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Role Of Nitric Oxide In Interleukin-2 Therapy-Induced Capillary Leak Syndrome, Amila Orucevic Jan 1996

Role Of Nitric Oxide In Interleukin-2 Therapy-Induced Capillary Leak Syndrome, Amila Orucevic

Digitized Theses

Systemic interleukin-2 (IL-2) therapy has been limited by a major side effect known as "capillary leak syndrome", characterized by retention of extravascular fluid, severe hypotension, and multiple organ system dysfunction. The present study tested the hypothesis that an overproduction of nitric oxide (NO) induced by IL-2 therapy was, at least in part, responsible for this syndrome. Studies were undertaken in healthy or C3-L5 mammary adenocarcinoma bearing C3H/HeJ mice to evaluate whether treatment with inhibitors of NO synthesis (N{dollar}\rm\sp{lcub}G{rcub}{dollar}-Methyl-L-Arginine, NMMA and N{dollar}\rm\sp{lcub}G{rcub}{dollar}-Nitro-L-Arginine methyl ester, L-NAME) can prevent IL-2 induced capillary leakage without compromising the therapeutic benefit of IL-2. Intraperitoneal IL-2 therapy …


Structural Basis For Human Anti-Dna Antibody Specificity, Mahmoud Mahmoudi Jan 1995

Structural Basis For Human Anti-Dna Antibody Specificity, Mahmoud Mahmoudi

Digitized Theses

Anti-DNA antibodies are hallmarks of SLE both in human and inbred lupus prone mice. The role of these antibodies in disease pathogenesis, particularly in glomerulonephritis has been documented. It is now well accepted that the genetic potential to generate anti-DNA antibodies also exists in the normal B cell immune repertoire. This genetic potential has been revealed by detection of anti-DNA antibodies in serum of normal individuals and by immortalizing DNA reactive B cells as hybridomas and as transformed cell lines. There is growing evidence that anti-DNA antibodies from the normal B cell repertoire and disease-associated anti-DNA antibodies share V region …


Modulation Of Experimental Allergic Encephalomyelitis In The Sjl/J Mice By Cytokines And Anti-Cytokine Antibodies, Trang Thi Duong Jan 1995

Modulation Of Experimental Allergic Encephalomyelitis In The Sjl/J Mice By Cytokines And Anti-Cytokine Antibodies, Trang Thi Duong

Digitized Theses

Immunization with myelin basic protein in complete Freund's adjuvant resulted in only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence in SJL/J mice, and no disease at all in A/J, BALB/c, C3H/HeJ, DBA/2, AKR and NZW mice. However, treatment of mice with anti-IFN{dollar}\gamma{dollar} (aIFN) monoclonal antibody (mAb) at the time of immunization determined severe disease in all those strains except AKR. Similarly, the passive induction of EAE in the SJL/J mice and in two of three resistant strains examined was significantly enhanced by aIFN mAb administration. In the SJL/J mice, administration of anti-interleukin 2 (aIL2) mAb had only …


Regulation Of Antibody Production And Its Dysregulation In Autoimmunity, Colin Charles Anderson Jan 1994

Regulation Of Antibody Production And Its Dysregulation In Autoimmunity, Colin Charles Anderson

Digitized Theses

B cells can be stimulated to produce antibody by antigens or by polyclonal activators such as bacterial lipopolysaccharide (LPS). Mechanisms of regulation of LPS driven antibody responses are often interpreted in terms of antigen driven responses even though there is much evidence to suggest that LPS and antigen trigger distinct activation pathways. LPS stimulated antibody responses can be prevented by ligation of the B cell antigen receptor (BCR), while antigen driven responses are shut down by the crosslinking of the BCR to the receptor for the Fc portion of IgG (Fc{dollar}\gamma{dollar}R). The present studies on murine splenic B cells in …


The Molecular Characterization Of Human Monoclonal Antiplatelet Autoantibodies, Gregory Andrew Denomme Jan 1993

The Molecular Characterization Of Human Monoclonal Antiplatelet Autoantibodies, Gregory Andrew Denomme

Digitized Theses

Autoimmune thrombocytopenia occurs in a number of clinical settings including idiopathic or autoimmune thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), and the lupus anticoagulant (LAC) syndrome. The etiology of the disease, the scope of the autoantigens targeted, and the epitopes involved in autoimmune thrombocytopenia are largely unknown. ITP has the hallmark of the presence of 'pathogenic' autoantibodies targeting platelet glycoproteins (GP) IIb/IIIa and GP Ib/IX. Associated with the thrombocytopenia in the LAC syndrome is the presence of anti-phospholipid antibodies (approximately 95% of cases). The detection of autoantibodies to a variety of self antigens in non-autoimmune individuals prompted this study to …


