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Medical Microbiology

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Articles 1951 - 1980 of 2009

Full-Text Articles in Medical Sciences

Assembly And Regulation Of The Cd40 Receptor Complex In Human B Cells, Michelle R. Kuhné, Michael Robbins, John E. Hambor, Matthew F. Mackey, Yoko Kosaka, Toshihide Nishimura, Jason P. Gigley, Randolph J. Noelle, David M. Calderhead Jul 1997

Assembly And Regulation Of The Cd40 Receptor Complex In Human B Cells, Michelle R. Kuhné, Michael Robbins, John E. Hambor, Matthew F. Mackey, Yoko Kosaka, Toshihide Nishimura, Jason P. Gigley, Randolph J. Noelle, David M. Calderhead

Dartmouth Scholarship

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily. Studies with human B cells show that the binding of CD154 (gp39, CD40L) to CD40 recruits TNF receptor– associated factor 2 (TRAF2) and TRAF3 to the receptor complex, induces the downregulation of the nonreceptor-associated TRAFs in the cell and induces an increased expression of Fas on the cell surface. Combined signaling through the interluekin 4 receptor and CD40 induces an increased expression of Fas with a commensurate increase in the level of TRAF2, but not TRAF3, that is recruited to the receptor complex. In contrast, engagement of the …

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Anti-Idiotype Monoclonal Antibody 1a7 And Use For The Treatment Of Melanoma And Small Cell Carcinoma, Malaya Chatterjee, Kenneth A. Foon Mar 1997

Anti-Idiotype Monoclonal Antibody 1a7 And Use For The Treatment Of Melanoma And Small Cell Carcinoma, Malaya Chatterjee, Kenneth A. Foon

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention relates isolation of anti-idiotypic antibody 1A7 raised against anti-GD2 mAb 14G2a and its use for the treatment of melanoma and small cell carcinoma. The antibody may be used as a substitute for isolated purified GD2 antigen in any appropriate application.

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Role Of Egr-1 Gene Expression In B Cell Receptor-Induced Apoptosis In An Immature B Cell Lymphoma, Subramanian Muthukkumar, Seong-Su Han, Sumathi Muthukkumar, Vivek M. Rangnekar, Subbarao Bondada Jan 1997

Role Of Egr-1 Gene Expression In B Cell Receptor-Induced Apoptosis In An Immature B Cell Lymphoma, Subramanian Muthukkumar, Seong-Su Han, Sumathi Muthukkumar, Vivek M. Rangnekar, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Ligation of B cell receptor (BCR) on BKS-2, an immature B cell lymphoma by anti-IgM antibodies (Ab) caused apoptosis. Here we report that signaling through B cell receptor in wild type BKS-2 cells down-regulated the expression of Egr-1, a zinc finger-containing transcription factor. A reduction in the level of Egr-1 mRNA could be demonstrated as early as 30 min after the ligation of BCR on BKS-2 cells. Immunocytochemical and Western blot analysis revealed that the expression of EGR-1 protein was also inhibited by anti-IgM treatment. Antisense oligonucleotides to Egr-1 caused growth inhibition and apoptosis in BKS-2 cells, suggesting that expression …

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Cyclic Amp And Its Receptor Protein Negatively Regulate The Coordinate Expression Of Cholera Toxin And Toxin-Coregulated Pilus In Vibrio Cholerae, Karen Skorupski, Ronald K. Taylor Jan 1997

Cyclic Amp And Its Receptor Protein Negatively Regulate The Coordinate Expression Of Cholera Toxin And Toxin-Coregulated Pilus In Vibrio Cholerae, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Insertion mutations in two Vibrio cholerae genes, cya and crp, which encode adenylate cyclase and the cyclic AMP (cAMP) receptor protein (CRP), respectively, derepressed the expression of a chromosomal cholera toxin (CT) promoter-lacZ fusion at the nonpermissive temperature of 37 degrees C. In the classical biotype strain O395, the crp mutation increased the production of both CT and toxin-coregulated pilus (TCP) in vitro under a variety of growth conditions not normally permissive for their expression. The most dramatic increase in CT and TCP was observed with the crp mutant in Luria-Bertani (LB) medium pH 8.5, at 30 degrees C. El …

