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1.
Nanotechnology ; 28(4): 044001, 2017 Jan 27.
Article in English | MEDLINE | ID: mdl-27981945

ABSTRACT

Poly(styrene)-block-poly(dimethylsiloxane) (PS-b-PDMS) is an excellent block copolymer (BCP) system for self-assembly and inorganic template fabrication because of its high Flory-Huggins parameter (χ âˆ¼ 0.26) at room temperature in comparison to other BCPs, and high selective etch contrast between PS and PDMS block for nanopatterning. In this work, self-assembly in PS-b-PDMS BCP is achieved by combining hydroxyl-terminated poly(dimethylsiloxane) (PDMS-OH) brush surfaces with solvent vapor annealing. As an alternative to standard brush chemistry, we report a simple method based on the use of surfaces functionalized with silane-based self-assembled monolayers (SAMs). A solution-based approach to SAM formation was adopted in this investigation. The influence of the SAM-modified surfaces upon BCP films was compared with polymer brush-based surfaces. The cylinder forming PS-b-PDMS BCP and PDMS-OH polymer brush were synthesized by sequential living anionic polymerization. It was observed that silane SAMs provided the appropriate surface chemistry which, when combined with solvent annealing, led to microphase segregation in the BCP. It was also demonstrated that orientation of the PDMS cylinders may be controlled by judicious choice of the appropriate silane. The PDMS patterns were successfully used as an on-chip etch mask to transfer the BCP pattern to underlying silicon substrate with sub-25 nm silicon nanoscale features. This alternative SAM/BCP approach to nanopattern formation shows promising results, pertinent in the field of nanotechnology, and with much potential for application, such as in the fabrication of nanoimprint lithography stamps, nanofluidic devices or in narrow and multilevel interconnected lines.

2.
Angew Chem Int Ed Engl ; 56(42): 12913-12918, 2017 10 09.
Article in English | MEDLINE | ID: mdl-28805991

ABSTRACT

We describe single-chain polymer nanoparticles (SCNPs) possessing intramolecular dynamic covalent crosslinks that can transform into polymer films through a molecular recognition-mediated crosslinking process. The SCNPs utilise molecular recognition with surface-immobilised proteins to concentrate upon a substrate, bringing the SCNPs into close spatial proximity with one another and allowing their dynamic covalent crosslinkers to undergo intra- to interpolymer chain crosslinking leading to the formation of polymeric film. SCNPs must possess both the capacity for specific molecular recognition and a dynamic nature to their intramolecular crosslinkers to form polymer films, and an investigation of the initial phase of film formation indicates it proceeds from features which form upon the surface then grow predominantly in the xy directions. This approach to polymer film formation presents a potential method to "wrap" surfaces displaying molecular recognition motifs-which could potentially include viral, cellular and bacterial surfaces or artificial surfaces displaying multivalent recognition motifs-within a layer of polymer film.

3.
Nanotechnology ; 27(9): 095704, 2016 Mar 04.
Article in English | MEDLINE | ID: mdl-26855053

ABSTRACT

A simple, convenient method for the formation of hybrid metal/conductive polymer nanostructures is described. Polyimidazole (PIm) has been templated on λ-DNA via oxidative polymerisation of imidazole using FeCl3 to produce conductive PIm/DNA nanowires. The PIm/DNA nanowires were decorated with Pd (Pd/PIm/DNA) by electroless reduction of PdCl4(-2) with NaBH4 in the presence of PIm/DNA; the choice of imidazole was motivated by the potential Pd(II) binding site at the pyridinic N atom. The formation of PIm/DNA and the presence of metallic Pd on Pd/PIm/DNA nanowires were verified by FTIR, UV-vis and XPS spectroscopy techniques. AFM studies show that the nanowires have diameters in the range 5-45 nm with a slightly greater mean diameter (17.1 ± 0.75 nm) for the Pd-decorated nanowires than the PIm/DNA nanowires (14.5 ± 0.89 nm). After incubation for 24 h in the polymerisation solution, the PIm/DNA nanowires show a smooth, uniform morphology, which is retained after decoration with Pd. Using a combination of scanned conductance microscopy, conductive AFM and two-terminal measurements we show that both types of nanowire are conductive and that it is possible to discriminate different possible mechanisms of transport. The conductivity of the Pd/PIm/DNA nanowires, (0.1-1.4 S cm(-1)), is comparable to the PIm/DNA nanowires (0.37 ± 0.029 S cm(-1)). In addition, the conductance of Pd/PIm/DNA nanowires exhibits Arrhenius behaviour (E(a )= 0.43 ± 0.02 eV) as a function of temperature in contrast to simple Pd/DNA nanowires. These results indicate that although the Pd crystallites on Pd/PIm/DNA nanowires decorate the PIm polymer, the major current pathway is through the polymer rather than the Pd.

