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Full-Text Articles in Medicine and Health Sciences

Identification And Characterization Of Spcu, A Chaperone Required For Efficient Secretion Of The Exou Cytotoxin, Viviane Finck-Barbançon, Timothy L. Yahr, Dara W. Frank Dec 1998

Identification And Characterization Of Spcu, A Chaperone Required For Efficient Secretion Of The Exou Cytotoxin, Viviane Finck-Barbançon, Timothy L. Yahr, Dara W. Frank

Dartmouth Scholarship

In recent studies, we have shown that Pseudomonas aeruginosa strains that are acutely cytotoxic in vitro damage the lung epithelium in vivo. Genetic analysis indicated that the factor responsible for acute cytotoxicity was controlled by ExsA and therefore was part of the exoenzyme S regulon. The specific virulence determinant responsible for epithelial damage in vivo and cytotoxicity in vitro was subsequently mapped to the exoU locus. The present studies are focused on a genetic characterization of the exoU locus. Northern blot analyses and complementation experiments indicated that a region downstream of exoU was expressed and that the expression of this …


Conserved Elements Containing Nf-E2 And Tandem Gata Binding Sites Are Required For Erythroid-Specific Chromatin Structure Reorganization Within The Human Beta-Globin Locus Control Region, Oded Pomerantz, Andrew J. Goodwin, Terrence Joyce, Christopher H. Lowrey Dec 1998

Conserved Elements Containing Nf-E2 And Tandem Gata Binding Sites Are Required For Erythroid-Specific Chromatin Structure Reorganization Within The Human Beta-Globin Locus Control Region, Oded Pomerantz, Andrew J. Goodwin, Terrence Joyce, Christopher H. Lowrey

Dartmouth Scholarship

Proper expression of the genes of the human β-globin gene locus requires the associated locus control region (LCR). Structurally, the LCR is defined by the presence of four domains of erythroid-specific chromatin structure. These domains, which have been characterized as DNase I hypersensitive sites (HSs), comprise the active elements of the LCR. The major focus of this research is to define the cis-acting elements which are required for the formation of these domains of unique chromatin structure. Our previous investigations on the formation of LCR HS4 demonstrated that NF-E2 and tandem, inverted GATA binding sites are required for the …


The Seca Subunit Of Escherichia Coli Preprotein Translocase Is Exposed To The Periplasm, Jerry Eichler, William Wickner Nov 1998

The Seca Subunit Of Escherichia Coli Preprotein Translocase Is Exposed To The Periplasm, Jerry Eichler, William Wickner

Dartmouth Scholarship

SecA undergoes conformational changes during translocation, inserting domains into and across the membrane or enhancing the protease resistance of these domains. We now show that some SecA bound at SecYEG is accessible from the periplasm to a membrane-impermeant probe in cells with a permeabilized outer membrane but an intact plasma membrane.


Exoy, An Adenylate Cyclase Secreted By The Pseudomonas Aeruginosa Type Iii System, Timothy L. Yahr, Amy J. Vallis, Michael Hancock, Joseph T. Barbieri, Dara W. Frank Nov 1998

Exoy, An Adenylate Cyclase Secreted By The Pseudomonas Aeruginosa Type Iii System, Timothy L. Yahr, Amy J. Vallis, Michael Hancock, Joseph T. Barbieri, Dara W. Frank

Dartmouth Scholarship

The exoenzyme S regulon is a set of coordinately regulated virulence genes of Pseudomonas aeruginosa. Proteins encoded by the regulon include a type III secretion and translocation apparatus, regulators of gene expression, and effector proteins. The effector proteins include two enzymes with ADP-ribosyltransferase activity (ExoS and ExoT) and an acute cytotoxin (ExoU). In this study, we identified ExoY as a fourth effector protein of the regulon. ExoY is homologous to the extracellular adenylate cyclases of Bordetella pertussis (CyaA) and Bacillus anthracis (EF). The homology among the three adenylate cyclases is limited to two short regions, one of which possesses an …