Suppression Of Eae In The Lewis Rat By Treatment With Neuroantigen-Containing Liposomes, Colleen Sheila Stein Jan 1993

Suppression Of Eae In The Lewis Rat By Treatment With Neuroantigen-Containing Liposomes, Colleen Sheila Stein

Digitized Theses

Treatment of Lewis rats with intracardiac injections of neuroantigen-containing liposomes significantly reduced the clinical severity of spinal cord-induced experimental allergic/autoimmune encephalomyelitis (EAE). Liposomes containing myelin basic protein (MBP), galactocerebroside (GC), or MBP + GC were effective in this respect, while liposomes containing proteolipid protein were not. The best protection was afforded by liposomes composed of whole myelin, as these ameliorated both the acute and relapsing phases of the disease, with a concomitant reduction in CNS pathology.;Neuroantigen-specific proliferative responses of lymphnode cells (LNC) taken from liposome-treated rats were markedly attenuated in comparison to control LNC, while delayed type hypersensitivity (DTH) reactions …


Characterization Of A Schistosoma Mansoni C(3) Receptor As A Potential Vaccine Candidate, Erika Eliana Silva Jan 1993

Characterization Of A Schistosoma Mansoni C(3) Receptor As A Potential Vaccine Candidate, Erika Eliana Silva

Digitized Theses

Schistosomiasis, a chronic and debilitating parasitic disease, infects an estimated 200 million people and causes 750,000 deaths a year. Therefore, the development of an effective vaccine is of high priority for the control of this disease.;The surface of the syncytial epithelium of Schistosoma mansoni consists of an apical plasma membrane and an overlying envelope. The rapid turnover of these membranes in response to the host's attack is considered to be one of the mechanisms by which this parasite escapes the effects of the host's immune system. Our approach has been to identify surface components which play a pivotal role in …


A Genetic Analysis Of Folate Transport In Chinese Hamster Ovary Cells, T Michael Underhill Jan 1991

A Genetic Analysis Of Folate Transport In Chinese Hamster Ovary Cells, T Michael Underhill

Digitized Theses

Chinese Hamster Ovary cells that are about 50x more resistant to the cytotoxic action of methotrexate than wild-type cells were deficient in the ability to take up methotrexate. In the absence of any exogeneous folates these cells require 100-250x the level of folinic acid as do wild-type cells to support growth at a similar level. Two classes of mutants were distinguishable by their revertability for growth on folinic acid and ability to take-up folic acid. Revertants derived from one class were similar to wild-type cells in their ability to grow in medium containing low levels of folinic acid and in …


The Cytoskeleton In The Syncytial Epithelium Of Adult Schistosoma Mansoni, You Zhou Jan 1991

The Cytoskeleton In The Syncytial Epithelium Of Adult Schistosoma Mansoni, You Zhou

Digitized Theses

The surface layer of Schistosoma mansoni is an anucleated syncytium, covered by an apical plasma membrane (APM) and an overlying envelope (En), and is connected with the subsyncytial cell bodies via the membrane-bound cytoplasmic connections (MCC). This syncytium is considered as an adaptation for rapid and synchronous renewal of the surface membranes which play an important role in evasion of the host's immune system.;The present studies demonstrated the effects of the third complement component (C{dollar}\sb3{dollar}) and serotonin (5HT) on the synthesis of the discoid bodies (DBs) and multilamellar bodies (MLBs), and major syncytial inclusion bodies in vitro. With short-time incubations …


Structure/Function Studies Of Trypanosome Variant Surface Glycoproteins, Vern Bruce Carruthers Jan 1991

Structure/Function Studies Of Trypanosome Variant Surface Glycoproteins, Vern Bruce Carruthers

Digitized Theses

Antigenic variation is manifested by many prominent infectious organisms in adaptive response to host immunity. However, polymorphism in antigenic structure is often limited by the necessity to maintain functionality of the antigen. It follows that it may be possible to design molecularly defined vaccines capable of accounting for variable antigenic phenotype. For this reason, the focus of the present thesis was to develop a model system using trypanosome variant surface glycoprotein (VSG) for examining the effects of amino acid sequence variation on the specificity of antigenic determinants.;In order to assess the suitability for a model system of four VSGs (isoVAT …