4.
Chemistry ; 21(36): 12611-5, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26216718

ABSTRACT

Diazido derivatives of 3,6-diamino acridine (proflavine) intercalate into DNA and undergo functionalization through click chemistry to form 1D nanostructures with redox active, conductive nanowire, and fluorescent properties. This two-step approach, intercalation followed by click modification allows for the controlled decoration of DNA nanostructures.


Subject(s)
Acridines/chemistry , DNA/chemistry , Intercalating Agents/chemistry , Nanostructures/chemistry , Click Chemistry , Molecular Structure
5.
Health Promot Pract ; 16(4): 560-70, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25761916

ABSTRACT

Health promotion programs that develop and implement strategies to promote sun safety practices to children have the potential to reduce skin cancer occurrence later in life. Go Sun Smart (GSS), a sun safety program for employees and guests of ski areas, was distributed to determine if an enhanced dissemination strategy was more effective than a basic dissemination strategy at reaching parents at ski and snowboard schools. On-site observations of GSS use and surveys of 909 parents/caregivers with children enrolled in ski and snowboard schools at 63 ski areas were conducted and analyzed using techniques for clustered designs. No differences were identified by dissemination strategy. Greater implementation of GSS (>5 messages posted) was associated with greater parental recall, 36.6% versus 16.7%, of materials, but not greater sun protection practices. Greater recall of messages, regardless of level of implementation, resulted in greater sun protection practices including applying sunscreen (p < .05), providing sunglasses and goggles (p < .01), and more use of all sun protection practices (p < .01). Ski areas with more program materials appeared to reach parents with sun safety advice and thus convinced them to take more precautions for their children. Sun safety need not be at odds with children's outdoor recreation activities.


Subject(s)
Health Promotion/methods , Skiing , Skin Neoplasms/prevention & control , Sunburn/prevention & control , Sunscreening Agents/therapeutic use , Adolescent , Adult , British Columbia , Child , Child, Preschool , Eye Protective Devices , Female , Health Behavior , Humans , Interviews as Topic , Male , Mental Recall , Pamphlets , Parents/psychology , ROC Curve , Safety Management/methods , Schools , United States , Young Adult
6.
J Am Chem Soc ; 136(18): 6649-55, 2014 May 07.
Article in English | MEDLINE | ID: mdl-24712548

ABSTRACT

Details of the mechanism of formation of supramolecular polymer nanowires by templating on DNA are revealed for the first time using AFM. Overall these data reveal that the smooth, regular, structures produced are rendered by highly dynamic supramolecular transformations occurring over the micrometre scale. In the initial stages of the process a low density of conducting polymer (CP) binds to the DNA as, essentially, spherical particles. Further reaction time produces DNA strands which are more densely packed with particles giving a beads-on-a-string appearance. The particles subsequently undergo dynamic reconfiguration so as to elongate along the template axis and merge to yield the highly regular, smooth morphology of the final nanowire. MD simulations illustrate the early stages of the process showing the binding of globular CP to duplex DNA, while the latter stages can be modeled effectively by a linear thermodynamic description based on the balance between the line energy, which accounts for adhesion of the material to the template, and its surface tension. This model accounts for the phenomena observed in the AFM studies: the relative success of DNA templating of polymers compared to metals; the slow approach to equilibrium; and the observed thinning and 'necking' phenomena as the structures transform from beads-on-a-string to smooth nanowire.


