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Articles 1 - 22 of 22
Full-Text Articles in Medicine and Health Sciences
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
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 …
Identification And Characterization Of Spcu, A Chaperone Required For Efficient Secretion Of The Exou Cytotoxin, Viviane Finck-Barbançon, Timothy L. Yahr, Dara W. Frank
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 …
The Seca Subunit Of Escherichia Coli Preprotein Translocase Is Exposed To The Periplasm, Jerry Eichler, William Wickner
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
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 …
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
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 …
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
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 …
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
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 …
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
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
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
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 …
How Do Hmos Achieve Savings? The Effectiveness Of One Organization's Strategies., Ann B. Flood, Allen M. Fremont, K Jin, David M. Bott
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.
Heterologous Complementation Reveals That Mutant Alleles Of Qsr1 Render 60s Ribosomal Subunits Unstable And Translationally Inactive, Frederick A. Dick, Bernard L. Trumpower
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 …
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
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
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
Interprofessional Working And Continuing Medical Education., Linda Headrick, Peter Wilcock, Paul Batalden
Dartmouth Scholarship
No abstract provided.
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
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.
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
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
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
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 …
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
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
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
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.