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Cold-inducible RNA-binding protein activates splenic T cells during sepsis in a TLR4-dependent manner

Cellular & Molecular Immunology 2018年第1期15卷 38-47页

作者： Alexandra C Bolognese Archna Sharma Weng-Lang Yang Jeffrey Nicastro gene F coppa Ping Wang Elmezzi Graduate School of Molecular Medicine Manhasset11030NYUSA Department of Surgery Hofstra Northwell School of MedicineManhasset11030NYUSA Center for Immunology and Inflammation The Feinstein Institute for Medical ResearchManhasset11030NYUSA

Cold-inducible RNA-binding protein (CIRP) is a novel inflammatory mediator that stimulates the release of proinflammatory cytokines from macrophages in sepsis. Given the immune dysregulation that characterizes sepsis, the effect of CIRP on other immune cells is an area of increasing interest that has not yet been studied. In the present study, we hypothesized that extracellular CIRP promotes activation of T lymphocytes in the spleen during sepsis. We observed that mice subjected to sepsis by cecal ligation and puncture showed significantly higher expression of the early activation markers CD69 and CD25 at 20 h on CD4+ splenic T cells, and significantly higher CD69 expression on CD8+ splenic T cells compared with sham-operated controls. Furthermore, at 20 h after receiving intravenous injection of recombinant murine CIRP (rmCIRP, 5 mg/kg body weight (BW)) or PBS (vehicle), those mice receiving rmCIRP showed significantly increased expression of CD69 and CD25 on both CD4+ and CD8+ splenic T cells. This effect, however, was not seen in TLR4-deficient mice after rmCIRP injection. In addition, treatment with CIRP predisposed CD4+ T cells to a Th1 hyperinflammatory response profile, and influenced CD8+ T cells toward a cytotoxic profile. Taken together, our findings indicate that CIRP is a proinflammatory mediator that plays an important role in T-cell dysregulation during sepsis in a TLR4-dependent manner.

关键词： CIRP immune response lymphocytes sepsis T-cell activation

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Monoclonal antibodies that target the immunogenic proteins expressed in colorectal cancer

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World Journal of Gastrointestinal Oncology 2014年第6期6卷 170-176页

作者： Myron Arlen Philip Arlen gene coppa Jim Crawford XuePing Wang Olga Saric Alex Dubeykovskiy Ernesto Molmenti Department of Surgery Division of Surgical Oncology and the Dept. of Pathology North Shore University HospitalManhasset NY 11030 United States Manhasset NY and Precision Biologics Great Neck NY 11021 United States

In an attempt to improve upon the end results obtained in treating colorectal cancer it was apparent that the earlier the diagnosis that could be obtained, the better the chance for obtaining desired results. In the case of more advanced tumors typified by later stage colorectal cancer, surgical debulking is an important part of the treatment strategy. Here the use of additional therapeu-tic modalities including chemotherapy and present day immunotherapy has failed to accomplish the desired im-provements that have been sought after. Adjuvant ther-apy, has offered little to the overall survival. The concept of early detection is now recognized as the initial step in reaching proper end results and can readily be demon-strated from colorectal cancer studies. Here survival has been found to be a reflection of the stage at which the tumor is first identified and treated. When specific mono-clonals targeting colorectal cancer are employed diagnos-tically, we have been able to demonstrate detection of colorectal cancer at its inception as a premalignant lesion, such that genotypic features can be identified before the phenotypic appearance of cancer can be noted.

