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https://www.readbyqxmd.com/read/27913649/identification-and-function-of-fibrocytes-in-skeletal-muscle-injury-repair-and-muscular-dystrophy
#1
Xingyu Wang, Wanming Zhao, Richard M Ransohoff, Lan Zhou
We identified and characterized the function of CD45(+)/collagen I(+) fibrocytes in acutely injured skeletal muscle of wild-type (WT) and Ccr2(-/-) mice, and in quadriceps and diaphragm muscles of mdx(5cv) mice, a mouse model for Duchenne muscular dystrophy. Fibrocytes were not detected in peripheral blood of WT mice after acute muscle injury or mdx(5cv) mice. Fibrocytes were detected in acutely injured muscles and in mdx(5cv) quadriceps and diaphragm muscles. These cells expressed F4/80 and CCR2, and they were mostly Ly6C(lo) They expressed a low level of collagens but a high level of profibrotic growth factors as compared with i...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27902821/risk-factors-for-basal-cell-carcinoma-among-patients-with-basal-cell-nevus-syndrome-development-of-a-basal-cell-nevus-syndrome-patient-registry
#2
Daniel C Solis, Gina P Kwon, Katherine J Ransohoff, Shufeng Li, Harvind S Chahal, Mina S Ally, Marieke A D Peters, Kristi Schmitt-Burr, Joselyn Lindgren, Irene Bailey-Healy, Joyce M Teng, Ervin H Epstein, Jean Y Tang
Importance: Patients with basal cell nevus syndrome (BCNS) have a greater risk of developing numerous basal cell carcinomas (BCCs). Risk factors influencing the wide variation in tumor burden are poorly understood. Objective: To describe the burden of BCCs in patients with BCNS in the United States and identify potential risk factors for BCCs. Design, Setting, and Participants: Prospective clinical registry with data collected from September 2014 to March 2016...
November 30, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27882502/institutional-responsibility-and-the-flawed-genomic-biomarkers-at-duke-university-a-missed-opportunity-for-transparency-and-accountability
#3
David L DeMets, Thomas R Fleming, Gail Geller, David F Ransohoff
When there have been substantial failures by institutional leadership in their oversight responsibility to protect research integrity, the public should demand that these be recognized and addressed by the institution itself, or the funding bodies. This commentary discusses a case of research failures in developing genomic predictors for cancer risk assessment and treatment at a leading university. In its review of this case, the Office of Research Integrity, an agency within the US Department of Health and Human Services, focused their report entirely on one individual faculty member and made no comment on the institution's responsibility and its failure to provide adequate oversight and investigation...
November 23, 2016: Science and Engineering Ethics
https://www.readbyqxmd.com/read/27796746/a-neuroprotective-effect-of-the-glutamate-receptor-antagonist-mk801-on-long-term-cognitive-and-behavioral-outcomes-secondary-to-experimental-cerebral-malaria
#4
Aline Silva de Miranda, Fátima Brant, Luciene Bruno Vieira, Natália Pessoa Rocha, Érica Leandro Marciano Vieira, Gustavo Henrique Souza Rezende, Pollyana Maria de Oliveira Pimentel, Marcio F D Moraes, Fabíola Mara Ribeiro, Richard M Ransohoff, Mauro Martins Teixeira, Fabiana Simão Machado, Milene Alvarenga Rachid, Antônio Lúcio Teixeira
Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection, which can result in long-term cognitive and behavioral deficits despite successful anti-malarial therapy. Due to the substantial social and economic burden of CM, the development of adjuvant therapies is a scientific goal of highest priority. Apart from vascular and immune responses, changes in glutamate system have been reported in CM pathogenesis suggesting a potential therapeutic target. Based on that, we hypothesized that interventions in the glutamatergic system induced by blockage of N-methyl-D-aspartate (NMDA) receptors could attenuate experimental CM long-term cognitive and behavioral outcomes...
October 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27668937/efficient-derivation-of-microglia-like-cells-from-human-pluripotent-stem-cells
#5
Julien Muffat, Yun Li, Bingbing Yuan, Maisam Mitalipova, Attya Omer, Sean Corcoran, Grisilda Bakiasi, Li-Huei Tsai, Patrick Aubourg, Richard M Ransohoff, Rudolf Jaenisch
Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions...