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Cellular Basis Of Decreased Immune Responses To Pneumococcal Vaccines In Aged Mice, Manju Garg, Wei Luo, Alan M. Kaplan, Subbarao Bondada Nov 1996

Cellular Basis Of Decreased Immune Responses To Pneumococcal Vaccines In Aged Mice, Manju Garg, Wei Luo, Alan M. Kaplan, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Previously, model systems were developed in our laboratory to study murine immune responses to the 23-valent pneumococcal polysaccharide vaccine Pnu-Imune, both in vivo and in vitro (M. Garg and B. Subbarao, Infect. Immun. 60:2329-2336, 1992; M. Garg, A. M. Kaplan, and S. Bondada, J. Immunol. 152: 1589-1596, 1994). Using these systems, we found that aged mice did not respond to the vaccine in vivo or in vitro. Cell separation studies showed that the unresponsiveness of the aged spleen cells to the vaccine was not due to an intrinsic B-cell defect or to T-cell-mediated immunosuppression but resulted from an accessory cell …

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Attachment Of Toxoplasma Gondii To Host Cells Is Host Cell Cycle Dependent., Jane Grimwood, Jose R. Mineo, Lloyd H. Kasper Oct 1996

Attachment Of Toxoplasma Gondii To Host Cells Is Host Cell Cycle Dependent., Jane Grimwood, Jose R. Mineo, Lloyd H. Kasper

Dartmouth Scholarship

The initial attachment of Toxoplasma tachyzoites to target host cells is an important event in the life cycle of the parasite and hence critical in the pathogenesis of this infection. The efficiency of Toxoplasma attachment to synchronized populations of Chinese hamster ovary cells and bovine kidney cells was investigated by using a glutaraldehyde-fixed host cell assay system. For both cell lines, parasite attachment increased as the synchronized host cells proceeded from the G1 phase to the mid-S phase and then decreased as the cells entered the G2-M boundary. Postulating that these differences in attachment reflect the upregulation of a specific …

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Activation Of The Human Thymidine Kinase (Tk) Promoter By Simian Virus 40 Large T Antigen Requires Both The T Antigen Prb Family-Binding Domain And Tk Promoter Sequences Resembling E2f-Binding Sites., Michelle M. Anderson, Jun Chen, Charles N. Cole, Susan E. Conrad Sep 1996

Activation Of The Human Thymidine Kinase (Tk) Promoter By Simian Virus 40 Large T Antigen Requires Both The T Antigen Prb Family-Binding Domain And Tk Promoter Sequences Resembling E2f-Binding Sites., Michelle M. Anderson, Jun Chen, Charles N. Cole, Susan E. Conrad

Dartmouth Scholarship

Infection of quiescent cells with the DNA tumor virus simian virus 40 induces expression of the cellular thymidine kinase (TK) gene a minimum of 10- to 20-fold, and this induction depends upon the viral protein large T antigen (T-Ag). To define both human TK promoter elements and T-Ag functional domains required for transcriptional induction, we have established a system in which stable Rat-1 transfectants harboring TK promoter-luciferase hybrid genes are infected with recombinant adenoviruses expressing either wild-type or mutant forms of T-Ag and luciferase expression is measured as an indicator of promoter activity. The results show that (i) a 135-bp …

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Differential Expression Of The Toxr Regulon In Classical And E1 Tor Biotypes Of Vibrio Cholerae Is Due To Biotype-Specific Control Over Toxt Expression., Victor J. Dirita, Melody Neely, Ronald K. Taylor, Paul M. Bruss Jul 1996

Differential Expression Of The Toxr Regulon In Classical And E1 Tor Biotypes Of Vibrio Cholerae Is Due To Biotype-Specific Control Over Toxt Expression., Victor J. Dirita, Melody Neely, Ronald K. Taylor, Paul M. Bruss

