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Immunology of Infectious Disease Commons™
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Articles 1 - 29 of 29
Full-Text Articles in Immunology of Infectious Disease
Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson
Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson
Electronic Thesis and Dissertation Repository
Macrophages are key mediators of efferocytosis – the phagocytic engulfment and removal of apoptotic cells. During engulfment, the coordinated activity of efferocytic receptors induces the remodeling of the actin cytoskeleton, which facilitates the envelopment of the cell by the plasma membrane. Mer receptor tyrosine kinase (MERTK) is a crucial efferocytic receptor, but its role during actin remodeling is not well understood. Previously, our lab showed that MERTK is an activator of β2 integrins – which are comprised of receptors known to induce the actin polymerization that is required for engulfment. We hypothesized that MERTK is an indirect stimulator of …
Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao
Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao
Graduate School of Biomedical Sciences Theses and Dissertations
Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …
The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton
The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton
Graduate School of Biomedical Sciences Theses and Dissertations
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.
The …
Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh
Undergraduate Research Posters
Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …
A Mechanistic Study On The Immunological Effects Of A Novel Anti-Schistosomal Compound, Caleb M. Sandall, Paul H. Davis
A Mechanistic Study On The Immunological Effects Of A Novel Anti-Schistosomal Compound, Caleb M. Sandall, Paul H. Davis
Theses/Capstones/Creative Projects
Schistosomiasis is a condition caused by a parasitic worm infection that is one of the primary neglected tropical diseases. It infects approximately 250 million people every year, and it causes the second largest economic impact from any parasitic disease. There exists a treatment for Schistosomiasis; however, it is ineffective against the juvenile stages of the worm. A novel drug has been developed that has been illustrated to have efficacy against all stages of worm infection. However, before this drug can be utilized, its method of action must be determined. Preliminary single cell transcriptomic data from our lab suggests that our …
Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen
Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen
Biological Sciences Undergraduate Honors Theses
My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure and specific …
Osmr Signaling Induces Tamp-Specific Bbb Dysfunction Following Autoimmune-Mediated Neutrophil Recruitment, Travis Scott Wertz
Osmr Signaling Induces Tamp-Specific Bbb Dysfunction Following Autoimmune-Mediated Neutrophil Recruitment, Travis Scott Wertz
Boise State University Theses and Dissertations
Integrity of the brain microvessels that form the blood-brain barrier (BBB) is maintained through fine-tuned regulation of endothelial tight junction proteins, chiefly represented by claudin 5 and the tight junction-associated MARVEL protein (TAMP) occludin. Under proinflammatory conditions in autoimmune-mediated multiple sclerosis (MS), autoreactive effector T cells are activated in white matter regions of the brain and spinal cord and release cytokines to recruit circulating neutrophils that, in turn, release neurotoxic substances. Lack of tight junctions in peripheral blood vessels allows neutrophils to exit blood vessels unhindered, but BBB tight junctions must first be downregulated before neutrophils can transmigrate into the …
Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek
Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek
Electronic Theses and Dissertations
JC polyomavirus (JCPyV) is a human-specific pathogen that infects 50-80% of the population, and can cause a deadly, demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). In most of the population, JCPyV persistently infects the kidneys but during immunosuppression, it can reactivate and spread to the central nervous system (CNS), causing PML. In the CNS, JCPyV targets two cell types, astrocytes, and oligodendrocytes. Due to the hallmark pathology of oligodendrocyte lysis observed in disease, oligodendrocytes were thought to be the main cell type involved during JCPyV infection. However, recent evidence suggests that astrocytes are targeted by the virus and act …
Characterization Of A Mycoplasma Pneumoniae Cards Toxin Mutant, Nikaash Pasnoori
Characterization Of A Mycoplasma Pneumoniae Cards Toxin Mutant, Nikaash Pasnoori
Honors Scholar Theses
Mycoplasma pneumoniae is a high-burden pathogen which causes mild to significant infections of the respiratory system. According to the CDC, an estimated two million cases occur yearly in the United States alone, demonstrating the widespread effect of the pathogen. In addition to being the cause of respiratory infections, M. pneumoniae has also been implicated in exacerbating pre-existing asthma conditions. These morbidities make finding a vaccine candidate a vital part of easing the healthcare burden caused by the pathogen. The current mechanism of infection is unknown, but recent evidence points to the Community Acquired Respiratory Distress Syndrome (CARDS) toxin as being …
Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath
Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath
Electronic Theses and Dissertations
Salmonella appears in the bloodstream of mice in as little as 15 minutes after oral inoculation and establishes persistent colonies in the spleen and liver. While its pathway to blood is undetermined, this phenomenon is dependent on the activity of Salmonella pathogenicity island 2 (SPI-2) coded type III secretion system (T3SS) and CD18+ phagocytes. We hypothesize that dendritic cells associated with the basal face of the gut epithelium, that are naturally migratory and known to sample for luminal antigens directly transport Salmonella to the bloodstream. This process comprises of at least two phases, dissociation and reverse transmigration. We define dissociation …
The Histoplasma Capsulatum Ddr48 Gene Is Required For Survival Within Macrophages And Resistance To Oxidative Stress And Antifungal Drugs, Logan Blancett
The Histoplasma Capsulatum Ddr48 Gene Is Required For Survival Within Macrophages And Resistance To Oxidative Stress And Antifungal Drugs, Logan Blancett
Dissertations
Histoplasma capsulatum(Hc)is a systemic, dimorphic fungal pathogen that affects upwards of 500,000 individuals in the United States annually. Hc grows as a multicellular mold at environmental temperatures; whereas, upon inhalation into a human or other mammalian host, it transforms into a unicellular, pathogenic yeast. The research presented in this dissertation is focused on characterizing the DNA damage-responsive gene HcDDR48. HcDDR48was originally isolated via a subtractive DNA library enriched for transcripts enriched in the mold-phase of Hcgrowth. Upon further analysis we found that HcDDR48is not just expressed in the mold morphotype, but both growth programs …
Role Of Host Cell B-Catenin During Toxoplasma Gondii Infection, Cameron Ranken
Role Of Host Cell B-Catenin During Toxoplasma Gondii Infection, Cameron Ranken
Biology ETDs
The microbial pathogen Toxoplasma gondii is an intracellular protozoan that actively invades host cells and simultaneously creates a specialized parasitophorous vacuole within which the parasite lives and replicates. The parasite molecular machinery that drives establishment of the intracellular niche is relatively well known. However, it is now emerging that Toxoplasma exploits less well-understood host cell components to enable successful infection. Here, we examined the role of host Wnt/β-catenin during T. gondii infection. Using human fibroblasts and a mouse dendritic cell line, we found that infection with Toxoplasma stimulated both upregulation and nuclear localization of β-catenin. Using a transwell experimental approach, …
Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney
Seton Hall University Dissertations and Theses (ETDs)
Using a murine model, we have previously showed that targeting an inactivated form of F.tularensis (iFt) bacteria to Fcg receptors by utilizing an IgG2a, anti-LPS monoclonal antibody (mAb) provides 100% protection against a lethal dose with the live vaccine strain (LVS). The binding of anti-LPS monoclonal antibodies and iFt create an immune complex (mAb-iFt) allowing the Fc-region of the antibody to target Fc receptors expressed on antigen presenting cells, leading to a more robust and effective processing and presentation of the bacterial antigens. Although the resulting protective response generated relies on both humoral and cell-mediated immunity, in our study we …
Assessment Of Melanocyte-Specific Primary And Memory Autoimmune Responses In Vitiligo-Prone Smyth And Vitiligo-Susceptible, Non-Expressing Brown Line Chickens, Daniel Morales Falcon
Assessment Of Melanocyte-Specific Primary And Memory Autoimmune Responses In Vitiligo-Prone Smyth And Vitiligo-Susceptible, Non-Expressing Brown Line Chickens, Daniel Morales Falcon
Graduate Theses and Dissertations
Vitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of white patches in the skin. The Smyth line of chicken is the only model for vitiligo that shares all the characteristics of the human condition including: spontaneous post-natal loss of melanocytes, interactions between genetic, environmental and immunological factors and associations with other autoimmune diseases. In addition, an avian model for vitiligo has the added benefit of an easily accessible target tissue (a growing feather) that allows for the repeated sampling of an individual and thus the continuous monitoring of …
Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz
Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz
Christian Mueller
Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with …
Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte
Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte
University Scholar Projects
Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …
Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang
Electronic Theses and Dissertations
Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.
