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Adenocarcinoma Arising At Ileostomy Sites: Two Cases And A Review Of The Literature, L. Procaccino, S. Rehman, A. Abdurakhmanov, P. McWhorter, N. La Gamma, M. C. Bhaskaran, J. Maurer, G. M. Grimaldi, H. Rilo, J. Nicastro, G. Coppa, E. P. Molmenti, J. Procaccino 2015 Northwell Health

Adenocarcinoma Arising At Ileostomy Sites: Two Cases And A Review Of The Literature, L. Procaccino, S. Rehman, A. Abdurakhmanov, P. Mcwhorter, N. La Gamma, M. C. Bhaskaran, J. Maurer, G. M. Grimaldi, H. Rilo, J. Nicastro, G. Coppa, E. P. Molmenti, J. Procaccino

Journal Articles

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 …


The Role Of B-1 Cells In Inflammation, M. Aziz, N. E. Holodick, T. L. Rothstein, P. Wang 2015 Northwell Health

The Role Of B-1 Cells In Inflammation, M. Aziz, N. E. Holodick, T. L. Rothstein, P. Wang

Journal Articles

B-1 lymphocytes exhibit unique phenotypic, ontogenic, and functional characteristics that differ from the conventional B-2 cells. B-1 cells spontaneously secrete germline-like, repertoire-skewed polyreactive natural antibody, which acts as a first line of defense by neutralizing a wide range of pathogens before launching of the adaptive immune response. Immunomodulatory molecules such as interleukin-10, adenosine, granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-35 are also produced by B-1 cells in the presence or absence of stimulation, which regulate acute and chronic inflammatory diseases. Considerable progress has been made during the past three decades since the discovery of B-1 cells, which has improved not only …


Post Splenectomy Related Pulmonary Hypertension, A.V. Palkar, A. Agrawal, S. Verma, A. Iftikhar, E.J. Miller, A. Talwar 2015 Northwell Health

Post Splenectomy Related Pulmonary Hypertension, A.V. Palkar, A. Agrawal, S. Verma, A. Iftikhar, E.J. Miller, A. Talwar

Journal Articles

No abstract provided.


Mfg-E8 Inhibits Neutrophil Migration Through Alpha(V)Beta(3)-Integrin-Dependent Map Kinase Activation, M. Aziz, W. L. Yang, L. M. Corbo, W. W. Chaung, S. Matsuo, P. Wang 2015 Northwell Health

Mfg-E8 Inhibits Neutrophil Migration Through Alpha(V)Beta(3)-Integrin-Dependent Map Kinase Activation, M. Aziz, W. L. Yang, L. M. Corbo, W. W. Chaung, S. Matsuo, P. Wang

Journal Articles

We have previously demonstrated the involvement of milk fat globule-epidermal growth factor-factor 8 (MFG-E8) in reducing neutrophil infiltration in a murine model of acute lung injury (ALI). In the present study, we aimed to delineate the mechanisms through which MFG-E8 attenuates neutrophil migration. Recombinant human MFG-E8 (rhMFG-E8) was expressed and purified in our facility. The human differentiated neutrophil cell line, dHL-60, was treated with rhMFG-E8 and cell migration assay was performed in a Boyden chamber using recombinant interleukin-8 (IL-8) as the chemoattractant. Surface CXCR2 and intracellular G protein-coupled receptor kinase 2 (GRK2) levels were evaluated by flow cytometry or western …


Milk Fat Globule-Egf Factor Viii Attenuates Cns Injury By Promoting Neural Stem Cell Proliferation And Migration After Cerebral Ischemia, C. Cheyuo, M. Aziz, W. L. Yang, A. Jacob, M. Zhou, P. Wang 2015 Northwell Health

Milk Fat Globule-Egf Factor Viii Attenuates Cns Injury By Promoting Neural Stem Cell Proliferation And Migration After Cerebral Ischemia, C. Cheyuo, M. Aziz, W. L. Yang, A. Jacob, M. Zhou, P. Wang

