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Full-Text Articles in Medicine and Health Sciences

Roc Curve Regression Analysis: The Use Of Ordinal Regression Models For Diagnostic Test Assessment, Anna N.A. Tosteson, Milton C. Weinstein, Jack Wittenberg, Colin B. Begg Nov 1994

Roc Curve Regression Analysis: The Use Of Ordinal Regression Models For Diagnostic Test Assessment, Anna N.A. Tosteson, Milton C. Weinstein, Jack Wittenberg, Colin B. Begg

Dartmouth Scholarship

Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) …


Regulation Of Collagenase Gene Expression By Il-1 Beta Requires Transcriptional And Post-Transcriptional Mechanisms, Matthew P. Vincenti, Charles I. Coon, Oneil Lee, Constance E. Brinckerhoff Sep 1994

Regulation Of Collagenase Gene Expression By Il-1 Beta Requires Transcriptional And Post-Transcriptional Mechanisms, Matthew P. Vincenti, Charles I. Coon, Oneil Lee, Constance E. Brinckerhoff

Dartmouth Scholarship

Interleukin-1 beta is believed to contribute to the pathophysiology of rheumatoid arthritis by activating collagenase gene expression. We have used a cell culture model of rabbit synovial fibroblasts to examine the molecular mechanisms of IL-1 beta-mediated collagenase gene expression. Stimulation of rabbit synovial fibroblasts with 10 ng/ml recombinant human IL-1 beta resulted in a 20-fold increase in collagenase mRNA by 12 h. Transient transfection studies using collagenase promoter-CAT constructs demonstrated that proximal sequences responded poorly to IL-1 beta, possibly due to insufficient activation of AP-1 by this cytokine. More distal sequences were required for IL-1 beta responsiveness, with a 4700 …


A Thyroid Hormone-Regulated Gene In Xenopus Laevis Encodes A Type Iii Iodothyronine 5-Deiodinase., Donald L. St Germain, Robert Schwartzman, Walburga Croteau, Akira Kanamori, Zhou Wang, Donald D. Brown, Valerie Galton Aug 1994

A Thyroid Hormone-Regulated Gene In Xenopus Laevis Encodes A Type Iii Iodothyronine 5-Deiodinase., Donald L. St Germain, Robert Schwartzman, Walburga Croteau, Akira Kanamori, Zhou Wang, Donald D. Brown, Valerie Galton

Dartmouth Scholarship

The type III iodothyronine 5-deiodinase metabolizes thyroxine and 3,5,3'-triiodothyronine to inactive metabolites by catalyzing the removal of iodine from the inner ring. The enzyme is expressed in a tissue-specific pattern during particular stages of development in amphibia, birds, and mammals. Recently, a PCR-based subtractive hybridization technique has been used to isolate cDNAs prepared from Xenopus laevis tadpole tail mRNA that represent genes upregulated by thyroid hormone during metamorphosis. Sequence analysis of one of these cDNAs (XL-15) revealed regions of homology to the mRNA encoding the rat type I (outer ring) 5'-deiodinase, including a conserved UGA codon that encodes selenocysteine in …


Contrast Enhancement Of Medical Images Using Multiscale Edge Representation, Jian Lu, Dennis M. Healy Jr., John B. Weaver Jul 1994

Contrast Enhancement Of Medical Images Using Multiscale Edge Representation, Jian Lu, Dennis M. Healy Jr., John B. Weaver

Dartmouth Scholarship

Experience suggests the existence of a connection between the contrast of a gray-scale image and the gradient magnitude of intensity edges in the neighborhood where the contrast is measured. This observation motivates the development of edge-based contrast enhancement techniques. We present a simple and effective method for image contrast enhancement based on the multiscale edge representation of images. The contrast of an image can be enhanced simply by stretching or upscaling the multiscale gradient maxima of the image. This method offers flexibility to selectively enhance features of different sizes and ability to control noise magnification. We present some experimental results …


Impairment Of The Cellular Immune Response In Acute Murine Toxoplasmosis: Regulation Of Interleukin 2 Production And Macrophage-Mediated Inhibitory Effects., Sakhina Haque, Imtiaz Khan, Azizul Haque, Lloyd Kasper Jul 1994

Impairment Of The Cellular Immune Response In Acute Murine Toxoplasmosis: Regulation Of Interleukin 2 Production And Macrophage-Mediated Inhibitory Effects., Sakhina Haque, Imtiaz Khan, Azizul Haque, Lloyd Kasper

Dartmouth Scholarship

Depression of the cellular immune response to Toxoplasma gondii has been reported in both mice and humans. The present study was undertaken to determine the kinetics and mechanism of the observed downregulation of interleukin 2 (IL-2) production during experimental murine toxoplasmosis. For these investigations, the cell-mediated immune response to the wild type (PTg) was compared with that to the less-virulent mutant parasite (PTgB), which is deficient in the major surface antigen, p30 (SAG-1). Spleen cells from infected A/J mice failed to proliferate in response to Toxoplasma antigens during the first week of infection. Both PTg- and PTgB-infected A/J mice exhibited …


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.


