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A review of the potential and versatility of colloidal gold cytochemical labeling for molecular morphology.

In the present article we review several postembedding cytochemical techniques using the colloidal gold marker. Owing to the high atomic number of gold, the colloidal gold particles are electron dense. They are spherical in shape and can be prepared in sizes from 1 to 25 nm, which renders this marker among the best for electron microscopy. In addition, because it can be bound to several molecules, this marker has the advantage of being extremely versatile. Combined to immunoglobulins or immunoglobulin-binding proteins (protein A), it has been applied successfully in immunocytochemistry. Colloidal gold particles 5-15 nm in size are excellent for postembedding cytochemistry. Particles of smaller size, such as 1 nm, must be silver enhanced to be visualized by transmission electron microscopy. We have elected to review the superiority of indirect immunocytochemical approaches using IgG-gold or protein A-gold (protein G-gold and protein AG-gold). Lectins or enzymes can be tagged with colloidal gold particles, and the corresponding lectin-gold and enzyme-gold techniques have specific advantages and great potential. Using an indirect digoxigenin-tagged nucleotide and an antidigoxigenin probe, colloidal gold technology can also be used for in situ hybridization at the electron microscope level. Affinity characteristics lie behind all cytochemical techniques and several molecules displaying high affinity properties can also be beneficial for colloidal gold electron microscopy cytochemistry. All of these techniques can be combined in various ways to produce multiple labelings of several binding sites on the same tissue section. Colloidal gold is particulate and can easily be counted; thus the cytochemical signal can be evaluated quantitatively, introducing further advantages to the use of the colloidal gold marker. Finally, several combinations and multiple step procedures have been designed to amplify the final signal which renders the techniques more sensitive. The approaches reviewed here have been applied successfully in different fields of cell and molecular biology, cell pathology, plant biology and pathology, microbiology and virology. The potential of the approaches is emphasized in addition to different ways to assess specificity, sensitivity and accuracy of results.

Animals↗

Action of gold sodium thiomalate on experimental thrombosis in vivo.

In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 X 10(-5) to 1.0 X 10(-4) M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Patterns of gold levels in urine, serum, and saliva in patients with rheumatoid arthritis undergoing chrysotherapy.

Twenty patients undergoing treatment with aurothiomalate for rheumatoid arthritis (RA) were studied for the presence of gold in all urine specimens passed over four days and for gold in the serum of blood drawn by venous section at 10.00, 16.00, and 22.00 hours on a single day of the study. Specimens of saliva collected at the same times as the blood specimens were also analysed for (total) gold content. Eighteen patients showed rhythmic urinary gold excretion. Variations were observed in the serum levels for total, free, and protein bound gold at different times of the day and night together with similar variations in the salivary total gold levels. It was established that a possible relation exists between urinary gold, serum gold, and salivary gold such that at times of higher urinary gold excretion the serum gold levels (total, free, and protein bound) and the total salivary gold levels were decreased. Conversely, at times of lower urinary gold excretion serum and salivary gold levels were increased.

Arthritis, Rheumatoid↗

Comparison of the kinetics of parenteral and oral gold.

The intramuscular (gold sodium thiomalate and aurothioglucose) and the orally (auranofin) administered gold compounds exhibit contrasting patterns of absorption, excretion and body tissue and fluid levels. The parenteral compounds are fully absorbed after injection but negligibly absorbed orally. Approximately 25% of the gold in auranofin is orally absorbed. Serum gold levels peak several hours after injection during conventional weekly treatment, attaining concentrations of 600-800 micrograms/dl, and then decline gradually, reaching 300-350 micrograms/dl before the next injection. Whole blood gold levels with auranofin vary from 10 to 90 micrograms/dl with doses of 1-9 mg/day. Blood gold levels plateau after 6-8 weeks with the injectable compounds and after 12 weeks with oral gold, reflecting the shorter blood half-life of gold sodium thiomalate (5.5 days) than of auranofin (17-26 days). A larger fraction of gold is within or attached to circulating blood cells, especially erythrocytes, with auranofin than with injectable gold. Fourty percent of the administered dose is excreted during injectable chrysotherapy, and 75-100% is recovered in excreta with auranofin. Parenteral gold is excreted primarily in urine (70%) while auranofin gold is recovered primarily in faeces (95%). Approximately 43% of intravenous radiolabelled gold sodium thiomalate is retained in the body at 60 days and 30% at 180 days; only 15% of radiolabelled auranofin remains at 10 days and less than 1% at 180 days. During injectable therapy, the total body burden of gold rises steadily; preliminary studies suggest minimal tissue accumulation with auranofin.