Journal Articles

The mediators in activating neural stem cells during the regenerative process of neurogenesis following stroke have not been fully identified. Milk fat globule-EGF Factor VIII (MFGE8), a secreted glycoprotein serves several cellular functions by binding to its receptor, alpha(v)beta(3)-integrin. However, its role in regulating neural stem cells after stroke has not been determined yet. We therefore, aim to reveal whether MFG-E8 promotes neural stem cell proliferation and migration during stroke. Stroke was induced in wild-type (Wt) and MFG-E8-deficinet (Mfge8(-/-)) mice by transient middle cerebral artery occlusion (tMCAO). Commercially available recombinant mouse MFG-E8 (rmMFG-E8) was used for mechanistic assays in neural …


Blocking Cold-Inducible Rna-Binding Protein Protects Liver From Ischemia-Reperfusion Injury, A. Godwin, W. L. Yang, A. Sharma, A. Khader, Z. Wang, F. Zhang, J. Nicastro, G.F. Coppa, P. Wang 2015 Northwell Health

Blocking Cold-Inducible Rna-Binding Protein Protects Liver From Ischemia-Reperfusion Injury, A. Godwin, W. L. Yang, A. Sharma, A. Khader, Z. Wang, F. Zhang, J. Nicastro, G.F. Coppa, P. Wang

Journal Articles

Cold-inducible RNA-binding protein (CIRP) is a nuclear protein that has been recently identified as a novel inflammatory mediator in hemorrhagic shock and sepsis. We hypothesized that CIRP acts as a potent inflammatory mediator in hepatic ischemia-reperfusion (I/R), and thus blocking CIRP protects against I/R-induced liver injury. Male C57BL/6 mice were subjected to 70% hepatic ischemia by microvascular clamping of the hilum of the left and median liver lobes for 60 min, followed by reperfusion. Anti-CIRP antibody (1 mg/kg body weight) or vehicle (normal saline) in 0.2 mL was injected via the internal jugular vein at the beginning of the reperfusion. …


Neutralization Of Osteopontin Attenuates Neutrophil Migration In Sepsis-Induced Acute Lung Injury, Y. Hirano, M. Aziz, W.L. Yang, Z. Wang, M. Zhou, M. Ochani, A. Khader, P. Wang 2015 Northwell Health

Neutralization Of Osteopontin Attenuates Neutrophil Migration In Sepsis-Induced Acute Lung Injury, Y. Hirano, M. Aziz, W.L. Yang, Z. Wang, M. Zhou, M. Ochani, A. Khader, P. Wang

Journal Articles

INTRODUCTION: Sepsis refers to severe systemic inflammation leading to acute lung injury (ALI) and death. Introducing novel therapies can reduce the mortality in ALI. Osteopontin (OPN), a secretory glycoprotein produced by immune reactive cells, plays a deleterious role in various inflammatory diseases. However, its role in ALI caused by sepsis remains unexplored. We hypothesize that treatment with an OPN-neutralizing antibody (anti-OPN Ab) protects mice against ALI during sepsis. METHODS: Sepsis was induced in 8-week-old male C57BL/6 mice by cecal ligation and puncture (CLP). Anti-OPN Ab or non-immunized IgG as control, at a dose of 50 mug/mouse, was intravenously injected at …


Endoplasmic Reticulum Stress In Sepsis, M. M. Khan, W.L. Yang, P. Wang 2015 Northwell Health

Endoplasmic Reticulum Stress In Sepsis, M. M. Khan, W.L. Yang, P. Wang

Journal Articles

Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units. Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration, is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle, is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. …


Stimulation Of Wnt/Beta-Catenin Signaling Pathway With Wnt Agonist Reduces Organ Injury After Hemorrhagic Shock, M. Kuncewitch, W.L. Yang, A. Jacob, A. Khader, M. Giangola, Jeffrey Nicastro, G. Coppa, P. Wang 2015 Northwell Health

Stimulation Of Wnt/Beta-Catenin Signaling Pathway With Wnt Agonist Reduces Organ Injury After Hemorrhagic Shock, M. Kuncewitch, W.L. Yang, A. Jacob, A. Khader, M. Giangola, Jeffrey Nicastro, G. Coppa, P. Wang

Journal Articles

BACKGROUND: Hemorrhagic shock is a leading cause of morbidity and mortality in surgery and trauma patients. Despite a large number of preclinical trials conducted to develop therapeutic strategies against hemorrhagic shock, there is still an unmet need for effective therapy for hemorrhage patients. Wnt/beta-catenin signaling controls developmental processes and cellular regeneration owing to its central role in cell survival and proliferation. We therefore hypothesized that the activation of Wnt signaling reduces systemic injury caused by hemorrhagic shock. METHODS: Adult male Sprague-Dawley rats underwent hemorrhagic shock by controlled bleeding of the femoral artery to maintain a mean arterial pressure of 30 …