Design Of An Epidemiologic Study Of Drinking Water Arsenic Exposure And Skin And Bladder Cancer Risk In A U.S. Population, Margaret R. Karagas, Tor D. Tosteson, Joel Blum, J Steven Morris, John A. Baron, Bjoern Klaue Aug 1998

Design Of An Epidemiologic Study Of Drinking Water Arsenic Exposure And Skin And Bladder Cancer Risk In A U.S. Population, Margaret R. Karagas, Tor D. Tosteson, Joel Blum, J Steven Morris, John A. Baron, Bjoern Klaue

Dartmouth Scholarship

Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients …


Molecular Basis For Effects Of Carcinogenic Heavy Metals On Inducible Gene Expression, Joshua W. Hamilton, Ronald C. Kaltreider, Olga V. Bajenova, Michael A. Ihnat, Jennifer Mccaffrey, Bruce W. Turpie, Erin E. Rowell, Jannet Oh, Michael J. Nemeth, Carrie A. Pesce, Jean P. Lariviere Aug 1998

Molecular Basis For Effects Of Carcinogenic Heavy Metals On Inducible Gene Expression, Joshua W. Hamilton, Ronald C. Kaltreider, Olga V. Bajenova, Michael A. Ihnat, Jennifer Mccaffrey, Bruce W. Turpie, Erin E. Rowell, Jannet Oh, Michael J. Nemeth, Carrie A. Pesce, Jean P. Lariviere

Dartmouth Scholarship

Certain forms of the heavy metals arsenic and chromium are considered human carcinogens, although they are believed to act through very different mechanisms. Chromium(VI) is believed to act as a classic and mutagenic agent, and DNA/chromatin appears to be the principal target for its effects. In contrast, arsenic(III) is considered nongenotoxic, but is able to target specific cellular proteins, principally through sulfhydryl interactions. We had previously shown that various genotoxic chemical carcinogens, including chromium (VI), preferentially altered expression of several inducible genes but had little or no effect on constitutive gene expression. We were therefore interested in whether these carcinogenic …


Cd4(+) T Cells Tolerized Ex Vivo To Host Alloantigen By Anti-Cd40 Ligand (Cd40l:Cd154) Antibody Lose Their Graft-Versus-Host Disease Lethality Capacity But Retain Nominal Antigen Responses., Bruce R. Blazar, Patricia A. Taylor, Randolph J. Noelle, Daniel A. Vallera Aug 1998

Cd4(+) T Cells Tolerized Ex Vivo To Host Alloantigen By Anti-Cd40 Ligand (Cd40l:Cd154) Antibody Lose Their Graft-Versus-Host Disease Lethality Capacity But Retain Nominal Antigen Responses., Bruce R. Blazar, Patricia A. Taylor, Randolph J. Noelle, Daniel A. Vallera

Dartmouth Scholarship

A major goal of the transplant field is to tolerize donor T cells to prevent graft-versus-host disease (GVHD) (1). We describe an ex vivo approach in which the blockade of CD40 ligand (CD40L:CD154):CD40 interactions, a pathway required for optimal T cell expansion, induces donor CD4(+) T cells to become tolerant to host alloantigens (2). High doses of tolerized cells did not cause GVHD lethality in vivo. T cells had intact responses to antigens not present during tolerization. Tolerance was long lived and not readily reversible in vivo. These data have significant implications for the use of tolerization approaches to prevent …


Expression Of Toxoplasma Gondii-Specific Heat Shock Protein 70 During In Vivo Conversion Of Bradyzoites To Tachyzoites, Neide M. Silva, Ricardo T. Gazzinelli, Deise A. O. Silva, Eloisa A. V. Ferro, Lloyd H. Kasper, Jose R. Mineo Aug 1998

Expression Of Toxoplasma Gondii-Specific Heat Shock Protein 70 During In Vivo Conversion Of Bradyzoites To Tachyzoites, Neide M. Silva, Ricardo T. Gazzinelli, Deise A. O. Silva, Eloisa A. V. Ferro, Lloyd H. Kasper, Jose R. Mineo

