with the Ru_RGT locus may assist the breeder selection. The observed segregations and the analysis of the 'Renetta Grigia di Torriana' haplotypic region in a panel of russeted and non-russeted cultivars may suggest the presence of other determinants for russeting in apple.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/s12870-015-0507-4

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[PMID]: 26013383
[Au] Autor:Kim KY; Lee G; Yoon M; Cho EH; Park CS; Kim MG
[Ad] Address:Department of Biological Sciences, Inha University, Incheon 402-720, Korea....
[Ti] Title:Expression Analyses Revealed Thymic Stromal Co-Transporter/Slc46A2 Is in Stem Cell Populations and Is a Putative Tumor Suppressor.
[So] Source:Mol Cells;38(6):548-61, 2015 Jun 30.
[Is] ISSN:0219-1032
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:By combining conventional single cell analysis with flow cytometry and public database searches with bioinformatics tools, we extended the expression profiling of thymic stromal cotransporter (TSCOT), Slc46A2/Ly110, that was shown to be expressed in bipotent precursor and cortical thymic epithelial cells. Genome scale analysis verified TSCOT expression in thymic tissue- and cell type- specific fashion and is also expressed in some other epithelial tissues including skin and lung. Coexpression profiling with genes, Foxn1 and Hoxa3, revealed the role of TSCOT during the organogenesis. TSCOT expression was detected in all thymic epithelial cells (TECs), but not in the CD31(+) endothelial cell lineage in fetal thymus. In addition, ABC transporter-dependent side population and Sca-1(+) fetal TEC populations both contain TSCOT-expressing cells, indicating TEC stem cells express TSCOT. TSCOT expression was identified as early as in differentiating embryonic stem cells. TSCOT expression is not under the control of Foxn1 since TSCOT is present in the thymic rudiment of nude mice. By searching variations in the expression levels, TSCOT is positively associated with Grhl3 and Irf6. Cytokines such as IL1b, IL22 and IL24 are the potential regulators of the TSCOT expression. Surprisingly, we found TSCOT expression in the lung is diminished in lung cancers, suggesting TSCOT may be involved in the suppression of lung tumor development. Based on these results, a model for TEC differentiation from the stem cells was proposed in context of multiple epithelial organ formation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.14348/molcells.2015.0044

  7 / 616118 MEDLINE  
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[PMID]: 25844930
[Au] Autor:Pescatore R; Marrone GF; Sedberry S; Vinton D; Finkelstein N; Katlowitz YE; Pasternak GW; Wilson KR; Majumdar S
[Ad] Address:†Department of Chemistry, Wingate University, PO Box 159, Wingate, North Carolina 28174, United States....
[Ti] Title:Synthesis and Pharmacology of Halogenated δ-Opioid-Selective [d-Ala(2)]Deltorphin II Peptide Analogues.
[So] Source:ACS Chem Neurosci;6(6):905-10, 2015 Jun 17.
[Is] ISSN:1948-7193
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II template, which is δ-selective in in vitro radioligand binding assays over the µ- and κ-opioid receptors. It is a full agonist in [(35)S]GTPγS functional assays and analgesic when administered supraspinally to mice. Analgesia of 3 (GATE3-8) is blocked by the selective δ receptor antagonist naltrindole, indicating that the analgesic action of 3 is mediated by the δ-opioid receptor. We have established a radioligand in which (125)I is incorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese hamster ovary (CHO) cells expressing the δ receptor. Additionally, a series of peptides based on 3 (GATE3-8) was synthesized by incorporating various halogens in the para position on the aromatic ring of Phe(3). The peptides were characterized for binding affinity at the µ-, δ-, and κ-opioid receptors, which showed a linear correlation between binding affinity and the size of the halogen substituent. These peptides may be interesting tools for probing δ-opioid receptor pharmacology.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1021/acschemneuro.5b00060