The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia …
Characterization Of Nuclear Factor-Kappab Binding Sites In The Freshwater Snail, Biomphalaria Glabrata, Laura E. Deneckere
Characterization Of Nuclear Factor-Kappab Binding Sites In The Freshwater Snail, Biomphalaria Glabrata, Laura E. Deneckere
Lawrence University Honors Projects
Biomphalaria glabrata is an intermediate snail host for the digenean trematode, Schistosoma mansoni, which causes the human disease schistosomiasis. A lot of research has focused on the snail-schistosome interaction, especially in regards to the immune response of the snail. The nuclear factor-kappaB (NF-κB) pathway, which is involved in regulating the immune response, can be triggered by the Toll-like receptor (TLR) signaling pathway. However, not much is known about the specific molecular mechanisms regulating these responses. Both NF-κB and TLR homologues have recently been reported in B. glabrata so it is of great interest to determine if BgNF-κB can regulate …
Comparison Of Different Modulators That Affect Macrophage Activation In Vitro, Alda Alexa Díaz Pérez
Comparison Of Different Modulators That Affect Macrophage Activation In Vitro, Alda Alexa Díaz Pérez
Graduate Theses and Dissertations
Inflammation is known as a mechanism to regulate and control infections as well as promote tissue repair. Macrophages (Mф) are known to be a major cell type in the initiation, sustainability and resolution of inflammation. Moreover, Mф are essential for the remodeling process that is also known as the wound healing response. The objective of this research was to compare five modulators (acetylsalicylic acid (ASA), dexamethasone (DEX), prostaglandin E2 (PGE2), iloprost, and resolvin D1 (RvD1) for their anti-inflammatory effects on macrophages in vitro. Then, Mф phenotype in terms of gene expression and secreted cytokine response was determined. Our study compared …
Inhibition Of Burkholderia Multivorans Adhesion To Lung Epithelial Cells By Bivalent Lactosides, Ciara Wight, Rosaria Leyden, Paul V. Murphy, Máire Callaghan, Trinidad Velasco-Torrijos, Siobhan Mcclean
Inhibition Of Burkholderia Multivorans Adhesion To Lung Epithelial Cells By Bivalent Lactosides, Ciara Wight, Rosaria Leyden, Paul V. Murphy, Máire Callaghan, Trinidad Velasco-Torrijos, Siobhan Mcclean
Articles
Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in cystic fibrosis patients which is inherently resistant to antimicrobial agents. The mechanisms of attachment and pathogenesis of Bcc, a group of 17 species, are poorly understood. The most commonly identified Bcc species in newly colonised patients, Burkholderia multivorans, continues to be acquired from the environment. Development of therapies which can prevent or reduce the risk of colonization on exposure to Bcc in the environment would be a better alternative to antimicrobial agents. Previously, it has been shown that Bcc strains bound to many glycolipid receptors on lung epithelia. Using a …
Cloning And Characterization Of The Cell Wall Acting Enzyme Cd1034 From The Pathogen Clostridium Difficile, Zachary Suter
Cloning And Characterization Of The Cell Wall Acting Enzyme Cd1034 From The Pathogen Clostridium Difficile, Zachary Suter
Honors Projects in Science and Technology