Dartmouth Scholarship

Stage conversion between bradyzoites and tachyzoites was investigated in C57BL/6 mice chronically infected with the ME-49 strain of Toxoplasma gondii. In order to promote bradyzoite-tachyzoite conversion, mice were treated in vivo with neutralizing doses of anti-gamma interferon (IFN-gamma) or anti-tumor necrosis factor alpha (TNF-alpha) antibodies. Expression of parasite-specific antigens SAG-1, SAG-2, and heat shock protein 70 (Hsp-70) was visualized in the central nervous system by immunocytochemistry and measured by photometric assay. The immunosuppressive effect of anti-IFN-gamma or anti-TNF-alpha treatment was immediate, leading to parasite stage conversion as indicated by the increased expression of tachyzoite-specific antigens (SAG-1 and SAG-2) and by …


Hormone Replacement Therapy And Risk Of Hip Fracture: Population Based Case-Control Study, Karl Michaëlsson, John A. Baron, Bahman Y. Farahmand, Olof Johnell, Cecilia Magnusson, Per-Gunnar Persson, Ingemar Persson, Sverker Ljunghall Jun 1998

Hormone Replacement Therapy And Risk Of Hip Fracture: Population Based Case-Control Study, Karl Michaëlsson, John A. Baron, Bahman Y. Farahmand, Olof Johnell, Cecilia Magnusson, Per-Gunnar Persson, Ingemar Persson, Sverker Ljunghall

Dartmouth Scholarship

Objective: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. Design: Population based case-control study. Setting: Six counties in Sweden. Subjects: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. Main outcome measure: Use of hormone replacement therapy. Results: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95% confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio …


The “Spot 14” Gene Resides On The Telomeric End Of The 11q13 Amplicon And Is Expressed In Lipogenic Breast Cancers: Implications For Control Of Tumor Metabolism, Joel T. Moncur, Jonathan P. Park, Vincent A. Memoli, T. K. Mohandas, William B. Kinlaw Jun 1998

The “Spot 14” Gene Resides On The Telomeric End Of The 11q13 Amplicon And Is Expressed In Lipogenic Breast Cancers: Implications For Control Of Tumor Metabolism, Joel T. Moncur, Jonathan P. Park, Vincent A. Memoli, T. K. Mohandas, William B. Kinlaw

Dartmouth Scholarship

Enhanced long chain fatty acid synthesis may occur in breast cancer, where it is necessary for tumor growth and predicts a poor prognosis. “Spot 14” (S14) is a carbohydrate- and thyroid hormone-inducible nuclear protein specific to liver, adipose, and lactating mammary tissues that functions to activate genes encoding the enzymes of fatty acid synthesis. Amplification of chromosome region 11q13, where the S14 gene (THRSP) resides, also predicts a poor prognosis in breast tumors. We localized the S14 gene between markers D11S906 and D11S937, at the telomeric end of the amplified region at 11q13, and found that it was …


Heterologous Complementation Reveals That Mutant Alleles Of Qsr1 Render 60s Ribosomal Subunits Unstable And Translationally Inactive, Frederick A. Dick, Bernard L. Trumpower May 1998

Heterologous Complementation Reveals That Mutant Alleles Of Qsr1 Render 60s Ribosomal Subunits Unstable And Translationally Inactive, Frederick A. Dick, Bernard L. Trumpower

Dartmouth Scholarship

QSR1 is a highly conserved gene which encodes a 60S ribosomal subunit protein that is required for joining of large and small ribosomal subunits. In this report we demonstrate heterologous complementation of a yeast QSR1 deletion strain with both the human and corn homologs and show that the human and corn proteins are assembled into hybrid yeast/human and yeast/corn ribosomes. While the homologous genes complement lethality of the QSR1 deletion, they also result in a diminished growth rate. Analyses of the translation rates of ribosomes containing the human and corn proteins reveal a partial loss of function. Velocity gradient analyses …


How Do Hmos Achieve Savings? The Effectiveness Of One Organization's Strategies., Ann B. Flood, Allen M. Fremont, K Jin, David M. Bott May 1998

How Do Hmos Achieve Savings? The Effectiveness Of One Organization's Strategies., Ann B. Flood, Allen M. Fremont, K Jin, David M. Bott

Dartmouth Scholarship

To examine how a group practice used organizational strategies rather than provider-level incentives to achieve savings for health maintenance organization (HMO) compared to fee-for-service (FFS) patients. A large group practice with a group model HMO also treating FFS patients. Data sources were all patient encounter records, demographic files, and clinic records covering 3.5 years (1986-1989). The clinic's procedures to record services and charges were identical for FFS and HMO patients. All FFS and HMO patients under age 65 who received any outpatient services during approximately 100,000 episodes of the seven study illnesses were eligible.