Dartmouth Scholarship

The two major disease-causing biotypes of Vibrio cholerae, classical and El Tor, exhibit differences in their epidemic nature. Their behavior in the laboratory also differs in that El Tor strains produce two major virulence factors, cholera toxin (CT) and the toxin coregulated pilus (TCP), only under very restricted growth conditions, whereas classical strains do so in standard laboratory medium. Expression of toxin and TCP is controlled by two activator proteins, ToxR and ToxT, that operate in cascade fashion with ToxR controlling the synthesis of ToxT. Both biotypes express equivalent levels of ToxR, but only classical strains appear to express ToxT …

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Toxin-Coregulated Pilus, But Not Mannose-Sensitive Hemagglutinin, Is Required For Colonization By Vibrio Cholerae O1 El Tor Biotype And O139 Strains., K Helene Thelin, Ronald K. Taylor Jul 1996

Toxin-Coregulated Pilus, But Not Mannose-Sensitive Hemagglutinin, Is Required For Colonization By Vibrio Cholerae O1 El Tor Biotype And O139 Strains., K Helene Thelin, Ronald K. Taylor

Dartmouth Scholarship

The relative contributions of toxin-coregulated pilus (TCP) and cell-associated mannose-sensitive hemagglutinin (MSHA) to the colonization ability of Vibrio cholerae O1 El Tor biotype strains and O139 Bengal strains was determined by using isogenic parental and in-frame deletion mutant pairs in the infant mouse cholera model. Both the El Tor and O139 tcpA mutant strains showed a dramatic defect in colonization as indicated by their competitive indices, whereas deletion of mshA had a negligible effect on colonization in either background.

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Toxoplasma Gondii-Induced Immune Suppression By Human Peripheral Blood Monocytes: Role Of Gamma Interferon., Jacqueline Y. Channon, Lloyd H. Kasper Apr 1996

Toxoplasma Gondii-Induced Immune Suppression By Human Peripheral Blood Monocytes: Role Of Gamma Interferon., Jacqueline Y. Channon, Lloyd H. Kasper

Dartmouth Scholarship

The ability of Toxoplasma gondii to evade the host immune response during primary infection in humans is poorly understood. In murine toxoplasmosis, infected spleen macrophages release soluble factors that mediate a transient immunosuppression, which may allow the parasite to become established. When an enriched population of human monocytes from seronegative individuals was incubated with toxoplasmas in vitro, soluble factors that mediated market suppression of mitogen-induced lymphocyte DNA synthesis were released. Irradiated tachyzoites that do not undergo replication were sufficient stimuli for near-maximal soluble factor release. Up to 50% of the soluble factor-mediated suppression is attributable to a gamma interferon (IFN-gamma)-dependent …

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Antibody To The Ligand For Cd40 (Gp39) Inhibits Murine Aids-Associated Splenomegaly, Hypergammaglobulinemia, And Immunodeficiency In Disease-Susceptible C57bl/6 Mice., Kathy A. Green, Karen M. Crassi, Jon D. Laman, Arjan Schoneveld, Rendall R. Strawbridge, Teresa M. Foy, Randolph J. Noelle, William R. Green Apr 1996

Antibody To The Ligand For Cd40 (Gp39) Inhibits Murine Aids-Associated Splenomegaly, Hypergammaglobulinemia, And Immunodeficiency In Disease-Susceptible C57bl/6 Mice., Kathy A. Green, Karen M. Crassi, Jon D. Laman, Arjan Schoneveld, Rendall R. Strawbridge, Teresa M. Foy, Randolph J. Noelle, William R. Green

Dartmouth Scholarship

Infection of genetically susceptible C57BL/6 mice with the LP-BM5 isolate of murine retroviruses cause profound splenomegaly, hypergammaglobulinemia, lymphadenopathy, and an immunodeficiency syndrome which includes the development of terminal B-cell lymphomas. Because many of these and the other manifestations of LP-BM5 virus-induced disease are similar to those seen in AIDS, this syndrome has been named murine AIDS, or MAIDS. Previous reports have shown that the onset of MAIDS depends on the presence of both CD41 T cells and B cells and have suggested that CD41 T-cell-B-cell interactions are important to disease pathogenesis. Here, we assessed the possibility that interactions between CD40 …

