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1.
Phys Rev Lett ; 124(2): 022501, 2020 Jan 17.
Article in English | MEDLINE | ID: mdl-32004026

ABSTRACT

Spectroscopic factors of neutron-hole and proton-hole states in ^{131}Sn and ^{131}In, respectively, were measured using one-nucleon removal reactions from doubly magic ^{132}Sn at relativistic energies. For ^{131}In, a 2910(50)-keV γ ray was observed for the first time and tentatively assigned to a decay from a 5/2^{-} state at 3275(50) keV to the known 1/2^{-} level at 365 keV. The spectroscopic factors determined for this new excited state and three other single-hole states provide first evidence for a strong fragmentation of single-hole strength in ^{131}Sn and ^{131}In. The experimental results are compared to theoretical calculations based on the relativistic particle-vibration coupling model and to experimental information for single-hole states in the stable doubly magic nucleus ^{208}Pb.

2.
AJNR Am J Neuroradiol ; 40(9): 1505-1510, 2019 09.
Article in English | MEDLINE | ID: mdl-31467234

ABSTRACT

BACKGROUND AND PURPOSE: 4D-DSA allows time-resolved 3D imaging of the cerebral vasculature. The aim of our study was to evaluate this method in comparison with the current criterion standard 3D-DSA by qualitative and quantitative means using computational fluid dynamics. MATERIALS AND METHODS: 3D- and 4D-DSA datasets were acquired in patients with cerebral aneurysms. Computational fluid dynamics analysis was performed for all datasets. Using computational fluid dynamics, we compared 4D-DSA with 3D-DSA in terms of both aneurysmal geometry (quantitative: maximum diameter, ostium size [OZ1/2], volume) and hemodynamic parameters (qualitative: flow stability, flow complexity, inflow concentration; quantitative: average/maximum wall shear stress, impingement zone, low-stress zone, intra-aneurysmal pressure, and flow velocity). Qualitative parameters were descriptively analyzed. Correlation coefficients (r, P value) were calculated for quantitative parameters. RESULTS: 3D- and 4D-DSA datasets of 10 cerebral aneurysms in 10 patients were postprocessed. Evaluation of aneurysmal geometry with 4D-DSA (r maximum diameter = 0.98, P maximum diameter <.001; r OZ1/OZ2 = 0.98/0.86, P OZ1/OZ2 < .001/.002; r volume = 0.98, P volume <.001) correlated highly with 3D-DSA. Evaluation of qualitative hemodynamic parameters (flow stability, flow complexity, inflow concentration) did show complete accordance, and evaluation of quantitative hemodynamic parameters (r average/maximum wall shear stress diastole = 0.92/0.88, P average/maximum wall shear stress diastole < .001/.001; r average/maximum wall shear stress systole = 0.94/0.93, P average/maximum wall shear stress systole < .001/.001; r impingement zone = 0.96, P impingement zone < .001; r low-stress zone = 1.00, P low-stress zone = .01; r pressure diastole = 0.84, P pressure diastole = .002; r pressure systole = 0.9, P pressure systole < .001; r flow velocity diastole = 0.95, P flow velocity diastole < .001; r flow velocity systole = 0.93, P flow velocity systole < .001) did show nearly complete accordance between 4D- and 3D-DSA. CONCLUSIONS: Despite a different injection protocol, 4D-DSA is a reliable basis for computational fluid dynamics analysis of the intracranial vasculature and provides equivalent visualization of aneurysm geometry compared with 3D-DSA.


Subject(s)
Angiography, Digital Subtraction/methods , Hydrodynamics , Intracranial Aneurysm/diagnostic imaging , Neuroimaging/methods , Algorithms , Female , Hemodynamics , Humans , Imaging, Three-Dimensional/methods , Male , Middle Aged
3.
J Bacteriol ; 201(6)2019 03 15.
Article in English | MEDLINE | ID: mdl-30602488

