4^th International Conference and Exhibition on Immunology September 28-30, 2015 Houston, Texas, USA

Biography:

Yong Li is an Associate Professor within the Department of Pediatric Surgery at the University of Texas, School of Medicine at Houston. He is also appointed as an Associate Professor in the Center Stem Cell for Regenerative Medicine at the Brown Foundation Institute of Molecular Medicine (IMM), UTHealth. He accomplished his MD and PhD training in China, and was a general surgeon before he went to London of UK in 1997. His first research career as a Post-Doctor fellow trained in Imperial College School of Medicine in UK (1998-1999), and later as a Post-doctoral Research Associate in Children’s Hospital of Pittsburgh of UPMC. He was promoted to a research Assistant Professor in 2002, Assistant Professor in 2004 (within tenure track system in 2006), and lead his research team approach success in the field of stem cell, anti-fibrosis in regeneration medicine. These projects also include the enlargement and application of adult stem cells (muscle and skin) to repair traumatic injury (muscle, tendon, spinal cord and brain) and congenital diseases. As in 2011, he has published over 66 refereed journal articles and review papers, and five book chapters. He has won twenty more international awards for his scientific advances, including most recently, he has won the Michael Miller Young Investigator Award at Children’s Hospital of UPMC.

Abstract:

Totipotent and pluripotent stem cells (e.g. ESCs or iPSCs) and adult tissue derived stem cells have been studied for many years. Stem cell transplantation has been considered a top priority for use to treat a variety of disease states and for various tissue regeneration regimes. Various autologous stem cells have been successfully used in clinical trials, though the scarcity of stem cells has limited their application. Allogeneic derived stem cells are a potential stem cell source; however, this remains a major challenge due to their potential to trigger an immune response or rejection after transplantation. Through several years of investigation, we have discovered and isolated a novel type of muscle derived small-size stem cells (Mu3SCs) from both mice and human tissues. These Mu3SCs have been characterized as being small in size, capable of multipotent differentiation and demonstrate a naturally aggressive migration capacity. We discovered that Mu3SCs were able to survive, proliferate and differentiate within a variety of tissues and are capable of engrafting throughout the skeletal muscles of mdx mice, a dystrophic mouse model of human Duchenne muscular dystrophy, via intravenous injection. We also demonstrated that GFP pre-labeled Mu3SCs remained in the blood stream for up to three weeks. We thus hypothesized that a percentage of small in size stem cells within the general stem cell populations that are “immune-privileged”, since the Mu3SCs have the ability to escape immunological recognition in the transplanted host, which is essential for inducing immunological tolerance.

Biography:

Kamalakannan Rajasekaran is a Research Scientist at Blood Research Institute, Milwaukee, WI. He obtained his PhD in Immunology from Madurai Kamaraj University. His studies are aimed at deciphering the signaling events that are responsible for NK cell-mediated cytotoxicity and pro-inflammatory cytokine production. His studies have led to the understanding of the role of signaling molecules such as Adap, Carma1 and TAK1 in the production of pro-inflammatory cytokines. His work, published in reputed scientific journals, including Nature Immunology, has paved the way for drafting a molecular ‘blueprint’ for targeting unique signaling molecules to regulate the production of inflammatory cytokines following cell-mediated immunotherapy.

Abstract:

Introduction: A strategy to contain the production of pro-inflammatory cytokines without affecting the cytotoxicity of Natural Killer (NK) or T cells will pave the way for preventing deleterious side effects of cellular immunotherapy to treat tumors. Our earlier studies have defined an essential role of the Carma1-Bcl-10-Malt1 signalosome for cytokine production. Cytotoxicity of NK cells that are deficient in Carma1 or Bcl-10 was moderately reduced. Following its activation by the Src family tyrosine kinase Fyn, the adapter protein ADAP plays a critical role in organizing this signalosome. Hence, we hypothesize that loss of ADAP in NK cells will result in a significant reduction in pro-inflammatory cytokine production without affecting its cytotoxic potential. Objective: 1. Analyze the tumoricidal and pro-inflammatory cytokine production efficiency of NK cells deficient in ADAP or its upstream activator Fyn. 2. Biochemical analysis of the signaling events associated with these effectors functions. Methods: NK cells derived from wild type, Fyn-/- and Adap-/- mice were analyzed for: 1. Tumoricidal activity using tumor cells labeled with 51Cr. 2.Pro-inflammatory cytokine production following stimulation with plate-bound mAbs to activate NK cell receptors 3. Phosphorylation of signaling molecules and 4.Nuclear translocation of transcription factors using western blot Results: In the Fyn-/- NK cells, cytotoxicity was significantly reduced where as cytokine production was significantly increased compared to wild type NK cells. In the Adap-/- NK cells cytotoxicity was unaffected while cytokine production was significantly decreased. In the absence of Fyn, phosphorylation of PI (3)-K-p85α and ERK1/2, events associated with cytotoxic granule mobilization were decreased. In the Adap-/- NK cells, while the phosphorylation of PI (3)-K-p85α was unaffected, phosphorylation of ERK1/2 was increased compared to wild type. In the Adap-/- NK cells, despite an increased phosphorylation of ERK1/2, there is a defect in its nuclear translocation, which may in turn account for a reduced nuclear translocation of c-Fos. Conclusions: The role of ADAP is redundant for NK cell-mediated cytotoxicity whereas, it is essential for pro-inflammatory cytokine production. Our analysis indicates that ADAP is essential for the nuclear translocation of ERK1/2 which is important for the activation of c-Fos and the induction of pro-inflammatory cytokines. In the absence of Fyn, cytotoxicity is reduced while cytokine production is significantly increased. Significance: Regulating the production of pro-inflammatory cytokines without affecting the cytotoxicity of the effectors cells by blocking the ADAP signaling module might help prevent the deleterious side effects such as ‘Cytokine Release Syndrome’ and improve the efficacy of cellular immunotherapy.

Biography:

Kristin Schmidt studied transcription factors involved in the development of the retina in a neurobiology lab at UCLA\'s Jules Stein Eye Institute. There, she became familiar with assorted tissue preparation techniques, IHC, IF, microscopy, and laser capture microdissection/microgenomics. In 2005 she joined Arcturus Bioscience and provided tech support for LCM instruments and reagents, troubleshooting issues ranging from harvesting tissue to biomolecule extraction and analysis via microarray, real-time PCR, or next-generation sequencing. In 2006 she moved into a global Field Applications Scientist role with Molecular Devices and in 2010 with Life Technologies where she trained LCM users and distributors all around the world. In 2015 she joined PerkinElmer Inc. as a Field Applications Scientist specializing in Phenoptics – multiplex staining in FFPE tissue, multispectral imaging, and image analysis

Abstract:

There has been a rapid growth in the field of tumor immunobiology in recent years as a result of recent successes in cancer immunotherapies, and it is becoming clear that immune cells play many sometimes conflicting roles in the tumor microenvironment. However, obtaining phenotypic information about the various immune cells that play these roles in and around the tumor has been a challenge. Existing methods can either deliver phenotypic information on homogenous samples (e.g., flow cytometry or PCR) or morphologic information on single immunomarkers (standard IHC). We present here a methodology for delivering quantitative per-cell marker expression and phenotyping, analogous to that obtained from flow cytometry, but from cells imaged in situ in FFPE tissue sections. This methodology combines: The sequential multi-marker labeling of up to 8 antigens using antibodies all of the same species in a single section; automated multispectral imaging (MSI) to remove the typically problematic FFPE tissue auto fluorescence and correct cross-talk between fluorescent channels; and an automated analysis that can quantitate the per-cell marker expression, determine the cellular phenotype, count these cells separately in the tumor compartment and in the stroma and provide high-resolution images of their distributions. We present here examples of this new methodology: The simultaneous labeling, analysis and validation of CD4, CD8, CD20, PD-L1, Foxp3, cytokeratin and DAPI in breast cancer; and CD8, CD34, PD-L1, FOXP3 and DAPI in head and neck squamous cell carcinoma. Each example will show the application of the multiplexed staining, per-cell quantitation and cellular phenotyping from multispectral images of FFPE tissue sections, as well as methods to explore the spatial distributions of the phenotype cells in and around the tumor.

Biography:

Takahiro Yamada graduated from Hokkaido University School of Medicine, Japan. He has completed his PhD from the same university and Post-doctoral studies from Nagasaki University School of Medicine, Japan and The Hospital for Sick Children, Toronto, Canada. Currently, he is the Lecturer of Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine and is the Chief Obstetrician of Obstetrics Clinic of Hokkaido University Hospital. He has published more than 90 papers in reputed journals.

Abstract:

Although, there were no mortalities from the pandemic (H1N1) 2009 among pregnant Japanese women, pregnant women with flu are at higher risk of hospitalization and mortality compared to general population. During the pandemic (H1N1) 2009, it is estimated that more than 60% of pregnant Japanese women were vaccinated against the novel virus. However, as we had no data regarding vaccination coverage rate for seasonal flu in pregnant Japanese women, we conducted a multi-center study to determine vaccination coverage against 2013 – 2014 seasonal flu and the prevalence rate of flu infection among pregnant Japanese women. In that study, 51% of participants reported having received vaccination in or after October 2013. The women aged <25 years had a lower vaccination rate than those aged ≥25 years (P=0.0000). Interestingly, although experience of prior birth did not affect vaccination coverage rate, multiparous women had a higher rate of contracting influenza than primiparous women irresp ective of vaccination status (P=0.0216 and P=0.0003 for women with and without vaccination, respectively). These results raised a question why multiparous pregnant women are more susceptible to flu than primiparous pregnant women. We conducted a study to address this issue during 2014-2015 flu season and results of this study will be presented.

Biography:

Igor Malyshev is a Head of the Department of Pathophysiology and Head of the Laboratory of Cell Biotechnology, Medical School at the Moscow State University of Medicine and Dentistry. He is also the Head of the Laboratory of Stress at the Institute of General Pathology and Pathophysiology, Moscow and Adjunct Professor of Biomedical Sciences at University of North Texas Health Science Center, USA. He is a Member of the Board of directors of the International Society for Adaptive Medicine and an Editorial Board Member of Journal of Biosciences and Medicines. He has published 3 books and monographs and 146 full length articles.

Abstract:

Introduction: An important factor of antitumor immune defence is macrophage NO. We hypothesized that the tumor vulnerability can be predetermined by genetic features of NO generating systems. Methods: The content of NO in tumor was changed by the iNOS inhibitor ITU, NO traps c-PTIO and NO donor. NO production was evaluated by nitrites. Macrophage phenotype was assessed by iNOS and CD markers. Results: The lifespan of mice C57BL/6N with carcinoma was 25% more than C57BL/6J. NO content reduction decreased lifespan of high-resistant to tumor subline C57BL/6N by 23%. NO content rise increased lifespan of low-resistant subline C57BL/6J by 26%. C57BL/6N M1 macrophages had a higher NO production, than C57BL/6J M2 macrophages. Discussion: Thus, the carcinoma vulnerability is determined by genetic features of macrophage NO generating systems. C57BL/6J and C57BL/6N have differences in SNP and NNT (nicotinamide nucleotide transhydrogenase) gene. NO, NNT and SNP deserve attention in developing methods for anticancer therapy.

Biography:

Francis Mussai is a Senior Clinical Lecturer at the University of Birmingham, UK and leads a research group investigating the immunosuppressive microenvironment created by both paediatric and adult malignancies. The group has identified key aspects of how arginine catabolism by both tumour cells and tumour associated myeloid cells can alter anti-cancer immunity. He is also a Consultant Paediatric Oncologist and is involved in the development of early phase clinical trials for paediatric malignancies in the UK and Europe.

Abstract:

Arginine is a semi-essential amino acid whose physiological levels are maintained principally from dietary intake and through intestinal-renal recycling of citrulline. At the cellular level, arginine metabolism is essential for cell division, protein synthesis and as a precursor for nitric oxide and polyamines. The role of arginine processing in the tumour microenvironment to impair anti-tumour immunity has become increasingly apparent. T cells, which provide the corner stone of the anti-cancer immune response, are notably arginine dependent. Tumour associated macrophages (TAMs) and the induction of Myeloid-derived suppressor cells (MDSCs) can decrease local and systemic arginine concentrations, through increased arginase 1 expression, suppressing T cell proliferation. TAM and MDSC derived reactive nitric oxide species production via expression of iNOS, may further inactivate T cell responses. More recently the malignant cells of some haematological and solid tumours have been recognised to be arginine addicted, due to the loss of critical arginine recycling enzymes – a state known as arginine auxotrophism. The resulting dependence on extracellular arginine from the blood and tumour microenvironment further suppresses both antigen-specific and non-specific T cell responses. The importance of these findings and their translational consequences will be presented in this meeting.

