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PubMed1992

Colloidal gold uptake as a marker for monocyte differentiation and maturation in normal and leukemic cells.

The uptake of colloidal gold particles by human monocytes was studied by electron microscopy, with special emphasis on changes in this uptake during the differentiation and maturation of these cells. The way in which leukemic cells of childhood acute non-lymphocytic leukemia (ANLL) can function in this gold uptake was also examined. In monocytes, microendocytosis was temperature-dependent; colloidal gold uptake increased as temperatures rose from 4 degrees C to 37 degrees C. It appeared that gold particles first adhered to the cell surface membrane, were then incorporated into the cytoplasmic vesicles, and then were transported into the granules. Original HL-60 cells and retinoic acid (RA)-treated HL-60 cells, which were differentiating and maturing along the granulocyte lineage, did not ingest colloidal gold particles, but 1,25(OH)2D3-treated HL-60 cells showed colloidal gold uptake during their differentiation and maturation along the monocyte lineage: 68.6% of the cells contained gold particles. Gold uptake was demonstrated in 27.3% of original U937 cells; the percentage increased to 70.3% when they were induced to mature by RA. In 15 specimens of childhood ANLL, none of the M1, M2 or M3 cells showed colloidal gold uptake, whereas 76-97% of M4 and M5 cells showed this uptake. These findings indicate that colloidal gold uptake is a marker of monocyte differentiation and maturation and can provide additional information for ANLL cytology.

Adolescent↗
PubMed2005

Positive patch-test reactions to gold: patients' perception of relevance and the role of titanium dioxide in cosmetics.

BACKGROUND: Positive patch-test reactions to gold that are without obvious clinical relevance are common. We speculate that titanium dioxide in cosmetics and sunscreens may adsorb gold particles in jewelry that occasionally contacts facial skin and cause contact dermatitis on this area despite the absence of dermatitis under gold jewelry worn on the hands. OBJECTIVE: To identify subgroups of gold allergic patients who improve with avoidance of gold. METHODS: A questionnaire was mailed to 102 gold-allergic patients. RESULTS: There were 49 responses, of which all but one were from women. When asked to evaluate the statement that patch testing with gold was useful to them, one-third of respondents agreed completely, one-third agreed in part, and one-third disagreed. The majority of patients reported that their dermatitis improved after patch testing, but most were avoiding other allergens in addition to gold. CONCLUSIONS: Avoidance of gold earrings did not appear to benefit patients with earlobe dermatitis, but total avoidance of gold jewelry on the hands and wrists did seem to benefit a subgroup of patients with facial and eyelid dermatitis who wore powder, eye shadow, or foundation on affected areas.

Allergens↗
PubMed1986

Non-specific binding of protein-stabilized gold sols as a source of error in immunocytochemistry.

The observation that protein-A conjugated gold sols bound to fibronectin-collagen (FNC) fibres in human fibroblast cultures prompted a series of studies on the binding of gold particles stabilized in various ways (Staphylococcal protein A, bovine serum albumin, avidin, streptavidin, gelatin, hemoglobin, polyethylene glycol (MW 20 000), methylcellulose and the nonionic detergent Tween 20) to cell and tissue components, to protein dot blots and SDS-PAGE blots on nitrocellulose paper. We found that binding of gold particles to certain cell and tissue components and to various immobilized proteins did occur irrespective of the stabilizing agent. We argue that, albeit gold sols are stabilized against salt coagulation by adsorption of proteins and other stabilizing agents, "naked areas" are (constantly or intermittently) present on particle surfaces, available for interaction with cell and tissue components that have a high electrostatic affinity for the charged gold surface under prevailing experimental conditions. Non-specific binding may be reduced or abolished by competing proteins (i.e. proteins with a higher affinity for gold than any component in the object studied) provided the proteins and the gold conjugate are present concomitantly during incubation. We found gelatin (Bloom number 60-100) to be an effective competitive protein probably due to its high affinity for gold over a wide pH range. Further, gelatin did not appreciably inhibit the specific interaction in dot blots between SpA and IgG except at very low IgG concentrations. A protocol for the use of gold-protein conjugates to circumvent the hazards of unspecific gold binding is suggested.

Cell Line↗
PubMed1984

Binding and degradation of proteoglycans by cultured arterial smooth muscle cells. I. Endocytosis and intracellular translocation of proteoglycan-gold conjugates.