ABSTRACT

S. epidermidis is a primary cause of biofilm-mediated infections in humans due to adherence to foreign bodies. A major staphylococcal biofilm accumulation molecule is polysaccharide intracellular adhesin (PIA), which is synthesized by enzymes encoded by the icaADBC operon. Expression of PIA is highly variable among clinical isolates, suggesting that PIA expression levels are selected in certain niches of the host. However, the mechanisms that govern enhanced icaADBC transcription and PIA synthesis in these isolates are not known. We hypothesized that enhanced PIA synthesis in these isolates was due to function of IcaR and/or TcaR. Thus, two S. epidermidis isolates (1457 and CSF41498) with different icaADBC transcription and PIA expression levels were studied. Constitutive expression of both icaR and tcaR demonstrated that both repressors are functional and can completely repress icaADBC transcription in both 1457 and CSF41498. However, it was found that IcaR was the primary repressor for CSF41498 and TcaR was the primary repressor for 1457. Further analysis demonstrated that icaR transcription was repressed in 1457 in comparison to CSF41498, suggesting that TcaR functions as a repressor only in the absence of IcaR. Indeed, DNase I footprinting suggests IcaR and TcaR may bind to the same site within the icaR-icaA intergenic region. Lastly, we found mutants expressing variable amounts of PIA could rapidly be selected from both 1457 and CSF41498. Collectively, we propose that strains producing enhanced PIA synthesis are selected within certain niches of the host through several genetic mechanisms that function to repress icaR transcription, thus increasing PIA synthesis.IMPORTANCEStaphylococcus epidermidis is a commensal bacterium that resides on our skin. As a commensal, it protects humans from bacterial pathogens through a variety of mechanisms. However, it is also a significant cause of biofilm infections due to its ability to bind to plastic. Polysaccharide intercellular adhesin is a significant component of biofilm, and we propose that the expression of this polysaccharide is beneficial in certain host niches, such as providing extra strength when the bacterium is colonizing the lumen of a catheter, and detrimental in others, such as colonization of the skin surface. We show here that fine-tuning of icaADBC transcription, and thus PIA synthesis, is mediated via two transcriptional repressors, IcaR and TcaR.


Subject(s)
Gene Expression Regulation, Bacterial , Operon , Repressor Proteins/metabolism , Staphylococcus epidermidis/genetics , Staphylococcus epidermidis/metabolism , Transcription, Genetic , Polysaccharides, Bacterial/biosynthesis
4.
ACS Appl Mater Interfaces ; 8(14): 9262-7, 2016 Apr 13.
Article in English | MEDLINE | ID: mdl-26958706

ABSTRACT

We report here an original approach to dope the semiconducting polymer-metal interface in an inverted bulk-heterojunction (BHJ) organic solar cell. Solution-processed 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ), is deposited on top of a P3HT:PC61BM layer before deposition of the top electrode. Doping of P3HT by F4-TCNQ occurs after thermally induced diffusion at 100 °C of the latter into the BHJ. Diffusion and doping are evidenced by XPS and UV-vis-NIR absorption. XPS highlights the decrease in Fluorine concentration on top of the BHJ after annealing. In the same time, a charge transfer band attributed to doping is observed in the UV-vis-NIR absorption spectrum. Inverted polymer solar cells using solution-processed F4-TCNQ exhibit power conversion efficiency of nearly 3.5% after annealing. This simple and efficient approach, together with the low annealing temperature required to allow diffusion and doping, leads to standard efficiency P3HT:PC61BM polymer solar cells, which are suitable for printing on plastic flexible substrate.

5.
Mol Microbiol ; 96(3): 651-69, 2015 May.
Article in English | MEDLINE | ID: mdl-25651868

ABSTRACT

Staphylococcus aureus nitrosative stress resistance is due in part to flavohemoprotein (Hmp). Although hmp is present in all sequenced S. aureus genomes, 37% of analyzed strains also contain nor, encoding a predicted quinol-type nitric oxide (NO) reductase (saNOR). DAF-FM staining of NO-challenged wild-type, nor, hmp and nor hmp mutant biofilms suggested that Hmp may have a greater contribution to intracellular NO detoxification relative to saNOR. However, saNOR still had a significant impact on intracellular NO levels and complemented NO detoxification in a nor hmp mutant. When grown as NO-challenged static (low-oxygen) cultures, hmp and nor hmp mutants both experienced a delay in growth initiation, whereas the nor mutant's ability to initiate growth was comparable with the wild-type strain. However, saNOR contributed to cell respiration in this assay once growth had resumed, as determined by membrane potential and respiratory activity assays. Expression of nor was upregulated during low-oxygen growth and dependent on SrrAB, a two-component system that regulates expression of respiration and nitrosative stress resistance genes. High-level nor promoter activity was also detectable in a cell subpopulation near the biofilm substratum. These results suggest that saNOR contributes to NO-dependent respiration during nitrosative stress, possibly conferring an advantage to nor+ strains in vivo.