Biography:

C C Yin has received her MD from Beijing Medical University and PhD from the University of Wisconsin-Madison. She is currently an Associate Professor in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center. In addition to clinical responsibilities on the leukemia, lymphoma and molecular diagnostic services, she has been actively participating in multiple research projects in the molecular genetic abnormalities in leukemia and lymphoma, which has led to over 100 research papers and over 20 book chapters.

Abstract:

Expression of immunoglobulin (Ig), a marker characteristic of B-cells, has been reported in epithelial cells and has been suggested to play a role in their survival and growth. We assessed the frequency and level of Ig gamma heavy chain (IgG) expression in acute myeloid leukemia (AML) and found that IgG was expressed at a high frequency and level in AML cell lines and primary myeloblasts, but not in monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. AML-derived IgG had the same molecular weight as B-cell-derived IgG and was secreted. We further detected IgG VHDJH transcripts in AML cell lines and sorted primary myeloblasts, confirming that IgG expression was indeed produced by AML cells. AML-derived IgG gene rearrangements showed evidence of somatic hyper mutation of the variable (V) gene segments and restricted (AML cell lines) or biased (primary myeloblasts) V usage. Anti-human IgG reduced cell viability and induced apoptosis in AML cell lines. Although the function of the AML-derived IgG is unclear, our findings suggest that AML-derived IgG may be a novel AML-related gene that contributes to leukemogenesis and AML progression. AML-derived IgG may serve as a useful molecular marker for monitoring minimal residual disease or designing target therapy.

Biography:

Nurieva Roza Insafetdinovna has completed her PhD from Pushchino State University, Russia and Post-doctoral studies from University of Washington, Seattle, USA. Currently, she is the Assistant Professor in Immunology Department at MD Anderson Cancer Center. She has published more than 50 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4 producing T cells, required for regulation of type 2 humoral immunity. Although the transcriptional control of IL-4 has been an area of extensive investigation, the precise regulation mechanism of IL-4 production in Tfh cells remains mainly unknown. In the current study, we found that the transcription factor BATF, a member of the AP-1/Jun family is essential for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, BATF in cooperation with Interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signaling is an important determinant of IL-4 expression in Tfh cells. BATF deficiency impairs the generation of IL-4 producing Tfh cells that results in protection against allergic asthma. IL-4 acts as an autocrine factor in controlling BATF-mediated IL-4 expression in Tfh cells. Our results thus indicate a critical role of BATF in promoting the generation of pro-allergic IL-4 producing Tfh cells.

Biography:

Navin K Verma completed his PhD and Post-doctoral training in Clinical Medicine at Trinity College Dublin, Ireland. In 2013, he joined Lee Kong Chan School of Medicine, Nanyang Technological University, Singapore, where he is currently an Assistant Professor of Immunology and Cell Biology. His research is focused on molecular processes involved in T-cell motility. In particular, he is investigating biological roles and functional significance of the integrin LFA-1 signalling for T-cell migration in health and immune-medicated diseases.

Abstract:

Introduction: The T-cell integrin LFA-1 interacts with the ligand ICAM-1 expressed on endothelium and this interaction is important in T-cell motility. But downstream signalling pathways triggered by LFA-1/ICAM-1 ligation in T-cells are not clear. Here, we show that LFA-1-signalling for T-cell migration modulates gene expression, induces notch and TGF-β pathways and influences T-cell differentiation. Methods: Primary human T-cells or T-cell line Hut78 were stimulated via LFA-1 by incubating on immobilised recombinant ICAM-1. Standard molecular, biochemical and imaging techniques including Affymetrix Gene Chip® microarrays, real-time PCR, Western-immunoblotting, siRNA, confocal microscopy and high content analysis were utilized. Results: LFA-1/ICAM-1 ligation in T-cells induced genomic signatures associated with Notch and TGF-β pathways. We verified the activation of notch signalling by nuclear translocation of its cleaved intracellular domain and up-regulation of target genes Hey1 and Hes1. Moreover, a subset of molecules associated with reduced TGF-β responsiveness including Smad7, Smurf2 and Ski were found to be up-regulated, which was dependent of Stat3 and/or JNK activation. While LFA-1/ICAM-1 promoted Notch-dependent Tbet+ Th1 polarization, LFA-1-stimulated T-cells were refractory to TGF-β-mediated induction of Foxp3+ iTreg or RORγt+ Th17 differentiation. Pre-treatment of cells with blocking anti-LFA-1 antibody, specific inhibitors or siRNA against identified molecules substantially suppressed LFA-1-mediated modulation of T-cell functional phenotypes. Conclusion: We demonstrate a novel mechanism by which LFA-1/ICAM-1 ligation regulates immune response through notch and TGF-β pathways concurrent with its role in T-cell migration. These new findings have implications for normal immunologic functions and may also have therapeutic relevance for immune-mediated diseases.

Biography:

Robert H Schiestl has obtained his PhD from the University of Vienna. He was a Post-doctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before working as a Professor at Harvard, where he stayed for 10 years. Since 15 years, he is working as a Professor at UCLA with 190 publications, 6 press releases, 10 patents and 2 startup companies.

Abstract:

To determine susceptibility of subpopulations of cells in the peripheral blood as well as of peripheral lymphoid organs to several types of DNA damage in genetic mouse models of spontaneous chronic intestinal inflammation and to determine the sufficiency of tumor necrosis factor α (TNF-α) in inducing this genotoxicity. By determining correlations of DNA damage to disease activity, we hope to substantiate systemic genotoxicity as a biomarker of inflammatory activity in intestinal inflammation. Peripheral blood subpopulations were isolated via magnetic bead sorting and cells from peripheral lymphoid organs were isolated incolitic IL-10 mice of various disease activity (3 and 6 months of age), Gαi2 mice (3 months of age) and in wild-type mice with no intestinal inflammation. DNA strand breaks were measured in cells with the alkaline comet assay with hOGG1 incubation to determine oxidative base damage and DNA double strand breaks specifically were quantified by γH2AX foci immune-staining. Recombinant mouse TNF-α or saline was injected (500 ng/mouse) into the tail vein of wild-type mice and peripheral blood was analyzed for DNA damage at several time points post injection. DNA single and double strand breaks were found in subpopulations of cells in the peripheral blood as well as in the peripheral lymphoid organs, which correlated to disease activity of mice with intestinal inflammation. CD4 and CD8 T-cells seemed most sensitive to DNA damage. TNF-α was sufficient to induce DNA damage in wild-type mice. Chronic intestinal inflammation induces systemic DNA damage, in which CD4 and CD8 T-cells are the most sensitive. TNF-α plays a role in inducing this damage though further mechanisms remain investigated. Levels of DNA damage in the peripheral blood correlated strongly to inflammatory activity and severity of disease, making DNA damage to leukocytes a good biomarker to diagnose and monitor disease in inflammatory bowel disease patients.

Biography:

Xiao-Xia Jiang has completed her PhD from Institute of Basic Medical Sciences. She is an Associate Professor in the Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences. She has published more than 40 papers in reputed journals.

Abstract:

B1 cells are the dominant population of B cells in the pleural and peritoneal cavities. They are a significant source of serum antibody, and they make a dominant contribution to low-affinity IgM antibodies that are present in serum of unimmunized mice. B1 cells in the mouse are thought to be derived from precursors in fetal liver rather than from adult bone marrow. They are believed to maintain their cell numbers in adult mice by longevity and homeostatic proliferation. Unlike conventional B cells (B2 cells) and despite the importance of B1 cells in protection from infections and their association with autoimmunity, the mechanism of B1 cell proliferation and function remained poorly understood. Mysm1 is a histone de-ubiquitinase and has been shown to play an essential role in hematopoiesis and lymphocyte development. Our previous study has demonstrated that in Mysm1 deficient mice, B2 cell development is blocked and B2 cell number is significantly lower compared with their counterpart. In this study we found that, in contrast to the dramatically decreased level of B2 cells, the percentage of B1 cells in the spleen and peritoneal cavity of Mysm1 deficient mice was increased compared with that in wild type mice. Mechanistic study has demonstrated that miR150 expression is compromised in B1 cells from Mysm1 deficient mice. Mysm1 controls the transcription of miR150 through regulating the chromatin state of miR150 locus. What’s more, forced expression of miR150 in B1 cells from Mysm1 mice can partly rescue the phenotype. Overall, our study, for the first time, reveals the important role of histone H2A de-ubiquitinase in B1 cell proliferation and development.

Biography:

Omar E Franco completed his MD at the “Universidad Nacional de Asunción”. After four years of medical training, he received a scholarship from the Japanese Government for a clinical fellowship, and then did his PhD at Mie University in Japan. Then he did a Post-doctoral training with Dr. Simon Hayward Lab at Vanderbilt University. More recently he was promoted to Research Assistant Professor and moved to North Shore University Health System as a Senior Research Scientist. He has more than 40 publications and is a member of the Society of Basic Urological Research. His main interest is in the tumor microenvironment.

Abstract:

Prostate cancer cells are surrounded by a complex tumor microenvironment. The stromal cells present in the vicinity of cancer cells and the extracellular matrix they deposit, play a key role in restraining or promoting tumorigenesis. We and others have shown that carcinoma associated fibroblasts (also known as CAF or reactive stroma) populations seen in human tumors are not, in fact, homogeneous, but, rather are mixed cell populations. Observations of human prostate tumors suggested that impaired TGFβ signaling in a proportion of normal human prostatic stromal cells is responsible for the pro-tumorigenic phenotype described in CAF. Our research was performed using fibroblasts derived from patient samples undergoing radical prostatectomy. Primary cell lines representing normal prostate fibroblasts (NPF) or CAF were generated. The non-malignant but initiated prostate epithelial cell line BPH1 was used to assess for paracrine tumor-inducing activity related to the fibroblasts. To evaluate the role of stromal TGFβ signaling we generated fibroblasts expressing the dominant negative TGFβR2 (DN) using a lentiviral system. Tissue recombinants composed of combinations of different stromal cells in the presence of epithelium were grafted beneath the renal capsule of SCID mice for 6-8 weeks. Macroscopical and histological analysis of the architecture as well as characterization of relevant downstream pathways was performed. Recombinants of NPF and BPH1 cells gave rise to small grafts composed of small, non-invasive cords. Stromal mixtures lacking at least 50% of proper TGFβ signaling were able to promote malignant transformation of the reporter prostate epithelial cell line. There was a robust infiltration of inflammatory cells correlated with the occurrence of tumors in our in vivo system. Tissue samples from prostate cancer patients and CAF/BPH1 recombinants showed mosaic TGFβ signaling activation depicted by phospho-Smad2 staining; supporting the notion of a mixed tumor microenvironment. In vitro studies showed that normal-looking fibroblasts cooperate with the impaired stroma in the secretion of factors commonly disregulated in cancer such as the chemokine SDF1α, little is known about the cross-talk between subpopulations of stromal cells in the tumor microenvironment. Our data supports the idea that heterogeneity (in this study TGFβ signaling) within fibroblastic populations can elicit local changes in paracrine signaling resulting in malignant changes in benign prostatic epithelial cells. A clear understanding of the role of the normal stroma and the complex interactions between different stromal cell types during carcinogenesis is required to develop better therapeutic strategies.

Biography:

Pieter Rousseau Fourie has completed his BSc in Electrical Engineering, MB ChB and PhD in Medical Physiology and Pediatric Specialty (MMed), all from the Stellenbosch University, South Africa. He holds an Associate Professorship in the Department of Critical Care and Anesthesiology, Faculty of Health Sciences, Stellenbosch University and runs a pediatric practice at Cape Gate Med clinic, Bracken fell, South Africa. He has published more than 35 papers in reputed journals.

Abstract:

Immune deficiencies in South Africa can be divided into two categories, primary and secondary immune deficiencies. In the private Paediatric clinic, children often present with a number of problems that can be traced to selective primary immune deficiencies. Not all children are eligible for intravenous immunoglobulin therapy, either due to costs or non-IgG immune deficiencies such as selective IgA or T-cell deficiencies. Intramuscular and sub dermal options are equally expensive and more uncomfortable. The use of oral immune modulators, such as the erythromycin derivatives, has raised some concern, mainly because of the potential risk of bacterial resistance. Other so called immune boosters, e.g. echinaceas, are being advertised as potential solutions but have yet to prove to be effective. A practical approach to immune modulation will be presented that has a direct beneficial effect on the health outcome of the children.

Biography:

Estibalitz Laresgoiti-Servitje is a Researcher at the Tecnológico de Monterrey. She received her Medical Doctorate in 1996. Her Post-graduate studies include a Master’s in Immunology, a Master’s in Neurosciences and a PhD in Health Psychology. Her research interests include the neuroendocrine regulation of the immune system and the modulation of the immune system during normal pregnancy and preeclampsia.