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A Tandem Duplication Within The Fibrillin 1 Gene Is Associated With The Mouse Tight Skin Mutation., Linda D. Siracusa, Rodney Mcgrath, Qing Ma, John J. Moskow, Jayanthi Manne, Paul J. Christner, Arthur M. Buchberg, Sergio A. Jimenez Apr 1996

A Tandem Duplication Within The Fibrillin 1 Gene Is Associated With The Mouse Tight Skin Mutation., Linda D. Siracusa, Rodney Mcgrath, Qing Ma, John J. Moskow, Jayanthi Manne, Paul J. Christner, Arthur M. Buchberg, Sergio A. Jimenez

Department of Medicine Faculty Papers

Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame …

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Analysis Of The Effects Of Overexpression Of Metallothionein-I In Transgenic Mice On The Reproductive Toxicology Of Cadmium., T Dalton, Kai Fu, G C Enders, R D Palmiter, G K Andrews Jan 1996

Analysis Of The Effects Of Overexpression Of Metallothionein-I In Transgenic Mice On The Reproductive Toxicology Of Cadmium., T Dalton, Kai Fu, G C Enders, R D Palmiter, G K Andrews

Journal Articles: Pathology and Microbiology

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. …

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Survival Of Immunoglobulin G-Opsonized Toxoplasma Gondii In Nonadherent Human Monocytes., Camilo E. Fadul, Jacqueline Y. Channon, Lloyd H. Kasper Nov 1995

Survival Of Immunoglobulin G-Opsonized Toxoplasma Gondii In Nonadherent Human Monocytes., Camilo E. Fadul, Jacqueline Y. Channon, Lloyd H. Kasper

Dartmouth Scholarship

Toxoplasma gondii is a protozoan parasite that is able to penetrate human monocytes by either passive uptake during phagocytosis or active penetration. It is expected that immunoglobulin G (IgG) opsonization will target the parasite to macrophage Fc gamma receptors for phagocytic processing and subsequent degradation. Antibody-opsonized T. gondii tachyzoites were used to infect nonadherent and adherent human monocytes obtained from the peripheral blood of seronegative individuals. The infected monocytes were evaluated for the presence of intracellular parasites and the degree of parasiticidal activity. A marked difference in both the numbers of infected macrophages and numbers of parasites per 100 macrophages …

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A Toxoplasma Gondii-Derived Factor(S) Stimulates Immune Downregulation: An In Vitro Model., Sakhina Haque, Azizul Haque, Lloyd H. Kasper Sep 1995

A Toxoplasma Gondii-Derived Factor(S) Stimulates Immune Downregulation: An In Vitro Model., Sakhina Haque, Azizul Haque, Lloyd H. Kasper

Dartmouth Scholarship

Suppression of the T-cell lymphoproliferative response and downregulation of interleukin 2 (IL-2) production by Toxoplasma gondii has been observed following in vivo infection. In this study, an experimental in vitro murine system was developed to evaluate the kinetics of these responses. Normal splenocytes from uninfected mice were stimulated with either concanavalin A or an anti-CD3 monoclonal antibody and cocultured with Toxoplasma tachyzoites either directly or separated by a transwell. A progressive decline in the lymphoproliferative response was observed as the concentration of parasites in culture increased. Neither heat-killed nor formaldehyde-fixed parasites stimulated this downregulatory response by the splenocytes. A decline …

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Involvement Of P59FynT In Interleukin-5 Receptor Signaling, Mark W. Appleby, James D. Kerner, Sylvia Chien, Charles R. Maliszewski, Subbarao Bondada, Roger M. Perlmutter Sep 1995

Involvement Of P59FynT In Interleukin-5 Receptor Signaling, Mark W. Appleby, James D. Kerner, Sylvia Chien, Charles R. Maliszewski, Subbarao Bondada, Roger M. Perlmutter

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Previous studies implicate the nonreceptor protein tyrosine kinase (PTK) p59fyn in the propagation of signals from the B cell antigen receptor. To elucidate the functions of this kinase, we examined B cell responsiveness in mice engineered to lack the hematopoietic isoform of p59fyn. Remarkably, antigen receptor signaling was only modestly defective in fynTnull B cells. In contrast, signaling from the interleukin (IL)-5 receptor which ordinarily provides a comitogenic stimulus with antiimmunoglobulin, was completely blocked. Our results document the importance of p59fynT in IL-5 responses in B cells, and they support a general model …

