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Tyler K Ulland, Nidhi Jain, Emma E Hornick, Eric I Elliott, Gwendolyn M Clay, Jeffrey J Sadler, Kathleen A M Mills, Ann M Janowski, A Paige Davis Volk, Kai Wang, Kevin L Legge, Lokesh Gakhar, Mohammed Bourdi, Polly J Ferguson, Mary E Wilson, Suzanne L Cassel, Fayyaz S Sutterwala
The inbred mouse strain C57BL/6J is widely used in models of immunological and infectious diseases. Here we show that C57BL/6J mice have a defect in neutrophil recruitment to a range of inflammatory stimuli compared with the related C57BL/6N substrain. This immune perturbation is associated with a missense mutation in Nlrp12 in C57BL/6J mice. Both C57BL/6J and NLRP12-deficient mice have increased susceptibility to bacterial infection that correlates with defective neutrophil migration. C57BL/6J and NLRP12-deficient macrophages have impaired CXCL1 production and the neutrophil defect observed in C57BL/6J and NLRP12-deficient mice is rescued by restoration of macrophage NLRP12...
October 25, 2016: Nature Communications
P Van Epps, D Oswald, P A Higgins, T R Hornick, H Aung, R E Banks, B M Wilson, C Burant, S Graventstein, D H Canaday
BACKGROUND: Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans. RESULTS: We analyzed 117 subjects (age range 62-95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty...
2016: Immunity & Ageing: I & A
Ailbhe C O'Neill, Sree Harsha Tirumani, Woo S Do, Abhishek R Keraliya, Jason L Hornick, Atul B Shinagare, Nikhil H Ramaiya
OBJECTIVE: The objective of our study was to evaluate the metastatic patterns and imaging features of solitary fibrous tumors (SFTs). MATERIALS AND METHODS: This retrospective study included 139 patients with pathologically proven SFT, 49 of whom developed metastases. Electronic medical records and all available images were reviewed to record the pattern and imaging appearances of metastatic disease, and comparisons of thoracic SFTs and extrathoracic SFTs were also performed...
October 20, 2016: AJR. American Journal of Roentgenology
Yuangang Liu, Zhiping Wang, Rachel De La Torre, Ashley Barling, Takahiro Tsujikawa, Noah Hornick, Jon Hanifin, Eric Simpson, Yun Wang, Emily Swanzey, Aaron Wortham, Hao Ding, Lisa M Coussens, Molly Kulesz-Martin
Altered innate immunity is a feature of certain skin inflammatory diseases such as psoriasis and atopic dermatitis (AD). In this study, we provide evidence that deficiency in Trim32 (a tripartite motif (TRIM) protein with innate antiviral activity) contributes to a Th2 biased response and predisposes to features of AD in mice. Upon treatment with the TLR7 agonist imquimod (IMQ), Trim32 knockout (KO) mice displayed compromised psoriasiform phenotypes and defective Th17 response. Instead, IMQ treatment of Trim32 KO mice induced AD-like phenotypes with enhanced skin infiltration of eosinophils and mast cells, elevation of Th2 cytokines/chemokines expression, and reduced expression of filaggrin protein expression...
October 5, 2016: Journal of Investigative Dermatology
Danielle M Richman, Sree Harsha Tirumani, Jason L Hornick, Charles S Fuchs, Stephanie Howard, Katherine Krajewski, Nikhil Ramaiya, Michael Rosenthal
Despite advances in molecular biology, imaging, and treatment, gastric neoplasms remain a significant cause of morbidity and mortality; gastric adenocarcinoma is the fifth most common malignancy and third most common cause of death worldwide (Brenner et al., Methods Mol Biol 472:467-477, 2009; Howson et al. Epidemiol Rev 8:1-27, 1986; Roder, Gastric Cancer 5(Suppl 1):5-11, 2002; Ferlay et al., GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. International Agency for Research on Cancer, 2013)...