November 2016: Nature Medicine
https://www.readbyqxmd.com/read/27601660/infiltrating-monocytes-promote-brain-inflammation-and-exacerbate-neuronal-damage-after-status-epilepticus
#6
Nicholas H Varvel, Jonas J Neher, Andrea Bosch, Wenyi Wang, Richard M Ransohoff, Richard J Miller, Raymond Dingledine
The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood-brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not infiltrate the healthy CNS, monocytes can enter the brain in response to injury and contribute to the immune response. We examined the cellular components of innate immune inflammation in the days following SE by discriminating microglia vs...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27582444/risk-of-advanced-neoplasia-using-the-national-cancer-institute-s-colorectal-cancer-risk-assessment-tool
#7
Thomas F Imperiale, Menggang Yu, Patrick O Monahan, Timothy E Stump, Rebeka Tabbey, Elizabeth Glowinski, David F Ransohoff
BACKGROUND: There is no validated, discriminating, and easy-to-apply tool for estimating risk of colorectal neoplasia. We studied whether the National Cancer Institute's (NCI's) Colorectal Cancer (CRC) Risk Assessment Tool, which estimates future CRC risk, could estimate current risk for advanced colorectal neoplasia among average-risk persons. METHODS: This cross-sectional study involved individuals age 50 to 80 years undergoing first-time screening colonoscopy...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27572431/cd62l-is-not-a-reliable-biomarker-for-predicting-pml-risk-in-natalizumab-treated-r-ms-patients
#8
Nicholas Schwab, Tilman Schneider-Hohendorf, Heinz Wiendl, Ellen Cahir-McFarland, Richard M Ransohoff, Linda Lieberman, Tatiana Plavina
No abstract text is available yet for this article.
August 30, 2016: Neurology
https://www.readbyqxmd.com/read/27540165/how-neuroinflammation-contributes-to-neurodegeneration
#9
REVIEW
Richard M Ransohoff
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal lobar dementia are among the most pressing problems of developed societies with aging populations. Neurons carry out essential functions such as signal transmission and network integration in the central nervous system and are the main targets of neurodegenerative disease. In this Review, I address how the neuron's environment also contributes to neurodegeneration. Maintaining an optimal milieu for neuronal function rests with supportive cells termed glia and the blood-brain barrier...
August 19, 2016: Science
https://www.readbyqxmd.com/read/27539887/genome-wide-association-study-identifies-14-novel-risk-alleles-associated-with-basal-cell-carcinoma
#10
Harvind S Chahal, Wenting Wu, Katherine J Ransohoff, Lingyao Yang, Haley Hedlin, Manisha Desai, Yuan Lin, Hong-Ji Dai, Abrar A Qureshi, Wen-Qing Li, Peter Kraft, David A Hinds, Jean Y Tang, Jiali Han, Kavita Y Sarin
Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression)...
2016: Nature Communications
https://www.readbyqxmd.com/read/27497314/variation-in-the-oxytocin-receptor-gene-oxtr-is-associated-with-differences-in-moral-judgment
#11
Regan M Bernhard, Jonathan Chaponis, Richie Siburian, Patience Gallagher, Katherine Ransohoff, Daniel Wikler, Roy H Perlis, Joshua D Greene
Moral judgments are produced through the coordinated interaction of multiple neural systems, each of which relies on a characteristic set of neurotransmitters. Genes that produce or regulate these neurotransmitters may have distinctive influences on moral judgment. Two studies examined potential genetic influences on moral judgment using dilemmas that reliably elicit competing automatic and controlled responses, generated by dissociable neural systems. Study 1 (N = 228) examined 49 common variants (SNPs) within 10 candidate genes and identified a nominal association between a polymorphism (rs237889) of the oxytocin receptor gene (OXTR) and variation in deontological vs utilitarian moral judgment (that is, judgments favoring individual rights vs the greater good)...
August 6, 2016: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/27459405/a-polarizing-question-do-m1-and-m2-microglia-exist
#12
Richard M Ransohoff
Microglial research has entered a fertile, dynamic phase characterized by novel technologies including two-photon imaging, whole-genome transcriptomic and epigenomic analysis with complementary bioinformatics, unbiased proteomics, cytometry by time of flight (CyTOF; Fluidigm) cytometry, and complex high-content experimental models including slice culture and zebrafish. Against this vivid background of newly emerging data, investigators will encounter in the microglial research literature a body of published work using the terminology of macrophage polarization, most commonly into the M1 and M2 phenotypes...
July 26, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27424798/genome-wide-association-study-identifies-novel-susceptibility-loci-for-cutaneous-squamous-cell-carcinoma
#13
Harvind S Chahal, Yuan Lin, Katherine J Ransohoff, David A Hinds, Wenting Wu, Hong-Ji Dai, Abrar A Qureshi, Wen-Qing Li, Peter Kraft, Jean Y Tang, Jiali Han, Kavita Y Sarin
Cutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7-11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance (P<5 × 10(-8)) including seven previously confirmed pigmentation-related loci: MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2...
July 18, 2016: Nature Communications
https://www.readbyqxmd.com/read/27367170/assessment-of-accuracy-of-patient-initiated-differential-diagnosis-generation-by-google-reverse-image-searching
#14
Julia D Ransohoff, Shufeng Li, Kavita Y Sarin
No abstract text is available yet for this article.