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A Tef-1-Independent Mechanism For Activation Of The Simian Virus 40 (Sv40) Late Promoter By Mutant Sv40 Large T Antigens., Paul Casaz, Phillip W. Rice, Charles N. Cole, Ulla Hansen Jun 1995

A Tef-1-Independent Mechanism For Activation Of The Simian Virus 40 (Sv40) Late Promoter By Mutant Sv40 Large T Antigens., Paul Casaz, Phillip W. Rice, Charles N. Cole, Ulla Hansen

Dartmouth Scholarship

Simian virus 40 (SV40) large tumor antigen (T antigen) stimulates the activity of the SV40 late promoter and a number of cellular and other viral promoters. We have characterized the ability of T antigens with mutations in the DNA-binding domain and within the N-terminal 85 residues to activate the SV40 late promoter. T antigens lacking both nonspecific and sequence-specific DNA-binding activities were able to induce the late promoter. Mutations within the N-terminal 85 residues of T antigen diminished activation by less than twofold. Activation by wild-type and most of the mutant T antigens required intact binding sites for the cellular …

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Polyclonal Mycobacterium Avium Infections In Patients With Aids: Variations In Antimicrobial Susceptibilities Of Different Strains Of M. Avium Isolated From The Same Patient., C Fordham Von Reyn, Nicholas J. Jacobs, Robert D. Arbeit, Joe N. Maslow, S Niemczyk Apr 1995

Polyclonal Mycobacterium Avium Infections In Patients With Aids: Variations In Antimicrobial Susceptibilities Of Different Strains Of M. Avium Isolated From The Same Patient., C Fordham Von Reyn, Nicholas J. Jacobs, Robert D. Arbeit, Joe N. Maslow, S Niemczyk

Dartmouth Scholarship

Broth microdilution MICs were determined for pairs of strains isolated from five AIDS patients with polyclonal Mycobacterium avium infection. Four (80%) of the five patients were infected simultaneously with strains having different antimicrobial susceptibility patterns. These findings have implications for the interpretation of susceptibility data in M. avium prophylaxis and treatment trials.

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A Novel Translational Regulation Function For The Simian Virus 40 Large-T Antigen Gene., Prithi Rajan, Sathyamagalam Swaminathan, Jiyue Zhu, Charles N. Cole Feb 1995

A Novel Translational Regulation Function For The Simian Virus 40 Large-T Antigen Gene., Prithi Rajan, Sathyamagalam Swaminathan, Jiyue Zhu, Charles N. Cole

Dartmouth Scholarship

Cells use the interferon-induced, double-stranded-RNA-dependent protein kinase PKR as a defense against virus infections. Upon activation, PKR phosphorylates and thereby inactivates the protein synthesis initiation factor eIF-2, resulting in the cessation of protein synthesis. Viruses have evolved various strategies to counteract this cellular defense. In this paper, we show that simian virus 40 (SV40) large-T antigen can antagonize the translational inhibitory effect resulting from the activation of PKR in virus-infected cells. Unlike the situation with other virus-host cell interactions, SV40 large-T antigen does not block the activation of PKR, suggesting that SV40 counteracts the cellular antiviral response mediated by PKR …

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Polyclonal Infections Due To Mycobacterium Avium Complex In Patients With Aids Detected By Pulsed-Field Gel Electrophoresis Of Sequential Clinical Isolates., Alexander M. Slutsky, Robert D. Arbeit, Thomas W. Barber, Josiah Rich, C Fordham Von Reyn Jul 1994

Polyclonal Infections Due To Mycobacterium Avium Complex In Patients With Aids Detected By Pulsed-Field Gel Electrophoresis Of Sequential Clinical Isolates., Alexander M. Slutsky, Robert D. Arbeit, Thomas W. Barber, Josiah Rich, C Fordham Von Reyn