Administration, Oral↗

[The pharmacology of gold compounds].

Parenterally administered gold compounds have been used for decades for treatment of rheumatoid arthritis. The new gold compound triethylphosphine gold (auranofin) can be partially absorbed in the gut following oral administration due to its higher lipophilic nature. This is probably also the main cause for the differences in kinetic properties versus the parenteral gold compounds. Following administration of auranofin, there are lower concentrations of gold in blood and organs; 95% of the gold is excreted in feces whereas 70% of gold, following gold sodium thiomalate, is excreted in the urine. These differences have consequences for the mode of adverse reactions. A common property of all gold compounds, however, is the relative distribution in organs. The highest concentrations of gold were found in the reticuloendothelial system, in liver, kidney and spleen, followed by joints. The mode of action of gold compounds is still unexplained. They inhibit some types of experimental inflammation and the activity of various cells involved in inflammatory processes. In some cases auranofin exerts a higher influence. Following incorporation of gold in lysosomes, the impairment of macrophage function appears to be most important. This effect probably influences (indirectly) the immune system since macrophages interact with T- and B-lymphocytes. The significance of these findings for the therapeutic effect of gold compounds is, however, not known. The rate of undesirable effects of gold compounds is very high requiring exact supervision during chrysotherapy. Mucosal and cutaneous reactions are very frequent, followed by proteinuria, diarrhea and thrombocytopenia. Bone marrow aplasia is most serious but relatively rare.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Microscopy and certification as tools for environmentally benign, mercury-free small-scale gold mining.

Small-scale gold miners lose annually 500-700 tonnes of mercury when amalgamating gold with mercury and subsequent burning. So far, mercury-free alternatives have been demanding more skill, time, or capital investments and the interest from the miners to reduce the mercury emissions has been limited. Recent development of mercury free methods, an increasing mercury price, and increased awareness of health and environmental damages caused by mercury is changing the attitudes. This trend could be spurred by certification of gold with added value due to clean production methods. Our objectives are to present a method to distinguish gold recovered without using mercury or harmful chemicals such as cyanide. Thereby, this gold could be certified and thus obtain a higher market price. The method is based on inspection of the gold grain surfaces with a light microscope. This method separated natural gold grains from gold recovered by amalgamation or cyanidation. The method also demonstrated different characteristics of gold grains from different gold fields and a basis for a catalogue with photomicrographs of gold grains from different gold fields has been established and partly presented in this article. In conclusion, studies of gold grains with a light microscope and photo documentation is an inexpensive but reliable method to distinguish environment-friendly recovered gold, which could be used for certification to get a higher market price.

Environmental Pollution↗

Formation process of two-dimensional networked gold nanowires by citrate reduction of AuCl4- and the shape stabilization.

Gold nanowires with a two-dimensional (2-D) network structure were formed by citrate reduction of AuCl4- with a low concentration of citrate. The structure change during the growth processes was observed by transmission electron microscopy (TEM) and the variation in concentrations of gold species in the aqueous solution was monitored by UV-vis spectra and Inductively Coupled Argon Plasma Emission Spectrophotometer (ICAP). The formation of 2-D gold nanowires was induced by the small amount of reducing agent because the preliminary gold nanoparticles formed by reduction of AuCl4- were thermodynamically unstable in the aqueous solution due to the insufficient capping of citrate. One of the key points of nanowire formation is the preferential adsorption of AuCl4- instead of citrate ions on the surface of the preliminary gold particles, which results in an attracting force between gold nanoparticles. We propose a hit-to-stick-to-fusion model, in which gold nanoparticles adhere by the attraction force and stick together, causing selective deposition of reduced gold metallic species on the concave surface of the two sticking particles, followed by fusion into nanowires. Nanowires then connect with each other, forming a network structure. The evidence obtained from TEM observation of transformation from gold nanowires on a TEM grid to large nanoparticles by hydrogen gas reduction and time-resolved measurements of gold ions suggest that gold ions not only are crucial for the growth of gold nanowires but also play an important role in stabilizing the shape of gold nanowires during the formation process. This method for synthesizing 2-D gold nanowires is simple and relatively easy application to the synthesis of other metallic nanowires such as silver or platinum is expected.