Stimulation Of Brain Amp-Activated Protein Kinase Attenuates Inflammation And Acute Lung Injury In Sepsis, N. Mulchandani, W.L. Yang, M. M. Khan, F. Zhang, P. Marambaud, J. Nicastro, G.F. Coppa, P. Wang 2015 Northwell Health

Stimulation Of Brain Amp-Activated Protein Kinase Attenuates Inflammation And Acute Lung Injury In Sepsis, N. Mulchandani, W.L. Yang, M. M. Khan, F. Zhang, P. Marambaud, J. Nicastro, G.F. Coppa, P. Wang

Journal Articles

Sepsis and septic shock are enormous public health problems with astronomical financial repercussions on health systems worldwide. The central nervous system (CNS) is closely intertwined in the septic process but the underlying mechanism is still obscure. AMP-activated protein kinase (AMPK) is a ubiquitous energy sensor enzyme and plays a key role in regulation of energy homeostasis and cell survival. In this study, we hypothesized that activation of AMPK in the brain would attenuate inflammatory responses in sepsis, particularly in the lungs. Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide riboneucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) …


Differential Alterations Of Tissue T-Cell Subsets After Sepsis, A. Sharma, W.L. Yang, S. Matsuo, P. Wang 2015 Northwell Health

Differential Alterations Of Tissue T-Cell Subsets After Sepsis, A. Sharma, W.L. Yang, S. Matsuo, P. Wang

Journal Articles

Among immune cells in responding to sepsis, macrophages and neutrophils have been extensively studied, while the contribution of T lymphocytes and natural killer T (NKT) cells is less well characterized. Here we monitored tissue specific changes of T cell subsets in male C57BL/6 mice subjected to sham operation or cecal ligation and puncture (CLP) to induce polymicrobial sepsis. Thymus, spleen, liver, lungs and blood were processed and analyzed 20h later. Total lymphocyte count showed a significant reduction in septic thymus, spleen and blood but not in lungs and liver. The septic thymi were hypocellular with severe reduction in cell numbers …


Human Ghrelin Mitigates Intestinal Injury And Mortality After Whole Body Irradiation In Rats, Z. M. Wang, W.L. Yang, A. Jacob, M. Aziz, P. Wang 2015 Hofstra Northwell School of Medicine

Human Ghrelin Mitigates Intestinal Injury And Mortality After Whole Body Irradiation In Rats, Z. M. Wang, W.L. Yang, A. Jacob, M. Aziz, P. Wang

Journal Articles

Widespread use of ionizing radiation has led to the realization of the danger associated with radiation exposure. Although studies in radiation countermeasures were initiated a half century ago, an effective therapy for a radiomitigator has not been identified. Ghrelin is a gastrointestinal hormone, and administration of ghrelin is protective in animal models of injuries including radiation combined injury. To test whether ghrelin can be protective in whole body irradiaton (WBI) alone, male Sprague Dawley (SD) rats were treated with human ghrelin (20 nmol/rat) daily for 6 days starting at either 24 h or 48 h after 10 Gray (Gy) WBI …


Combination Of Adrenomedullin With Its Binding Protein Accelerates Cutaneous Wound Healing, J. P. Idrovo, W. L. Yang, A. Jacob, M. A. Ajakaiye, C. Cheyuo, Z. M. Wang, J. M. Prince, J. Nicastro, G.F. Coppa, P. Wang 2015 Northwell Health

Combination Of Adrenomedullin With Its Binding Protein Accelerates Cutaneous Wound Healing, J. P. Idrovo, W. L. Yang, A. Jacob, M. A. Ajakaiye, C. Cheyuo, Z. M. Wang, J. M. Prince, J. Nicastro, G.F. Coppa, P. Wang