Dartmouth Scholarship

Invasive infection with organisms of the Mycobacterium avium complex (MAC) is common among patients with advanced human immunodeficiency virus infection. In previous studies, we analyzed multiple individual colonies of MAC isolated from specimens obtained at the same time and observed that 14 to 20% of patients are simultaneously infected with more than one strain. In this study, we examined sequential isolates from 12 patients with AIDS who had two or more MAC isolates available from clinical specimens collected more than 1 week apart; the intervals between the first and last specimens ranged from 8 to 192 (median, 46) days. For …

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Adoptive Transfer Of Polyclonal And Cloned Cytolytic T Lymphocytes (Ctl) Specific For Mouse Aids-Associated Tumors Is Effective In Preserving Ctl Responses: A Measure Of Protection Against Lp-Bm5 Retrovirus-Induced Immunodeficiency., William R. Green, Kathy A. Green, Karen M. Crassi Jul 1994

Adoptive Transfer Of Polyclonal And Cloned Cytolytic T Lymphocytes (Ctl) Specific For Mouse Aids-Associated Tumors Is Effective In Preserving Ctl Responses: A Measure Of Protection Against Lp-Bm5 Retrovirus-Induced Immunodeficiency., William R. Green, Kathy A. Green, Karen M. Crassi

Dartmouth Scholarship

Cytolytic T lymphocytes (CTL) can be raised against C57BL/6 B-cell lymphomas from mice with LP-BM5 murine leukemia virus-induced AIDS (MAIDS). Adoptive transfer of polyclonal anti-MAIDS tumor CTL or two CTL clones specific for the B6-1710 MAIDS lymphoma caused preservation of major histocompatibility complex-restricted and allogeneic CTL responses, which may be interpreted as indices of protection from LP-BM5 murine leukemia virus-induced immunodeficiency.

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Comparison Of Cytotoxic Properties Of Neonatal And Adult Neutrophils And Monocytes And Enhancement By Cytokines., E . R. Stiehm, R. L. Roberts, B. J. Ank, S. Plaeger-Marshall, N. Salman, L. Shen, M. W. Fanger May 1994

Comparison Of Cytotoxic Properties Of Neonatal And Adult Neutrophils And Monocytes And Enhancement By Cytokines., E . R. Stiehm, R. L. Roberts, B. J. Ank, S. Plaeger-Marshall, N. Salman, L. Shen, M. W. Fanger

Dartmouth Scholarship

We studied cytotoxic capabilities of newborn polymorphonuclear leukocytes (PMNs) and monocytes and their enhancement by cytokines and antibodies. Umbilical cord PMNs were assessed for their ability to kill various target cells spontaneously, after activation with phorbol myristate acetate, in the presence of antiserum (antibody-dependent cellular cytotoxicity), and in the presence of dually specific antibody (heteroantibody-mediated cytotoxicity). Target cells included the K562 cell line (natural killer cell target), chicken erythrocytes (CRBCs), and herpes simplex virus-infected CEM cell lines. Newborn PMNs were equivalent to adult PMNs in their cytotoxic capacity in several cytotoxicity assays. Neither adult nor newborn PMNs lyse tumor cell …

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Interleukin-12 Enhances Murine Survival Against Acute Toxoplasmosis., Imtiaz A. Khan, Tadashi Matsuura, Lloyd H. Kasper May 1994

Interleukin-12 Enhances Murine Survival Against Acute Toxoplasmosis., Imtiaz A. Khan, Tadashi Matsuura, Lloyd H. Kasper

Dartmouth Scholarship

Protective immunity against Toxoplasma gondii is mediated by the host cellular immune response. Interleukin-12 (IL-12), a recently described cytokine that stimulates NK cells to produce gamma interferon (IFN-gamma), is able to enhance host protection against this parasite in SCID mice. Administration of IL-12 to A/J mice significantly increased survival over that of control mice when IL-12 was delivered early in the course of acute infection. If it was administered at day 3 or thereafter, there was no observed difference in mortality between treated and control mice. Antibody depletion of IL-12 increased susceptibility to infection, as measured by mortality, only when …

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Enhanced Immunogenicity Of Protein-Dextran Conjugates: I. Rapid Stimulation Of Enhanced Antibody Responses To Poorly Immunogenic Molecules, Andrew Lees, Fred Finkelman, John K. Inman, Kim Witherspoon, Penny Johnson, Jasiri Kennedy, James J. Mond Jan 1994