Subject(s)
Nitric Oxide/metabolism , Oxidoreductases/metabolism , Staphylococcus aureus/enzymology , Staphylococcus aureus/metabolism , Gene Deletion , Genetic Complementation Test , Nitric Oxide/toxicity , Oxidation-Reduction , Oxidoreductases/genetics , Staphylococcus aureus/genetics , Staphylococcus aureus/growth & development , Stress, Physiological
6.
Nanotechnology ; 26(6): 065602, 2015 Feb 13.
Article in English | MEDLINE | ID: mdl-25605224

ABSTRACT

We report on the formation of Ge/Si quantum dots with core/shell structure that are arranged in a three-dimensional body centered tetragonal quantum dot lattice in an amorphous alumina matrix. The material is prepared by magnetron sputtering deposition of Al2O3/Ge/Si multilayer. The inversion of Ge and Si in the deposition sequence results in the formation of thin Si/Ge layers instead of the dots. Both materials show an atomically sharp interface between the Ge and Si parts of the dots and layers. They have an amorphous internal structure that can be crystallized by an annealing treatment. The light absorption properties of these complex materials are significantly different compared to films that form quantum dot lattices of the pure Ge, Si or a solid solution of GeSi. They show a strong narrow absorption peak that characterizes a type II confinement in accordance with theoretical predictions. The prepared materials are promising for application in quantum dot solar cells.

7.
Clin Exp Immunol ; 177(3): 652-61, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24813051

ABSTRACT

Interleukin (IL)-17 plays a critical role in inflammation. Most studies to date have elucidated the inflammatory role of IL-17A, often referred to as IL-17. IL-17F is a member of the IL-17 family bearing 50% homology to IL-17A and can also be present as heterodimer IL-17AF. This study elucidates the distribution and contribution of IL-17A, F and AF in inflammatory arthritis. Neutralizing antibody to IL-17A alone or IL-17F alone or in combination was utilized in the mouse collagen-induced arthritis (CIA) model to elucidate the contribution of each subtype in mediating inflammation. IL-17A, F and AF were all increased during inflammatory arthritis. Neutralization of IL-17A reduced the severity of arthritis, neutralization of IL-17A+IL-17F had the same effect as neutralizing IL-17A, while neutralization of IL-17F had no effect. Moreover, significantly higher levels of IL-17A and IL-17F were detected in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA). IL-17A and AF were detected in synovial fluid mononuclear cells (SFMC) in RA and OA, with IL-17A being significantly higher in RA patients. Enriched CD3(+) T cells from RA PBMCs produced singnificantly high levels of IL-17A and IL-17AF in comparison to OA peripheral blood CD3(+) T cells. IL-17A, F and AF were undetectable in T cells from SFMCs from RA and OA. While IL-17A, F, and AF were all induced during CIA, IL-17A played a dominant role. Furthermore, production of IL-17A, and not IL-17F or IL-17AF, was elevated in PBMCs, SFMCs and enriched peripheral blood CD3(+) T in RA.


Subject(s)
Arthritis, Experimental/immunology , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/metabolism , Interleukin-7/immunology , Interleukin-7/metabolism , Animals , Antibodies/blood , Antibodies/immunology , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/immunology , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Disease Models, Animal , Female , Granulocyte Colony-Stimulating Factor/blood , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Interleukin-6/blood , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , Mice , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
8.
Phys Rev Lett ; 111(17): 172501, 2013 Oct 25.
Article in English | MEDLINE | ID: mdl-24206482

ABSTRACT

The nucleus (154)Gd is located in a region of the nuclear chart where rapid changes of nuclear deformation occur as a function of particle number. It was investigated using a combination of γ-ray scattering experiments and a γγ-coincidence study following electron capture decay of (154)Tb(m). A novel decay channel from the scissors mode to the first excited 0(+) state was observed. Its transition strength was determined to B(M1;1(sc)(+)→0(2)(+))=0.031(4)µ(N)(2). The properties of the scissors mode of (154)Gd imply a much larger matrix element than previously thought for the neutrinoless double-ß decay to the 0(2)(+) state in such a shape-transitional region. Theory indicates an even larger effect for (150)Nd.