Subject(s)
DNA/chemistry , Nanowires , Polymers/chemistry , Thermodynamics
7.
Chemistry ; 19(39): 13030-9, 2013 Sep 23.
Article in English | MEDLINE | ID: mdl-23934688

ABSTRACT

Stable colloidal dispersions of polyaniline (PAni) nanofibers with controlled lengths from about 200 nm-1.1 µm and narrow length distributions (Lw/Ln < 1.04; Lw = weight average micelle length, Ln = number average micelle length) were prepared through the template-directed synthesis of PAni using monodisperse, solution-self-assembled, cylindrical, block copolymer micelles as nanoscale templates. These micelles were prepared through a crystallization-driven living self-assembly method from a poly(ferrocenyldimethylsilane)-b-poly(2-vinylpyridine) block copolymer (PFS25 -b-P2VP425). This material was initially self-assembled in iPrOH to form cylindrical micelles with a crystalline PFS core and a P2VP corona and lengths of up to several micrometers. Sonication of this sample then yielded short cylinders with average lengths of 90 nm and a broad length distribution (Lw/Ln = 1.32). Cylindrical micelles of PFS25 -b-P2VP425 with controlled lengths and narrow length distributions (Lw/Ln < 1.04) were subsequently prepared using thermal treatment at specific temperatures between 83.5 and 92.0 °C using a 1D self-seeding process. These samples were then employed in the template-directed synthesis of PAni nanofibers through a two-step procedure, where the micellar template was initially stabilised by deposition of an oligoaniline coating followed by addition of a polymeric acid dopant, resulting in PAni nanofibers in the emeraldine salt (ES) state. The ES-PAni nanofibers were shown to be conductive by scanning conductance microscopy, whereas the precursor PFS25-b-P2VP425 micelle templates were found to be dielectric in character.

8.
Chemistry ; 18(38): 12008-19, 2012 Sep 17.
Article in English | MEDLINE | ID: mdl-22887143

ABSTRACT

Supramolecular polymer nanowires have been prepared by using DNA-templating of 2,5-(bis-2-thienyl)-pyrrole (TPT) by oxidation with FeCl(3) in a mixed aqueous/organic solvent system. Despite the reduced capacity for strong hydrogen bonding in polyTPT compared to other systems, such as polypyrrole, the templating proceeds well. FTIR spectroscopic studies confirm that the resulting material is not a simple mixture and that the two types of polymer interact. This is indicated by shifts in bands associated with both the phosphodiester backbone and the nucleobases. XPS studies further confirm the presence of DNA and TPT, as well as dopant Cl(-) ions. Molecular dynamics simulations on a [{dA(24):dT(24)}/{TPT}(4)] model support these findings and indicate a non-coplanar conformation for oligoTPT over much of the trajectory. AFM studies show that the resulting nanowires typically lie in the 7-8 nm diameter range and exhibit a smooth, continuous, morphology. Studies on the electrical properties of the prepared nanowires by using a combination of scanned conductance microscopy, conductive AFM and variable temperature two-terminal I-V measurements show, that in contrast to similar DNA/polymer systems, the conductivity is markedly reduced compared to bulk material. The temperature dependence of the conductivity shows a simple Arrhenius behaviour consistent with the hopping models developed for redox polymers.


Subject(s)
Chlorides/chemistry , DNA/chemistry , Ferric Compounds/chemistry , Nanowires/chemistry , Polymers/chemistry , Pyrroles/chemistry , Pyrroles/chemical synthesis , Electric Conductivity , Molecular Conformation , Oxidation-Reduction , Spectroscopy, Fourier Transform Infrared , Temperature
9.
Nanotechnology ; 23(50): 505603, 2012 Dec 21.
Article in English | MEDLINE | ID: mdl-23196424

ABSTRACT

The thermodynamics of the templating of materials on one-dimensional templates, such as DNA, is modeled by considering two terms: the surface tension of the material (γ) and a line energy (σ = 2πr(T)γ(T)) that represents the adhesion of the material to the template (radius r(T)). We show that as long as the reaction stoichiometry does not exceed a certain limit (√[3ν/2π] < r(T) [absolute value]γ(T)[absolute value]/γ ; ν = volume of material per unit length of template) then a sample of smooth, uniform wires is the equilibrium state. If the amount of material exceeds this limit, then the material will comprise a single macroscopic particle at equilibrium. The behavior of the system is similar to a morphological wetting transition and the model can rationalize the available experimental data on the reaction conditions required to form smooth DNA-templated nanowires. Using the framework of linear non-equilibrium thermodynamics, we also show that the model can describe qualitatively the observed evolution of these nanostructures from beads-on-a-string morphologies to smooth nanowires and construct a stochastic differential equation for the process. Numerical simulations and scaling arguments suggest that the same scaling behavior as the Edwards-Wilkinson equation is observed.