Enhanced Immunogenicity Of Protein-Dextran Conjugates: I. Rapid Stimulation Of Enhanced Antibody Responses To Poorly Immunogenic Molecules, Andrew Lees, Fred Finkelman, John K. Inman, Kim Witherspoon, Penny Johnson, Jasiri Kennedy, James J. Mond

Microbiology, Immunology, and Molecular Genetics Faculty Publications

In view of our observation that anti-immunoglobulin antibody conjugated to high-molecular-weight dextran stimulates high levels of B-cell activation (Brunswick et al. J. Immunol . 1989, 143, 1239), we coupled T cell-dependent antigens to dextran. When mice were immunized, in the absence of adjuvant, with a BSA-dextran conjugate (BSA-dex), a persistent, high-titre anti-BSA IgG1 response was induced. Titres were dose-dependent and seen with as little as 10 I~g of conjugated protein. Anti-BSA titres were detected as early as day 7, usually peaked at about day 14 and persisted for at least 4 weeks. Anti-hapten antibodies were also elicited in mice that …

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Antiparasitic And Antiproliferative Effects Of Indoleamine 2,3-Dioxygenase Enzyme Expression In Human Fibroblasts., Sohan L. Gupta, Joseph M. Carlin, Padma Pyati, Wei Dai, Elmer R. Pfefferkorn, Martin J. Murphy Jr Jan 1994

Antiparasitic And Antiproliferative Effects Of Indoleamine 2,3-Dioxygenase Enzyme Expression In Human Fibroblasts., Sohan L. Gupta, Joseph M. Carlin, Padma Pyati, Wei Dai, Elmer R. Pfefferkorn, Martin J. Murphy Jr

Dartmouth Scholarship

Studies were carried out to evaluate the proposed role of indoleamine 2,3-dioxygenase (INDO) induction in the antimicrobial and antiproliferative effects of gamma interferon (IFN-gamma) in human fibroblasts. The INDO cDNA coding region was cloned in the pMEP4 expression vector, containing the metallothionein (MTII) promoter in the sense (+ve) or the antisense (-ve) orientation. Human fibroblasts (GM637) stably transfected with the sense construct expressed INDO activity after treatment with CdCl2 or ZnSO4, but cells transfected with the antisense construct did not. The growth of Chlamydia psittaci was strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment …

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Use Of Yeast Artificial Chromosomes (Yacs) For Studying Control Of Gene Expression: Correct Regulation Of The Genes Of A Human Beta-Globin Locus Yac Following Transfer To Mouse Erythroleukemia Cell Lines., Kenneth Peterson, Galynn Zitnik, Clare Huxley, Christopher Lowrey Dec 1993

Use Of Yeast Artificial Chromosomes (Yacs) For Studying Control Of Gene Expression: Correct Regulation Of The Genes Of A Human Beta-Globin Locus Yac Following Transfer To Mouse Erythroleukemia Cell Lines., Kenneth Peterson, Galynn Zitnik, Clare Huxley, Christopher Lowrey

Dartmouth Scholarship

We demonstrate that transfer of a yeast artificial chromosome (YAC) containing 230 kb of the human beta-globin locus into mouse erythroleukemia cells by fusion results in correct developmental regulation of the human beta-like globin genes. Additionally, we show that early after hybrid formation, human embryonic epsilon- and fetal gamma-globin genes are coexpressed with the adult beta gene but that after 10-20 weeks in culture, globin gene expression switches to predominantly adult. Thus, in contrast to shorter gene constructs, the globin genes of the beta-globin locus YAC are regulated like the chromosomal globin genes. These results indicate that transfer of YACs …

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Molecular Cloning Of Infectious Ecotropic Murine Leukemia Virus Ak7 From An Emv-14-Positive Akxl-5 Mouse And The Resistance Of Ak7 To Recognition By Cytotoxic T Lymphocytes., Hillary D. White, William R. Green, Nuria R. Giné Aug 1993