9.
J Phys Condens Matter ; 25(17): 175802, 2013 May 01.
Article in English | MEDLINE | ID: mdl-23567796

ABSTRACT

We present a generalization of the Dodson-Tsao kinematic model of misfit dislocation for graded SixGe1-x/Si(001) layers. The layers were prepared under different growing conditions (temperature). The misfit dislocation distribution has been determined by means of high-resolution x-ray scattering. Analysis of the reciprocal space maps was compared with the kinematic Dodson-Tsao model and the equilibrium Tersoff model.

10.
Food Chem Toxicol ; 49(5): 1174-82, 2011 May.
Article in English | MEDLINE | ID: mdl-21338652

ABSTRACT

Some strains of Bacillus coagulans can survive extremes of heat, stomach acid and bile acids, to which commonly consumed probiotics are susceptible. A toxicological safety assessment was published in 2009 on a proprietary preparation of B. coagulans - GanedenBC(30)™ - a novel probiotic. It was concluded that GanedenBC(30)™ is safe for chronic human consumption based upon scientific procedures, supported by a safe history of use (Endres et al., 2009). A one-year chronic oral toxicity study combined with a one-generation reproduction study was conducted to further investigate safety of long-term consumption. The one-year study of GanedenBC(30)™ administered to male and female HsdBrlHan: Wistar rats in their diet showed no signs of toxicity at the highest dose tested. The conclusion from the reproduction toxicity study is that administration of GanedenBC(30)™ in the diet caused no signs of toxicity in the parental generation (male or female) nor the F1 offspring. Using the lowest NOEL of 1948 mg/kg concluded at the end of the 1-year feeding study, a 100-fold safety factor, a test article concentration of 6.88×10(10) CFU (colony forming units) per gram, and an average 70 kg human, it is determined that GanedenBC(30)™ is safe for chronic consumption at up to 9.38×10(10) CFUs per day.


Subject(s)
Bacillus , Dietary Supplements , Probiotics/toxicity , Reproduction/drug effects , Administration, Oral , Animals , Consumer Product Safety , Diet , Dose-Response Relationship, Drug , Female , Food Analysis , Male , No-Observed-Adverse-Effect Level , Rats , Rats, Wistar , Toxicity Tests, Chronic
11.
Regul Toxicol Pharmacol ; 57(1): 55-61, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20043970

ABSTRACT

The dietary supplement, 112 Degrees, was formulated with the goal of supporting sexual functioning in men. Due to rampant problems with drug adulteration for this category of products, a comprehensive screening for active pharmaceutical agents, with an emphasis on drugs prescribed for erectile dysfunction such as type 5 phosphodiesterase (PDE-5) inhibitors, and known unapproved PDE-5 drug analogues, was performed along with preclinical toxicology studies prior to the introduction of this product into the marketplace. 112 Degrees was found to be free of all pharmaceutical adulterants tested, and was not mutagenic, clastogenic, or genotoxic as demonstrated by the Ames test, chromosomal aberration assay, and mouse micronucleus assay, respectively. The LD(50) in the 14-day acute oral toxicity study was greater than 5000 mg/kg, the highest dose tested.


Subject(s)
Consumer Product Safety , Dietary Supplements/toxicity , Sexual Behavior/drug effects , Animals , CHO Cells , Cricetinae , Cricetulus , Dose-Response Relationship, Drug , Drug Contamination , Drug Evaluation, Preclinical , Female , Humans , Lethal Dose 50 , Male , Mice , Mice, Inbred BALB C , Micronuclei, Chromosome-Defective/chemically induced , Micronucleus Tests , Mutation , Rats , Rats, Sprague-Dawley , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Toxicity Tests, Chronic
12.
Phys Rev Lett ; 105(21): 212503, 2010 Nov 19.
Article in English | MEDLINE | ID: mdl-21231295

ABSTRACT

The pygmy dipole resonance has been studied in the proton-magic nucleus 124Sn with the (α, α'γ) coincidence method at Eα=136 MeV. The comparison with results of photon-scattering experiments reveals a splitting into two components with different structure: one group of states which is excited in (α, α'γ) as well as in (γ, γ') reactions and a group of states at higher energies which is only excited in (γ, γ') reactions. Calculations with the self-consistent relativistic quasiparticle time-blocking approximation and the quasiparticle phonon model are in qualitative agreement with the experimental results and predict a low-lying isoscalar component dominated by neutron-skin oscillations and a higher-lying more isovector component on the tail of the giant dipole resonance.