Subject(s)
DNA/chemistry , Nanowires/chemistry , Thermodynamics , Computer Simulation , Models, Chemical , Nanowires/ultrastructure , Surface Tension
10.
Langmuir ; 27(1): 304-11, 2011 Jan 04.
Article in English | MEDLINE | ID: mdl-21141948

ABSTRACT

The propensity of a matrix protein from an enveloped virus of the Mononegavirales family to associate with lipids representative of the viral envelope has been determined using label-free methods, including tensiometry and Brewster angle microscopy on lipid films at the air-water interface and atomic force microscopy on monolayers transferred to OTS-treated silicon wafers. This has enabled factors that influence the disposition of the protein with respect to the lipid interface to be characterized. In the absence of sphingomyelin, respiratory syncytial virus matrix protein penetrates monolayers composed of mixtures of phosphocholines with phosphoethanolamines or cholesterol at the air-water interface. In ternary mixtures composed of sphingomyelin, 1,2-dioleoyl-sn-glycero-3-phosphocholine, and cholesterol, the protein exhibits two separate behaviors: (1) peripheral association with the surface of sphingomyelin-rich domains and (2) penetration of sphingomyelin-poor domains. Prolonged incubation of the protein with mixtures of phosphocholines and phosphoethanolamines leads to the formation of helical protein assemblies of uniform diameter that demonstrate an inherent propensity of the protein to assemble into a filamentous form.


Subject(s)
Lipids/chemistry , Respiratory Syncytial Viruses , Viral Proteins/chemistry , Adsorption , Crystallography, X-Ray , Microscopy , Surface Properties , Viral Proteins/metabolism
11.
Vox Sang ; 100(3): 336-9, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21392023

ABSTRACT

Bacterial contamination of platelet concentrates represents the greatest post-transfusion infectious risk. Biofilm formation in this environment resulting from platelet-bacteria interactions can lead to non-uniform contaminant distribution and thus missed detection. As formation of platelet-bacteria aggregates is largely based on receptor-ligand interactions, we examined whether shielding these events would result in reduced biofilm formation by contaminant bacteria. We introduced methoxypoly(ethylene glycol) to covalently modify the platelet surface using a process termed 'PEGylation'. In the first study of its kind, we demonstrate that PEGylated platelet concentrates inoculated with Staphylococcus epidermidis display a significant reduction in bacterial binding and biofilm formation.


Subject(s)
Bacteria/drug effects , Biofilms/drug effects , Blood Platelets/chemistry , Blood Preservation/methods , Platelet Activation/drug effects , Polyethylene Glycols/chemistry , Bacteria/pathogenicity , Bacterial Adhesion/drug effects , Blood Platelets/microbiology , Humans , Platelet Transfusion/standards , Staphylococcus epidermidis/drug effects
12.
Spinal Cord ; 49(8): 880-5, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21445081

ABSTRACT

STUDY DESIGN: Multi-center, prospective, cohort study. OBJECTIVES: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). SETTING: Inpatient rehabilitation hospitals in the United States (US). METHODS: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. RESULTS: Total agreement between raters was above 70% on most SCIM III tasks and all κ-coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-α was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (P<0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (P<0.0001). CONCLUSION: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.