Journal Articles

Cutaneous wound continues to cause significant morbidity and mortality in the setting of diseases such as diabetes and cardiovascular diseases. Despite advances in wound care management, there is still an unmet medical need exists for efficient therapy for cutaneous wound. Combined treatment of adrenomedullin (AM) and its binding protein-1 (AMBP-1) is protective in various disease conditions. To examine the effect of the combination treatment of AM and AMBP-1 on cutaneous wound healing, full-thickness 2.0-cm diameter circular excision wounds were surgically created on the dorsum of rats, saline (vehicle) or AM/AMBP1 (96/320 mu g kg BW) was topically applied to the …


An Interesting Cause Of Mechanical Small Bowel Obstruction, S. A. Sathyanarayana, G. B. Deutsch, B. Friedman 2015 Northwell Health

An Interesting Cause Of Mechanical Small Bowel Obstruction, S. A. Sathyanarayana, G. B. Deutsch, B. Friedman

Journal Articles

Foreign body ingestion is a known cause of abdominal pain in pediatric population occurring between 6 months and 3 years of age (Wyllie Curr Opin Pediatr 18:563, 2006, Uyemura Am Fam Physician 72:287, 2005, Banerjee Indian J Pediatr 72:173, 2005). Most of the ingested foreign bodies pass spontaneously with 10-20 % requiring endoscopic retrieval, and < 1 % of cases require a surgical intervention (Wyllie Curr Opin Pediatr 18:563, 2006, Uyemura Am Fam Physician 72:287, 2005, Shivakumar Indian J Pediatr 71:689, 2004). Presence of intestinal obstruction necessitates surgical intervention to extract the ingested foreign body. Initial abdominal plain radiograph should be obtained when foreign body ingestion is suspected, which differentiates a radiopaque from radiolucent foreign bodies. A computed tomography with 3D reconstruction (3D-CT) is recommended with radiolucent foreign bodies (Uyemura Am Fam Physician 72:287, 2005, Kazam Am J Emerg Med 23:897, 2005). After 24 h of expectant management, failure of spontaneous passage requires further intervention. Timely intervention to relieve the obstruction is pivotal to prevent undue complications. We present an interesting case of a boy who ingested a radiolucent foreign body diagnosed on 3D-CT, successfully treated with surgical extraction.


Combining Task-Evoked And Spontaneous Activity To Improve Pre-Operative Brain Mapping With Fmri, M. D. Fox, T. Qian, J. R. Madsen, D. Wang, M. Ge, H. C. Zuo, D. M. Groppe, A. D. Mehta, B. Hong, H. Liu, +1 additional author 2015 Northwell Health

Combining Task-Evoked And Spontaneous Activity To Improve Pre-Operative Brain Mapping With Fmri, M. D. Fox, T. Qian, J. R. Madsen, D. Wang, M. Ge, H. C. Zuo, D. M. Groppe, A. D. Mehta, B. Hong, H. Liu, +1 Additional Author

Journal Articles

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional …


Galantamine Attenuates Type 1 Diabetes And Inhibits Anti-Insulin Antibodies In Non-Obese Diabetic Mice, W. M. Hanes, P. S. Olofsson, K. Kwan, L. K. Hudson, S. S. Chavan, V. A. Pavlov, K. J. Tracey 2015 Northwell Health

Galantamine Attenuates Type 1 Diabetes And Inhibits Anti-Insulin Antibodies In Non-Obese Diabetic Mice, W. M. Hanes, P. S. Olofsson, K. Kwan, L. K. Hudson, S. S. Chavan, V. A. Pavlov, K. J. Tracey

Journal Articles

Type 1 diabetes in mice is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Disease pathogenesis involves invasion of pancreatic islets by immune cells, including macrophages and T cells, and production of antibodies to self-antigens, including insulin. Activation of the inflammatory reflex, the neural circuit that inhibits inflammation, culminates on cholinergic receptor signals on immune cells to attenuate cytokine release and inhibit B cell antibody production. Here, we show that galantamine, a centrally acting acetylcholinesterase inhibitor and an activator of the inflammatory reflex, attenuates murine experimental type 1 diabetes. Administration of galantamine to animals immunized with keyhole limpet hemocyanin …


Damp Signaling Is A Key Pathway Inducing Immune Modulation After Brain Injury, A. Liesz, A. Dalpke, E. Mracsko, D. J. Antoine, S. Roth, W. Zhou, H. Yang, P. P. Nawroth, K. J. Tracey, R. Veltkamp, +4 additional authors 2015 Northwell Health