13.
Food Chem Toxicol ; 48(3): 831-8, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20035819

ABSTRACT

Rev7 is an indigestible gum polymer used for the manufacturing of chewing gum. It allows for the formulation of chewing gum with low adhesion; thus can be readily removed from surfaces such as sidewalks, clothing, carpets and furniture. In a toxicological safety assessment, Rev7 was found to be non-mutagenic in the AMES assay. The highest concentration tested in a mouse lymphoma thymidine kinase locus gene mutation assay induced a slight but biologically relevant increase in mutations under non-metabolic activation conditions after 24h. Because of this finding, a mouse micronucleus assay was performed, and the test article was found to be negative for inducing chromosomal damage. A 28-day repeated oral toxicity study resulted in a NOAEL of 80,000 ppm; the highest concentration tested. Rev7 was found to be free from contaminants such as heavy metals, monomers, and solvents. Lastly, Rev7 did not demonstrate skin-sensitizing properties in the murine local lymph node assay.


Subject(s)
Chewing Gum/toxicity , Polymers/therapeutic use , Succinates/therapeutic use , Animals , Butylated Hydroxytoluene/analysis , Erythrocytes/drug effects , Erythrocytes/ultrastructure , Female , Local Lymph Node Assay , Male , Metals, Heavy/analysis , Mice , Micronucleus Tests , Mutagenicity Tests , Rats , Rats, Sprague-Dawley , Safety , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Solvents/analysis , Thymidine Kinase/drug effects , Thymidine Kinase/genetics
14.
Int J Toxicol ; 28(6): 479-87, 2009.
Article in English | MEDLINE | ID: mdl-19966140

ABSTRACT

The dietary supplement Citicoline free-base (choline cytidine 5'-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.


Subject(s)
Cytidine Diphosphate Choline/toxicity , Nootropic Agents/toxicity , Administration, Oral , Animals , Blood Cell Count , Blood Chemical Analysis , Calcinosis/chemically induced , Calcinosis/pathology , Creatinine/blood , Female , Kidney/pathology , Kidney Diseases/chemically induced , Kidney Diseases/pathology , Kidney Tubules/pathology , Lethal Dose 50 , Male , Organ Size/drug effects , Rats , Rats, Sprague-Dawley , Time Factors , Urodynamics/drug effects
15.
Food Chem Toxicol ; 47(6): 1231-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19248815

ABSTRACT

It has been demonstrated that some strains of Bacillus coagulans can survive extremes of heat, acidity of the stomach, and bile acids, to which commonly consumed probiotics are susceptible. A toxicological safety assessment was performed on a proprietary preparation of B. coagulans - GanedenBC(30) - a novel probiotic. Seven toxicologic studies were conducted and included: in vitro bacterial reverse mutation assay; in vitro chromosomal aberration assay; micronucleus assay in mice; acute and 90 day subchronic repeated oral toxicity studies were conducted in Wistar Crl:(WI) BR rats; acute eye and skin irritation studies were conducted in rabbits. The results of this toxicological safety assessment indicate that GanedenBC(30)B. coagulans does not demonstrate mutagenic, clastogenic, or genotoxic effects. Furthermore, the results of the acute and 90-day subchronic oral toxicity studies in rats resulted in the conclusion of a NOAEL greater than 1000 mg/kg per day. Since the concentration of the cell mass used in the 90-day study was 1.36 x 10(11) CFUs/g, this corresponds to 95.2 x 10(11) CFUs for a 70 kg human and since the suggested human dose is in the range of 100 x 10(6) to 3 x 10(9) CFUs, this gives a safety factor ranging from 3173 to 95,200 times. Based upon scientific procedures and supported by history of use, GanedenBC(30) is considered safe for chronic human consumption.