September 19, 2016: Abdominal Radiology
Tatiana Kelil, Abhishek R Keraliya, Stephanie A Howard, Katherine M Krajewski, Marta Braschi-Amirfarzan, Jason L Hornick, Nikhil H Ramaiya, Sree Harsha Tirumani
Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Ann M Janowski, Oscar R Colegio, Emma E Hornick, Jennifer M McNiff, Matthew D Martin, Vladimir P Badovinac, Lyse A Norian, Weizhou Zhang, Suzanne L Cassel, Fayyaz S Sutterwala
Members of the NLR family can assemble inflammasome complexes with the adaptor protein ASC and caspase-1 that result in the activation of caspase-1 and the release of IL-1β and IL-18. Although the NLRC4 inflammasome is known to have a protective role in tumorigenesis, there is an increased appreciation for the inflammasome-independent actions of NLRC4. Here, we utilized a syngeneic subcutaneous murine model of B16F10 melanoma to explore the role of NLRC4 in tumor suppression. We found that NLRC4-deficient mice exhibited enhanced tumor growth that was independent of the inflammasome components ASC and caspase-1...
October 3, 2016: Journal of Clinical Investigation
Noah I Hornick, Ben Doron, Sherif Abdelhamed, Jianya Huan, Christina A Harrington, Rongkun Shen, Xiaolu A Cambronne, Santhosh Chakkaramakkil Verghese, Peter Kurre
Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors. We found that the systemic loss of hematopoietic function is also in part a consequence of AML exosome-directed microRNA (miRNA) trafficking to HSPCs. Exosomes isolated from cultured AML or the plasma from mice bearing AML xenografts exhibited enrichment of miR-150 and miR-155...
September 6, 2016: Science Signaling
John R Hornick, Joshua A Balderman, Ronnie Eugea, Luis A Sanchez, Mohamed A Zayed
OBJECTIVE: Compared with other populations, patients who undergo vascular surgery have higher 30-day hospital readmission rates of up to 25%. Postdischarge telephone call assessments have demonstrated utility in patients with significant medical comorbidities and traditionally high readmission rates. Therefore, we hypothesized that a 1-week postdischarge telephone call evaluation can identify risk factors for readmission among vascular surgery patients. METHODS: Patients who underwent a vascular surgery procedure during a 1-year period by a single vascular surgeon at one hospital received a postdischarge telephone call questionnaire to review postoperative pain, surgical site, constitutional symptoms, and follow-up arrangement...
September 2016: Journal of Vascular Surgery
Jaclyn C Watkins, Eric J Yang, Michael G Muto, Colleen M Feltmate, Ross S Berkowitz, Neil S Horowitz, Sapna Syngal, Matthew B Yurgelun, Anu Chittenden, Jason L Hornick, Christopher P Crum, Lynette M Sholl, Brooke E Howitt
Although consensus has yet to be reached on universal mismatch-repair (MMR) protein immunohistochemical (IHC) screening for Lynch syndrome (LS) in endometrial cancer (EC), an increasing number of institutions have adopted universal screening protocols similar to those used for colorectal carcinoma. Here we describe our institution's experience with a prospective universal screening protocol in which all ECs resected over a period of 19 months (n=242) were screened for MLH1, PMS2, MSH2, and MSH6 deficiencies using IHC, followed by MLH1 promoter methylation testing when appropriate...
August 23, 2016: International Journal of Gynecological Pathology
Lennart T Bach, Jan Taucher, Tim Boxhammer, Andrea Ludwig, Eric P Achterberg, María Algueró-Muñiz, Leif G Anderson, Jessica Bellworthy, Jan Büdenbender, Jan Czerny, Ylva Ericson, Mario Esposito, Matthias Fischer, Mathias Haunost, Dana Hellemann, Henriette G Horn, Thomas Hornick, Jana Meyer, Michael Sswat, Maren Zark, Ulf Riebesell
Every year, the oceans absorb about 30% of anthropogenic carbon dioxide (CO2) leading to a re-equilibration of the marine carbonate system and decreasing seawater pH. Today, there is increasing awareness that these changes-summarized by the term ocean acidification (OA)-could differentially affect the competitive ability of marine organisms, thereby provoking a restructuring of marine ecosystems and biogeochemical element cycles. In winter 2013, we deployed ten pelagic mesocosms in the Gullmar Fjord at the Swedish west coast in order to study the effect of OA on plankton ecology and biogeochemistry under close to natural conditions...
2016: PloS One
Jonathan A Nowak, Jason L Hornick
Molecular testing in colorectal cancer helps to address multiple clinical needs. Evaluating the mismatch repair pathway status is the most common use for molecular diagnostics and this testing provides prognostic information, guides therapeutic decisions and helps identify Lynch syndrome patients. For patients with metastatic colorectal cancer, testing for activating mutations in downstream components of the EGFR signaling pathway can identify patients who will benefit from anti-EGFR therapy. Emerging molecular tests for colorectal cancer will help further refine patient selection for targeted therapies and may provide new options for monitoring disease recurrence and the development of treatment resistance...