Molecular Cloning Of Infectious Ecotropic Murine Leukemia Virus Ak7 From An Emv-14-Positive Akxl-5 Mouse And The Resistance Of Ak7 To Recognition By Cytotoxic T Lymphocytes., Hillary D. White, William R. Green, Nuria R. Giné

Dartmouth Scholarship

The AKXL-5 recombinant inbred mouse strain is positive for the endogenous ecotropic murine leukemia virus emv-14, the only emv present in its germ line. emv-14 is of particular interest because spleen cells expressing emv-14 virus escape recognition by anti-AKR/Gross virus-specific cytotoxic T lymphocytes. We report here the isolation and characterization of a replication-competent emv clone, pAK7, derived from an AKXL-5 mouse. This clone is novel in that it encodes a variant ecotropic murine leukemia virus that, when expressed in SC.Kb target cells, fails to be recognized efficiently by anti-AKR/Gross virus cytotoxic T lymphocytes. The pAK7 clone can therefore be used …

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Reversal Of Age-Associated Decline In Immune Response To Pnu-Imune Vaccine By Supplementation With The Steroid Hormone Dehydroepiandrosterone, Manju Garg, Subbarao Bondada May 1993

Reversal Of Age-Associated Decline In Immune Response To Pnu-Imune Vaccine By Supplementation With The Steroid Hormone Dehydroepiandrosterone, Manju Garg, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Recently, we reported that murine antibody responses to the 23-valent pneumococcal polysaccharide (Pnu-Imune) vaccine declined with age. Here we present data to support the concept that age-associated immune defects are not only due to intrinsic defects in immune cells but are also due to extrinsic factors emanating from the neuroendocrine system. We found that supplementation with dehydroepiandrosterone, a steroid hormone known to be reduced in the aged, corrects the immune deficiency of aged mice and significantly enhanced their splenic immune responses to the Pnu-Imune vaccine.

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Immune Responses Of Systemic And Mucosal Lymphoid Organs To Pnu-Imune Vaccine As A Function Of Age And The Efficacy Of Monophosphoryl Lipid A As An Adjuvant, Manju Garg, Subbarao Bondada Jun 1992

Immune Responses Of Systemic And Mucosal Lymphoid Organs To Pnu-Imune Vaccine As A Function Of Age And The Efficacy Of Monophosphoryl Lipid A As An Adjuvant, Manju Garg, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A murine model system was established to study immune responses to the Pnu-Imune vaccine, which is made up of 23 different pneumococcal capsular polysaccharides. In this animal model, antibody-forming cell responses to 21 of 23 individual polysaccharides in the vaccine were detected. The Pnu-Imune vaccine elicited good antibody responses from the spleens and mesenteric lymph nodes (MLN) of young mice, whereas a variety of other peripheral lymph nodes were unresponsive. The immunoglobulin M plaque-forming cell (PFC) response in the spleen to the Pnu-Imune vaccine (given intraperitoneally or subcutaneously) decreased dramatically with increasing age. However, the spleen and MLN differed in …

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Cytolytic T Lymphocytes Specific For Tumors And Infected Cells From Mice With A Retrovirus-Induced Immunodeficiency Syndrome., Jennifer G. Erbe, Kathy A. Green, Karen M. Crassi, Herbert C. Morse, W R. Green May 1992

Cytolytic T Lymphocytes Specific For Tumors And Infected Cells From Mice With A Retrovirus-Induced Immunodeficiency Syndrome., Jennifer G. Erbe, Kathy A. Green, Karen M. Crassi, Herbert C. Morse, W R. Green

Dartmouth Scholarship

LP-BM5 retrovirus complex-infected C57BL/6 mice develop immunodeficiency, somewhat analogous to AIDS, termed murine AIDS (MAIDS). After secondary stimulation with syngeneic B-cell lymphomas from LP-BM5-infected mice, C57BL/6 mice produced vigorous CD8+ cytotoxic T lymphocytes specific for MAIDS-associated tumors. An anti-LP-BM5 specificity was suggested because spleen and lymph node cells from LP-BM5-infected mice served as target cells in competition assays, and cells from LP-BM5, but not ecotropic, virus-infected mice functioned as secondary in vitro stimulators to generate cytotoxic T lymphocytes to MAIDS tumors.

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