Natural Lta Tumor Cell Resistance To Malignant Conversion By Oncogenesras Andmyc, Alan Bradley Tuck Jan 1991

Natural Lta Tumor Cell Resistance To Malignant Conversion By Oncogenesras Andmyc, Alan Bradley Tuck

Digitized Theses

A tumorigenic, non-metastatic murine fibroblast cell line (LTA) was here used to study aspects of natural cellular resistance to induction of progression to malignancy. The nature of LTA cell growth was established by testing both in vitro and in vivo. In vitro growth showed some but not all characteristic features of transformation (eg. cells showed little contact inhibition of cell growth and were able to multilayer, but were not serum independent). In vivo tumor growth was that of a benign (non-metastatic) fibrosarcoma. Attempts were made to induce LTA cell progression to malignancy by both epigenetic and genetic means. Treatment of …


Immunoregulatory Cells And Mediators In Murine Bone Marrow, Douglas Chauncey Saffran Jan 1990

Immunoregulatory Cells And Mediators In Murine Bone Marrow, Douglas Chauncey Saffran

Digitized Theses

This thesis defines distinct immunoregulatory mechanisms which naturally exist in murine bone marrow (BM). Physical separation of BM cells revealed two immunoregulatory cell populations: a suppressor activity present in a fraction of large, low density BM cells predominantly of myeloid and blast cell morphology; and an enhancing activity contained in a fraction of small, high density BM cells enriched for lymphocytes. Both activities are associated with the production of soluble mediators which possess analogous function to the immunoregulatory cells.;The population of cells responsible for immune suppression have been referred to as Natural Suppressor (NS) cells. NS cells are unique in …


Prediction Of The Nerve Conduction Abnormalities Frequently Associated With Carpal Tunnel Syndrome From Clinical Features, M Gail Woodbury Jan 1990

Prediction Of The Nerve Conduction Abnormalities Frequently Associated With Carpal Tunnel Syndrome From Clinical Features, M Gail Woodbury

Digitized Theses

This study was undertaken to develop a clinically useful model for predicting electrophysiological abnormality in the nerve conduction tests used in the diagnosis of carpal tunnel syndrome (CTS). The prediction model combined commonly recorded clinical history, signs, and symptoms in a multivariate analysis. Electrophysiological abnormality and adjustments for the influencing variables (sex, distance, and temperature) were based on normative nerve conduction values obtained in a control group (n = 104). This was the first study in this topic area in which prediction bands were used to adjust the criteria for assigning abnormality to account for influencing variables. The variables used …


Regulation Of Immune Responses To Self And Nonself, Angela Panoskaltsis Jan 1990

Regulation Of Immune Responses To Self And Nonself, Angela Panoskaltsis

Digitized Theses

B cells are regulated early upon exposure to antigen by negative Fc signals generated by the crosslinking of antigen receptors with Fc receptors which is mediated by antigen-IgG-antibody complexes. This negative end-product feedback can be overcome by T helper cells, but in their absence, agents which bind to the Fc portion of IgG can replace the need for T cell help. Rheumatoid factor (RF) is a naturally occurring antibody with specificity for IgG-Fc and was investigated for its ability to block negative Fc signals. Monoclonal murine RF was shown to reconstitute, in an antigen-specific and dose-dependent fashion, both the primary …


Individual Differences In The Appraisal Of Stress And The Immunologic Consequences: Psychological Moderation Of Lymphocyte Activation And Cytokine Production, James Patrick Dobbin Jan 1990

Individual Differences In The Appraisal Of Stress And The Immunologic Consequences: Psychological Moderation Of Lymphocyte Activation And Cytokine Production, James Patrick Dobbin

Digitized Theses

A number of studies have adduced evidence suggesting that stressful events affect immunity in humans. The present research was designed to extend this earlier work by assessing cytokine production and blast transformation in mononuclear cells obtained from medical students writing an academic examination. Additionally, the hypothesis that personality characteristics can moderate the relationship between stress and immune functioning was investigated.;A number of response measures were assessed at each of 3 sample times: baseline (time 1); one month later, immediately after subjects had written an examination (time 2); and again 15 days later (time 3). The response measures included mood (subjective …


The T Cell-Mediated Response To A Syngeneic Tumour: Precytotoxic T Lymphocyte Frequency Measured By Limiting Dilution Assay, Robert Llewellyn Howell Jan 1990