September 2016: Surgical Pathology Clinics
Shawn M Briley, Susmita Jasti, Jennifer M McCracken, Jessica E Hornick, Barbara Fegley, Michele T Pritchard, Francesca E Duncan
Under normal physiological conditions, tissue remodeling in response to injury leads to tissue regeneration without permanent damage. However, if homeostasis between synthesis and degradation of extracellular matrix (ECM) components is altered, fibrosis - or the excess accumulation of ECM - can disrupt tissue architecture and function. Several organs, including the heart, lung and kidney, exhibit age-associated fibrosis. Here we investigated whether fibrosis underlies aging in the ovary - an organ that ages chronologically before other organs...
September 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
T Mentzel, A Rütten, M Hantschke, J L Hornick, T Brenn
Spindle cell lipoma represents a distinct clinicopathological entity and is related to cellular angiofibroma and mammary-type myofibroblastoma. Spindle cell lipomas are composed of mature lipogenic cells and a variable number of CD34-positive spindle cells that show loss of retinoblastoma protein expression. Spindle cell lipomas occasionally express S-100 protein. We studied one case of purely dermal spindle cell lipoma and four cases of classical subcutaneous spindle cell lipoma arising in one female and four male patients (age ranged from 55 to 69 years)...
October 2016: Virchows Archiv: An International Journal of Pathology
Yin P Hung, Christopher Dm Fletcher, Jason L Hornick
A distinct subset of round cell sarcomas harbors capicua transcriptional repressor (CIC) rearrangement. Diagnosing these sarcomas can be difficult owing to their resemblance to Ewing sarcoma and other 'small round blue cell tumors'; molecular techniques are generally required. Recent gene expression studies of CIC-rearranged sarcomas identified the upregulation of ETV4. We assessed the sensitivity and specificity of ETV4 and WT1 immunohistochemistry for CIC-rearranged sarcoma. We evaluated whole-tissue sections from 40 CIC-rearranged sarcomas, 40 Ewing sarcomas, 4 BCOR-CCNB3 sarcomas, 6 unclassified round cell sarcomas, and 150 histologic mimics...
July 22, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Matthew S Davids, Haesook T Kim, Pavan Bachireddy, Caitlin Costello, Rebecca Liguori, Alexandra Savell, Alexander P Lukez, David Avigan, Yi-Bin Chen, Peter McSweeney, Nicole R LeBoeuf, Michael S Rooney, Michaela Bowden, Chensheng W Zhou, Scott R Granter, Jason L Hornick, Scott J Rodig, Masahiro Hirakawa, Mariano Severgnini, F Stephen Hodi, Catherine J Wu, Vincent T Ho, Corey Cutler, John Koreth, Edwin P Alyea, Joseph H Antin, Philippe Armand, Howard Streicher, Edward D Ball, Jerome Ritz, Asad Bashey, Robert J Soiffer
BACKGROUND: Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS: We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT...
July 14, 2016: New England Journal of Medicine
Emily F Mason, Jason L Hornick
Gastrointestinal stromal tumors (GISTs) that lack kinase mutations often show loss of function of the succinate dehydrogenase (SDH) complex, due to germline mutation or promoter hypermethylation. SDH-deficient GISTs are exclusive to the stomach and have a multinodular architecture. It has been suggested that conventional risk stratification criteria may not predict outcome for this group of tumors, although data are limited. Here, we report the clinical, histologic, and genetic findings from a large cohort of 76 SDH-deficient GISTs diagnosed from 2005 to 2015, identified on the basis of histologic features or family history (45 female/31 male; mean age at diagnosis 32 y; range 11 to 71 y; 10 patients 50 y of age or above)...
June 23, 2016: American Journal of Surgical Pathology
Austin L Chiang, Jason L Hornick, V Anik Sahni, Thomas E Clancy, Marvin Ryou
No abstract text is available yet for this article.
July 2016: Pancreas
David N Hornick, Christopher Paynter, Michael W Dailey, Yuchi Young
No abstract text is available yet for this article.
September 2016: Journal of Palliative Medicine
Qingqing Liu, Keith Tomaszewicz, Lloyd Hutchinson, Jason L Hornick, Bruce Woda, Hongbo Yu
Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls...
August 2016: Virchows Archiv: An International Journal of Pathology
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