Adsorption↗

Gold concentrations in abiotic materials, plants, and animals: a synoptic review.

Gold (Au) is ubiquitous in the environment and mined commercially at numerous locations worldwide. It is also an allergen that induces dermatitis in sensitive individuals. Gold concentrations were comparatively elevated in samples collected near gold mining and processing facilities, although no data were found for birds and non-human mammals. Maximum gold concentrations reported in abiotic materials were 0.001 microg L(-1) in rainwater; 0.0015 microg L(-1) in seawater near hydrothermal vents vs. < 0.00004-0.0007 microg L(-1) elsewhere; 5.0 microg kg(-1) dry weight (DW) in the Earth's crust; 19.0 microg L(-1) in a freshwater stream near a gold mining site; 440 microg kg(-1) DW in atmospheric dust near a high traffic road; 843 microg kg(-1) DW in alluvial soil near a Nevada gold mine vs. < 29 microg kg(-1) DW premining; 2.53 mg kg(-1) DW in snow near a Russian smelter vs. < 0.35 mg kg(-1) DW at a reference site; 4.5 mg kg(-1) DW in sewage sludge; 28.7 mg kg(-1) DW in polymetallic sulfides from the ocean floor; and 256.0 mg kg(-1) DW in freshwater sediments near a gold mine tailings pile vs. < 5 microg kg(-1) DW prior to mining. In plants, elevated concentrations of 19 microg Au kg(-1) DW were reported in terrestrial vegetation near gold mining operations vs. < 4 microg kg(-1) DW at a reference site; 37 microg kg(-1) DW in aquatic bryophytes downstream from a gold mine; 150 microg Au kg(-1) DW in leaves of beans grown in soil containing 170 microg kg(-1) DW; up to 1.06 mg kg(-1) DW in algal mats of rivers receiving gold mine wastes; and 0.1-100 mg kg(-1) DW in selected gold accumulator plants. Fish and aquatic invertebrates contained 0.1-38.0 microg Au kg(-1) DW. In humans, gold concentrations up to 1.1 microg L(-1) were documented in urine of dental technicians vs. 0.002-0.85 microg L(-1) in reference populations; 2.1 microg L(-1) in breast milk, attributed to gold dental fillings and jewelry of mothers; 1.4 mg kg(-1) DW in hair of goldsmiths vs. a normal range of 6-880 microg kg(-1) DW; 2.39 mg L(-1) in whole blood of rheumatoid arthritis patients receiving gold thiol drugs to reduce inflammation (chrysotherapy) vs. a normal range of 0.2-2.0 microg L(-1); and 60.0 to 233.0 mg kg(-1) fresh weight (FW) in kidneys of rheumatoid arthritis patients undergoing active chrysotherapy vs. < 42.0 mg kg(-1) FW kidney 140 months posttreatment.

Animals↗

Type IV hypersensitivity reactions to upper lid gold weight implants-is patch testing necessary?

AIMS: To report two cases of allergic reaction to upper lid gold weight implants in patients with facial nerve palsy and to identify the use of pre-implantation patch testing in predicting gold hypersensitivity. METHODS: One patient who had a positive family history of gold allergy and had undergone previous gold dental restoration underwent patch testing with gold sodium thiosulphate. The gold weight from the same patient was analysed using scanning electron microscopy and energy dispersive X-ray analysis, which can detect surface impurities. Tissue obtained during surgery to remove the gold weight from the second patient was examined histologically. RESULTS: Patch testing in the first patient gave a positive result. Analysis of the gold weight removed from the same patient confirmed 99.99% purity, and hence sensitivity to the gold itself was considered to be the cause of the inflammatory reaction. Histology of tissue taken from the eyelid of the second patient was consistent with type IV hypersensitivity. CONCLUSION: A personal and family history of gold allergy should be looked for before upper eyelid gold weight implantation. Patch testing should be performed for patients where there is doubt about whether gold has been the specific cause of previous allergic reactions, for patients who have undergone previous dental restoration involving gold, or if there is a positive family history of gold allergy.

Aged↗

Ultrastructural localization of nuclei acids by the use of enzyme-gold complexes.