Abstract:

Introduction: The placenta is a complex organ that mediates maternal-fetal exchange. Placental perfusion models have shown that there is minimal transfer of certain inflammatory cytokines to the fetal circulation, but bidirectional transfer of cytokines also exists. Objective: This study evaluated if cytokine concentrations in normal and overweight mothers may be similar to the ones of their newborn babies. Methods: Thirty-four pregnant women were included in this study after being admitted to the labor and delivery unit of the National Institute of Perinatology. All participants had single non-complicated pregnancies and did not receive any medication at least three weeks prior to pregnancy termination. Immediately after delivery, maternal blood was obtained by venipuncture and fetal blood was obtained from the umbilical artery. Clinical and demographic data was obtained from clinical records. Cytokine concentrations were measured in maternal and umbilical blood serum using a 27 plex-panel cytokine assay from Bio-Plex (BioRad). Results: Related t-test of all the participants’ samples revealed significant differences between mother and baby’s concentrations of IL1-RA, IL-4, IL-6, IL-7, IL-12, IL-13, IL-17, Eotaxin, G-CSF, GM-CSF, IP-10, MCP, MIP-1, RANTES and VEGF. MANOVA results showed higher but non-significant concentrations of IL-10 in normal weight women and their babies, compared to those in overweight women. No significant differences were found for any cytokine among weight groups. Conclusion: The placenta is an important mediator of maternal-fetal cytokine exchange because it exerts control over the cytokines that are transferred to the fetal circulation. Cytokine transfer appears to be similar in normal and overweight women. However, the effect of co-variables was not evaluated.

Biography:

Ebtesam H M Al-Ali has completed her BSc degree at 1993 from Kuwait University and joined the work as Scientific Researcher at Kuwait Institute for Scientific Research with the molecular genetics group. She led 5 completed projects and has published more than 7 papers in reputed journals and international conferences.

Abstract:

Mycoplasma has a wide distribution in nature, they lack the cell wall and they include important pathogens of animals, plants insects and human. It is difficult to diagnose the Mycoplasma infection based on symptoms alone, therefore a faster and more specific method is needed because of the difficulties of culturing them in laboratory. The objective of this work was to detect avian Mycoplasmosis using PCR diagnostic kit (VenoMGs) and Enzyme Linked Immunosorbant Assay (ELISA) diagnostic kit (ProFLOK) in comparison to culture method. Two advanced techniques were applied: The results obtained from Polymerase Chain Reaction (PCR) technique were compared with serological detection method using ELISA, to study the spread of this disease in sample from broiler and layer flocks. Fifty bird samples were tested for Mycoplamosis. 25 positives (50%) were from ELISA test and 29 positives (58%) from PCR, where only 7 were positive (14%) with culture methods. Swab samples obtained from the choanal cleft gave more positive (60%) with PCR than tracheal samples (56%) and cultures were grown in broth media with a pH indicator. Rapid, sensitive and specific tests that detect nucleic acid from pathogenic Mycoplamas are very attractive for the laboratory detection of infected flocks, and methods reported here are of high sensitivity and specificity for Mycoplasma. The use of these methods for surveillance of the disease will establish data concerning the predominant Mycoplasmosis diseases in Kuwait and improves the veterinary medical service in Kuwait.

Biography:

Eman H Abdel-Rahman is currently working as a Professor in National Research Center, Egypt since 2005. In 1990, she was appointed as Assistant Researcher, in 1995, as a Researcher and in 2000, as an Associate Professor at the National Research Center, Egypt. She received her BSc degree in Zoology in 1981 at Cairo University, Egypt. She completed her MSc in Immunoparasitology in 1990 from Cairo University, Egypt. She obtained PhD from Cairo University, Egypt in 1995 in Immunoparasitology. Her current research interests are immunoparasitology, biological control, DNA technology, glycoprotein antigens and parasitology.

Abstract:

Cystic echinococcosis is a worldwide zoonotic disease caused by larval stages of Echinococcus granulosus. The persistence of cysts in the intermediate hosts as sheep, camels and humans is of interest since, once fully formed, cysts are apparently unaffected by the host’s immune response. Moreover, E. granulosus larval stages possess various molecules which modulate the host immune response and promote parasite survival and development as antigen B and antigen 5 of hydatid cyst fluid. The advent of proteomic analysis of the larval stages proteins has significantly improved the identification and characterization of proteins to use as potential new diagnostics as heat shock protein 20. During cystic echinococcosis, host immune responses switch from Immunoglobulin G1 and interferon gamma to IgG4, IgE, Interleukin 4, IL-5, IL- 6, IL-10 and tumor necrosis factor. Despite of this humoral and cellular immune responses evoked by the host, the parasite not only escape but impair the response and survive for a long time in the host. Among the immunologic tests for assessing the host-parasite relationship, assays of immunoglobulin isotypes detection with the use of distinct parasite antigens, circulating antigens detection and detection of Th1/Th2 cytokine expression. Enzyme Linked Immunosorbent Assay is the most commonly used in the immunodiagnosis of cystic echinococcosis. Accurate serological diagnosis of the cystic echinococcosis, as other helminthiasis, requires highly specific and sensitive antigens to be used in the assays. The choice of an appropriate source of antigenic material is a crucial point in the improvement of the diagnostic features of tests, and must be based on the developmental stage of the parasite. The current review emphasizes recent advances in the identification and characterization of novel antigens with potential for the immunodiagnosis of cystic echinococcosis. The need to search for new antigenic components with high diagnostic sensitivity and specificity remains a crucial task in the improvement of immunodiagnosis of the disease.

Biography:

Gregory Lee received his Ph. D from the California Institute of Technology and completed his postdoctoral studies at the University of California, San Diego. He became a full Professor at the University of British Columbia in 1989, and retired in 2012 with the title of Professor Emeritus. He is the co-founder of Vancouver Biotech Ltd. He has published more than 200 papers, including 30 papers in cancer research. He has been serving as an editorial board member of the Journal of Carcinogenesis and Mutagenesis, and the Journal of Cancer Science and Therapy since 2012.

Abstract:

RP215 is a monoclonal antibody generated against ovarian cancer cell extract and has been shown to react with a carbohydrate-associated epitope located mainly on the heavy chains of immunoglobulins expressed on the surface of most cancer cells. In contrast, these cancerous immunoglobulins, designated in general as CA215, are not found on normal human B cells. Upon isolation from the shed medium of cultured cancer cells, CA215 was found to recognize numerous human serum protein components or fragments, of which both anti- and pro-cancer activities have been identified. These observations strongly support the hypothesis of cancerous immunoglobulins possessing dual functions in cancer cells. Through decades of investigations, it was also revealed that apoptosis and complement-dependent cytotoxicity can be induced by RP215 or its humanized forms, as well as by antibodies against antigen receptors, such those against immunoglobulins or T cell receptors. For example, RP215 and these anti-antigen receptors were found to demonstrate a high degree of correlation in terms of the regulations of many genes involved in the growth and proliferation of cancer cells (EX: NFκB-1, IgG, P21, cyclin D1, ribosomal P1, and c-fos), as well as for toll-like receptors. Furthermore, significant dose-dependent reductions of implanted tumors were also observed following treatment with RP215 in nude mouse animal models. RP215-based immunodiagnostics were also developed for monitoring of the serum levels of CA215 among cancer patients. Judging from these experimental observations, humanized RP215 may be a suitable candidate for antibody-based anti-cancer drug development as it targets cancerous immunoglobulins which are widely expressed on the surface of most cancer cells in humans.

Biography:

Born in 1959 in Brussels, Pierre van der Bruggen completed in 1982 studies in the Faculty of Agronomy at the Université catholique de Louvain and, in 1987, a Ph.D in Agronomical Sciences on a fungus pathogenic for cassava. In 1988, he joined the research group of Thierry Boon at the Ludwig Institute for Cancer Research. He became Associate Professor in 2000 at the Medical Faculty of the Université catholique de Louvain, where is is now Full Professor. Pierre van der Bruggen identified in 1991 the first human gene, MAGE-1, coding for a tumor antigen recognized by cytolytic T lymphocytes. He and his group identified over the years several other cancer germline genes and defined a large number of antigenic peptides, which are encoded by these genes and recognized on tumors by CD8 or CD4 T lymphocytes. Efforts have then been devoted to set up assays that accurately monitor CD4+ T cell responses to cancer vaccines. The group is currently involved in the study of MAGE-3-specific regulatory T cells and anergy of human tumor-infiltrating lymphocytes. Together with Nathalie Demotte, a Ph.D. student in his group, Pierre van der Bruggen identified a novel mechanism causing anergy of CD8 T lymphocytes, including human tumor-infiltrating lymphocytes. Their observations indicate that human tumor-infiltrating lymphocytes, which are very often anergic, can recover ex vivo their effector functions with galectin antagonists. A clinical trial with cancer patients started recently on the basis of these results. Pierre van der Bruggen received the Prize of the "Fondation Maggy et Robert de Hovre" in 1995, the Prize of the "Fondation Alexandre et Gaston Tytgat" in 1998, and the Prize "Wivine et Jacques Allard-Janssen" in 2009. He is the author of 98 research articles (40 as first or last author, 58 as co-author) and 31 review articles.

Abstract:

Freshly collected human tumor-infiltrating CD8 T lymphocytes (TILs) are often defective for the secretion of cytokines and lytic enzymes. We reported previously that these functions could be restored with agents that release the galectin present at the TIL surface. We show here that the non-secreting TILs nevertheless produce normal amounts of intracellular cytokines. We observed poor LFA-1 recruitment and defective actin rearrangement at the TIL secretory synapse. These defects were relieved by galectin removal. Mild LFA-1 blockade by antibodies on normal CD8 blood T cells also blocked actin rearrangement and abolished cytokine secretion but not production. We conclude that galectin prevents the formation of a functional secretory immunological synapse by preventing optimal LFA-1 recruitment. This is the first observation of uncoupled cytokine production and secretion, a defect which is not revealed by intracellular cytokine immunomonitoring assays.

Biography:

I have completed philosophy degree in Biochemistry from Awadhes Pratap Singh University, Rewa, Madhya Pradesh, India. Recently working as a Senior Research Fellow at Immunology Division, NIMR, and Delhi, India. Working on Stem cells therapy to explore scientific knowledge and its future prospectus.

Abstract:

Introduction: Malaria is vector born diseases caused by plasmodium species, survive and replicated into two (Human and Mosquito) host systems. In human, malaria parasite escapes immune response and replicate. In our experiments we found that, accumulation of mesenchymal stem cells in the secondary lymphoid organ using the mouse model of malaria with Plasmodium berghei and imbalance of immune cells during malaria infection. We used rodent malaria parasite to understand host systems. Surprisingly we found that imbalanced numbers of immune cells with the infection were unable to protect. A part from these cells types, increased number of mesenchymal stem cells were unable to protect during malaria infection. Mesenchymal stromal cells or mesenchymal stem cells (MSCs) are multipotent in nature and able to differentiate into different cell types. These differentiating cells were able to express Notch1 may underline mechanism of action of mesenchymal stem cells by production of soluble factors such as IL6 and MIP1a. We also found that these Sca-1+ cells were able to modulate immune response by modulating regulatory T cells with disease progression. Regulatory T cells modulation also dependent upon expression of Notch-1+ cells. Sca-1+ mesenchymal stem cells able to express Notch-1+ during infection, may suggesting that partially Sca-1+Notch-1+ mesenchymal stem cell dependent protection during malaria infection.

Biography:

Manhal Khuder Hasso is a Associate Professor in Duhok Polytechnic University, Iraq

Abstract:

Introduction
Liver X receptors (LXRα and LXRβ) are members of the nuclear receptor superfamily of ligand-activated transcription factors that regulate many biological and physiological processes. LXRs are important regulators of cholesterol and lipid metabolism and this is mediated by regulating a wide range of genes such as ABCA1 and ABCG1 that are involved in lipogenesis, cholesterol efflux and absorption, and bile acid synthesis. Since there is a relationship between chronic inflammatory diseases and lipid metabolic dysfunction, the role of LXRs has been investigated in different inflammatory diseases and disease models. Generally, LXRs have an anti-inflammatory effector function, however occasionally pro-inflammatory effects have also been reported. MicroRNAs (MiRNAs) are small, evolutionary conserved, single-stranded, non-coding RNA molecules with 20- 22 nucleotide base pairs. They regulate mRNA translation by fine tuning the production of proteins involved in the initiation or maintenance of inflammation. MiR-155 is one of the most studied members of miRNAs, and it has a regulatory role in certain inflammatory diseases such as collagen induced arthritis, lung fibrosis, and cardiovascular diseases. Idiopathic pulmonary fibrosis (IPF) is a devastating inflammatory disease of unknown aetiopathogenesis characterised by progressive breathlessness. IPF is characterised by approximately 50% survival of around 3 years after diagnosis, and there is no effective treatment. The main imperative for pulmonary fibrosis research is to identify potential causal inflammatory and remodelling pathways that contribute to IPF initiation and progression in order to determine possible candidate pathways for therapeutic intervention.