The Sequential Role Of Lymphotoxin And B Cells In The Development Of Splenic Follicles, Mercedes Gonzalez, Fabienne Mackay, Jeffrey L. Browning, Marie H. Kosco-Vilbois, Randolph J. Noelle Apr 1998

The Sequential Role Of Lymphotoxin And B Cells In The Development Of Splenic Follicles, Mercedes Gonzalez, Fabienne Mackay, Jeffrey L. Browning, Marie H. Kosco-Vilbois, Randolph J. Noelle

Dartmouth Scholarship

The transfer of lymphocytes into severe combined immunodeficiency (SCID) mice induces a series of histological changes in the spleen, including the appearance of mature follicular dendritic cells (FDCs). Studies were undertaken to clarify the role of lymphotoxin (LT) in this process. The results show that SCID mice have a small and partially differentiated white pulp containing marginal zone and interdigitating dendritic cells, but lacking FDCs. Transferred spleen cells can segregate into T and B cell areas shortly after their injection to SCID mice. This ability is dependent on signaling through LT-β receptor (LT-βR), since blocking ligand–receptor interaction in recipient SCID …


Antigen-Specific Cd8+ T Cells Protect Against Lethal Toxoplasmosis In Mice Infected With Neospora Caninum, Lloyd H. Kasper, Imtiaz A. Khan Apr 1998

Antigen-Specific Cd8+ T Cells Protect Against Lethal Toxoplasmosis In Mice Infected With Neospora Caninum, Lloyd H. Kasper, Imtiaz A. Khan

Dartmouth Scholarship

Neospora caninum is a coccidial protozoan parasite that appears morphologically indistinguishable from Toxoplasma gondii and that infects a large range of mammals. Both inbred and outbred strains of mice exhibit a high degree of resistance to infection with N. caninum. Three inbred strains of mice (A/J, BALB/c, and C57BL/6) that were infected intraperitoneally with N. caninum were protected against a lethal challenge from T. gondii. Vaccine-induced protection was Neospora dose dependent. A rise in the CD8+ T-cell population in mice that had been vaccinated with N. caninum and challenged with T. gondii was observed. Adoptive transfer of CD8+ T-cell splenocytes …


Interprofessional Working And Continuing Medical Education., Linda Headrick, Peter Wilcock, Paul Batalden Mar 1998

Interprofessional Working And Continuing Medical Education., Linda Headrick, Peter Wilcock, Paul Batalden

Dartmouth Scholarship

No abstract provided.


Overexpression Of Glyoxalase-I In Bovine Endothelial Cells Inhibits Intracellular Advanced Glycation Endproduct Formation And Prevents Hyperglycemia-Induced Increases In Macromolecular Endocytosis., Moritsugu Shinohara, P J. Thornalley, Ida Giardino, Paul Beisswenger, Suzanne R. Thorpe, Joelle Onorato, Michael Brownlee Mar 1998

Overexpression Of Glyoxalase-I In Bovine Endothelial Cells Inhibits Intracellular Advanced Glycation Endproduct Formation And Prevents Hyperglycemia-Induced Increases In Macromolecular Endocytosis., Moritsugu Shinohara, P J. Thornalley, Ida Giardino, Paul Beisswenger, Suzanne R. Thorpe, Joelle Onorato, Michael Brownlee