A cytochemical technique for the ultrastructural localization of substrates using enzyme-gold complexes is reported. RNase A and DNase I have been labeled with gold particles. The RNase-gold and dNase-gold complexes obtained were applied on thin sections of glutaraldehyde-fixed and Epon-embedded tissues. Different cellular compartments were labeled by these enzyme-gold complexes. Using the RNase-gold complex the rough endoplasmic reticulum appeared decorated with gold particles. The gold marker was also present over the nucleus, especially over the nucleolus; mitochondria were weakly labeled. Using the DNase-gold complex, gold particles were concentrated over the euchromatin of the nucleus and the mitochondria. The heterochromatin and the nucleolus showed a less intense labeling. For both enzyme-gold complexes, the Golgi area, the secretory granules and the extracellular space appeared free of label. In those control conditions where the substrates were added to the enzyme-gold complexes a major reduction in the labeling was observed. A quantitative evaluation of the labeling was performed. This evaluation confirmed the qualitative observations and the marked reduction of labeling occurring under the control conditions. The combination of the specificity of the enzyme-substrate interactions with the size and electron density of the gold particles and the good ultrastructural preservation of the tissues resulted in a very specific labeling with high resolution. These results demonstrate the possibility of detecting substrates by means of enzyme-gold complexes at the electron microscope level.

Animals↗

Enhanced values of the RBE and H ratio for cytogenetic effects induced by secondary electrons from an X-irradiated gold gurface.

The low-energy secondary electrons emerging from the entrance surface of an X-irradiated gold foil increase the dose to cells in contact with or at micrometer distances from this surface (Radiat. Res. 150, 92-100, 1998). We examined the effect of the spectrum of these low-energy electrons on the RBE for cytogenetic effects and showed that this RBE was increased. A monolayer of surface-attached human T lymphocytes was exposed to 60 kV X rays in the absence or presence of a gold foil positioned immediately behind the cell layer or separated from it by a Mylar foil 0.9 or 2 microm thick. The enhancement of dose in the cell nuclei caused by the photoelectrons and Auger electrons emerging from the entrance surface of the gold foil was measured by TSEE dosimetry. Dose enhancement factors of 55.7, 46.6 and 37.5 were obtained with 0, 0.9 and 2 microm of Mylar inserted between the gold surface and the cell layer. This large enhancement results from the photoelectric effect in the gold foil, as shown by the accompanying Monte Carlo calculations of the secondary electron spectra at the gold surface. Auger electrons from the gold foil generally were not able to penetrate into the cell nuclei except for that fraction of the cells that had a very thin (< 0.7 microm) layer of cytoplasm and membranes between gold surface and cell nucleus. The dose-yield curves for dicentric chromosomes plus centric rings and for acentric fragments obtained after exposures without or with the gold foil were linear-quadratic. The coefficient alpha, the slope of the linear yield component, was increased in the presence of the gold foil and showed RBE values ranging from 1.7 to 2.2 compared to exposures in absence of the gold foil. The ratio of the yield of interstitial deletions and dicentrics (H ratio) was significantly increased from about 0.17 in the absence of the gold foil to about 0.22 in the presence of the gold foil. The increases in the RBE and the H ratio are interpreted in microdosimetric terms: The preferred occurrence of electron track ends in the vicinity of the gold surface causes an increase in the dose-mean restricted linear energy transfer in cell nuclei exposed to the photoelectrons and Auger electrons.

Chromosome Aberrations↗

Adverse immune reactions to gold in rheumatoid arthritis: lack of skin reactivity.

Adverse immune reactions develop in up to 30% of patients treated with gold compounds. However, sensitization to gold(I) drugs is rarely demonstrated by in vivo or in vitro testing. Recent data from a mouse model provides evidence that gold(I) is oxidized to gold(III) before T cells are sensitized. To study the diagnostic value of skin tests, patch testing with various gold compounds - including gold(I) and gold(III) - was performed in 50 patients with rheumatoid arthritis treated with gold(I) drugs. Positive patch test reactions to either gold(I) or gold(III) compounds were not detected. In contrast, the lymphocyte transformation test (LTT) revealed a gold(III)-induced response in one of the 7 patients being tested. We conclude that patch testing fails to indicate T cell sensitization to gold(I) drugs in rheumatoid arthritis patients. The in vitro response to gold(III) obtained by LTT supports the hypothesis that biooxidation of gold(I) compounds may play a crucial role for sensitization.

Arthritis, Rheumatoid↗

E-Z Gold: the new Goldent.