The manifestation of multidrug resistance in bacteria over the past several decades has resulted in one of the foremost challenges in the management of infectious diseases. The question arises, “How do we address this growing problem?” One solution to stem the growing rise in antimicrobial resistance is to investigate new targets, while another approach is to re-examine classical antibacterial targets with a fresh perspective. The aim of this paper is to begin the process of antibacterial development for the pathogen Clostridium difficile by characterizing the cell wall acting glucosaminidase CD1034. It is inunderstanding how CD1034 functions biochemically that it can …
Activation Of Mmp-9 By Human Lung Epithelial Cells In Response To The Cystic Fibrosis-Associated Pathogen Burkholderia Cenocepacia Reduced Wound Healing In Vitro, Ciara Wright ], Ruth Pilkington, Máire Callaghan, Siobhan Mcclean
Activation Of Mmp-9 By Human Lung Epithelial Cells In Response To The Cystic Fibrosis-Associated Pathogen Burkholderia Cenocepacia Reduced Wound Healing In Vitro, Ciara Wright ], Ruth Pilkington, Máire Callaghan, Siobhan Mcclean
Articles
Burkholderia cepacia complex is a group of bacterial pathogens that cause opportunistic infections in cystic fibrosis (CF). The most virulent of these is Burkholderia cenocepacia. Matrix metalloproteinases (MMPs) are upregulated in CF patients. The aim of this work was to examine the role of MMPs in the pathogenesis of B. cepacia complex, which has not been explored to date. Real-time PCR analysis showed that B. cenocepacia infection upregulated MMP-2 and MMP-9 genes in the CF lung cell line CFBE41o- within 1 h, whereas MMP-2, -7, and -9 genes were upregulated in the non-CF lung cell line 16HBE14o-. Conditioned media from …
In Vivo Mature Immunological Synapses Forming Smacs Mediate Clearance Of Virally Infected Astrocytes From The Brain, Carlos Barcia, Clare Thomas, James Curtin, Gwendalyn King, Kolja Wawrowsky, Marianela Candolfi, Weidong Xiong, Chunyan Liu, Kurt Kroeger, Olivier Boyer, Jerzy Kupiec-Weglinski, David Klatzmann, Maria Castro, Pedro Lowenstein
In Vivo Mature Immunological Synapses Forming Smacs Mediate Clearance Of Virally Infected Astrocytes From The Brain, Carlos Barcia, Clare Thomas, James Curtin, Gwendalyn King, Kolja Wawrowsky, Marianela Candolfi, Weidong Xiong, Chunyan Liu, Kurt Kroeger, Olivier Boyer, Jerzy Kupiec-Weglinski, David Klatzmann, Maria Castro, Pedro Lowenstein
Articles
The microanatomy of immune clearance of infected brain cells remains poorly understood. Immunological synapses are essential anatomical structures that channel information exchanges between T cell–antigen-presenting cells (APC) during the priming and effector phases of T cells' function, and during natural killer–target cell interactions. The hallmark of immunological synapses established by T cells is the formation of the supramolecular activation clusters (SMACs), in which adhesion molecules such as leukocyte function-associated antigen 1 segregate to the peripheral domain of the immunological synapse (p-SMAC), which surrounds the T cell receptor–rich or central SMAC (c-SMAC). The inability so far to detect SMAC formation in …
Compartmental Specificity Of Cellular Membrane Fusion Encoded In Snare Proteins, James Mcnew, Frank Parlati, Ryorichi Fukuda, Robert Johnston, Keren Paz, Fabienne Paumet, Thomas Sollner, James Rothman
Compartmental Specificity Of Cellular Membrane Fusion Encoded In Snare Proteins, James Mcnew, Frank Parlati, Ryorichi Fukuda, Robert Johnston, Keren Paz, Fabienne Paumet, Thomas Sollner, James Rothman
Fabienne Paumet
No abstract provided.