The T Cell-Mediated Response To A Syngeneic Tumour: Precytotoxic T Lymphocyte Frequency Measured By Limiting Dilution Assay, Robert Llewellyn Howell

Digitized Theses

The T cell-mediated response to a syngeneic tumour has been studied using the DBA{dollar}\\{dollar} 2-P815X mouse tumour model. If one hopes to intervene to change (improve) the immune response of a cancer patient to their tumour, it is necessary to understand the role(s) of the cells involved in that response.;The potential magnitude of a cytotoxic T lymphocyte (CTL) response depends, in part, upon the precursor or pCTL frequency. A limiting dilution assay (LDA) has been developed and used to measure the frequency of pCTL's in the animal both prior to tumour implantation and during the growth of the tumour. As …


Antigen-Specific Ige Suppression Induced By Immunization With Dinitrophenyl-Bordetella Pertussis Is Mediated Through Interferon-Gamma, Michael Hagen Jan 1989

Antigen-Specific Ige Suppression Induced By Immunization With Dinitrophenyl-Bordetella Pertussis Is Mediated Through Interferon-Gamma, Michael Hagen

Digitized Theses

Immunization of mice with dinitrophenyl-Bordetella pertussis (DNP-BP) failed to induce anti-DNP IgE responses. Administration of DNP-BP induced however, the formation of anti-DNP IgE B memory cells, as demonstrated by adoptive transfer. Furthermore, mice pretreated with DNP-BP and primed with 2 {dollar}\mu{dollar}g DNP-OA in alum 2 weeks later produced high day 7 anti-DNP IgE levels. These subsided to near undetectable levels by day 12-14. The transient expression of serum IgE levels was accompanied by normal levels of anti-DNP IgG. The anti-OA response induced as a result of priming with DNP-OA in alum was not affected by pretreatment with DNP-BP. IgG subclass …


Characterization Of Immunoregulatory Cells And Factors Derived From Normal Human Bone Marrow, Franco Mortari Jan 1989

Characterization Of Immunoregulatory Cells And Factors Derived From Normal Human Bone Marrow, Franco Mortari

Digitized Theses

The bone marrow is a primary lymphoid organ whose main function is to provide a continuous source of hematopoietic cells to the peripheral immune system. This study was undertaken to elucidate the roles of bone marrow cells and their mediators in immunoregulation.;Fractionation of bone marrow cells resolved two distinct immunoregulatory activities. A population of bone marrow cells of the phenotype HNK-1{dollar}\sp{lcub}+{rcub}{dollar} (human natural killer cell antigen, CD57), SSEA-1{dollar}\sp{lcub}+{rcub}{dollar} (stage specific embryonic antigen) and OKM1{dollar}\sp{lcub}+{rcub}{dollar} (human monocyte antigen, CD11B) was found to be highly suppressive for primary antibody responses. Conversely, a lymphocyte enriched bone marrow cells fraction could enhance the same …


Characterization Of Anti-Dna Autoantibody Responses From Lymphoid Cells Of Normal Human Origin, Ewa Cairns Jan 1987

Characterization Of Anti-Dna Autoantibody Responses From Lymphoid Cells Of Normal Human Origin, Ewa Cairns

Digitized Theses

Spontaneous and pokeweed mitogen (PWM) induced anti-nucleic acid antibodies were assayed in cultures of tonsillar and peripheral blood lymphocytes (PBLs) of healthy donors as well as in PBLs from systemic lupus erythematosus (SLE) patients. IgM antibodies (Abs) to single stranded DNA (ssDNA) were detected frequently in PWM cultures of both SLE PBLs (88%) and normal tonsillar lymphocytes (78%). IgM and IgG anti-double stranded DNA Abs were found at high frequencies of 73% and 59% respectively with PWM stimulated SLE PBLs.;Spontaneous production of IgM Abs to ssDNA was identical (44%) in normal tonsillar lymphocytes and PBLs of SLE patients. Human:human hybridomas …


Myelin Lipids In The Induction And Suppression Of Experimental Allergic Encephalomyelitis, Zobeeda Zanimun Hosein Jan 1985

Myelin Lipids In The Induction And Suppression Of Experimental Allergic Encephalomyelitis, Zobeeda Zanimun Hosein