E-Z Gold is a new direct filling gold material that is similar to existing powdered gold formulations but more user-friendly. It is a mixture of pure gold powder and wax (less than 0.01% organic wax), wrapped in gold foil introduced to the dental profession in the late 1980s, and similar metallurgically to gold foil and powdered gold (Goldent) in that, when properly and thoroughly compacted, it has comparable properties: inertness (biocompatibility) and permanence. E-Z Gold's manipulative characteristics are similar to that of a very stiff amalgam, yet more sticky (cohesive) than gold foil, hence the name E-Z Gold. There is no reported research related to physical properties regarding shear, tensile, and cohesive strength. One can assume that E-Z Gold is similar to old Goldent but with improved softness and working characteristics. Clinical experience in the use of this new restorative direct filling gold material has been encouraging. We anticipate that in the near future, clinical and laboratory research comparing this gold to other types of direct filling golds will be forthcoming.

Dental Materials↗

[Molecular mechanisms of action of gold in treatment of rheumatoid arthritis--an update].

Gold was first used 90 years ago by Robert Koch for the treatment of tuberculosis based on the assumption that rheumatoid arthritis was caused by microbacteria. It soon became clear that this would not explain the action of gold in rheumatoid arthritis, and since then scientists have been struggling to elucidate the mechanisms of gold's action in the treatment of rheumatic diseases. In nearly every area of immunology inhibiting actions of gold could be documented; however, it is still unclear if there is a common denominator or if there are parallel modes of actions which are independent of each other. In any case, also based on recent studies the reactivity of gold compounds with thiol groups appears to the predominant factor. Analyzing the actions of gold in the different phases of an immune reaction suggested that gold plays an important role already in the initiation, namely the uptake and presentation of foreign antigens. Thus, gold is taken up by the macrophages and stored in the lysosomes which are called aureosomes where gold inhibits antigen processing. Especially peptide antigens, which contain sulfur such as cysteine and methionine, are important. Moreover, it could be shown that gold suppresses NF-kappa B binding activity as well as the activation of the I-kappa B-kinase. This mechanism results in a subsequently reduced production of pro-inflammatory cytokines, most notably TNF-alpha, interleukin-1 and interleukin-6. On the subsequent T-cell level, gold has been shown to induce an upregulation of IL-4 mRNA, resulting in a shift of the T-cell population to the Th2 phenotype. Moreover, the activation of T-cells is inhibited. On the effector level, gold inhibits proteolytic enzymes and can result in the destruction of synovial fibroblasts. In conclusion, gold remains one of the most fascinating antirheumatic drugs with multiple modes of actions. The future analysis of molecular mechanisms, especially with regard to signal transduction, will lead to new fundamental knowledge of gold action, possible allowing a further understanding of the pathogenesis of rheumatoid arthritis.

Antigen Presentation↗

Gold nanolayer-encapsulated silica particles synthesized by surface seeding and shell growing method: near infrared responsive materials.

Gold nanolayer-encapsulated silica particles whose optical resonance is located in 750-900 nm spectral region were synthesized by combining Sn (tin)-surface seeding and a shell growing process. The synthesized composite particles can be potentially used in wide biological fields, due to biocompatibility and a well-known bioconjugation technique of gold layer. Sn atoms, which can act not only as a catalytic surface for reduction of gold but also as a linker between silica surface and gold nanoparticles, were chemically deposited on hydroxylated silica particles. Then, we introduced another reductant with gold chloride in order to produce a multilayer of Au shell. In the process, Au shells grew by the reduction of additional gold ions on the Sn-functionalized silica surface and resulted in the subsequent coalescence and growth of the deposited gold nanoparticles. Finally, a complete gold nanoshell was formed on the silica surface by the one-step method, without a repeated coating process. The deposition of a gold nanolayer on the silica particles was easily controlled by the concentration ratio of Sn-functionalized silica particles and gold chloride solutions. Transmission electron microscopy (TEM) images and optical extinction spectra clearly showed that gold nanolayers were successfully deposited on the silica surface by the novel method. As the gold colloids attached on the silica surface grew, their optical plasmon peak became red-shifted until complete a gold shell was formed. After the gold shell was completed, the optical plasmon resonance became blue-shifted and the extinction spectra were functions of a relative ratio of the core to shell thickness.

Journal Article↗

Bimodal Size Distribution of Gold Nanoparticles under Picosecond Laser Pulses.