Dartmouth Scholarship

Methylglyoxal (MG), a dicarbonyl compound produced by the fragmentation of triose phosphates, forms advanced glycation endproducts (AGEs) in vitro. Glyoxalase-I catalyzes the conversion of MG to S-D-lactoylglutathione, which in turn is converted to D-lactate by glyoxalase-II. To evaluate directly the effect of glyoxalase-I activity on intracellular AGE formation, GM7373 endothelial cells that stably express human glyoxalase-I were generated. Glyoxalase-I activity in these cells was increased 28-fold compared to neo-transfected control cells (21.80+/-0.1 vs. 0. 76+/-0.02 micromol/min/mg protein, n = 3, P < 0.001). In neo-transfected cells, 30 mM glucose incubation increased MG and D-lactate concentration approximately twofold above 5 MM (35.5+/-5.8 vs. 19.6+/-1.6, P < 0.02, n = 3, and 21.0+/-1.3 vs. 10.0+/-1.2 pmol/ 10(6) cells, n = 3, P < 0.001, respectively). In contrast, in glyoxalase-I-transfected cells, 30 mM glucose incubation did not increase MG concentration at all, while increasing the enzymatic product D-lactate by > 10-fold (18.9+/-3.2 vs. 18.4+/- 5.8, n = 3, P = NS, and 107.1+/-9.0 vs. 9.4+/-0 pmol/10(6) cells, n = …


Chlamydia Trachomatis Infection In The Female Reproductive Tract Of The Rat: Influence Of Progesterone On Infectivity And Immune Response, Charu Kaushic, Andrew D. Murdin, Brian J. Underdown, Charles R. Wira Mar 1998

Chlamydia Trachomatis Infection In The Female Reproductive Tract Of The Rat: Influence Of Progesterone On Infectivity And Immune Response, Charu Kaushic, Andrew D. Murdin, Brian J. Underdown, Charles R. Wira

Dartmouth Scholarship

As the most common cause of sexually transmitted disease in women, chlamydial infections can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To better understand the role played by sex hormones in modulating the immune response of the genital tract to microbial infections, we have developed a rat model to study Chlamydia trachomatis infection. Inbred female Lewis rats were primed with progesterone and inoculated by intrauterine instillation of C. trachomatis (mouse pneumonitis strain MoPn) into each uterine horn. When infected animals were examined for the presence of chlamydial antigens 14 days postinfection, both the uterus and vagina were found …


Subcellular Localization Of Mineralocorticoid Receptors In Living Cells: Effects Of Receptor Agonists And Antagonists, Géza Fejes-Tóth, David Pearce, Anikó Náray-Fejes-Tóth Mar 1998

Subcellular Localization Of Mineralocorticoid Receptors In Living Cells: Effects Of Receptor Agonists And Antagonists, Géza Fejes-Tóth, David Pearce, Anikó Náray-Fejes-Tóth

Dartmouth Scholarship

Results on the subcellular localization of the mineralocorticoid receptor (MR) have been controversial. To determine the subcellular distribution and trafficking of the MR in living cells after binding of agonists and antagonists, we expressed a MR-green fluorescent protein (GFP) chimera in mammalian cells lacking endogenous MR. The GFP-tagged MR (GFP-MR) remained transcriptionally active, as determined in cotransfection experiments with the MR-responsive reporter, TAT3-LUC. The subcellular localization of GFP-MR was monitored by fluorescence time-lapse microscopy. In the absence of hormone, MR was present both in the cytoplasm and nucleus. Aldosterone induced a rapid nuclear accumulation of the MR. Aldosterone-bound GFP-MR was …


A Longitudinal Study Of Hospitalization Rates For Patients With Chronic Disease: Results From The Medical Outcomes Study., Eugene C. Nelson, Colleen A. Mchorney, Willard G. Manning, W H. Rogers Mar 1998

A Longitudinal Study Of Hospitalization Rates For Patients With Chronic Disease: Results From The Medical Outcomes Study., Eugene C. Nelson, Colleen A. Mchorney, Willard G. Manning, W H. Rogers

Dartmouth Scholarship

To prospectively compare inpatient and outpatient utilization rates between prepaid (PPD) and fee-for-service (FFS) insurance coverage for patients with chronic disease. Data from the Medical Outcomes Study, a longitudinal observational study of chronic disease patients conducted in Boston, Chicago, and Los Angeles.A four-year prospective study of resource utilization among 1,681 patients under treatment for hypertension, diabetes, myocardial infarction, or congestive heart failure in the practices of 367 clinicians.