Soluble Nsf Attachment Protein Receptors (Snares) In Rbl-2h3 Mast Cells: Functional Role Of Syntaxin4 In Exocytosis And Identification Of A Vamp8-Containing Secretory Compartment, Fabienne Paumet, Joelle Le Mao, Sophie Martin, Thierry Galli, Bernard David, Ulrich Blank, Michele Roa
Soluble Nsf Attachment Protein Receptors (Snares) In Rbl-2h3 Mast Cells: Functional Role Of Syntaxin4 In Exocytosis And Identification Of A Vamp8-Containing Secretory Compartment, Fabienne Paumet, Joelle Le Mao, Sophie Martin, Thierry Galli, Bernard David, Ulrich Blank, Michele Roa
Fabienne Paumet
No abstract provided.
Diphtheria Toxin Fusion Proteins, Frank Foss, Mansoor Saleh, James Krueger, John Nichols, John Murphy
Diphtheria Toxin Fusion Proteins, Frank Foss, Mansoor Saleh, James Krueger, John Nichols, John Murphy
Haematology and Oncology, East Africa
Two different approaches have been undertaken to develop targeted biomolecules for therapeutics. The first was the construction of immunotoxins consisting of monoclonal antibodies chemically linked through a disulfide bond to a plant or bacterial toxin or radionuclide. Instability of the chemical conjugation of some of the earlier immunotoxins led to the concept of using protein engineering and recombinant DNA to assemble fusion genes combining the sequences for the enzymatically active and translocation domains of a toxin with those of a specific targeting ligand. From the outset, the prospect of using recombinant DNA methods to assemble the structural genes encoding bacterial …
Involvement Of The Ras-Like Gtpase Rab3d In Rbl-2h3 Mast Cell Exocytosis Following Stimulation Via High Affinity Ige Receptors (Fcεri), Michele Roa, Fabienne Paumet, Joelle Le Mao, Bernard David, Ulrich Blank
Involvement Of The Ras-Like Gtpase Rab3d In Rbl-2h3 Mast Cell Exocytosis Following Stimulation Via High Affinity Ige Receptors (Fcεri), Michele Roa, Fabienne Paumet, Joelle Le Mao, Bernard David, Ulrich Blank
Fabienne Paumet
No abstract provided.
Phase Ii Trial Of Murine Monoclonal Antibody D612 Combined With Recombinant Human Monocyte Colony-Stimulating Factor (Rhm-Csf) In Patients With Metastatic Gastrointestinal Cancer, Mansoor Saleh, Michael Khazaeli, Richard Wheeler, Pat Bucy, Tiepe Liu, Michael Everson, David Mun, Jeff Schlom
Phase Ii Trial Of Murine Monoclonal Antibody D612 Combined With Recombinant Human Monocyte Colony-Stimulating Factor (Rhm-Csf) In Patients With Metastatic Gastrointestinal Cancer, Mansoor Saleh, Michael Khazaeli, Richard Wheeler, Pat Bucy, Tiepe Liu, Michael Everson, David Mun, Jeff Schlom
Haematology and Oncology, East Africa
In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 ug/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral mono- cytosis (peak absolute monocyte count, 1444 ±394/mm3) and thrombocytopenia (nadir count, 78 ±10/nim '). Monocyte surface marker analysis revealed a …
Monocyte-Platelet Interaction In Immune And Nonimmune Thrombocytopenia, Mansoor Saleh, D L. Moore, J Y. Lee, A F. Lobuglio
Monocyte-Platelet Interaction In Immune And Nonimmune Thrombocytopenia, Mansoor Saleh, D L. Moore, J Y. Lee, A F. Lobuglio
Haematology and Oncology, East Africa
Platelets from 24 patients with immune thrombocytopenia resistant to standard therapy (refractory ITP), 35 patients with nonimmune thrombocytopenia (non-ITP), and 32 normal donors were studied in regard to platelet surface-bound IgG (PBIgG) and the ability of these platelets to be bound by human monocytes in vitro (monocyte-platelet rosette assay). Fourteen (58%) of the platelet samples from refractory ITP patients but none (0%) from the non-ITP or control donors had PBIgG greater than 800 molecules IgG/platelet. Seventeen of 24 (71%) of the ITP patients had platelets which demonstrated increased monocyte- platelet rosette formation [rosette index (RI) greater than 2], whereas only …