Proteoglycans (Mr approximately 200 000) isolated from bovine arterial tissue were decorated with 17 nm diameter gold particles for tracing in electron microscopic thin sections and surface replicas. Lysine and arginine residues of their proteoglycan protein core are assumed to be essential for gold conjugation. The resulting proteoglycan-gold conjugates, which appear as pearl string-like gold strands of about 170 nm in length were used to visualize binding, endocytosis and intracellular translocation of proteoglycans by homologous cultured arterial smooth muscle cells. The proteoglycan-gold conjugates bind to coated as well as to non-coated cell surface membrane areas at 4 degrees C. This is followed by the formation of membrane invaginations. Postincubation at 37 degrees C leads to a time-dependent uptake of proteoglycan-gold conjugates via non-coated and coated vesicles which after fusion are translocated to multivesicular bodies and to large sized vesicles within 1 h. After conversion of these vesicles to lysosomal compartments the gold particles are uncoupled from the proteoglycans and are concentrated within residual vacuoles. From these vacuoles the gold particles are extruded. In contrast to the surface-bound proteoglycan-gold conjugates the released gold particles are condensed to bulky aggregates. The results, which include competition, inhibition and pulse chase experiments, extend biochemical data on endocytosis and degradation of proteoglycans.

Animals↗
PubMed1981

Colloidal gold : a cytochemical marker for light and fluorescent microscopy and for transmission and scanning electron microscopy.

Gold sols are orange to violet, display electron dense properties and are capable of strong emission of secondary electrons. These properties enable gold particles to be used as specific markers in microscopy both at the low and high resolution level (light and fluorescent microscopy, scanning and transmission electron microscopy). Monodisperse colloidal gold can be produced by several methods in a size range of 5 nm to 150 nm. As a consequence, the gold method is well suited for multiple marking experiment at the high resolution level. Since gold markers bind non-specifically to a very low extent, the technique has found application in TEM for marking intracellular components on thin sections. Both the one step and the two step marking procedures have been utilized in the various modes of microscopy. Under appropriate conditions, gold particles can be labelled with a variety of macromolecules (polysaccharides, glycoproteins, proteins, lectins, antibodies), presumably through a noncovalent binding process. Generally the probes acquire the specific activity of the adsorbed macromolecule and their stability upon storage is good. A number of factors which influence the adsorption process are discussed in relation to the more general problems of adsorption of macromolecules onto metallic surfaces. The stability of gold markers is also best understood by the DLVO theory for disperse systems. The preparation, labelling, stabilization, stability and binding characteristics of gold markers are reviewed. Since the binding of gold probes to cell surfaces is primarily determined by the size of the particle, several problems related to steric hindrance and quantification of the method are also discussed. The advantages of the method over others are compared. The different modes of microscopy and the several gold methods available for marking cell surface and intracellular components are illustrated by micrographs.

Adsorption↗
PubMed1976

Spread of gold injected into the joints of healthy rabbits.

This study shows that after intra-articular injection, aurothiomalate and colloidal gold of small (200 A) particle size were rapidly absorbed from joints while the larger, 300 A, particle size colloidal radioactive gold could not be found outside them. Larger particle size suspensions seem therefore more likely to remain localised in the joint and its lining synovium after intra-articular injection, the systemic absorption from the joint cavity diminishing with increasing particle size. It was also found that the intra-articular injection of small amounts of aurothiomalate, of colloidal gold and of colloidal radioactive gold produces identical degenerative lesions in the lining cells of the proximal convoluted tubules of the kidneys. These lesions were always found, although gold particles were demonstrated only in sampled kidney tissues of the animals injected with the soluble gold preparation whereas no gold could be detected in the tissues of animals injected with colloidal non-radioactive or radioactive gold. Electron microscopic evidence is presented to suggest the possibility that the mitochondria are the "target" organelles of the gold-induced cellular damage. Mitochondrial damage was demonstrated in liver and spleen in addition to the already described kidney damage. The correlation between structure and function of the mitochondrial changes is not clear, and ionic shifts may be both a cause and a result of damage.

Animals↗
PubMed2005

Electrochemical thinning of thicker gold film with qualified thickness for surface plasmon resonance sensing.