Damp Signaling Is A Key Pathway Inducing Immune Modulation After Brain Injury, A. Liesz, A. Dalpke, E. Mracsko, D. J. Antoine, S. Roth, W. Zhou, H. Yang, P. P. Nawroth, K. J. Tracey, R. Veltkamp, +4 Additional Authors

Journal Articles

Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and investigated its inflammatory potency and signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, …


Regulation Of Post-Translational Modifications Of Hmgb1 During Immune Responses, B. Lu, Y. Tang, X. Zhao, D. Antoine, X. Xiao, H. Wang, U. Andersson, T. Billiar, K. J. Tracey 2015 Northwell Health

Regulation Of Post-Translational Modifications Of Hmgb1 During Immune Responses, B. Lu, Y. Tang, X. Zhao, D. Antoine, X. Xiao, H. Wang, U. Andersson, T. Billiar, K. J. Tracey

Journal Articles

SIGNIFICANCE: High mobility group protein 1 (HMGB1) is an evolutionarily conserved and multi-functional protein. The biological function of HMGB1 depends on its cellular locations, binding partners, and redox states. Extracellular HMGB1 is a mediator of inflammation during infection or tissue injury. Immune cells actively release HMGB1 in response to infection, which in turn orchestrates both innate and adaptive immune responses. RECENT ADVANCES: Hyperacetylation of HMGB1 within its nuclear localization sequences mobilizes HMGB1 from the nucleus to the cytoplasm and subsequently promotes HMGB1 release. The redox states of the cysteines in position 23, 45 and 106 determine the biological activity of …


A Unifying Principle Underlying The Extracellular Field Potential Spectral Responses In The Human Cortex, E. Podvalny, N. Noy, M. Harel, S. Bickel, G. Chechik, C. E. Schroeder, A. D. Mehta, M. Tsodyks, R. Malach 2015 Northwell Health

A Unifying Principle Underlying The Extracellular Field Potential Spectral Responses In The Human Cortex, E. Podvalny, N. Noy, M. Harel, S. Bickel, G. Chechik, C. E. Schroeder, A. D. Mehta, M. Tsodyks, R. Malach

Journal Articles

Electrophysiological mass potentials show complex spectral changes upon neuronal activation. However, it is unknown to what extent these complex band-limited changes are interrelated or, alternatively, reflect separate neuronal processes. To address this question, intracranial electrocorticograms (ECoG) responses were recorded in patients engaged in visuomotor tasks. We found that in the 10- to 100-Hz frequency range there was a significant reduction in the exponent chi of the 1/f(chi) component of the spectrum associated with neuronal activation. In a minority of electrodes showing particularly high activations the exponent reduction was associated with specific band-limited power modulations: emergence of a high gamma (80-100 …


Acute Surgical Pulmonary Embolectomy: A 9-Year Retrospective Analysis, A. R. Hartman, F. Manetta, R. Lessen, R. Pekmezaris, A. Kozikowski, L. Jahn, M. Akerman, M. L. Lesser, L. R. Glassman, M. Graver, J. S. Scheinerman, R. Kalimi, R. Palazzo, S. Vatsia, G. Pogo, M. Hall, P. J. Yu, V. Singh 2015 Hofstra Northwell School of Medicine

Acute Surgical Pulmonary Embolectomy: A 9-Year Retrospective Analysis, A. R. Hartman, F. Manetta, R. Lessen, R. Pekmezaris, A. Kozikowski, L. Jahn, M. Akerman, M. L. Lesser, L. R. Glassman, M. Graver, J. S. Scheinerman, R. Kalimi, R. Palazzo, S. Vatsia, G. Pogo, M. Hall, P. J. Yu, V. Singh

Journal Articles

Acute pulmonary embolism is a substantial cause of morbidity and death. Although the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines recommend surgical pulmonary embolectomy in patients with acute pulmonary embolism associated with hypotension, there are few reports of 30-day mortality rates. We performed a retrospective review of acute pulmonary embolectomy procedures performed in 96 consecutive patients who had severe, globally hypokinetic right ventricular dysfunction as determined by transthoracic echocardiography. Data on patients who were treated from January 2003 through December 2011 were derived from health system databases of the New York State Cardiac Surgery Reporting System and the …


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