Subject(s)
Disability Evaluation , Spinal Cord Injuries/diagnosis , Spinal Cord Injuries/epidemiology , Activities of Daily Living , Adolescent , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Reproducibility of Results , Spinal Cord Injuries/rehabilitation , Statistics as Topic , United States/epidemiology , Young Adult
13.
Langmuir ; 26(3): 2068-75, 2010 Feb 02.
Article in English | MEDLINE | ID: mdl-19754197

ABSTRACT

The synthesis of one-dimensional metal nanostructures can be achieved through the use of DNA molecules as templates to control and direct metal deposition. Copper nanostructures have been fabricated using this strategy, through association of Cu(2+) ions to DNA templates and reduced with ascorbic acid. Due to the possibility that the reduction of the Cu(2+) can result in the preferential formation of Cu(2)O over metallic Cu(0), X-ray photoelectron spectroscopy and X-ray diffraction have been carried out to establish the chemical identity of the nanostructures. Conclusive evidence is found that reduction of the Cu(2+) ions does result in the formation of the desired metallic Cu(0) structures. The morphology of the nanostructured Cu(0) material has also been observed by atomic force microscopy, showing the structures to have a "beads-on-a-string" appearance and being 3.0-5.5 nm in height. The electrical properties of the structures have been investigated by scanned conductance microscopy, showing the Cu(0) structures exhibit much larger electrical resistance than expected for a metallic nanowire. This is thought to be a consequence of their "beads-on-a-string" morphology and small lateral dimensions (sub-10 nm); both these factors would be expected to increase the electron scattering rate, and, further, there are likely to be significant tunneling barriers at the Cu(0) particle-particle junctions.


Subject(s)
Copper/chemistry , DNA/chemistry , Electric Conductivity , Metal Nanoparticles/chemistry , Electric Impedance , Microscopy , Microscopy, Atomic Force , Oxidation-Reduction , Photoelectron Spectroscopy , X-Ray Diffraction
14.
J Clin Invest ; 91(4): 1706-12, 1993 Apr.
Article in English | MEDLINE | ID: mdl-7682576

ABSTRACT

While red cells from individuals with beta thalassemias are characterized by evidence of elevated in vivo oxidation, it has not been possible to directly examine the relationship between excess alpha-hemoglobin chains and the observed oxidant damage. To investigate the oxidative effects of unpaired alpha-hemoglobin chains, purified alpha-hemoglobin chains were entrapped within normal erythrocytes. These "model" beta-thalassemic cells generated significantly (P < 0.001) greater amounts of methemoglobin and intracellular hydrogen peroxide than did control cells. This resulted in significant time-dependent decreases in the protein concentrations and reduced thiol content of spectrin and ankyrin. These abnormalities correlated with the rate of alpha-hemoglobin chain autoxidation and appearance of membrane-bound globin. In addition, alpha-hemoglobin chain loading resulted in a direct decrease (38.5%) in catalase activity. In the absence of exogenous oxidants, membrane peroxidation and vitamin E levels were unaltered. However, when challenged with an external oxidant, lipid peroxidation and vitamin E oxidation were significantly (P < 0.001) enhanced in the alpha-hemoglobin chain-loaded cells. Membrane bound heme and iron were also significantly elevated (P < 0.001) in the alpha-hemoglobin chain-loaded cells and lipid peroxidation could be partially inhibited by entrapment of an iron chelator. In contrast, chemical inhibition of cellular catalase activity enhanced the detrimental effects of entrapped alpha-hemoglobin chains. In summary, entrapment of purified alpha-hemoglobin chains within normal erythrocytes significantly enhanced cellular oxidant stress and resulted in pathological changes characteristic of thalassemic cells in vivo. This model provides a means by which the pathophysiological effects of excess alpha-hemoglobin chains can be examined.


Subject(s)
Erythrocyte Membrane/metabolism , Erythrocytes/chemistry , Hemoglobins/chemistry , Hemoglobins/pharmacology , beta-Thalassemia/blood , Amitrole/pharmacology , Antioxidants/pharmacology , Deferoxamine/pharmacology , Dextrans/pharmacology , Erythrocyte Deformability/drug effects , Glutathione/blood , Heme/metabolism , Hemoglobins/metabolism , Humans , Iron/metabolism , Lipid Peroxidation , Mass Spectrometry , Membrane Proteins/metabolism , Oxidation-Reduction , Peroxides/metabolism , Reactive Oxygen Species/metabolism
15.
Oncogenesis ; 5: e207, 2016 Mar 07.
Article in English | MEDLINE | ID: mdl-26950599

ABSTRACT

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer.