To meet the requirement of surface plasmon resonance (SPR) sensing, controlling the thickness of the gold film is very important. Here, we report an efficient and simple approach to prepare a SPR-active substrate when the thickness of the gold film is larger than the optimizing 50 nm and smaller than 100 nm. This method is based on anodic electrodissolution of gold in electrolyte containing chloride ions. Using this method, the thickness of gold films can be easily changed at a nanometer scale by controlling the number of potential scans and the concentrations of chloride ions in the electrolyte. At the same time, the influence of gold film thickness on the SPR signal is recorded by SPR in real time. To assess the change of the surface roughness and morphology of gold film through anodic electrodissolution, atomic force microscopy was used. The surface roughness of the same Au film before and after anodic electrodissolution is 1.179 and 2.767 nm, respectively. The change of the surface roughness of Au film brings out a slight angle shift of SPR. This indicates that surface electrodissolution of the gold does not affect the character of the original bulk film and this film can be used for SPR experiments. To confirm our expectation, a simple adsorption experiment of cytochrome c (Cyt c) on the gold film treated with anodic electrodissolution modified by 11-mercaptoundecanic acid was carried out. The angle shift of SPR confirmed the adsorption of Cyt c, and the cyclic voltammetry of Cyt c provided a complementary confirmation for the adsorption of Cyt c. These results show that this approach provides a good way to change the thicker gold film to an optimized thickness of SPR sensing. The great advantage brought by this approach is in that it can convert the waste gold films with greater thicknesses fabricated by the vacuum deposition method or other methods into useful materials as active SPR substrates.

Journal Article↗
PubMed2002

Aurophilicity-based one-dimensional arrays of gold(I) phenylene-1,3- and -1,4-dithiolates.

Phenylene-1,3-dithiol is converted into a trinuclear gold complex by treatment with 1 equiv of [[(Ph(3)P)Au](3)O](+)BF(4)(-). In the product, the phenylene unit bears one gold thiolate and one di(gold)sulfonium function. These components aggregate into one-dimensional arrays through head-to-tail aurophilic contacts between the two functions. In the association process, the Au[bond]S[bond]Au angle of the sulfonium group is opened up to accommodate the incoming gold atom between its metal centers. A similar mode of aggregation is found for the triply aurated biphenylene-4,4'-dithiol obtained using the tri(gold)oxonium salt with tri(p-tolyl)phosphine ligands. Probably for steric reasons, in this oligomerization process, the gold(I) thiolate unit is attached side-on to the digold sulfonium unit with retention of the small Au[bond]S[bond]Au angle. Under similar reaction conditions, and with the same molar ratio of the components, phenylene-1,4-dithiol is converted into the bis-sulfonium salt: 1,4-[[(p-Tol)(3)PAu](2)S](2)C(6)H(4)(BF(4))(2), the dications of which also associate into chains. Along the chains, the phenylene spacers alternate with tetranuclear gold clusters which arise from intimate aggregation of pairs of gold atoms. Together with previous findings, the present results show that gold thiolate (-SAuL) and digold sulfonium functions [-S(AuL)(2)(+)] in proper orientation at an arene unit (alpha-omega) can be considered as "soldering" points which can be used for joining up the molecular units into one-dimensional arrays solely through metal-metal contacts, which appear to be operative even against Coulomb repulsion between cations. The reaction of biphenylene-4,4'-dithiol with 2 equiv of sodium methoxide and [tri(c-hexyl)phosphine]gold chloride gives only neutral digold dithiolate complex 4 which is not associated owing to the steric bulk of the tri(c-hexyl)phosphine ligands.

Journal Article↗
PubMed2006

Growth of gold nanorods and bipyramids using CTEAB surfactant.

Gold nanorods and bipyramids have been synthesized using the seed-mediated approach in aqueous cetyltriethylammonium bromide (CTEAB) solutions in the presence of silver nitrate. Gold nanoparticle seeds that are stabilized with either CTEAB or sodium citrate have been used. The use of the CTEAB-stabilized seeds gives gold nanorods in high yield in one step with the longitudinal plasmon wavelength ranging from 750 to 1030 nm, depending on the amount of the seeds. The longitudinal plasmon wavelength can be extended to 1100 nm by the use of a two-step growth method. The growth of gold nanorods in CTEAB solutions takes 5-10 h, more than 5 times slower than that in cetyltrimethylammonium bromide solutions at the same concentration of surfactants. The use of the citrate-stabilized seeds gives both gold bipyramids and a small percentage of gold nanorods. The longitudinal plasmon wavelength of the bipyramids is tunable from 700 to 1100 nm by varying the amount of the citrate-stabilized seeds. The growth of gold bipyramids takes more than 1 day. Transmission electron microscopy characterizations reveal that the gold nanorods grown from both types of gold nanoparticle seeds are single-crystalline and that the gold bipyramids are penta-twinned.