Subject(s)
Bacillus/physiology , Probiotics/adverse effects , Animals , Blood Chemical Analysis , Chromosome Aberrations/drug effects , Eye/drug effects , Eye/pathology , Food , In Vitro Techniques , Irritants/toxicity , Male , Mice , Mice, Inbred BALB C , Micronucleus Tests , Mutagenicity Tests , No-Observed-Adverse-Effect Level , Rabbits , Rats , Rats, Wistar , Safety , Skin/drug effects , Skin/pathology , Weight Gain/drug effects
16.
Surg Endosc ; 16(5): 799-802, 2002 May.
Article in English | MEDLINE | ID: mdl-11997825

ABSTRACT

BACKGROUND: Intraoperative cholangiography (IOC) is frequently omitted in patients undergoing laparoscopic cholecystectomy (LC) if they have had successful preoperative endoscopic retrograde cholangiography (ERC). METHODS: A prospectively maintained divisional laparoscopic cholecystectomy database was searched from 1991 to 1997 for patients who had IOC after preoperative ERC. The presence of recurrent or residual common duct stones seen on IOC and their impact on subsequent management were evaluated. RESULTS: We identified a group of 127 patients who underwent preoperative ERC. Thirty-one patients (31/127, or 24%) went on to receive an IOC during cholecystectomy. In 15 patients whose preoperative ERC was reported normal, five (33%) had an abnormal IOC. In 16 patients whose ERC was reported as having cleared the duct, eight (50%) had an IOC abnormality. Eight of these 31 patients required a further procedure to clear the duct. CONCLUSION: Retained or recurrent common duct stones at cholecystectomy following diagnostic or therapeutic ERC were more common than expected. Therefore, IOC is recommended during LC regardless of the findings yielded by the preoperative ERC.


Subject(s)
Cholangiography/methods , Cholelithiasis/surgery , Endoscopy, Digestive System/methods , Adult , Aged , Cholecystectomy, Laparoscopic/methods , Cholelithiasis/diagnostic imaging , Diagnostic Errors/methods , Female , Gallstones/diagnostic imaging , Gallstones/surgery , Humans , Prospective Studies , Recurrence , Treatment Failure
17.
J Clin Invest ; 107(10): 1275-84, 2001 May.
Article in English | MEDLINE | ID: mdl-11375417

ABSTRACT

Dendritic cells (DCs) are specialized antigen-presenting cells that migrate from the periphery to lymphoid tissues, where they activate and regulate T cells. Genetic modification of DCs to express immunoregulatory molecules would provide a new immunotherapeutic strategy for autoimmune and other diseases. We have engineered bone marrow-derived DCs that express IL-4 and tested the ability of these cells to control murine collagen-induced arthritis (CIA), a model for rheumatoid arthritis in which Th1 cells play a critical role. IL-4-transduced DCs inhibited Th1 responses to collagen type II in vitro. A single injection of IL-4-transduced DCs reduced the incidence and severity of CIA and suppressed established Th1 responses and associated humoral responses, despite only transient persistence of injected DCs in the spleen. In contrast, control DCs and IL-4-transduced T cells or fibroblastic cells failed to alter the course of the disease. The functional effects correlated well with the differential efficiency of DC migration from various sites of injection to lymphoid organs, especially the spleen. The ability of splenic T cells to produce IL-4 in response to anti-CD3 was enhanced after the administration of IL-4-transduced DCS: These results support the feasibility of using genetically modified DCs for the treatment of autoimmune disease.


Subject(s)
Arthritis, Rheumatoid/therapy , Dendritic Cells/transplantation , Interleukin-4/biosynthesis , Interleukin-4/genetics , Animals , Arthritis, Rheumatoid/chemically induced , Bone Marrow Transplantation , Cell Movement , Collagen , Genetic Engineering , Immunotherapy/methods , Mice , Retroviridae/genetics , Spleen/cytology , Spleen/immunology
18.
J Immunol ; 166(4): 2270-5, 2001 Feb 15.
Article in English | MEDLINE | ID: mdl-11160281

ABSTRACT

Synovial tissue in rheumatoid arthritis is characterized by infiltration with large numbers of T lymphocytes and APCs as well as hyperplasia of synovial fibroblasts. Current understanding of the pathogenesis of RA includes the concept that synovial fibroblasts, which are essential to cartilage and bone destruction, are regulated by cytokines derived primarily from monocyte-macrophage cells. Recently it has been found that synovial fibroblasts can also function as accessory cells for T cell activation by superantigens and other stimuli. We have now found that highly purified resting T cells, even in the absence of T cell mitogens, induce activation of synovial fibroblasts when cocultured for 6-24 h. Such activation was evident by induction or augmentation of mRNA for stromelysin, IL-6, and IL-8, gene products important in joint inflammation and joint destruction. Furthermore, increased production of IL-6 and IL-8 was quantitated by intracellular cytokine staining and flow cytometry. This technique, previously used for analysis of T cell function, was readily adaptable for assays of synovial fibroblasts. Resting T cells also induced synovial fibroblasts to produce PGE(2), indicating activation of expression of the cyclooxygenase 2 gene. Synergy was observed between the effects of IL-17, a cytokine derived from stimulated T cells that activates fibroblasts, and resting T lymphocytes. Various subsets of T cells, CD4(+), CD8(+), CD45RO(+), and CD45RA(+) all had comparable ability to induce synovial fibroblast activation. These results establish an Ag-independent effector function for resting T cells that is likely to be important in inflammatory compartments in which large numbers of T lymphocytes and fibroblasts can come into direct contact with each other.