Hypothesis:
LXRs play an important role in lipid metabolism and cholesterol homeostasis and because there is a strong relationship between metabolic disease and chronic inflammatory and fibrotic diseases, e.g. LXR agonists may be beneficial for the treatment of RA. We proposed the following hypothesis ‘’ Liver X Receptors can modulate bleomycin-induced pulmonary fibrosis and therapeutic intervention with LXR agonists may be beneficial for the treatment of pulmonary fibrosis.

Methods & Results:
Administration of the LXR agonist GW3965 to LXR-/--/- or LXRwild type mice given bleomycin to induce pulmonary fibrosis significantly exacerbated the severity of the disease only in LXRwild type mice. The worsening of disease was seen as enhanced loss of body weight, increased inflammatory and fibrotic pathomorphological changes in the lung, increased inflammatory cells in the bronchoalveolar lavage, increased concentrations of several pro-inflammatory and pro-fibrotic mediators, and increased expression of genes that regulate inflammation and fibrosis, such as collagen and TGF, increased lung collagen content, and finally up-regulation of the expression of the alternative activated macrophages (M2)markers arginase 2 and IL-13 receptor The effect of the LXR agonist was mediated specifically by LXRs because the severity of disease did not change in LXR-/--/- mice given bleomycin and treated with GW3965, nor on similarly treated single LXRα or LXRβ gene-deleted mice. Furthermore, similar activation of LXRs in primary human or murine fibroblasts demonstrated up-regulation of the expression of collagen. The function of LXR agonist was directly on collagen gene expression and did not require de novo protein synthesis as demonstrated by the addition of cycloheximide as a translation inhibitor to murine primary fibroblasts activated with LXR agonist. This suggested that the LXR may have acted directly on the promoter region of the collagen gene. Also I investigated if the collagen genes have response elements for LXR in their promoter regions using a cell reporter system. I demonstrated that the collagen genes have response elements for LXR in their promoter regions. In a parallel set of experiments, administration of bleomycin or PBS to miR-155-/- and miR-155 wild type mice demonstrated a significantly stronger inflammatory and fibrotic process in the miR-155 gene-deleted mice. This worsening of disease was seen as an enhanced loss of body weight, increased inflammatory and fibrotic pathomorphological changes in the lung, increased inflammatory cells in the bronchoalveolar lavage, increased concentration of several pro-inflammatory and pro-fibrotic mediators, and increased expression of genes that regulate inflammation and fibrosis; such as collagen and TGFincreased lung collagen content, and finally up-regulation of the expression of the alternative activated macrophages (M2) markers arginase 2 and IL-13 receptor. The effect was mediated specifically by miR-155 because the severity of disease was increased in miR-155-/- mice compared with miR-155 wild type mice given bleomycin. Also no differences were observed in miR-155-/- and miR-155 wild type mice given PBS.

Conclusion:
My results demonstrate that both the LXR and miR-155 have an important impact on the progression and extent of murine pulmonary fibrosis. Since completing the work for this thesis some of my additional pilot work has shown that LXR is a target for miR-155 and therefore both may have an important role in lung homeostasis. My results suggest the therapeutic approaches for IPF might include targeting the LXRs or LXR-regulated pathways, including potential fine tuning levels of LXR with miR-155 antagonists. The aim would be to prevent excessive remodelling. Furthermore, any such therapeutic intervention would need to be done in a very careful way because LXRs are involved in many other physiological processes. Therefore, more targeted therapy perhaps controlling miR-155 may be of clinical relevance for therapeutic strategies.

Biography:

Dr. Kiran Sharma is presently working as post doc fellow in the Department of Biochemistry and Medical Genetics, University of Manitoba from May 2013 till present. She received her MSc (2007) from Guru Nanak Dev University, Punjab, India and BSc (2004) from the Himachal Pradesh University, Shimla, India. Dr. Sharma received her Ph.D. from Dept. of Surgical Oncology, King George Medical University, Lucknow, India in 2013. Her thesis work was entitled as “Role of Genetic Variants of Hormonal, Inflammatory and Xenobiotic metabolism pathway genes to Gallbladder cancer susceptibility”.

Abstract:

Gallbladder cancer (GBC) is a violent neoplasm associated with late diagnosis, unsatisfactory treatment, and poor prognosis. The disease shows complex interplay between multiple genetic variants associated inflammation and tumorigenesis. We analyzed 15 polymorphisms in nine genes involved in various pathways to find out combinations of genetic variants contributing to GBC risk. The genes included in the study were (matrix etallopeptidase-2, MMP-7, MMP-9), tissue inhibitor of metalloproteinases (TIMP-2), cytochrome P450 (CYP)1A1, CYP1B1, phospholipase C epsilon 1 (PLCE1), liver X receptor (LXR)-alpha and LXR-beta. Genotypes were determined by PCR-RFLP andTaqMan probes. Statistical analysis was done by SPSS version 16.Multilocus analysis was performed by Classification and RegressionTree (CART) analysis and multifactor dimensionality reduction(MDR) to gene–gene interactions in modifying GBC risk. In silicoanalysis was done using various bioinformatics tools (F-SNP,FAST-SNP). Single locus analysis showed association of MMP-2(−735 C > T, −1306 C > T), MP-7 − 181 A > G, MMP-9 (P574R,R668Q), TIMP-2 − 418 G > C, CYP1A1-MspI, CYP1A1-Ile462Val,PLCE1 (rs2274223 A > G, rs7922612 T > C) and LXR-beta T > C(rs3546355 G > A, rs2695121 T > C) polymorphisms with GBC risk (p < 0.05) whereas CYP1B1 and LXR-α variants were not associatedwith GBC risk. Multidimensional reduction analysis revealed LXR-β(rs3546355 G > A, rs2695121 T > C), MMP-2 (−1306 C > T), MMP-9(R668Q), and PLCE1 rs2274223 A > G to be key players in GBCcausation (p < 0.001, CVC = 7/10). The results were further supportedby independent CART analysis (p < 0.001). In-silico analysis ofassociated variants suggested change in splicing or transcriptionalregulation. Interactome and STRING analysis showed network ofassociated genes. The study found PLCE1 and LXR-β networkinteractions as important contributory factors for geneticpredisposition in gallbladder cancer.

Biography:

Assistant Professor of Molecular Microbiology and Immunology (Research) My primary research interests are directed towards understanding the immunopathogenesis of lung injury and repair. I have interrogated the roles of a chitinase-like protein and its receptors in a variety of lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. My future research plans are aimed at dissecting the common mechanisms that underlie the pathogenesis of pulmonary fibrosis, specifically the role of intracellular receptor trafficking pathways in disease progress. My long-range research goals are to identify the immune and cellular responses that mediate lung injury and repair responses and to identify specific molecular targets that can be targeted in the treatment of related disorders.

Abstract:

Rationale:
Tissue injury and repair are juxtaposed inlungs from patients with Idiopathic Pulmonary Fibrosis (IPF). IPF is characterized by epithelial apoptosis, aberrant fibroblast and myofibroblast proliferation, and matrix deposition.Studies from our laboratory and others have demonstrated that injury and fibroproliferative repair are essential events in the pathogenesis of IPF. They also demonstrated that interventions that abrogate injury also prevent excessive fibroproliferative repair. Chitinase 3-like 1(CHI3L1) (also called YKL-40 in man and BRP-39 in mouse) is a prototypic chitinase-like protein that has been retained over species and evolutionary time. Dysregualted expression of CHI3L1has been noted in a variety of human diseases characterized by inflammation, tissue remodeling, and fibrosis.Previous studies from our laboratory demonstrated that CHI3L1 mediates aeroallergen-induced adaptive Th2 inflammation and IL-13-induced pulmonary fibrosis, while itinhibits apoptosis and confers tissue cytoprotection in the setting of a variety of pulmonary injuries including Streptococcus pneumoniae infection, and oxidant injury. However, the ability of CHI3L1 to regulate injury and/or fibroproliferative repair and the regulation of CHI3L1 in IPF have not been adequately defined.
Hypothesis:

We hypothesized that (a) CHI3L1 is differentially regulated and has distinct effects on the injury and repair phases of PF; (b) CHI3L1 is expressed in an exaggerated manner and is a useful biomarker in IPF.
Methods:

We characterized the expression of CHI3L1 afterbleomycin administration and used CHI3L1-/- and YKL-40 transgenic miceto define the roles of CHI3L1 in bleomycin-induced injury and repair. We also characterized the levels of CHI3L1 in plasma fromIPF patients and the relationships between the levels of CHI3L1 and disease progression.

Results:
CHI3L1 expression was acutely and transiently decreased during the injury phase and returned to normal or super normal levels during the fibrotic phase following bleomycin administration. Overexpression of CHI3L1during “injury” significantly amelioratedbleomycin-induced inflammation and cell death. In contrast, overexpression of CHI3L1 solely during fibroproliferative repair enhanced tissue fibrosis andaugmented extracellular matrix gene expression, TGF-β production, and alternative macrophage activation. The levels of circulating CHI3L1 were elevated in IPF patients compared to normal controls. Importantly,high levels ofCHI3L1were associated with increased risk of disease progression.
Conclusions:

CHI3L1 plays a protective role in the injury phase and a pro-fibrotic role in the repair phase of pulmonary fibrosis. CHI3L1 is increased in the circulation of patients with IPF where it likely represents an attempt on the part of the host to diminish injury and induce repair which correlates with disease progression.

Biography:

Abdul-Rahman Mubarak studied Bachelor of Science Molecular Biology and Biotechnology at University of Cape Coast and M.PHIL. In Clinical Immunology at University of Ghana Medical School.

Abstract:

Introduction
Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy.

Methods
The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. The sHLA-G level was measured using BiovendersHLA-G ELISA kit following the manufacturer’s protocol.

Results
sHLA-G levels was found to be higher in women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. sHLA-G level was also found to be higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery.

Conclusion
Although sHLA-G level was found to be higher in women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, it may not be playing any role in implantation rather playing a role in the maintenance of maternal immune tolerance to foetal antigen after implantation because plasma sHLA-G levels was found to increase with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion

Biography:

Sthiti Porna Dutta has joined as Ph.D scholar in the Department of Biochemistry in the immunology laboratory of North Eastern Hill University in 2012. She has completed her Msc in Biochemistry at an age of 23 from Annamalai University, Tamilnadu in 2012 .She has attended several national conferences and workshops and participated as young scientist in the National Seminar organised by NORTH EAST BIOLOGICAL CONSORTIUM .She has done dissertation projects on Protein analysis of kumal rice and Production of Bio-Electricity from organic and sewage waste and the antibiotic sensivity test of the micro organisms isolated and identified from them.

Abstract:

Effects of N-Nitrosodibutylamine on the expression of the liver mitochondrial membrane surface proteins in mice: N-Nitrosodibutylamine (DBN) is an established hepatocarcinogen in rodents and its effects on liver mitochondria in Swiss albino mice have been examined. In the present investigation, DBN at a dosage of 10 mg kg-1 body weight was used to induce carcinogenesis in male mice by intravenous administration of the carcinogen at weekly intervals for a period of 16 weeks. This protocol triggered the initiation of carcinogenesis. Cancer induction was followed by monitoring the activities of marker enzymes such as acetylcholine esterase (AChE), glutathione-S-transferase (GST) and gamma-glutamyl transpeptidase(GGT), which was further supported by the histological examination of liver tissue of DBN exposed mice. The observed alteration in marker enzymes activities indicate hepatic dysfunction and damage to liver caused by DBN-treatment in mice. Whether, the DBN exposure also affect on mitochondrial membrane surface protein was of great concern to us. Hence liver mitochondria are chosen as our target of interest. Our preliminary observations indicate a drastic distortion in shape and size of liver mitochondria in mice upon DBN exposure. The membrane was highly disrupted and mitochondria contained large vacuoles or enlarged cristae compartments in comparison to the normal control mice. The proteomic analysis of the liver mitochondrial membrane surface proteins showed differential expression in DEN-treated mouse compared to that of the normal control. These results suggest that specific mitochondrial proteins are uniquely susceptible to alterations in expression and carry implications for the further investigation of their potential as therapeutic and prognostic markers.

