Karim Essani

Bio: Karim Essani is an academic researcher from Western Michigan University. The author has contributed to research in topics: Oncolytic virus & Virus. The author has an hindex of 15, co-authored 51 publications receiving 1129 citations. Previous affiliations of Karim Essani include University of Western Ontario & St. Jude Children's Research Hospital.

Multiple organ-reactive monoclonal autoantibodies

Abstract: Autoantibodies directed against a wide range of normal tissue antigens have been found in the sera of patients with autoimmune diseases1–8. It is generally thought that different and specific autoantibodies react with different tissues but the possibility exists that some autoantibodies may react with common antigens found in different tissues and organs. Recently, we showed that mice infected with reovirus developed a polyendocrine disease with autoantibodies to the pancreas, anterior pituitary, thymus and gastric mucosa9,10. Using hybridoma technology, we obtained a number of monoclonal autoantibodies11 which reacted with antigens in single organs. We now report the production and pattern of reactivity of seven multiple organ-reactive monoclonal autoantibodies. By using antibody-affinity columns, autoantigens also have been isloated and their molecular weights determined. The results suggest that monoclonal multiple organ-reactive autoantibodies react either with the same molecule present in several organs or with common antigenic determinants on different molecules in multiple organs. In either case, the existence of multiple organ-reactive antibodies may be a partial explanation for multiple organ autoimmunity.

Methotrexate-resistant Chinese hamster ovary cells contain a dihydrofolate reductase with an altered affinity for methotrexate

Abstract: Previous reports [Flintoff, W. F., Davidson, S. V., & Siminovitch, L. (1976) Somatic Cell Genet. 2, 245--261; Gupta, R. S., Flintoff, W. F., & Siminovitch, L. (1977) Can. J. Biochem. 55, 445--452] described a series of Chinese hamster ovary cells that were resistant to the cytotoxic action of methotrexate and contained a dihydrofolate reductase that was less sensitive to inhibition by the drug than wild-type enzyme. In this study, binding of labeled methotrexate to the reductase--NADPH complex and separation of free and bound drug by filtration through Sephadex G--25 have been used to demonstrate that clonal isolates of these resistant cells contain a dihydrofolate reductase varying between 2.5- and 6-fold lower in affinity for the drug than the wild-type enzyme. The apparent dissociation constant for the wild-type enzyme is 0.5 x 10(-9) M. Using two-dimensional polyacrylamide gel electrophoresis, 11 independently selected resistant isolates have been shown to contain a reductase with a similar overall net charge as the wild-type enzyme. Reductase purified from either wild-type or resistant cells contains two components after isoelectric focusing in polyacrylamide gels. The major component represents about 90% of the total protein and has a pI of about 8.0. The minor component representing about 10% of the reductase protein has a pI between 7.2 and 7.6.

Murine models of systemic lupus erythematosus.

Abstract: Publisher Summary This chapter reviews the histopathologic, serologic, lymphocytic, virological, hormonal, and genetic characteristics of murine models of systemic lupus erythematosus (SLE). The pathogenetic mechanisms underlying murine SLE are highly complex, apparently well-programmed genetically, but still diverse and their bases not as yet well defined. Significant serologic and cellular experimental data support the statement that the final immunopathologic perturbation in murine (and human) SLE is a B lymphocyte hyperactivity with corresponding enhancement of serum antibodies and autoantibodies, particularly IgG, and consequent formation of pathogenic antigen–antibody ICs. On the basis of the available data, it appears that this B cell hyperactivity is polyclonal but not necessarily panclonal in nature, because not only antibodies against a wide array of autoantigens but also antibodies against incidental antigens, such as haptens, can be detected. The presence of autoantibodies and of their idiotypes in some recombinant lupus x normal murine lines expressing the normal partner's V genes, normal mice in which an exogenous or endogenous (Ipr gene) immunostimulator has been introduced, and unmanipulated normal mice indicate that lupus mice are not unique in their structural genetic Ig elements, whose presence determines the development of their autoimmune disease. The cause of B cell hyperactivity in lupus has not yet been fully elucidated. Autonomous B cell maturation does not appear likely, because B cell proliferation and differentiation in lupus mice was found to be dependent on the same number of accessory signals as in normal mice.

Viral Subversion of the Immune System

Abstract: This review describes the diverse array of pathways and molecular targets that are used by viruses to elude immune detection and destruction. These include targeting of pathways for major histocompatibility complex-restricted antigen presentation, apoptosis, cytokine-mediated signaling, and humoral immune responses. The continuous interactions between host and pathogens during their coevolution have shaped the immune system, but also the counter measures used by pathogens. Further study of their interactions should improve our ability to manipulate and exploit the various pathogens.

The pharmacology and clinical use of methotrexate

Abstract: METHOTREXATE, the most widely used antimetabolite in cancer chemotherapy, has an essential role in the treatment of such diverse diseases as acute lymphocytic leukemia, non-Hodgkin's lymphoma, oste...

Poxviruses and Immune Evasion

Abstract: Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleukins, complement, and chemokines. Poxviruses also manipulate a variety of intracellular signal transduction pathways such as the apoptotic response. Many of the poxvirus genes that disrupt these pathways have been hijacked directly from the host immune system, while others have demonstrated no clear resemblance to any known host genes. Nonetheless, the immunological targets and the diversity of strategies used by poxviruses to disrupt these host pathways have provided important insights into diverse aspects of immunology, virology, and inflammation. Furthermore, because of their anti-inflammatory nature, many of these poxvirus proteins hold promise as potential therapeutic agents for acute or chronic inflammatory conditions.

Viral mimicry of cytokines, chemokines and their receptors

Abstract: Viruses have evolved elegant mechanisms to evade detection and destruction by the host immune system. One of the evasion strategies that have been adopted by large DNA viruses is to encode homologues of cytokines, chemokines and their receptors — molecules that have a crucial role in control of the immune response. Viruses have captured host genes or evolved genes to target specific immune pathways, and so viral genomes can be regarded as repositories of important information about immune processes, offering us a viral view of the host immune system. The study of viral immunomodulatory proteins might help us to uncover new human genes that control immunity, and their characterization will increase our understanding of not only viral pathogenesis, but also normal immune mechanisms. Moreover, viral proteins indicate strategies of immune modulation that might have therapeutic potential.