Subject(s)
Fibroblasts/immunology , Fibroblasts/metabolism , Synovial Membrane/immunology , Synovial Membrane/metabolism , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/immunology , Adjuvants, Immunologic/pharmacology , Antigens, Differentiation, T-Lymphocyte/analysis , Antigens, Differentiation, T-Lymphocyte/biosynthesis , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Cell Communication/immunology , Cell Line , Coculture Techniques , Cytokines/biosynthesis , Cytokines/genetics , Dinoprostone/biosynthesis , Humans , Immunophenotyping , Interleukin-17/pharmacology , Interphase/immunology , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Synovial Membrane/cytology , Synovial Membrane/pathology , T-Lymphocyte Subsets/metabolism , T-Lymphocyte Subsets/pathology
19.
J Nutr Educ ; 33(1): 37-42, 2001.
Article in English | MEDLINE | ID: mdl-12031204

ABSTRACT

A multimedia touch-screen kiosk was used to assess food safety knowledge and convey food safety principles to 93 high school science teachers and 165 students. The kiosk program based on the FightBAC messages informed users of correct responses and reasons for the response. Teachers correctly answered more questions than students; however, for the areas of hand washing, sources of foodborne illness, and handling of leftover foods, at least 40% of both students and teachers provided incorrect answers.


Subject(s)
Computer-Assisted Instruction , Food Handling , Foodborne Diseases/prevention & control , Hygiene , Adolescent , Adult , Faculty , Humans , Science , Students
20.
Arthritis Rheum ; 43(2): 329-35, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10693872

ABSTRACT

OBJECTIVE: CD6, a cell surface glycoprotein expressed primarily on T cells, may function as a costimulatory molecule and may play a role in autoreactive immune responses. Recently, a CD6 ligand termed CD166 (previously known as activated leukocyte cell adhesion molecule [ALCAM]) has been identified and shown to be expressed on activated T cells, B cells, thymic epithelium, keratinocytes, and in rheumatoid arthritis synovial tissue. However, the results of functional studies have suggested the existence of a second CD6 ligand. The present study was undertaken to seek evidence for a second CD6 ligand on cultured synovial fibroblasts. METHODS: Flow cytometric and biochemical techniques were applied, using anti-CD166 monoclonal antibody (mAb) and a recombinant CD6 fusion protein, to determine whether cultured synovial fibroblasts and other cell types expressed a non-ALCAM CD6 ligand. RESULTS: CD14- fibroblastic synoviocytes showed greater binding of a recombinant CD6 fusion protein than of anti-ALCAM mAb. With interferon-gamma treatment of synovial fibroblasts, binding of both reagents increased, but this was more marked for binding of CD6 fusion protein. Exposure of synovial fibroblasts to other cytokines or to the superantigen staphylococcal enterotoxin A also regulated binding of CD6 fusion protein and anti-ALCAM mAb in a discordant manner. Immunoprecipitation of proteins from membrane extracts of synovial fibroblasts with a CD6-Ig fusion protein revealed a novel 130-kd band distinct from CD166; an identical molecule was also precipitated from membranes of HBL-100 tumor cells. CONCLUSION: Taken together with previous data regarding CD6 and CD166 function, the present findings strongly suggest the existence of a second CD6 ligand distinct from CD166, which can be expressed by synovial fibroblasts as well as other cells.


Subject(s)
Activated-Leukocyte Cell Adhesion Molecule/biosynthesis , Fibroblasts/chemistry , Synovial Membrane/cytology , Activated-Leukocyte Cell Adhesion Molecule/chemistry , Cytokines/pharmacology , Fibroblasts/drug effects , Humans , Superantigens/pharmacology
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