Biography:

Kanga Rani Selvaduray is a Assistant Professor, International Medical University, Malaysia

Abstract:

Several mechanisms have been postulated for the anti-cancer effects of tocotrienols. In this study, the anti-cancer mechanism of tocotrienols is for the first time linked to increased expression of interleukin-24 (IL-24) mRNA, a cytokine reported to have anti-tumor effects in many cancer models. The anti-proliferative effects of tocotrienol-rich fraction (TRF) from palm oil, γ- and δ-tocotrienol (γ-T3 and δ-T3) and α-tocopherol (α-T) were studied on 4T1 murine mammary cancer cells. TRF, γ-T3 and δ-T3 significantly inhibited the growth of the 4T1 cells with IC50 values of 8.99, 4.79 and 3.73μg/ml respectively. Tumor incidence and tumor load in BALB/c mice were decreased by 57.1% and 93.6% respectively (p<0.05) with TRF supplementation. Tumourigenesis was examined and compared against control in both nude and BALB/c mice models. The mice were injected with MDA-MB-231 and 4T1 cells respectively for the different models, and were fed with TRF by oral gavage. This study shows that palm tocotrienols have strong inhibitory effects on the growth of both MDA-MB-231 and 4T1 cells both in vitro and in vivo. In addition the immune modulatory effects of tocotrienols were also investigated and it was found that TRF enhanced production of NK cells (P < 0.05) as well as IFN-γ (P < 0.05), which in turn regulate the immune protection against cancer cells. These observations were recorded in both mice models. The 4T1 cells treated with TRF, δ-T3 and α-T exhibited highest levels of IL-24 mRNA in δ-T3 treated cells, followed by TRF and α-T. The IL-24 mRNA levels in tumor tissues of BALB/c mice supplemented with TRF increased two-fold as compared to control mice. Increased levels of IL-24 have been associated with inhibition of tumor growth and angiogenesis. TRF and δ-T3 treated 4T1 cells significantly decreased IL-8 and vascular endothelial growth factor (VEGF) mRNA levels. We hereby report that the anti-tumor including the anti-angiogenic effects of tocotrienols are associated with increased levels of IL-24 mRNA.

Biography:

Divocha Valentina in 1967 she graduated from I. I. Mechnikov Odessa State University, Faculty of Biology (Department of Virology). In 1973 continued her postgraduate study ate Odessa Institute of Virology and Epidemiology (specialty virology). In 1974 she was awarded her candidate degree with the thesis "Interaction of Coxsackie B viruses with sensitive cell cultures and their antigenic relationships." In 2009 she was awarded her doctoral degree with the thesis entitled "Biological basis antiprotease therapy of influenza." Under her leadership performed a doctoral and two master's theses. Scientific experience is 35 years. I have more than 180 scientific publications, 2011 monograph, textbook "Virology" (2012), 10 patents, 3 innovations. I am currently working as the head of the Laboratory of Experimental and Clinical Pathology for Ukrainian Research Institute of Transport Medicine, is the supervisor of the nine research programs in virology and biochemistry.

Abstract:

Introduction:
Interaction of virus and cell in the pathogenesis of viral diseases is insufficiently studied. The main point here is penetration of virus into a healthy cell with an obligatory virus’ deproteinization. However the deproteinization of viruses is studied insufficiently. First of all it refers to the mechanisms of introduction of flu virus in the cells of mammals, including humans. In this regard in 1983 we offered the new theory of flu pathogenesis with participation of proteinazno-inhibitory system.

Objective:
To study the state and role antiproteinasis systems of the virus and recipient in the development of an influenzal infection for receiving essentially new medical preparations on the basis of inhibitors of trypsin-like proteinases.

Methods:
In work presented we used flu viruses, A/PR/8/34 (H1N1), AO/32(H1N1) strains, white mice, chicken embryos, white rats, waste of γ-globulin and albumin manufacturing, human interferon and immunoglobulin, herpetic, gonococcus and tularemia vaccines and medicines: Influvac, Fluarix, Vaxigrip – anti-influenzal vaccines, Avaxim – vaccine for hepatitis A and blood preparations - Fraxiparine, Solcoseryl.

Results:
It has been established that cleaning and concentration of influenzal virus A by different methods doesn't exempt virus from cellular enzymes – trypsin-like proteinases and their inhibitors. Both domestic (human immunoglobulin and interferon, anti-influenzal and herpetic vaccines), and foreign preparations (Influvac, Fluarix, Vaxigrip, Avaxim, Fraxiparine and Solcoseryl) had trypsin-like proteinase and its inhibitor in their structure. In the experiments on the white mice at infection with flu A virus there was a violation of proteinase - inhibitory balance, especially during the first hours after contamination. From the lungs of healthy mice six isoforms of trypsin-like proteinase have been allocated and antiproteinase immune serums were received to them. At the treatment of the animals infected with a lethal dose of flu A virus, only one serum (to the third isoform) has protected white mice from death. From the waste of γ-globulin manufacture of donor blood, inhibitor of trypsin - like proteinases which protected for 80% of white mice from death, was emitted.

Conclusions:
Endogenous inhibitors of human blood proteinases are perspective preparations in the fight with flu in humans.

Biography:

Assi Flaviurs is a Public Health researcher in Cameroon. He is participating in PhD program of School of Medicine, University of Buea- Cameroon. His research concentrates on transmission, knowledge, attitude and sex behaviors among female sex workers in Cameroon. Before the PhD program, Assi taught and studied in Public Health and Health Promotion for 5 years with a number of researches and projects in health prevention field.

Abstract:

Female sex workers (FSWs) are at heightened risk of sexually transmitted infections (STIs) and HIV. The purpose of this systematic literature review of STI/HIV prevalence for FSWs in central African is to appraise and understand the burden of STIs and HIV. Electronic databases searched included PubMed (MEDLINE), Embase, Global Health, MeSH, Cochrane Library, Health Reference Centre, Pro Quest, Psyc INFO, Science Direct, Social Services Abstracts, SCOPUS, CINAHL, Web of Science, and POP Line. Relevant articles published from 2007 to 2012 were identified. The findings of this multi-country regional review provided reliable evidence that despite prevention efforts, FSWs remain one of the main populations most affected by HIV/STIs. The review reveals that the prevalence of HIV/STIs among FSWs in a number of African countries is high, especially in Cameroon and Nigeria, two countries with the highest HIV and STI prevalence. Furthermore, FSWs who work on the street, or freelance, or use multiple venues are significantly more likely to be infected with HIV/STIs than those who work from a single venue.

Biography:

Place and date of birth: Yerevan, Armenia, April 29, 1953 Education: MD, Yerevan State Medical Institute, Armenia, 1976.Scientific degrees: Candidate of Medical sciences (PhD): Leningrad Military-Medical Academy, 1984. Doctor of Medical Sciences (DSci): Leningrad Military-Medical Academy, 1988. Research interests: Gastroenterology, Immunology, Bacteriology. Publications: over 80 peer-reviewed journal papers, 1 monography (book) “The Functional Blocks And The Problems Of Clinical Medicine”, Moscow-Leningrad, 1990, 360 pp. 4 Patents regarding new methods of treatment. Memberships in professional societies: Academician of the Academy of Natural Sciences of Russia Academician of the Academy of Ecology (Russia) Member of the editorial board of “Russian Journal of Gastroente rology, Hepatology, Coloproctology” (Moscow).

Abstract:

Background:
The mechanism of bloodstream bacteria clearing is unknown. Bloodstream high velocity prevents bacteria recognition and phagocytosis by leukocytes, besides, erythrocytes are 99.9% of blood cells and leukocyte chance to get in contact with bacteria is extremely low. Many bacterial species that enter bloodstream and are resistant to blood humoral bactericidal factors nevertheless are rapidly cleared from bloodstream. Till now there is no reasonable explanation how blood bacteria clearing really happens.

Methods:
Phase-contrast immersion vital microscopy with high speed video camera registration and standard microbiologic laboratory research methods in patients with bacteremia and sepsis. Results: It was revealed that bacteria cannot grow and proliferate in bloodsream because they become triboelectrically charged and this electric charge stops trans membrane inflow of nutrients and outflow of metabolites. Interaction of both bacteria and erythrocyte electric charge provides bacteria attraction and fixation on erythrocyte surface that stimulate erythrocyte membrane receptors and causes oxygen release and bacteria killing by oxidation. Killed bacteria lose zeta potential and cannot be kept on the surface of erythrocyte and are released back to plasma and then are digested in the liver and spleen by local macrophages. Bacteria that are resistant to released oxygen concentration on the surface of erythrocyte may penetrate erythrocyte membrane producing variety of enzymes (hemolysins, hyaluronidases, kinases, exfoliatins, lipases, etc.) and enter erythrocyte. Inside erythrocyte bacteria are killed by reactive oxygen species (ROS) and are released back to plasma. Very few bacteria resist ROS and survive inside erythrocyte by means of catalase production and metabolism slowing down. Erythrocyte with bacteria inside may continue to function for a while but usually it is decomposed during passing the spleen and released bacteria are digested by local macrophages. Conclusion: From bacteria elimination point of view human body consists of two separate but interacting compartments: (a) compartment of blood circulation (pulmonary circulation and systemic circulation); (b) compartment out of blood circulation (the tissues that get oxygen from blood circulation, lymphatic vessels, lymph nodes, etc.). The liver and spleen are some special kind of interface between these compartments. In bloodstream bacteria clearing is performed by erythrocyte: bacteria attraction and fixation is an electric charge interaction phenomenon whereas bacteria killing are provided by bacteria oxidation on the surface or inside erythrocyte. Erythrocytes in arterial blood have maximal bactericidal activity whereas in venous blood erythrocytes attract and fix or engulf bacteria but cannot kill them because of lack of oxygen (oxyhemoglobin). Venous blood erythrocytes kill fixed or engulfed bacteria during blood oxygenation in the lungs. Compartment out of circulation is the realm of leukocytes and bacteria killing occurs by means of phagocytosis and production of different humoral factors.

Biography:

Stefano D’Errico is a Professor in Department of Legal Medicine,Ospedale Campo di Marte, Italy

Abstract:

Learning objective:
After attending this presentation, attendees will understand the relevance of a complete methodological approach in fatal cases of anaphylactic shock and the opportunity of a complete immunoserological investigation. Synopsis of content: The most frequent reactions to cephalosporins are non pruritic, non-urticarial rashes which occur in 1.0% to 3% of patients for most, the mechanism is considered idiopathic and not a contraindication for future use. Anaphylactic reactions from cephalosporins are extremely rare with the risk estimated at 0.0001% to 0.1%. Several studies suggest that cephalosporin-induced anaphylaxis occurs no more frequently among patients with known penicillin allergy than among those without such allergy. Allergic reaction to cephalosporins may occur because of sensitization to unique cephalosporin haptens or to determinants shared with penicillins, although the different epitopes have not been defined. Lack of knowledge of the exact chemical structure of cephalosporin antigen determinants has hindered clinical interpretation of allergic reactions and cross-reactivity. In patients with a primary response to cephalosporins, selective recognition of the R1 side chain has been observed with some degree of cross-reactivity between different cephalosporins, which almost always concerned cephalosporins with identical or similar R1 side chains. Authors present the case of a 79 y.o. man who suddenly died after i.m. administration of ceftriaxone. Dyspnoea, cyanosis and cardiac arrest occurred immediately after administration. Resuscitation manoeuvres were unsuccessful. In the history coronary by-pass and multiple administration of different antibiotics were recorded in the last ten years from general practitioner, without symptoms. Lipotimic crisis after administration of cefepime occurred few month before death. A complete post-mortem examination was performed. Gross examination was unremarkable except for mild pulmonary oedema. Histological examination revealed polivisceral stasis, mild cerebral oedema and acute pulmonary oedema mixed to acute pulmonary emphysema. Myocardial interstitial oedema was also detected. An immunohistochemical technique was used to estimate mast-cell population, using the anti-tryptase antibody as a mast-cell specific marker. Pulmonary mast cells were identified and a great number of degranulating mast cell with tryptase-positive material outside were observed. Toxicological analysis on blood specimens was unremarkable. Serum dosage of mast cell tryptase from femoral blood detected serum values of 93.5 kUA/ml. Research of total and specific IgE was performed showing that the subject was sensible for penicillins, amoxicillin, cephalosporins and also for the most common allergens. Death was due to anaphylactic shock; past administrations of cefepime sensitized the man to cephalosporins and a fatal cross reactivity of ceftriaxone with cefepime occurred due to the identical 7 position side chain structure in both molecules.

Paper’s proposition:
This presentation will impact the forensic community by alerting on the cross reactivity between cephalosporins as a potential cause of malpractice claim in general practice and by advising on the importance of collecting more evidence as possible in fatal cases of anaphylaxis.

Keywords:
cephalosporins, anaphylactic shock, tryptase.

Biography:

Rebekah Diamond will complete her MD at the Icahn School of Medicine at Mount Sinai in New York, NY in May 2015. Her paper “Elucidating the novel finding of an increased incidence of hypertension in patients with biliary atresia” was just accepted in the Journal of Pediatric Gastroenterology and Nutrition. She is currently applying for a residency program in Pediatrics.