Investigation Of The Roles Of Toxin-Coregulated Pili And Mannose-Sensitive Hemagglutinin Pili In The Pathogenesis Of Vibrio Cholerae O139 Infection, Carol O. Tacket, Ronald K. Taylor, Genevieve Losonsky, Yu Lim Feb 1998

Investigation Of The Roles Of Toxin-Coregulated Pili And Mannose-Sensitive Hemagglutinin Pili In The Pathogenesis Of Vibrio Cholerae O139 Infection, Carol O. Tacket, Ronald K. Taylor, Genevieve Losonsky, Yu Lim

Dartmouth Scholarship

In this study, adult volunteers were fed tcpA and mshA deletion mutants of V. cholerae O139 strain CVD 112 to determine the role of toxin-coregulated pili (TCP) and mannose-sensitive hemagglutinin (MSHA) in intestinal colonization. Eight of 10 volunteers who received CVD 112 or CVD 112 ΔmshA shed the vaccine strains in their stools; the geometric mean peak excretion for both groups was 1.4 × 105 CFU/g of stool. In contrast, only one of nine recipients of CVD 112 ΔtcpA shed vibrios in his stool (P < 0.01); during the first 24 h after inoculation, 3 × 102 CFU/g was recovered from this volunteer. All recipients of CVD …


A Vacuolar V–T-Snare Complex, The Predominant Form In Vivo And On Isolated Vacuoles, Is Disassembled And Activated For Docking And Fusion, Christian Ungermann, Benjamin J. Nichols, Hugh R. B. Pelham, William Wickner Jan 1998

A Vacuolar V–T-Snare Complex, The Predominant Form In Vivo And On Isolated Vacuoles, Is Disassembled And Activated For Docking And Fusion, Christian Ungermann, Benjamin J. Nichols, Hugh R. B. Pelham, William Wickner

Dartmouth Scholarship

Homotypic vacuole fusion in yeast requires Sec18p (N-ethylmaleimide-sensitive fusion protein [NSF]), Sec17p (soluble NSF attachment protein [alpha-SNAP]), and typical vesicle (v) and target membrane (t) SNAP receptors (SNAREs). We now report that vacuolar v- and t-SNAREs are mainly found with Sec17p as v-t-SNARE complexes in vivo and on purified vacuoles rather than only transiently forming such complexes during docking, and disrupting them upon fusion. In the priming reaction, Sec18p and ATP dissociate this v-t-SNARE complex, accompanied by the release of Sec17p. SNARE complex structure governs each functional aspect of priming, as the v-SNARE regulates the rate of Sec17p release and, …


Adenoma Characteristics At First Colonoscopy As Predictors Of Adenoma Recurrence And Characteristics At Follow-Up, Rosalind U. Van Stolk, Gerald J. Beck, John A. Baron, Robert Haile, Robert Summers Jan 1998

Adenoma Characteristics At First Colonoscopy As Predictors Of Adenoma Recurrence And Characteristics At Follow-Up, Rosalind U. Van Stolk, Gerald J. Beck, John A. Baron, Robert Haile, Robert Summers

Dartmouth Scholarship

All patients with colorectal adenomas may not require identical follow-up. We aimed to determine if adenoma characteristics at initial colonoscopy could predict adenoma recurrence or characteristics at follow-up. The number of adenomas and the size, type, and degree of atypia in 479 patients in a polyp prevention trial were evaluated as predictors of the same characteristics at follow-up using odds ratios (ORs) with 95% confidence intervals (CIs). Multiple logistic regression analysis was performed to determine if several baseline characteristics were simultaneously associated with outcome.