Journal Article↗
PubMed2004

Role of CO2 in the formation of gold deposits.

Much of global gold production has come from deposits with uneconomic concentrations of base metals, such as copper, lead and zinc. These 'gold-only' deposits are thought to have formed from hot, aqueous fluids rich in carbon dioxide, but only minor significance has been attached to the role of the CO2 in the process of gold transport. This is because chemical bonding between gold ions and CO2 species is not strong, and so it is unlikely that CO2 has a direct role in gold transport. An alternative indirect role for CO2 as a weak acid that buffers pH has also appeared unlikely, because previously inferred pH values for such gold-bearing fluids are variable. Here we show that such calculated pH values are unlikely to record conditions of gold transport, and propose that CO2 may play a critical role during gold transport by buffering the fluid in a pH range where elevated gold concentration can be maintained by complexation with reduced sulphur. Our conclusions, which are supported by geochemical modelling, may provide a platform for new gold exploration methods.

Journal Article↗
PubMed1995

The second course of gold.

OBJECTIVE: To determine the outcomes in patients who receive more than one course of intramuscular gold therapy. METHODS: Gold clinic records of all patients who had received more than one course of gold at the Arthritis Centre, Vancouver, British Columbia were reviewed to extract clinical and laboratory data. RESULTS: Between 1949 and 1992, 1148 patients received injectable gold in the gold clinic of the Arthritis Centre, Vancouver, British Columbia. Forty-two patients received 2 courses and 3 patients 3 courses of gold separated by intervals of greater than 8 months. Twenty-one patients were markedly improved when the first course of gold was discontinued. Twenty of these 21 patients experienced a similar marked improvement from a 2nd course of gold. Three patients who received 3 courses had marked improvement with each course. Only 1 patient who experienced marked improvement with the first course of gold failed to respond to a 2nd course. CONCLUSION: In contrast to the published literature, our experience suggests that the response to the 2nd course of gold is similar to the response to the first in most patients with arthritis.

Adult↗
PubMed1988

Use of colloidal gold complexes of wheat germ agglutinin as a label for neural cells.

We have made stable complexes between wheat germ agglutinin and either 5 or 10 nm particles of colloidal gold. These complexes were phagocytosed by neuronal and glial cells in embryonic rat hippocampal cultures and the incorporated gold gave intense, low-background staining in the light microscope either directly, for the most heavily labelled cells, or after intensification by physical development of silver. Cells were labelled in a punctate fashion over perikarya and processes. In the electron microscope, particles of gold were observed in lysosomal vesicles, frequently in an aggregated form. Gold complex incorporated into cells in culture was retained by those cells over periods up to 20 days. Embryonic hippocampal cells were labelled in suspension culture by incorporation of wheat germ agglutinin-gold complexes and transplanted into the brains of syngeneic adult host rats. Grafted neurons and glia were observed in the electron microscope to retain high levels of gold label over periods up to 30 days. Receipt of synaptic connections by transplanted neurones was observed. Complexes of wheat germ agglutinin with 10 nm gold particles were injected unilaterally into field CA3 of the hippocampus of adult rats. Specific retrograde transport of gold was observed in the light and electron microscopes to pyramidal and hilar neurones of the contralateral hippocampus and to neurones of the medial septal nucleus. Colloidal gold-wheat germ agglutinin complexes appear to be useful cellular markers that can be visualized at both light and electron microscope levels.

Animals↗
PubMed2005

Gold nanocluster formation using metallothionein: mass spectrometry and electron microscopy.

Clonable contrasting agents for light microscopy, such as green fluorescent protein, have revolutionized biology, but few such agents have been developed for transmission electron microscopy (TEM). As an attempt to develop a novel clonable contrasting agent for TEM, we have evaluated metallothionein, a small metal-binding protein, reacted with aurothiomalate, an anti-arthritic gold compound. Electro spray ionization and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry measurements show a distribution of gold atoms bound to individual metallothionein molecules. Unlike previous reports, these data show gold binding occurred as the addition of single atoms without retention of additional ligands. Moreover, under certain conditions, MALDI spectra show gold binding ratios of greater than 1:1 with the cysteine residues of metallothionein. Together, this may hint at a gold-binding mechanism similar to gold nanocluster formation. Finally, metallothionein-gold complexes visualized in the TEM show a range of sizes similar to those used as current TEM labels, and show the potential of the protein as a clonable TEM label in which the gold cluster is grown on the label, thereby circumventing the problems associated with attaching gold clusters.