Abstract:

Introduction:
Chimeric antigen receptor therapy (CART) is a decades old approach to cancer immunotherapy that has gained recent attention as clinical trials show its efficacy in treating chemotherapy resistant leukemia. This technology is a powerful, targeted immunotherapy therapy. Given the rapid advances in CART and increasingly efficient production techniques, it follows that this therapy could be used for other disease processes with targetable molecules for engineered immune cells. This study evaluated current scientific investigation into the uses of chimeric antigen receptor therapy in treating non-oncological disease.

Methods:
A literature database review was conducted using Pubmed.com. The phrase “chimeric antigen receptor” was typed into the database search engine. All resulting titles were assessed and those relating to CART or chimeric antigen receptors in non-oncological disease were noted and reviewed.

Results:
The Pubmed.com search returned 2706 results with the above-described parameters. Of these, approximately one half resulted from the individual search words and deemed irrelevant. Of the remaining, only 16 papers meeting the description of non-oncological chimeric antigen receptors (N=11 infectious disease, N=4 autoimmune, N=1 allergy).

Conclusion:
The investigation into non-oncological uses of CAR therapy is extremely limited but early studies show promise. The majority of research is in preclinical investigation. This technology should emerge as an important therapy as CART research continues to show efficacy cancer treatment.

Biography:

Nashwa Khairat Abousamra received her MD in Clinical Pathology, Hematology, April 2004 , Mansoura University, Egypt. Masters Degree in Clinical Pathology (Hematology), May 1997, Mansoura University, Egypt. She has many international publications. She has experienced as an internship house officer in Mansoura University hospital from 1 March 1993 to 28 February 1994. General practitioner in Egyptian Ministry of Health, Mansoura from 1 March 1994 to 15 May 1994. Resident in Clinical Pathology, Clinical Pathology Department, Mansoura University from 17 May 1994 to 28 May 1998. Demonstrator of Clinical Pathology, Clinical Pathology Department, Mansoura University from 28 May 1998 to 28 July 1998. Assistant lecturer in Clinical Pathology, Clinical Pathology Department, Mansoura University from 28 July 1998 to 28 September 2004. Lecturer in Clinical Pathology, Hematology Unit, Clinical Pathology Department, Mansoura University from 28 September 2004 to 22 November 2009. She is continuing as Assistant Prof of Clinical Pathology, Hematology Unit and as Professor of Clinical Pathology, Hematology Unit, Clinical Pathology Department, Mansoura University

Abstract:

B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease with a wide variability in patients' clinical course. Numerous prognostic markers were introduced to screen for patients likely to have progressive course of B-CLL bearing the potential to facilitate risk-adapted treatment strategies. Extracellular ATP functions as a "natural adjuvant" that boosts immune responses in the tumor micro environment but might also contribute directly to cancer cell death. CD39/ENTPD1 is the dominant ecto nucleotidase catalyzes the sequential hydrolysis of ATP to AMP that is further degraded to adenosine. The present study was conducted to analyze CD39 expression in T cells and B-CLL cells by flow cytometry to evaluate its impact on the clinical course of 68 unselected B-CLL patients and correlate it with well-established risk factors. CD39 expression in T cells was increased in the peripheral blood of B-CLL patients compared to healthy controls. The higher levels were associated with the advanced stage of disease. CD39 expression in T cells negatively interacted with patients' time to first treatment (TFT). Although our results revealed CD39 expression in B-CLL cells as a marker of less aggressive disease, our attempt to correlate its level with TFT failed to give any prognostic relevance. Overall, our data indicate that T-cell CD39 expression may identify subsets of B-CLL patients with unfavorable clinical outcome in term of therapeutic need. Moreover, it can be incorporated into prognostic schema to improve the prediction of disease progression in CLL. CD39 may find utility as a future target for the development of novel therapies with immune-modulating antitumor agents in CLL.

Biography:

Iulia Popescu is a Senior Scientist in University of Pittsburgh, USA

Abstract:

CMV remains an important opportunistic pathogen in solid organ transplantation, particularly in lung transplant recipients (LTRs). LTRs mismatched for CMV (donor+/recipient-; D+R-) are at high-risk for active CMV infection and increased mortality; however the immune correlates of viral control remain incompletely understood. We prospectively studied 23 D+R- LTRs during primary CMV infection to determine whether acute CD8+ T-cell parameters differentiated the capacity for viral control in early chronic infection. T-box transcription factors expression patterns of T-bet >Eomes differentiated LTR controllers from viremicrelapsers, and reciprocally correlated with granzyme B loading, and CMV phosphoprotein 65 (pp65)-specific CD8+IFN-+ and CD107a+ frequencies. LTR relapsers demonstrated reduced CD8+Ki67+ cells ex vivo and substantially impaired CD8+pp65-specific in vitro proliferative responses at 6 days, with concomitantly lower pp65-specific CD4+IL-2+ frequencies, as compared to LTR controllers. However, CMV-specific in vitro proliferative responses could be significantly rescued, most effectively with pp65 antigen and exogenous IL-2, resulting in an increased T-bet:Eomes balance, and enhanced effector function. Using class I CMV tetramers, we observed similar frequencies between relapsers and controllers, though reduced T-bet: Eomes balance in tetramer+ cells from relapsers, along with impaired CD8+ effector responses to tetramer-peptide re-stimulation. Together, these data show impaired CMV-specific CD8+ effector responses is not for complete lack of CMV-specific cells, but rather, underscores the importance of the T-bet:Eomes balance, with CMV-specific proliferation a key factor driving early T-bet expression and effector function in CD8+ T cells during primary infection, and differentiating the capacity of high-risk LTRs to establish immune control during early chronic infection.

Biography:

Rajesh K. Sharma is Assistant Professor at University of Louisville. He completed his Ph.D. in immunology at Banaras Hindu University in India. Dr. Sharma pursued his postdoctoral studies in cancer immunology and immunotherapy at the University of Louisville. Dr. Sharma serves as reviewer for various journals. His research interests are in the area of cancer vaccines, cancer immunotherapies, particularly development of combinatorial therapeutic approaches for cancer. Dr. Sharma is also involved in understanding the role of chemokine and its receptors in cancer-immune interplay and if these chemokine networks could be exploited to enhance the therapeutic efficacy of immunotherapies.

Abstract:

Cancer immunotherapy has recently emerged as a viable alternative to standard of care therapies and many FDA approved immunotherapies are in clinic. Several new forms of immunotherapies targeting cytotoxic-T-lymphocytes (CTLs) such as adoptive cell therapies and vaccines are in advanced clinical trials. In all of these, trafficking of CTLs to tumor is a critical step for achieving therapeutic efficacy. However, inefficient infiltration of activated CTLs into tumors is increasingly being recognized as one of the major hurdles limiting efficacy. We herein investigated the roles of chemokine receptors in regulation of CTL migration to tumor. Using tumor studies in receptor knockout mice, depletion of CTLs, adoptive transfer in Rag2-/- mice, we have demonstrated the critical role of BLT1 in controlling the migration of CTLs to tumor in cervical cancer model. Furthermore B16 melanoma model was used for validation of this notion and evaluation of the involvement of another chemokine receptor CXCR3 that has been widely implicated in migration of CTLs in context of infection or autoimmunity. We herein demonstrate that BLT1 and CXCR3 both receptor play a critical and combinatorial role in controling the CTL traficking to tumor. We finally showed that anti-PD-1 antibody immunotherapy failed in BLT1-/- and CXCR3-/- mice suggesting the indisapansable requirement of these receptor during therapy. These studies provides further insights in CTL migration to tumor during tumor development as well as the course of cancer immunotherapies. The findings may have translational implications for improving inharent as well as immunotherapy induced CTL responses in cancer patients.

Biography:

Award: "Prof. Dr. Juan Carlos Arauz " First Prize for “A new technique for treating recurrent respiratory papillomatosis using chromoendoscopy associated with Endoscopic Laryngotracheal Surgery (ELS)” research paper

Abstract:

Introduction:
Chromo endoscopy is an endoscopic technique which uses a contrast stain to paint the aero digestive tract mucosal lining followed by an optical assessment to highlighting any epithelial abnormalities. Detailed and high-definition magnified views achieved with the aid of rigid endoscopes can often allow for identification of the tissue type or pathology based upon the pattern uncovered. According to the literature we reviewed, we may have been the first ones to use indigo carmine in the field of otolaryngology. Tiny lesions that usually go overlooked with conventional micro laryngoscopy become visible upon the instillation of indigo carmine and further decreasing the chances of an early lesion post-operative recurrence. Chromo endoscopy, in recurrent respiratory papillomatosis (RRP), helps identify unsuspected intraoperative lesions by clearly enhancing the view of their boundaries and surface type. It is also suitable to assess the presence of residual lesions, if any, after their surgical removal.

Objectives:
To demonstrate the usefulness of chromo endoscopy in RRP in laryngotracheal surgery.

Material & Methods:
We used indigo carmine associated with endoscopic laryngeal surgery. Before staining, the mucosa may need to be treated with a mucolytic agent to get rid of excess mucus to boost staining. Rigid suspension laryngoscopes of different proximal and distal diameters were used with chromo endoscopy. Patients underwent chromo endoscopy associated with endoscopic laryngeal surgery under general anesthesia in the O.R.

Results:
In this second phase of our research work, this diagnostic technique was applied to eighteen patients with recurrent laryngeal papillomatosis and two patients with suspected carcinoma of the larynx. We were able to optimize the intraoperative diagnosis and reduce the likelihood of the relapse risk in all patients.

Conclusion:
Chromo endoscopy associated with endoscopic laryngeal surgery is an excellent low-cost intraoperative diagnostic method for the treatment of invasive diseases of the larynx such as laryngeal papillomatosis.

Biography:

Dharmendra Jain, Asst Prof Of Cardiology, Ims, Banarasi Hindu University, , Varanasi, India

Abstract:

Introduction & Aim:
Donor-specific complement-fixing alloantibody identification is known to play a major role in antibody-mediated renal transplantation rejection and management. Specifically, the deposition of C4d in the peritubular capillaries in a kidney biopsy is a valuable marker of antibody-mediated rejection (AMR). Various methods have been reported for the detection of allo-antibodies in recipient sera. These antibodies can be HLA or non-HLA, complement-fixing or non-complement fixing, donor T and/or B cell specific. The C4d Flow-PRA is one of the screening methods to identify the HLA specific complement fixing antibodies. However, the results are limited by the lack of donor specificity in this method.

Method:
We hereby report a novel method christened Donor-specific-Flow-C4d (DFC) of identifying donor-specific (T and/or B cell), C4d-fixing alloantibodies. The test was validated using pooled reference serums and comparing the results with immunohistochemistry findings.

Results:
In present report we have discussed a series of cases representing a variety of cases in renal transplants wherein the newer method i.e. DFC was beneficial. Some of the prototype cases cited was of AMR, where initially there was a dilemma of AMR versus ACR as the result of histopathological finding of allograft biopsy and FCXM were not sufficient to confirm it as complement mediated rejections. The positivity on the DFC method confirmed the diagnosis of AMR due to donor B cell specific, complement fixing, alloantibodies for both of these cases. An another case was of a deferred pre-transplant donor, wherein the recipient serum was confirmed to be positive for donor T and B cell specific; complement fixing, HLA alloantibodies without using an invasive procedure of allograft biopsy. This was helpful in pre- transplant prediction of a possibility of an AMR. There were also a few cases with a clear indication of correlation of the DFC and the histopathological findings. The patients were managed with the therapeutic protocols used for an ACR.

Conclusion:
With the added advantage of being non-invasive and Donor T and B cell specificity, this newer method provides information pre-transplant; whereas kidney biopsy based C4d evaluation can only be done post-transplant. It helps in decision of donor deferral, which is important in Asian countries like India, where most of the transplants are live related. We postulate that this method incorporates the best features of all the available modalities (i.e. FCXM, C4d-FlowPRA and NIH-CDC).