  8 / 616118 MEDLINE  
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[PMID]: 26077348
[Au] Autor:Jun JI; Kim KH; Lau LF
[Ad] Address:Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, 900 South Ashland Avenue, Chicago, Illinois 60607, USA.
[Ti] Title:The matricellular protein CCN1 mediates neutrophil efferocytosis in cutaneous wound healing.
[So] Source:Nat Commun;6:7386, 2015.
[Is] ISSN:2041-1723
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Neutrophil infiltration constitutes the first step in wound healing, although their timely clearance by macrophage engulfment, or efferocytosis, is critical for efficient tissue repair. However, the specific mechanism for neutrophil clearance in wound healing remains undefined. Here we uncover a key role for CCN1 in neutrophil efferocytosis by acting as a bridging molecule that binds phosphatidylserine, the 'eat-me' signal on apoptotic cells and integrins αvß3/αvß5 in macrophages to trigger efferocytosis. Both knockin mice expressing a mutant CCN1 that is unable to bind αvß3/αvß5 and mice with Ccn1 knockdown are defective in neutrophil efferocytosis, resulting in exuberant neutrophil accumulation and delayed healing. Treatment of wounds with CCN1 accelerates neutrophil clearance in both Ccn1 knockin mice and diabetic Lepr(db/db) mice, which suffer from neutrophil persistence and impaired healing. These findings establish CCN1 as a critical opsonin in skin injury and suggest a therapeutic potential for CCN1 in certain types of non-healing wounds.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/ncomms8386

  9 / 616118 MEDLINE  
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[PMID]: 25939507
[Au] Autor:Gonzalez RJ; Weening EH; Lane MC; Miller VL
[Ad] Address:Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA....
[Ti] Title:Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to the Dermis.
[So] Source:Infect Immun;83(7):2855-61, 2015 Jul.
[Is] ISSN:1098-5522
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: Vector-borne pathogens are inoculated in the skin of mammals, most likely in the dermis. Despite this, subcutaneous (s.c.) models of infection are broadly used in many fields, including Yersinia pestis pathogenesis. We expand on a previous report where we implemented intradermal (i.d.) inoculations to study bacterial dissemination during bubonic plague and compare this model with an s.c. MODEL: We found that i.d. inoculations result in faster kinetics of infection and that bacterial dose influenced mouse survival after i.d. but not s.c. inoculation. Moreover, a deletion mutant of rovA, previously shown to be moderately attenuated in the s.c. model, was severely attenuated in the i.d. MODEL: Lastly, based on previous observations where a population bottleneck from the skin to lymph nodes was observed after i.d., but not after s.c., inoculations, we used the latter model as a strategy to identify an additional bottleneck in bacterial dissemination from lymph nodes to the bloodstream. Our data indicate that the more biologically relevant i.d. model of bubonic plague differs significantly from the s.c. model in multiple aspects of infection. These findings reveal adaptations of Y. pestis to the dermis and how these adaptations can define the progression of disease. They also emphasize the importance of using a relevant route of infection when addressing host-pathogen interactions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1128/IAI.00140-15

  10 / 616118 MEDLINE  
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[PMID]: 25916987
[Au] Autor:Liu M; Feng W; Zhu H; Lei B
[Ad] Address:Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA....
[Ti] Title:A Neutralizing Monoclonal IgG1 Antibody of Platelet-Activating Factor Acetylhydrolase SsE Protects Mice against Lethal Subcutaneous Group A Streptococcus Infection.
[So] Source:Infect Immun;83(7):2796-805, 2015 Jul.
[Is] ISSN:1098-5522
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Group A Streptococcus (GAS) can cause life-threatening invasive infections, including necrotizing fasciitis. There are no effective treatments for severe invasive GAS infections. The platelet-activating factor (PAF) acetylhydrolase SsE produced by GAS is required for invasive GAS to evade innate immune responses and to invade soft tissues. This study determined whether the enzymatic activity of SsE is critical for its function in GAS skin invasion and inhibition of neutrophil recruitment and whether SsE is a viable target for immunotherapy for severe invasive GAS infections. An isogenic derivative of M1T1 strain MGAS5005 producing SsE with an S178A substitution (SsE(S178A)), an enzymatically inactive SsE mutant protein, was generated. This strain induced higher levels of neutrophil infiltration and caused smaller lesions than MGAS5005 in subcutaneous infections of mice. This phenotype is similar to that of MGAS5005 sse deletion mutants, indicating that the enzymatic activity of SsE is critical for its function. An anti-SsE IgG1 monoclonal antibody (MAb), 2B11, neutralized the PAF acetylhydrolase activity of SsE. Passive immunization with 2B11 increased neutrophil infiltration, reduced skin invasion, and protected mice against MGAS5005 infection. However, 2B11 did not protect mice when it was administered after MGAS5005 inoculation. MGAS5005 induced vascular effusion at infection sites at early hours after GAS inoculation, suggesting that 2B11 did not always have access to infection sites. Thus, the enzymatic activity of SsE mediates its function, and SsE has the potential to be included in a vaccine but is not a therapeutic target. An effective MAb-based immunotherapy for severe invasive GAS infections may need to target virulence factors that are critical for systemic survival of GAS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150620
[Lr] Last revision date:150620
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1128/IAI.00073-15


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