关键词： Colorectal cancer Monoclonal antibodies Immunohistochemistry Antibody dependent cell cytotoxicity Tumor associated antigens

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Outcomes following operative vs. non-operative management of blunt traumatic pancreatic injuries: a retrospective multi-institutional study

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Burns & Trauma 2016年第4期4卷 316-322页

作者： Poppy Addison Toni Iurcotta Leo I.Amodu Geoffrey Crandall Meredith Akerman Daniel Galvin Annemarie Glazer Nathan Christopherson Jose Prince Matthew Bank Christopher Sorrentino Joaquin Cagliani Jeffrey Nicastro gene coppa Ernesto P.Molmenti Horacio L.Rodriguez Rilo Department of Surgery Hofstra-Northwell School of MedicineHempsteadNYUSA Pancreas Disease Center Northwell HealthManhassetNYUSA Department of Surgery Hofstra-Northwell School of MedicineHempsteadNYUSA Department of Biostatistics Feinstein Institute for Medical ResearchManhassetNYUSA Pancreas Disease Center Northwell HealthManhassetNYUSA Department of Surgery Hofstra-Northwell School of MedicineHempsteadNYUSA Pancreas Disease Center Northwell HealthManhassetNYUSA Northwell Health 900 Northern BoulevardSuite 150Great NeckNY 11020USA

Background:Traumatic pancreatic injuries are rare,and guidelines specifying management are controversial and difficult to apply in the acute clinical *** to sparse data on these injuries,we carried out a retrospective review to determine outcomes following surgical or non-surgical management of traumatic pancreatic *** hypothesize a higher morbidity and mortality rate in patients treated surgically when compared to patients treated ***:We performed a retrospective review of data from four trauma centers in New York from 1990–2014,comparing patients who had blunt traumatic pancreatic injuries who were managed operatively to those managed *** compared continuous variables using the Mann-Whitney U test and categorical variables using the chi-square and Fisher’s exact *** analysis was performed to determine the possible confounding factors associated with mortality in both treatment ***:Twenty nine patients were managed operatively and 32 *** was a significant difference between the operative and non-operative groups in median age(37.0 vs.16.2 years,P=0.016),grade of pancreatic injury(grade I;30.8 vs.85.2%,P value for all comparisons<0.0001),median injury severity score(ISS)(16.0 vs.4.0,P=0.002),blood transfusion(55.2 vs.15.6%,P=0.0012),other abdominal injuries(79.3 vs.38.7%,P=0.0014),pelvic fractures(17.2 vs.0.00%,P=0.020),intensive care unit(ICU)admission(86.2 vs.50.0%,P=0.003),median length of stay(LOS)(16.0 vs.4.0 days,P<0.0001),and mortality(27.6 vs.3.1%,P=0.010).Conclusions:Patients with traumatic pancreatic injuries treated operatively were more severely injured and suffered greater complications than those treated *** greater morbidity and mortality associated with these patients warrants further study to determine optimal triage strategies and which subset of patients is likely to benefit from surgery.

关键词： Injury Management Non-operative Operative Pancreas Trauma

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Adenocarcinoma arising at ileostomy sites:Two cases and a review of the literature

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World Journal of Gastrointestinal Surgery 2015年第6期7卷 94-97页

作者： Lauren Procaccino Sameer Rehman Alexander Abdurakhmanov Peter McWhorter Nicholas La Gamma Madhu C Bhaskaran James Maurer Gregory M Grimaldi Horacio Rilo Jeffrey Nicastro gene coppa Ernesto P Molmenti John Procaccino Department of Surgery North Shore University Hospital

Total colectomy with ileostomy placement is a treatment for patients with inflammatory bowel disease or familial adenomatous polyposis(FAP). A rare and late complication of this treatment is carcinoma arising at the ileostomy site. We describe two such cases: a 78-year-old male 30 years after subtotal colectomy and ileostomy for FAP, and an 85-year-old male 50 years after colectomy and ileostomy for ulcerative colitis. The long latency period between creation of the ileostomies and development of carcinoma suggests a chronic metaplasia due to an irritating/inflammatory causative factor. Surgical excision of the mass and relocation of the stoma is the mainstay of therapy, with possible benefits from adjuvant chemotherapy. Newly developed lesions at stoma sites should be biopsied to rule out the possibility of this rare ileostomy complication.

关键词： Ileostomy Carcinoma Adenocarcinoma Familial adenomatous polyposis Inflammatory boweldisease Complication of ileostomy

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