Biography:

Dr. S.C.K. Tay earned his MPH in Veterinary Public health, Parasitology, Zoonoses, Epidemiology and Clinical Microbiology from the University of Minnesota, Minneapolis St. Paul, U.S.A and his MSc. Vet, Med., D.V.M from the Central University of Timisoara, Romania. He obtained his BSc. from the University of California Davis. Presently, he is a professor in the department of Clinical Microbiology School of Medical Sciences, KNUST. He joined the department in 1989 and served as the head of the department for three years. Committee member special Primary Interest Group for Veterinary Public Health of America Public Health Association for three years. He has published more than twenty (20) papers. He is currently the coordinator for KNUST QWeCI Project, Impact of Climate variability on Human and Animal Health, EU funded project

Abstract:

Lympatic filariasis(LF) is a parasitic disease of public health concern in Northern Ghana. Since mass drug administration of ivermectin and albendazole began in 2000 with Kassena-Nankana district as one of the implementing units, no studies has been conducted among pre-school and school-age children on the prevalence of W. bancrofti antigenaemia in spite of 3.5% prevalence reported among adults in 2008. This study was therefore carried out in four communities in the Kassena-Nankana district between December 2010 and May 2012 where mass drug administration has been administered and continued to be administered to investigate the prevalence of W.bancrofti antigenaemia among school children to aid advocacy for more comprehensive treatment coverage for children. The study was a cross sectional analytical survey, restricted to school children between the ages of 2-10 years. Four hundred(400) school children aged 2-10 years were randomly selected from a list of compounds in the communities. About 3-5 mls of blood was collected into heparinized test tube and tested during immunochromatographic test to detect W.bancrofti antigen(ICT-Filariasis card test). Of the 200 children tested before MDA, 25(12.5%) children tested positive for filarial antigen and of the 200 school children tested after MDA, 13(6.5%) children tested positive for circulating filarial W.bancrofti antigen. The microfilaria antigen prevalence among the communities after MDA ranged from 0% in Bui to 4.0% in Manyoro and 22% in Gumongo. This study has demonstrated that community variations in the prevalence of filarial antigen exist in Kassena-Nankana district. There is the need for regular surveillance thatwill inform treatment coverage and effectiveness.

Biography:

Abstract:

Abstract Background: Bacterial pathogens isolated from dacryocystitis patients are diverse and complex in terms of their distribution, prevalence, and antimicrobial susceptibility pattern. The clinical importance of microbial causes of dacryocystitis and pattern of drug resistance has not been reported in northwest Ethiopia. Moreover, the management of dacryocystitis is based on only clinical observation Therefore, this study attempted to identify and define clinical and microbiological characteristics of microbial agents of dacryocystitis and its antibiotic susceptibility patterns. Methods: A cross sectional study was conducted from January 2011-January 2012 among dacryocystitis patients attending ophthalmology outpatient department of Gondar University teaching Hospital. Socio demographic and clinical data collection, microbiological analysis and antibiotic susceptibility test patterns were done following standard procedures. Results: From the total of 51 dacryocystitis cases, bacterial origins were isolated among 31(60.8%) cases. The dominant isolates were Coagulase negative Staphylococci (CNS) 9(29.0%), Staphylococcus aureus (S. aureus) 6(19.4%), and Pseudomonas species 3(9.7%). S. pneumoniae, Entrobacter species, K. pnemoniae and H. influenzae were each accounted 6.5% isolation rate. Among the commonly prescribed antimicrobials tested for susceptibility pattern; amoxicillin 38.7%, ciprofloxacin 25.8%, chloramphinicol 25.8%, co-trimoxazole 25.8%, and ampicillin 19.4% were resistant to the overall bacterial isolates identified. Only Citrobacter species were sensitive to all antibiotics tested but the rest bacterial isolates were resistant for at least to one, two, three, four and more antibiotics tested. Overall, 9(29.0%) of the bacterial isolates were resistant to only one antibiotics and resistance to two, three and four antibiotics each accounted 5(16.1%) rate. Conclusions: Though the information derived from this study was very meaningful, further studies encompassing viral, fungal, parasitic and anaerobic bacterial origin are important to better define the spectrum and relative incidence of pathogens causing dacryocystitis. Microbiological analysis and antimicrobial susceptibility pattern is mandatory for the selection of a specific antimicrobial therapy and to the control of further resistance development of bacterial strains.

Biography:

Abstract:

Hermansky-Pudlak Syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in BLOC-3 mutant HPS-1 and HPS-4 patients. Chitinase 3-like-1 (CHI3L1), a prototypic chitinase-like protein, plays a protective role by ameliorating cell death and stimulating fibroproliferative repair. Here we demonstrate that circulating CHI3L1 levels are higher in HPS patients with pulmonary fibrosis compared to those that remain fibrosis-free, and that these levels associate with disease severity. Using murine models we also demonstrate that a defect in CHI3L1 inhibition of epithelial apoptosis and exaggerated CHI3L1-driven fibroproliferation play important roles in HPS fibrosis. Lastly we demonstrate that these divergent responses are mediated by differences in the trafficking and effector functions of two CHI3L1 receptors. Specifically, the enhanced sensitivity to apoptosis is due to the BLOC-3 dependent, and thus abnormal, trafficking of IL-13Ra2. In contrast, the fibrosis is due to interactions of CHI3L1 and CRTH2, which traffics normally in BLOC-3 HPS.

Biography:

ppointments 2007-present:Lecturer (Pharmacology), School of Biomedical and Biomolecular Science, UCD 2004-2007: Principal Investigator, SMMS, UCD 2003-2004: Research Manager/Research Fellow, RCSI, Dublin 2001-2003: Locum Lecturer, Clinical Pharmacology, RCSI, Dublin 1999-2003 Postdoctoral Research Fellow, RCSI, Dublin 1995-1999: Postgraduate student, Department of Clinical Pharmacology, RCSI, Dublin 1994-1995: Research Assistant, Cell and Molecular Biology Group, NUIG, Galway

Abstract:

Conjugated linoleic acid (CLA) has the unique property of inducing regression of pre-established murine atherosclerosis despite a continuing high cholesterol challenge. Our previous findings and those of others cumulatively point to the monocyte/macrophage as the cellular target through which CLA mediates its effect. Understanding the mechanism(s) involved may help identify pathways that limit human disease. In this study, we aimed to define and validate potential mechanisms through which CLA alters monocyte function and confers an atheroprotective phenotype. Transcriptomic analysis of aortic tissue during CLA-induced regression of atherosclerosis identified an enrichment of the IL-10 signalling pathway coincident with increased circulating IL-10 serum levels. Interestingly, we found significantly increased IL-10 production in bone marrow derived macrophages from CLA fed mice. Importantly, CLA supplementation regulated immune cell infiltration of the aorta with increased numbers of Ly6C lo monocytes evident. In addition, we identified increased numbers of Ly6Clo monocytes in the spleen of CLA fed mice and furthermore showed that bone-marrow progenitor cells differentiate to an M2 phenotype during regression of atherosclerosis. As chronic recruitment of monocytes and their subsequent migration through the activated endothelium contributes to atherosclerotic plaque development we next investigated the effect of CLA on monocyte adhesion in vitro and in vivo. We showed that CLA inhibits human peripheral blood monocyte cell (HPBMC) adhesion to activated endothelial cells via loss of CD18 expression, the β2 chain of LFA-1 and Mac-1 integrins. In addition, using a static adhesion assay, we identified that CLA prevents monocytes from binding to ICAM-1 and subsequently reduces the capacity of these cells to polarise. CXCL12-CXCR4 interactions induce a conformational change in β2 integrins, facilitating leukocyte adhesion. We found that CLA inhibits CXCR4 expression, resulting in a failure of monocytes to directionally migrate towards CXCL12. Finally, using intravital microscopy we showed that during CLA induced regression of pre-established atherosclerosis in apoE-/- mice there is reduced leukocyte adhesion and decreased CD18 expression on Gr1+/CD115+ pro-inflammatory monocytes. In summary, the data presented describe a novel immunoregulatory role for CLA in atherosclerosis regression specifically in the alteration of the circulating phenotype of monocytes and in the regulation of monocyte adhesion, polarisation and migration. Overview of Current Research Programmes: The current focus of my research group is the identification ofmechanisms governing the regression of atherosclerosis. My laboratory has established a novel model of atherosclerosis regression in vivo, achieved by administration of conjugated linoleic acid (CLA) in theapoE knockout mouse model of atherosclerosis.We have previously shown that dietary CLAinduces resolution of pre-established lesions in vivo. Importantly we have identified that the monocyte/macrophage is the cellular target through which CLA mediates this effect. Our recent research efforts have focused on the identification of distinct genes/pathways regulated by CLA that may yield further information as to how atherosclerosis can be reversed. To do this we employ an approach that involves confirmation of a phenotypic change in vivo by en face analysis and intravital microscopy. Using a transcriptomic and proteomic approach we then construct networks associated with the altered phenotype, followed by identification of central or “hub” genes which regulate the network. Using cellular models and functional assays we validate a functional role for these hub genes in vitro examining the effect of gene deletion or over expression on, monocyte-endothelial interactions, integrin regulation, adhesion, migration and foam cell formation. We then extend this study into human patients to seek evidence for regulation of the target genes in atherosclerotic disease progression. Through this approach we have identified novel pathways. Some have complimentarity with pathways associated with atherosclerosis susceptibility for example we have recently characterized and ascribed a functional role forSorLA in monocyte migration and have confirmed its regulation in human disease (McCarthy et al 2010). Furthermore, we identified the nuclear receptor co-activator PGC-1as a nexus gene in a network regulated by CLA. In collaboration with Christopher Glass and colleagues at UCSD, we have recently identified that macrophage specific deletion of PGC-1α increases atherosclerosis in vivo. Importantly, we showed that PGC1α is expressed in the plaques of patients where its expression is inversely related to disease progression, raising the possibility that this is a regulatory pathway in human atherosclerosis. Our other research goals arise from our findings that that CLA functions as an anti-inflammatory lipid mediator in vivo, by modifying its Ly6Clo infiltration of the aorta and M2 macrophage polarisation. We have shown that bone-marrow progenitor cells from CLA fed mice differentiate to an M2 phenotype suggesting that the cells derived from these sources may be pre-programmed towards an anti-inflammatory profile before entering established plaques. Thus, CLA may modulate the phenotype of macrophages in vascular lesions that in turn impacts on the progression of atherosclerosis (McCarthy et al., 2013).

Biography:

Eitan Rubin received PhD from The Weizmann Insitute of Science. Upon graduation, he worked in the bioinformatics company Compugen and managed the bioinformatics core facilities for the Wezimann Institute of Science and for Harvard University. He joined Ben-Gurion University in 2005, and have been exploring various avenues of computaional medicine since then. Starting in 2011, his lab is now compeltly focused on the computational investigation of cancer care. He has published more than 30 papers in reputed journals and edited one book.

Abstract:

The move toward precision cancer medicine challenges traditional approaches both in terms of cancer medicine and in terms of clincal trial designs. The WIN consortium was established to promote translational cancer research by facilitating the translation of innovative methodologies to cancer care via collaborative and create clinical trials. The consortium has launched the Winter trial, in which mutations profiling and expression profiling are used to prioritize therapeutic approaches in advanced cancer patients. We are also launching two additional trials, Spring and Summer, which gradually attempt to benefit earlier stages of specific cancers. In this presentation the 3 trials will be briefly described, both in terms of the unique trial designs and in terms of the prioritization principles. I will then show the results we have recently obtained that show that exploring the immune system in situ in the tumor is feasible, and that immune monitoring is useful for predicting treatment efficacy. Altogether we will present exampels of modern, personalized clinical trials and propose that adding immune-monitoring to such trials could strengthen our ability to utilize immunological breakthroughs at the bedside.

Biography:

Faten Ismail Mohammed has studied rhematology and autoimmune diseases for more than 25 years, during which he has authored many international papers. He has served as the head of rheumatology and rehabilitation department at El Minia University hospitals and a reviewer for many international journals as clinical rheumatology. He is a member of the scientific advisory committees for Upper Egypt, Rheumatology and Immunology Society.

Abstract:

Introduction:
Primary Sjögren's syndrome (pSS) is associated with increased risk of lympho proliferative malignancy, B- cell Non Hodgkin lymphoma (B-NHL) is the most frequent type.

Objective:
To evaluate CD4+ T lymphocytes distributions in patients with (pSS) and the association of CD4+T lymphocytopenia with the development of (B-NHL).

Patients & Methods:
This study included 8 (pSS) patients associated with B-NHL (group l), 50 (pSS) patients without B-NHL (group ll), and 30 Healthy volunteers served as controls. The frequency of circulating CD4+and CD8+ T lymphocytes distributions and CD4+/CD8+T cell ratio was assessed using Flowcytometry Coulter EPICS-XL and compared between patients groups and controls.

Results:
There was statistically significant CD4+ T lymphocytopenia in (pSS) patients with B-NHL than those without lymphoma and controls (p0.001), moreover, a significant low CD4+/CD8+T cell ratio 0.8 in group1 than group II and controls (p0.001) was found. Significant positive correlations of CD4+T lymphocytopenia with other risk factors (parotid swelling, vasculitis, rheumatoid factors, low complement, cryoglobulinemia were detected.

Conclusion:
CD4+T lymphocytopenia is associated with B-NHL developed in patients with pSS and can be considered as an important predictor of lymphoma

Biography:

H Al-Khalaifa holds a PhD in immuno-nutrition from the University of Reading- United Kingdom and MSc in medical immunology from the University of Manchester. She has been working in Kuwait Institute for Scientific Research since 1996. She participated in many research projects and activities. She gained skills and experience in immunological techniques, immunonutrition approaches, biodiversity monitoring and assessment techniques, poultry production research, production of added-value products, analysis techniques including gas chromatography, proximate analysis, flow cytometry, etc. She published more than 20 scientific papers in refereed journals and conferences.