The evolution of size distributions of gold nanoparticles under pulsed laser irradiation (Nd:YAG, lambda = 355 nm, pulse width 30 ps) was carefully observed by transmission electron microscopy. Interestingly, the initial monomodal size distribution of gold nanoparticles turned into a bimodal one, with two peaks in the number of particles, one at 6 nm and the other at 16-24 nm. The sizes for small particles depended very little on the irradiated laser energy. This change is attributed to laser-induced size reduction of the initial gold nanoparticles followed by the formation of small particles. In our analysis, we extracted a characteristic value for the size-reduction rate per one pulse and revealed that laser-induced size reduction of gold nanoparticles occurred even below the boiling point. When laser energy is insufficient for the boiling of particles, formation of gold vapor around liquid gold drops is thought to cause the phenomenon. With enough laser energy for the boiling, the formation of gold vapor around and inside liquid gold drops is responsible for the phenomenon. We also observed particles with gold strings after one pulse irradiation with a laser energy of 43 mJ cm(-2) pulse(-1), which is sufficient energy for the boiling. It is considered that such particles with gold strings are formed by the projection of gaseous gold from liquid gold drops with some volume of liquid gold around the bubble. On the basis of comparison with previous work, picosecond laser pulses are thought to be the most efficient way to cause laser-induced size reduction of gold nanoparticles.

Journal Article↗

Investigation of the core-shell interface in gold@silica nanoparticles: a silica imprinting approach.

The nature of the self-assembled core-shell interface in gold@silica nanoparticles synthesized via a 3-aminopropyltrimethoxysilane (APTMS) route is investigated using materials synthesis as a sensitive tool for elucidating interfacial composition and organization. Our approach involves condensation of the gold@silica nanoparticles within a silica framework for synthesis of a composite gold-silica material containing approximately 30 wt % gold. This material contains one of the highest gold loadings reported, but maintains gold core isolation as ascertained via a single surface plasmon resonance absorption band frequency corresponding to that of gold nanoparticles in dilute aqueous solution. The immobilized gold cores are subsequently etched using cyanide anion for the synthesis of templated porosity, which corresponds to the space that was occupied by the gold. Characterization of immobilized amines is performed using probe molecule binding experiments, which demonstrate a lack of accessible amines after gold removal. Solid-state 13C CPMAS NMR spectroscopy on these materials demonstrates that the amount of amine immobilization must be less than 10% of the expected yield, assuming that all of the APTMS becomes bound to the gold nanoparticle template. These results require a core-shell interface in the gold@silica nanoparticles that is predominantly occupied by inorganic silicate species, such as Si-O-Si and Si-OH, rather than primary amines. Such a result is likely a consequence of the weak interaction between primary amines and gold in aqueous solution. Our method for investigating the core-shell interface of gold@silica nanoparticles is generalizable for other interfacial structures and enables the synthesis of bulk imprinted silica using colloidal templates.

Journal Article↗

Comparison of microscopy and radiography as gold standards in radiographic caries diagnosis.

OBJECTIVES: To compare the effect of the choice of gold standard on the diagnostic outcome of approximal caries detection in original and compressed digital radiographs. METHODS: 116 extracted teeth radiographed with a storage phosphor system constituted the original images. These images were compressed at 1:20 and 1:33 with the JPEG irreversible compression standard. Five radiologists scored the three sets of images for the presence of approximal caries on a five-rank confidence scale. The radiographic scores were validated by stereomicroscopy (the true gold standard). The individual ROC areas for the five observers were used to select the worst (obsworst) and the best (obsbest) performer: Their scores in the original images were used as the second and third 'gold standards' for the remaining observers. Mean ROC areas for the three observers with the three types of images were calculated using these two new 'gold standards'. Differences between the ROC areas when using microscopy, obsworst, and obsbest as the 'gold standard' were compared. RESULTS: The mean ROC areas in the original images were 0.66, 0.74 and 0.91 using the true gold standard and obsbest and obsworst as the 'gold standards' respectively. The difference between the true gold standard and obsworst was statistically significant (P < 0.001). The mean ROC areas using the true gold standard decreased with increasing compression whereas they were constant or increased using obsworst and obsbest as 'gold standards', respectively. CONCLUSIONS: Accuracy in approximal caries diagnosis was significantly higher when an observer was the 'gold standard' than when the true gold standard was obtained by microscopy. Paradoxically, the compressed, degraded images were more accurate than the originals when an observer was the 'gold standard' while they were less accurate with the true gold standard. Thus, results obtained using observers' scores from the radiographs which are being evaluated, as validation for the presence of caries may mislead the clinician.

Bicuspid↗