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 …


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 …


Subunit Dynamics In Escherichia Coli Preprotein Translocase., John C. Joly, Marilyn R. Leonard, William T. Wickner May 1994

Subunit Dynamics In Escherichia Coli Preprotein Translocase., John C. Joly, Marilyn R. Leonard, William T. Wickner

Dartmouth Scholarship

SecY, SecE, and band 1 copurify as the SecY/E integral membrane domain of Escherichia coli preprotein translocase. To measure the in vivo association of these polypeptides and assay possible exchange, plasmid-borne secY and secE genes were placed under control of the ara regulon and fused to DNA encoding the influenza hemagglutinin epitope. Cells were incubated with [35S]methionine, grown for a "chase" period, and then induced with arabinose to express epitope-tagged, nonradioactive SecY and SecE. Both the wild-type and epitope-tagged polypeptides assembled into functional, heterotrimeric SecY/E complex. However, immunoprecipitation with antibody to the epitope tag did not cross-precipitate radiolabeled SecY or …


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 …


The Amino-Terminal Functions Of The Simian Virus 40 Large T Antigen Are Required To Overcome Wild-Type P53-Mediated Growth Arrest Of Cells., Robin S. Quartin, Charles N. Cole, James M. Pipas, Arnold J. Levine Mar 1994

The Amino-Terminal Functions Of The Simian Virus 40 Large T Antigen Are Required To Overcome Wild-Type P53-Mediated Growth Arrest Of Cells., Robin S. Quartin, Charles N. Cole, James M. Pipas, Arnold J. Levine

Dartmouth Scholarship

High levels of the p53 tumor suppressor protein can block progression through the cell cycle. A model system for the study of the mechanism of action of wild-type p53 is a cell line (T64-7B) derived from rat embryo fibroblasts transformed by activated ras and a temperature-sensitive murine p53 gene. At 37 to 39 degrees C, the murine p53 protein is in a mutant conformation and the cells actively divide, whereas at 32 degrees C, the protein has a wild-type conformation and the cells arrest in the G1 phase of the cell cycle. Wild-type simian virus 40 large T antigen and …


Bcl-2 Protein Expression Is Widespread In The Developing Nervous-System And Retained In The Adult Pns, Diane E. Merry, Deborah J. Veis, William F. Hickey, Stanley J. Korsmeyer Feb 1994

Bcl-2 Protein Expression Is Widespread In The Developing Nervous-System And Retained In The Adult Pns, Diane E. Merry, Deborah J. Veis, William F. Hickey, Stanley J. Korsmeyer

Dartmouth Scholarship

Cell death is a common feature of neural development in all vertebrates. The bcl-2 proto-oncogene has been shown to protect a variety of cell types from programmed cell death. We have examined the distribution of bcl-2 protein in the developing and adult nervous systems. bcl-2 protein is widespread during embryonic development. Proliferating neuroepithelial cells of ventricular zones as well as the postmitotic cells of the cortical plate, cerebellum, hippocampus and spinal cord express bcl-2. Postnatally, bcl-2 is principally retained in the granule cells of the cerebellum and dentate gyrus of the hippocampus. bcl-2 expression in the CNS declines with aging. …


Cd40 Ligand Expression Is Defective In A Subset Of Patients With Common Variable Immunodeficiency., Mary Farrington, Laura S. Grosmaire, Shigeaki Nonoyama, Susanna H. Fischer, Diane Hollenbaugh, Jeffrey A. Ledbetter, R. J. Noelle Feb 1994

Cd40 Ligand Expression Is Defective In A Subset Of Patients With Common Variable Immunodeficiency., Mary Farrington, Laura S. Grosmaire, Shigeaki Nonoyama, Susanna H. Fischer, Diane Hollenbaugh, Jeffrey A. Ledbetter, R. J. Noelle

Dartmouth Scholarship

Common variable immunodeficiency (CVI) is characterized by hypogammaglobulinemia and recurrent bacterial infections due to failure of CVI B cells to differentiate in vivo into immunoglobulin-secreting plasma cells. We hypothesized that T-cell dysfunction resulting in abnormal contact-mediated B-cell activation may play a prominent role in the failure of CVI B cells to produce specific antibody. We have previously shown that B-cell proliferation and IgE production after stimulation with anti-CD40 and interleukin (IL) 4 were normal in 22 CVI patients evaluated, indicating that CVI B cells respond to signals delivered via CD40. Here we report that CD40 ligand (gp39) mRNA expression by …


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 …


Cooperative Binding Of Ets-1 And Core Binding Factor To Dna., David Wotton, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen Jan 1994

Cooperative Binding Of Ets-1 And Core Binding Factor To Dna., David Wotton, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen

Dartmouth Scholarship

Two phorbol ester-inducible elements (beta E2 and beta E3) within the human T-cell receptor beta gene enhancer each contain consensus binding sites for the Ets and core binding factor (CBF) transcription factor families. Recombinant Ets-1 and purified CBF bound individually to beta E2 and beta E3, in which the Ets and core sites are directly adjacent. In this report, we show that CBF and Ets-1 bind together to beta E2 and beta E3 and that Ets-1-CBF-DNA complexes are favored over the binding of either protein alone to beta E2. Formation of Ets-1-CBF-DNA complexes increased the affinity of Ets-1-DNA interactions and …