Abstract:

The main immune organs in poultry are the thymus, spleen and bursa of Fabricius. During an immune response, mature lymphocytes and other immune cells interact with antigens in these tissues. Consequently, the mass of these organs can in some cases indicate immune status. It was observed that feeding laying chickens on diets rich in PUFA, especially n-3 PUFA, promoted the growth of the thymus, spleen and bursa up to 4 weeks of age. From the age of 4 weeks onwards, the immune tissue weight started to be suppressed and the bursa was degenerated in the course of 4 to 8 weeks of age. The objective of the current study is to investigate the effect of feeding flaxseed on immune tissue weights. Cobb 500 broiler chickens were fed flaxseed at 15%, the control diet did not contain any flaxseed. Values are presented as a percentage of body weight to account for differences in weights between different birds. Results showed that dietary supplementation with flaxseed did not affect the weights of the spleens of broiler chickens. However, it significantly lowered bursa weights (p<0.01), compared to the control diet. In addition, the bursae were thinner in appearance compared with bursii from chickens fed the control diets. In conclusion, dietary supplementation with flaxseed did not affect the growth of the spleen of the chickens. Conversely, it was reported in some studies that feeding PUFA to chickens and mice results in increased spleen weights. However, chickens fed a diet containing flaxseed had smaller and thinner bursii than chickens fed the control diets (P=0.001). This modulation in the weight of immune organs may indicate immunomodulation effect of fatty acids in flaxseed. More investigation studies need to be applied to shed light on the mechanism behind this immunomodulation.

Biography:

Kim Do Won is Assistant Professor - Hallym University, South Korea

Abstract:

Cholesterol is one of the important components for necessary to maintain the body. It is related to function as a component of cell membranes and it is also an important raw material of sex hormone and cortical hormone. For function of cholesterol, it needs movement through blood. Because cholesterol does not dissolve in water, it moves through lipoprotein in blood. The lipoproteins can be divided into LDL (Low Density Lipoprotein) and HDL (High Density Lipoprotein) depending on the density. When LDL-cholesterol is present in high amount in blood, wall of blood vessels will be covered with lipid component. Therefore, it is important to measure value of LDL-cholesterol and diagnose diseases such as Cardiovascular Disease (CVD), obesity, diabetes, atherosclerosis, hypertension and stroke. In this paper, it shows that measuring the LDL-cholesterol in blood through an immunological method. The paper suggests double bio marker, using two types of immunological measuring methods. One is streptolysin O (SLO) recombinant protein that it can specifically combine with cholesterol because carboxyl-terminal of SLO has tryptophan-rich. The other is a monoclonal antibody about Apolipoproetin B-100 existing in surface of LDL particle. The experimental results show that measuring LDL-cholesterol is dependent concentration and LDL- cholesterol of 2㎍/ml recognize the value of O.D. 630nm <0.77. Also, the method recognized concentration of cholesterol until 125 to 250ng/ml. For those reasons, this method can consider measuring LDL- cholesterol in serum.

Biography:

Abstract:

The net outcome of the battle between the anti-tumor and the tumor promoting immune cells and their associated cytokines within the tumor environment will determine the ultimate fate of the affected tumors. Th17 cells and their effector cytokines have emerged as important mediators in inflammatory and autoimmune diseases and serve as an ambitious field in current immunology research. Recent studies suggest a potential impact of Th17 cells on solid tumors but relatively little is known about their contribution in hematological malignancies. The current study was designed to investigate the possible involvement and clinical significance of circulating Th17 cells in acute leukemia patients. Compared with healthy controls, acute leukemia patients had a higher proportion of circulating Th17 cells accompanied with increased serum concentrations of IL-17 and IL-21. Circulating Th17 cells were reduced in patients achieved complete remission (CR) after chemotherapy, suggesting that circulating Th17 cells can be used to evaluate therapeutic efficacy in acute leukemia patients. Notably, the increased prevalence of initial Th17 cells was significantly associated with probability of achieving CR as well as with longer overall survival of acute leukemia patients. These results strongly suggest that Th17 cells may be a powerful new prognostic determinant which could serve as a potential therapeutic target to modulate anti-tumor response in acute leukemia patients. Mechanisms by which Th17 cells influence acute leukemia, and whether these mechanisms mediate direct or indirect effects need to be determined.

Biography:

Shimelis Dagnachew is Asst.Professor of Addis Ababa University, Ethiopia

Abstract:

Immune reactions do not always lead to protection in trypanosomoses, though they appear to be involved in immunopathological processes. Therefore, the objective of this experimental study was to determine cytokine responses upon infection with tsetse-adapted and mechanically transmitted Trypanosoma vivax in cattle of Northwest Ethiopia. Eighteen trypanosome-naïve Bos indicus cattle were assigned randomly into three groups of six (group TT= infected with a T. vivax isolate from tsetse infested area, group NT = infected with a T. vivax isolate from non-tsetse infested area and group C=non-infected control). Each infected animal received approximately 3x106 trypanosomes intravenously. Blood samples were collected in a week interval for parasitological examination, packed cell volume (PCV) determination and cytokine assay. The experimental infection caused an acute disease with detectable parasitaemia from 5 and 12 days and peak parasitaemia 8 and 14 days post infection for NT and TT infected cattle, respectively. There were significant reduction (P<0.05) after the infection in mean PCV value with 21.861.56% (TT), 22.760.90% (NT) and 30.670.64 (control). Significant increases were observed for all cytokines (P<0.05) in both the infected groups and no significant differences (P>0.05) between TT and NT groups. Interferon gamma, tumor necrosis factor alpha and interleukin-12 increased quickly at the first peak parasitaemia and persists with a steady pattern whereas an increase of interleukin-10 appeared only at the second peak parasitaemia. In conclusion, the magnitude and secretion patterns of cytokines responses were similar in TT and NT infected groups of cattle, although the responses occurred one week earlier in the later group.

Biography:

Haleh Talaie has completed her MD at the age of 28 years from Shahid Beheshti University of Medical Sciences and Research fellow, Division of Clinical Pharmacology & Toxicology, University of Toronto, Canada (2004). she is the director of Iranian Healing Oriented Integrative Medicine Institute.she has published more than 30 papers in reputed journals. Spring/Autumn 2014 : Accepted as postdoctoral integrative medicine fellowship in Arizona Center for Integrative Medicine University of Arizona ,USA(financial support not yet approved) March 2011- up to present: Integrative Medicine self education in Toxicological Research Center (TRC) and in Taleghani General Hospital,SBMU. April 2009 – Feb 2011: Integrative Medicine Courses in Clinical Excellence Center of SBMU. Oct. 2005- Nov 2005: Participation in Toxicology Rounds of Toronto, Canada poison center and Clinical pharmacology and toxicology of HSC of university of Toronto. Oct. 2003- May 2004: Research fellow, Division of Clinical Pharmacology & Toxicology by supervision of Dr Gideon Koren, M.D., A.B.M.T., F.R.C.P.C The Hospital for Sick Children, University of Toronto, Canada March 1997- 2003: Trainer & coordinator of Medical Education, Shahid Beheshti University (formerly Melli University) Medical Sciences & Health Services (SBUM), Tehran, Iran 1994 -1997: Board of Infectious Diseases specialty (SBUM) 1995-1997: Master in Public Health, Tehran University of Medical Sciences, Tehran, Iran 1987-1994: Training in Emergency ward & Outpatient clinic, Gillan Medical university,Iran 1978-1987: Shahid Beheshti University of Medical Sciences, (SBUM), Tehran, Iran

Abstract:

Background
Acinetobacter baumannii is an important opportunistic pathogen which causes complications in hospitalized patients, especially those in ICU. The aim of this study was to determine the frequency of class 1 and 2 integrons in multi-drug resistance A. baumannii and to investigate the association between the presence of integrons and antibiotic resistance patterns.

Methods:
A total of 40 A. baumannii strains were isolated from 372 ICU patients from June to Oct 2012. A. baumannii was detected in 50% of tracheal cultures, 15% in blood, 15% in urine samples, and 22.5% in other locations. In accordance with CLSI 2011, 12 antibiotics were used through disc diffusion method. Existence of integron classes was investigated by PCR assay with the amplification of integrase genes.

Results:
The most effective antibiotic against Acinetobacter baumannii was polymyxin B with 100% susceptibility, followed by meropenem, piperacillin, cotrimoxazole, ceftazidime with 100% resistance; this was followed by ciprofloxacin 97.5%, tetracycline, 92.5%, imipenem 62.5%, and gentamicin 60% resistance. The presence of integron class 1 was 7.5%, class 2 was 67.5%, and non-integron was 20%.

Conclusion:
The association between multidrug resistance and class 2 integron was not statistically significant. Other factors accounting for the lack of significance of the findings may be the impact of other resistance determinants such as transposons or plasmids, not investigated in the current study. Considering the increasing trend of MDR infections among ICU patients with critical problems in follow up, the use of appropriate infection control strategy and a regular surveillance system is necessary in our hospital.

Keywords:
Acinetobacter Baumannii, Class 1 Integron, Class 2 Integron, Multidrug Resistance, and PCR Assay.

Biography:

Mahsa Sedighi completed her MD degree at the of 32 years from Shiraz Medical School. She was among the founders of Shiraz Medical College Research Club. She has been invited as Editorial Board Member and Reviewer from international journals. She is currently an independent researcher.

Abstract:

Background: Vitamin D receptors have been identified in the spinal cord, nerve roots, dorsal root ganglia and glial cells, and its genetic polymorphism association with the development of lumbar disc degeneration and herniation has been documented. Metabolic effects of active vitamin D metabolites in the nucleus pulposus and annulus fibrosus cells have been studied. Lumbar disc herniation is a process that involves immune and inflammatory cells and processes that are targets for immune regulatory actions of vitamin D as a neurosteroid hormone. In additionto vitamin D’s immune modulatory properties, its receptors have been identified in skeletal muscles. It also affects sensory neurons to modulate pain. Aim: In this study, we aim to study the role of vitamin D3 in discogenic pain andrelated sensory deficits. Additionally, we will address how post-treatment 25-hydroxy vitamin D3 level influences pain and sensory deficits severity. The cut-off value for serum 25-hydroxy vitamin D3 that would be efficacious in improving pain and sensory deficits in lumbar disc herniation will also be studied. Methods/Design: We will conduct a randomized, placebo-controlled, double-blind clinical trial. Our study population will include 380 cases with one-level and unilateral lumbar disc herniation with duration of discogenic pain less than 8 weeks. Individuals who do not have any contraindications, will be divided into three groups based on serum 25-hydroxy vitamin D3 level, and each group will be randomized to receive either a single-dose 300,000-IU intramuscular injection of vitamin D3 or placebo. All patients will be under conservative treatment. Pre-treatment and post-treatment assessments will be performed with the McGill Pain Questionnaire and a visual analogue scale. For the 15-day duration of this study, questionnaires will be filled out during telephone interviews every 3 days (a total of five times). The initial and final interviews will be scheduled at our clinic. After 15 days, serum 25-hydroxy vitamin D3 levels will be measured for those who have received vitamin D3 (190 individuals).

Biography:

Shailasree S is Asst Professor University of Mysore, India

Abstract:

Systematic screening of chemical libraries for small molecules revealed limited studies involving promising small molecules (lacking details on studies inferring drug-target interactions) with a capacity to kill cancer cells in-vitro. In the present study, myricetin was evaluated for its capacity to induce cytotoxic effect to neuroblastoma N2a cell and have listed the multi-target paradigm leading to its growth inhibition, apoptosis/autophagy. Toxic pathway, especially the upstream network of responses happening in toxicant-treated cancer cells prior to their programmed cell death is reported to provide an unbiased approach in unraveling changes deciding on the final fate of the cell. Studies preceding cell death by probe sets strongly pointed to changes in cluster related to genes with a role in chromosomal stability, eg., heterogeneous nuclear ribonucleoprotein (HNRNPM), that was down regulated. Those involved in adaptive carbon metabolism eg., argininosuccinate synthase (ASS1) were upregulated identified as intermediate response upon exposure to toxicant. Consumption of phosphocreatine and a parallel accumulation of creatine indicated exhaustion of cellular energy buffer. The prominent role of GSH to counter increasing cell stress as early adaptation before breakdown of cellular homeostatis was observed. Direct data substantiating cell death by apoptosis with p38 MAP kinase mediated p53 activated upregulation of caspase 3 is reported and will be discussed. Our data report on autophagy, representing an additional mechanism inducing cell death detected by accumulation of LC3-II protein and acridine-orange stained autophagosomes is included.