A Dichotomous Role For Nitric Oxide During Acute Toxoplasma Gondii Infection In Mice, Imtiaz A. Khan, Joseph D. Schwartzman, Tadashi Matsuura, Lloyd H. Kasper Dec 1997

A Dichotomous Role For Nitric Oxide During Acute Toxoplasma Gondii Infection In Mice, Imtiaz A. Khan, Joseph D. Schwartzman, Tadashi Matsuura, Lloyd H. Kasper

Dartmouth Scholarship

Production of nitric oxide by macrophages is believed to be an important microbicidal mechanism for a variety of intracellular pathogens, including Toxoplasma gondii. Mice with a targeted disruption of the inducible nitric oxide synthase gene (iNOS) were infected orally with T. gondii tissue cysts. Time to death was prolonged compared with parental controls. Histologic analysis of tissue from infected mice showed scattered small foci of inflammation with parasites in various tissues of iNOS−/− mice, whereas tissue from the parental C57BL/6 mice had more extensive tissue inflammation with few visible parasites. In particular, extensive ulceration and necrosis of distal small …


Mitotic Spindle Poles Are Organized By Structural And Motor Proteins In Addition To Centrosomes, Tirso Gaglio, Mary A. Dionne, Duane A. Duane A. Compton Sep 1997

Mitotic Spindle Poles Are Organized By Structural And Motor Proteins In Addition To Centrosomes, Tirso Gaglio, Mary A. Dionne, Duane A. Duane A. Compton

Dartmouth Scholarship

The focusing of microtubules into mitotic spindle poles in vertebrate somatic cells has been assumed to be the consequence of their nucleation from centrosomes. Contrary to this simple view, in this article we show that an antibody recognizing the light intermediate chain of cytoplasmic dynein (70.1) disrupts both the focused organization of microtubule minus ends and the localization of the nuclear mitotic apparatus protein at spindle poles when injected into cultured cells during metaphase, despite the presence of centrosomes. Examination of the effects of this dynein-specific antibody both in vitro using a cell-free system for mitotic aster assembly and in …


The Type 2 Iodothyronine Deiodinase Is Expressed Primarily In Glial Cells In The Neonatal Rat Brain, Ana Guadaño-Ferraz, Maria Jesus Obregón, Donald L. St. Germain, Juan Bernal Sep 1997

The Type 2 Iodothyronine Deiodinase Is Expressed Primarily In Glial Cells In The Neonatal Rat Brain, Ana Guadaño-Ferraz, Maria Jesus Obregón, Donald L. St. Germain, Juan Bernal

Dartmouth Scholarship

Thyroid hormone plays an essential role in mammalian brain maturation and function, in large part by regulating the expression of specific neuronal genes. In this tissue, the type 2 deiodinase (D2) appears to be essential for providing adequate levels of the active thyroid hormone 3,5,3′-triiodothyronine (T3) during the developmental period. We have studied the regional and cellular localization of D2 mRNA in the brain of 15-day-old neonatal rats. D2 is expressed in the cerebral cortex, olfactory bulb, hippocampus, caudate, thalamus, hypothalamus, and cerebellum and was absent from the white matter. At the cellular level, D2 is expressed predominantly, if not …


A Novel Polymorphism Of Fcgammariiia (Cd16) Alters Receptor Function And Predisposes To Autoimmune Disease, Jianming Wu, Jeffrey C. Edberg, Patricia B. Redecha, Vipin Bansal, Paul M. Guyre, Kimberly Coleman, Jane E. Salmon, Robert P. Kimberly Sep 1997

A Novel Polymorphism Of Fcgammariiia (Cd16) Alters Receptor Function And Predisposes To Autoimmune Disease, Jianming Wu, Jeffrey C. Edberg, Patricia B. Redecha, Vipin Bansal, Paul M. Guyre, Kimberly Coleman, Jane E. Salmon, Robert P. Kimberly

Dartmouth Scholarship

A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects ligand binding by natural killer (NK) cells and monocytes from genotyped homozygous normal donors independently of receptor expression. The nonconservative T to G substitution at nucleotide 559 predicts a change of phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes bound more IgG1 and IgG3 despite identical levels of receptor expression. In response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on NK cells from V/V (high-binding) homozygotes led to a larger …


Sqt1, Which Encodes An Essential Wd Domain Protein Of Saccharomyces Cerevisiae, Suppresses Dominant-Negative Mutations Of The Ribosomal Protein Gene Qsr1., Dominic P. Eisinger, Frederick A. Dick, Elke Denke, Bernard L. Trumpower Sep 1997