June 29, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27325505/cx3cr1-dependent-recruitment-of-mature-nk-cells-into-the-central-nervous-system-contributes-to-control-autoimmune-neuroinflammation
#15
Laura Hertwig, Isabell Hamann, Silvina Romero-Suarez, Jason M Millward, Rebekka Pietrek, Coralie Chanvillard, Hanna Stuis, Karolin Pollok, Richard M Ransohoff, Astrid E Cardona, Carmen Infante-Duarte
Fractalkine receptor (CX3CR1)-deficient mice develop very severe experimental autoimmune encephalomyelitis (EAE), associated with impaired NK cell recruitment into the CNS. Yet, the precise implications of NK cells in autoimmune neuroinflammation remain elusive. Here, we investigated the pattern of NK cell mobilization and the contribution of CX3CR1 to NK cell dynamics in the EAE. We show that in both wild-type and CX3CR1-deficient EAE mice, NK cells are mobilized from the periphery and accumulate in the inflamed CNS...
August 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27304798/clinical-practice-guidelines-for-colorectal-cancer-screening-new-recommendations-and-new-challenges
#16
EDITORIAL
David F Ransohoff, Harold C Sox
No abstract text is available yet for this article.
June 21, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27208841/third-party-assessment-of-resection-margin-status-in-head-and-neck-cancer
#17
Amy Ransohoff, Douglas Wood, A Solomon Henry, Vasu Divi, A Colevas
BACKGROUND: Definitive assessment of primary site margin status following resection of head and neck cancer is necessary for prognostication, treatment determination and qualification for clinical trials. This retrospective analysis determined how often an independent reviewer can assess primary tumor margin status of head and neck cancer resections based on review of the pathology report, surgical operative report, and first follow-up note alone. METHODS: We extracted from the electronic medical record pathology reports, operative reports, and follow-up notes from head and neck cancer resections performed at Stanford Hospital...
June 2016: Oral Oncology
https://www.readbyqxmd.com/read/27153844/impact-of-residential-uv-exposure-in-childhood-versus-adulthood-on-skin-cancer-risk-in-caucasian-postmenopausal-women-in-the-women-s-health-initiative
#18
Katherine J Ransohoff, Mina S Ally, Marcia L Stefanick, Elizabeth Keiser, Katrina Spaunhurst, Kristopher Kapphahn, Sherry Pagoto, Catherine Messina, Haley Hedlin, JoAnn E Manson, Jean Y Tang
BACKGROUND: Sun exposure is a major risk factor for skin cancer; however, the relative contribution of ultraviolet (UV) exposure during childhood versus adulthood on skin cancer risk remains unclear. OBJECTIVE: Our goal was to determine the impact of residential UV, measured by AVerage daily total GLObal solar radiation (AVGLO), exposure during childhood (birth, 15 years) versus adulthood (35, 50 years, and present) on incident non-melanoma skin cancer (NMSC) and malignant melanoma (MM) in postmenopausal women...
June 2016: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/27145382/cancer-stem-cell-secreted-macrophage-migration-inhibitory-factor-stimulates-myeloid-derived-suppressor-cell-function-and-facilitates-glioblastoma-immune-evasion
#19
Balint Otvos, Daniel J Silver, Erin E Mulkearns-Hubert, Alvaro G Alvarado, Soumya M Turaga, Mia D Sorensen, Patricia Rayman, William A Flavahan, James S Hale, Kevin Stoltz, Maksim Sinyuk, Qiulian Wu, Awad Jarrar, Sung-Hak Kim, Paul L Fox, Ichiro Nakano, Jeremy N Rich, Richard M Ransohoff, James Finke, Bjarne W Kristensen, Michael A Vogelbaum, Justin D Lathia
Shifting the balance away from tumor-mediated immune suppression toward tumor immune rejection is the conceptual foundation for a variety of immunotherapy efforts currently being tested. These efforts largely focus on activating antitumor immune responses but are confounded by multiple immune cell populations, including myeloid-derived suppressor cells (MDSCs), which serve to suppress immune system function. We have identified immune-suppressive MDSCs in the brains of GBM patients and found that they were in close proximity to self-renewing cancer stem cells (CSCs)...
August 2016: Stem Cells
https://www.readbyqxmd.com/read/27112670/the-blood-brain-barrier
#20
Birgit Obermeier, Ajay Verma, Richard M Ransohoff
In autoimmune neurologic disorders, the blood-brain barrier (BBB) plays a central role in immunopathogenesis, since this vascular interface is an entry path for cells and effector molecules of the peripheral immune system to reach the target organ, the central nervous system (CNS). The BBB's unique anatomic structure and the tightly regulated interplay of its cellular and acellular components allow for maintenance of brain homeostasis, regulation of influx and efflux, and protection from harm; these ensure an optimal environment for the neuronal network to function properly...
2016: Handbook of Clinical Neurology
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