16.
Biochim Biophys Acta ; 1181(2): 163-8, 1993 Apr 30.
Article in English | MEDLINE | ID: mdl-8481405

ABSTRACT

Historically, it has been theorized that the enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes arises as a direct consequence of an inability to maintain cellular glutathione (GSH) levels. This study alternatively hypothesizes that decreased NADPH concentration leads to impaired catalase activity which, in turn, underlies the observed oxidant susceptibility. To investigate this hypothesis, normal and G6PD-deficient erythrocytes and hemolysates were challenged with a H2O2-generating agent. The results of this study demonstrated that catalase activity was severely impaired upon H2O2 challenge in the G6PD-deficient cell while only a transient decrease was observed in normal cells. Supplementation of either normal or G6PD-deficient hemolysates with purified NADPH was found to significantly (P < 0.001) inhibit catalase inactivation upon oxidant challenge while addition of NADP+ had no effect. Analysis of these results demonstrated direct correlation between NADPH concentration and catalase activity (r = 0.881) and an inverse correlation between catalase activity and erythrocyte oxidant sensitivity (r = 0.906). In contrast, no correlation was found to exist between glutathione concentration (r = 0.170) and oxidant sensitivity. Analysis of NADPH/NADPt ratio in acatalasemic mouse erythrocytes demonstrated that NADPH maintenance alone was not sufficient to explain oxidant resistance, and that catalase activity was required. This study supports the hypothesis that impaired catalase activity underlies the enhanced oxidant sensitivity of G6PD-deficient erythrocytes and elucidates the importance of NADPH in the maintenance of normal catalase activity.


Subject(s)
Catalase/metabolism , Erythrocytes/enzymology , Glucosephosphate Dehydrogenase/metabolism , Hydrogen Peroxide/pharmacology , Animals , Erythrocyte Membrane/enzymology , Erythrocytes/drug effects , Humans , Mice , NAD/metabolism , NADP/metabolism
17.
Free Radic Biol Med ; 12(3): 213-8, 1992.
Article in English | MEDLINE | ID: mdl-1563647

ABSTRACT

Primaquine is an important antimalarial drug which causes hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PDH) deficiency, probably due to oxidant generation by its metabolites. One of primaquine's metabolites, 5,6-dihydroxy-8-aminoquinoline (AQD), was found to cause chemiluminescence (CL) in vitro when incubated in the presence of luminol. This CL is inhibited by catalase and deferoxamine, unaffected by mannitol, and stimulated by superoxide dismutase (SOD), suggesting that it is mediated by H2O2. Three antioxidants (daphnetin, ferulate, and maltol), derived from Chinese herbal remedies, inhibited AQD- and H2O2-mediated CL, whereas a fourth, anisodamine, had no effect. Daphnetin also potently inhibited H2O2-mediated lipid peroxidation as measured by the production of thibarbituric acid reacting substances (TBARS). Thus, the possibility is raised that an antioxidant might be able to mitigate the oxidant hemolytic effects of primaquine.


Subject(s)
Antioxidants/pharmacology , Drugs, Chinese Herbal/pharmacology , Oxygen/metabolism , Primaquine/metabolism , Aminoquinolines/pharmacology , Erythrocyte Membrane/drug effects , Erythrocyte Membrane/metabolism , Free Radicals , Humans , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , Iron/chemistry , Lipid Peroxidation/drug effects , Luminescent Measurements , Oxidation-Reduction , Oxygen/antagonists & inhibitors , Primaquine/antagonists & inhibitors , Primaquine/pharmacology , Thiobarbiturates/metabolism
18.
Curr Pharm Des ; 4(6): 423-38, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10197054