Sqt1, Which Encodes An Essential Wd Domain Protein Of Saccharomyces Cerevisiae, Suppresses Dominant-Negative Mutations Of The Ribosomal Protein Gene Qsr1., Dominic P. Eisinger, Frederick A. Dick, Elke Denke, Bernard L. Trumpower

Dartmouth Scholarship

QSR1 is an essential Saccharomyces cerevisiae gene, which encodes a 60S ribosomal subunit protein required for joining of 40S and 60S subunits. Truncations of QSR1 predicted to encode C-terminally truncated forms of Qsr1p do not substitute for QSR1 but do act as dominant negative mutations, inhibiting the growth of yeast when expressed from an inducible promoter. The dominant negative mutants exhibit a polysome profile characterized by 'half-mer' polysomes, indicative of a subunit joining defect like that seen in other qsr1 mutants (D. P. Eisinger, F. A. Dick, and B. L. Trumpower, Mol. Cell. Biol. 17:5136-5145, 1997.) By screening a high-copy …


Increased Focal Adhesion Kinase- And Urokinase-Type Plasminogen Activator Receptor-Associated Cell Signaling In Endothelial Cells Exposed To Asbestos, A Barchowsky, B M. Lannon, L C. Elmore, M D. Treadwell Sep 1997

Increased Focal Adhesion Kinase- And Urokinase-Type Plasminogen Activator Receptor-Associated Cell Signaling In Endothelial Cells Exposed To Asbestos, A Barchowsky, B M. Lannon, L C. Elmore, M D. Treadwell

Dartmouth Scholarship

Exposure of low-passage endothelial cells in culture to nonlethal amounts of asbestos, but not refractory ceramic fiber-1, increases cell motility and gene expression. These changes may be initiated by the fibers mimicking matrix proteins as ligands for receptors on the cell surface. In the present study, 1- to 3-hr exposures of endothelial cells to 5 mg/cm2 of chrysotile asbestos caused marked cell elongation and motility. However, little morphological change was seen when chrysotile was added to cells pretreated with either mannosamine to prevent assembly of glycophosphatidylinositol (GPI)-anchored receptors or with herbimycin A to inhibit tyrosine kinase activity. Affinity purification of …


Cell Signaling Pathways Elicited By Asbestos, B T. Mossman, S Faux, Y Janssen, L A. Jimenez, Cynthia Timblin, Christine Zanella, Jonathan Goldberg, Eric Walsh, Aaron Barchowsky, Kevin Driscoll Sep 1997

Cell Signaling Pathways Elicited By Asbestos, B T. Mossman, S Faux, Y Janssen, L A. Jimenez, Cynthia Timblin, Christine Zanella, Jonathan Goldberg, Eric Walsh, Aaron Barchowsky, Kevin Driscoll

Dartmouth Scholarship

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to …


Qsr1p, A 60s Ribosomal Subunit Protein, Is Required For Joining Of 40s And 60s Subunits., Dominic P. Eisinger, Frederick A. Dick, Bernard L. Trumpower Sep 1997

Qsr1p, A 60s Ribosomal Subunit Protein, Is Required For Joining Of 40s And 60s Subunits., Dominic P. Eisinger, Frederick A. Dick, Bernard L. Trumpower

Dartmouth Scholarship

QSR1 is a recently discovered, essential Saccharomyces cerevisiae gene, which encodes a 60S ribosomal subunit protein. Thirty-one unique temperature-sensitive alleles of QSR1 were generated by regional codon randomization within a conserved 20-amino-acid sequence of the QSR1-encoded protein. The temperature-sensitive mutants arrest as viable, large, unbudded cells 24 to 48 h after a shift to 37 degrees C. Polysome and ribosomal subunit analysis by velocity gradient centrifugation of lysates from temperature-sensitive qsr1 mutants and from cells in which Qsr1p was depleted by down regulation of an inducible promoter revealed the presence of half-mer polysomes and a large pool of free 60S …