Digitized Theses

Hartley guinea pig central nervous system (CNS) myelin was purified and fractionated. Both lyophilized and "wet" myelin induced chronic experimental allergic encephalomyelitis (EAE) in juvenile strain 13/N guinea pigs. Total myelin lipids (TL), galactocerebrosides (GC), gangliosides (GANG), phospholipids or proteolipids in association with a non-encephalitogenic dose (2ug) of MBP did not induce EAE; however, in MBP-TL animals, cell-mediated immune responses (CMI) were augmented. Only the proteolipids elicited delayed hypersensitivity. When TL was associated with an encephalitogenic dose (50ug) of MBP in CFA, juvenile strain 13 animals developed acute EAE with 100% recovery and 50% relapses.;Combinations of 50ug MBP and GC …


Influence Of Host Factors On Phosphatidylcholine Synthesis In Schistosoma Mansoni, Bruce William Young Jan 1984

Influence Of Host Factors On Phosphatidylcholine Synthesis In Schistosoma Mansoni, Bruce William Young

Digitized Theses

This study provides information concerning the factors involved in regulating apical bilayer formation and turnover in the human parasite Schistosoma mansoni. The major phospholipid of cercaria, adults and the outer bilayer and plasma membrane of the apical bilayer complex of the adult parasites is phosphatidylcholine. Phosphatidylcholine was synthesized through the incorporation of choline but not through the methylation of phosphatidylethanolamine.;The uptake and incorporation of choline into phosphatidylcholine by adult S. mansoni was examined in the presence of a variety of sera, hormonal and pharmacologic factors. The examination of sera from a number of sources revealed that permissiveness to infection was …


Characteristics Of Human Cytotoxic Lymphocytes Specific For Haptenic And Non-Major Histocompatibility Complex (Mhc) Cell Surface Antigens, Michael John Ward Jan 1984

Characteristics Of Human Cytotoxic Lymphocytes Specific For Haptenic And Non-Major Histocompatibility Complex (Mhc) Cell Surface Antigens, Michael John Ward

Digitized Theses

Cell mediated immune responses (CMIR), mediated by T-lymphocytes, have been shown to play a role in tumour immunity and allograft rejection. Studies of specific cytotoxic responses indicate that the cells involved in the CMIR are capable of recognizing various cell surface markers. Although many investigations have been conducted the exact nature of the target antigens are not known.;Sensitization of human T cells in Marbrook tissue culture vessels and microtitre trays resulted in the production of effector cells capable of lysing certain target cells. The characterization of the reactivity of these cells was carried out in two systems, the first in …


Induction Of Antigen-Specific, Isotype-Selective Suppression Of Immunoglobulin-E Responses With Glutaraldehyde - Polymerized Ovalbumin, Kent Taylor Hayglass Jan 1983

Induction Of Antigen-Specific, Isotype-Selective Suppression Of Immunoglobulin-E Responses With Glutaraldehyde - Polymerized Ovalbumin, Kent Taylor Hayglass

Digitized Theses

Polymerization of protein allergens with glutaraldehyde (GA) has been shown to lead to decreased local or systemic adverse reactions when used in human hyposensitization therapy. At the same time, clinical trials have revealed that their immunotherapeutic value was at least as good, and in many cases significantly better than that of the corresponding conventional native allergen extracts. Despite these advantages their mechanism of action remains unclear.;The purpose of this study was to determine the characteristics and classification of immunosuoppressive activity established as a consequence of treatment with GA-proteins.;Treatment of mice, a widely accepted animal prototype for human allergy, with GA-polymerized …


Regulation Of The Immune Response By Bone Marrow Cells, Axel Ken Duwe Jan 1977

Regulation Of The Immune Response By Bone Marrow Cells, Axel Ken Duwe

Digitized Theses

No abstract provided.


Regulation Of The Immune Response In Autoimmune Mice, John Carling Roder Jan 1977

Regulation Of The Immune Response In Autoimmune Mice, John Carling Roder

Digitized Theses

No abstract provided.


Studies On The Regulation Of The Immune Response: Importance Of The Fragment Crystalline Portion Of Antibody And Thymus-Derived Cells, Penelope Louise Chan Jan 1972

Studies On The Regulation Of The Immune Response: Importance Of The Fragment Crystalline Portion Of Antibody And Thymus-Derived Cells, Penelope Louise Chan

Digitized Theses

No abstract provided.


Some Factors Controlling Immunological Memory Of The Immunoglobulin-M Type, Rashid Hussain Khan Jan 1972

Some Factors Controlling Immunological Memory Of The Immunoglobulin-M Type, Rashid Hussain Khan

Digitized Theses

No abstract provided.