ABSTRACT

Immunological recognition of foreign cells is a primary concern in both transfusion and transplantation medicine. Our unique approach to this problem is to globally camouflage the surface of the foreign cell using nonimmunogenic, long chain polymers such as methoxypoly(ethylene glycol) [mPEG]. mPEG-modification of red blood cells effectively attenuates both antibody binding to surface epitopes and decreases the inherent immunogenicity of foreign, even xenogeneic red cells. These cells exhibit normal structural and functional characteristicsin vitro and exhibit normal in vivo survival in animal models. Pegylation of white blood cells (particularly antigen presenting cells and T lymphocytes) surprisingly prevents recognition of foreign class II molecules and prevents T cell proliferation in response to foreign MHC molecules. Potential applications for the covalent binding of nonimmunogenic, long chain polymers (e.g., PEG) to intact cells include, but are not limited to: 1) derivatized RBC to diminish transfusion reactions arising from sensitization to minor blood group antigens (allosensitization) in the chronically transfused (e.g., sickle and thalassemia patients); 2) use of mPEG modification of "passenger" lymphocytes to prevent immune recognition and graft versus host disease; and 3) derivatization of the vascular endothelium of donor tissues prior to transplantation to prevent/diminish acute tissue rejection. In contrast to highly specific blocking mechanisms (e.g., anti-CD4; proteolytic removal of RBC A/B antigens), the generation of globally camouflaged (i.e., stealth) cells may more effectively prevent the often complex and redundant events leading to immune recognition of foreign cells.


Subject(s)
Antigens, Surface/immunology , Cell Membrane/immunology , Erythrocytes/immunology , Graft Rejection/prevention & control , Immune System/physiology , Polymers/pharmacology , T-Lymphocytes/immunology , Blood Transfusion/methods , Cell Division/physiology , Endothelium, Vascular/immunology , Erythrocytes/physiology , Forecasting , Humans , Major Histocompatibility Complex/immunology , Polyethylene Glycols/pharmacology
19.
Pediatrics ; 58(4): 521-5, 1976 Oct.
Article in English | MEDLINE | ID: mdl-972793

ABSTRACT

Solitary thyroid nodules in childhood had a 40% to 70% incidence of malignancy in the era of low-dose therapeutic irradiation. In the last 15 years, 36 children have been evaluated for such nodules, with a final diagnoses of carcinoma in 17%, adenoma in 58%, and miscellaneous diagnoses in 26%. All patients with carcinoma were euthyroid and had no history of irradiation in infancy. Treatment included thyroidectomy and full-replacement thyroid therapy. Benign neoplasms were often "cold" by scan; all patients were euthyroid except one adolescent body with T3 toxicosis. A majority proved to be follicular adenomas at surgery. Miscellaneous benign conditions outnumbered carcinoma and included variations in migration or embryologic development of the thyroid anlagen, thyroiditis, and a thyroid abcess. A 99mTc scan proved more valuable in diagnosis than thyroid function tests: a "hot" nodule usually suggested a developmental abnormality of the thyroid rather than a tumor. Our series of children, born since the dangers of irradiation have become common knowledge, suggests there may be a changing trend in the pathology encountered in solitary thryoid nodules.


Subject(s)
Thyroid Neoplasms/epidemiology , Abscess/diagnosis , Adenoma/diagnosis , Adolescent , Carcinoma/diagnosis , Carcinoma, Papillary/diagnosis , Child , Female , Humans , Male , Massachusetts , Radionuclide Imaging , Technetium , Thyroid Gland/abnormalities , Thyroid Neoplasms/diagnosis , Thyroidectomy , Thyroiditis/diagnosis
20.
J Nucl Med ; 32(8): 1614-6, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1869988

ABSTRACT

An 8-yr-old boy with a 1-mo history of culture-negative fever and anemia underwent gallium, ultrasound, and computed tomography studies as part of the evaluation of a fever of unknown origin. These studies revealed a mobile gallium-avid solid abdominal mass subsequently proven to be an inflammatory pseudotumor of the mesentery, a rare benign mass. This report documents the gallium-avid nature of this rare lesion and discusses associated characteristic clinical, pathologic, and radiographic features.


Subject(s)
Diagnostic Imaging , Fibroma/diagnosis , Mesentery , Peritoneal Neoplasms/diagnosis , Child , Fibroma/complications , Gallium Radioisotopes/therapeutic use , Humans , Male , Peritoneal Neoplasms/complications , Tomography, X-Ray Computed , Ultrasonography
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