Gold↗
PubMed1956

The uptake of radiocolloids by macrophages in vitro; a kinetic analysis with radioactive colloidal gold.

Macrophages isolated from the rabbit peritoneal cavity extract radioactive colloidal gold from solutions in vitro. This reaction (ultraphagocytosis) involves two phases: the reversible adsorption of gold on the cell surface and the subsequent irreversible removal of surface-bound colloid into the cell. The latter process (called ingestion) appears to proceed at a rate which is proportional at any moment to the amount of gold attached to the cell surface; the latter in turn can be related to the concentration in extracellular fluid by a simple adsorption isotherm. In terms of rate, therefore, ingestion is related to the extracellular gold concentration in the same way that many enzyme reactions are related to the substrate concentration. Although enzyme kinetics are useful in describing rates of ultraphagocytosis, there is no evidence that enzymes participate in either adsorption or ingestion or that metabolic energy is required of the macrophage. Exudative leucocytes of the heterophilic series show little or no interaction with these finely dispersed gold sols (mean particle diameter 6 to 9 millimicrons). 37 degrees C. three parameters are sufficient to characterize the reaction between gold and a suspension of macrophages, namely an affinity constant (1/K(s)), an adsorption maximum (L), and a rate constant of ingestion (k(3)). Although numerical values differed markedly among cells of different exudates, all three parameters were estimated in three instances. In these suspensions between 2 and 20 per cent of the surface-bound gold was ingested each minute (37 degrees C., pH 7.4). Under conditions of surface saturation, it was estimated that tens of thousands of gold particles were attached to the surface of an average macrophage; this amount of colloid, however, occupied less than 1 per cent of the geometric area of the cell surface. Although surface saturation imposed an upper limit on the rate of ingestion, no practical limit was noted in the capacity of macrophages to continue the reaction. Optical measurements imply that within the cell agglutination of colloidal gold began promptly after its ingestion. These data are compared with published kinetic studies on the phagocytosis of microscopic particulates and on the parasitism of bacteria by virus.

Animals↗
PubMed1975

The quantitative distribution of gold in skin during chrysotherapy.

Gold concentrations in epidermis, dermis, and whole skin were measured by neutron activation analysis after formation of suction bullae in 8 patients who had received protracted cyrysotherapy. Epidermis contained 3% (median) of the gold content of whole skin. A direct correlation between cumulative gold dose and skin gold level was noted. These findings suggest that apparent gold concentrations in skin are influenced by the depth of the biopsy, that keratinous tissues have little affinity for gold, and that the gold storage capability of skin is not saturated by large cumulative doses of gold. The beneficial effect of gold in pemphigus may not be mediated at the site of blister formation.

Adult↗
PubMed1996

Contact allergy to gold in dental patients.

Gold sodium thiosulphate (GSTS) in patch test series commonly yields positive reactions. In this study of dental patients, the clinical relevance of these positive reactions, the suitability of gold compounds as patch test materials, and value of the lymphocyte proliferation test in gold contact allergy, were evaluated. The frequency of positive patch test reactions to GSTS was 12.4% in the dental series. Fifty-two patients, only two of whom were male, were studied. Thirteen (25%) had had symptoms from jewellery or dental restorations. However, in most cases gold allergy was subclinical. A 10% aqueous solution of gold sodium thiomalate (GSTM) was almost as good as 0.5% GSTS in petrolatum as a marker of gold contact allergy, but 0.001% potassium dicyanoaurate (PDCA) yielded a high percentage of false-negative results. Seventy-three per cent of the subjects with positive patch tests to GSTS responded to gold compounds in vitro in the lymphocyte proliferation test, whereas 13 controls without gold contact sensitivity were negative. Consistent results in skin and lymphocyte proliferation tests provide support for the concept that gold salt-induced 'allergic-like' reactions are truly allergic in nature.

Adolescent↗
PubMed1987

Gold disposition in the rat: studies of its plasma half-life and its urinary, biliary and fecal elimination pathways.

The biologic half-life of gold, a subject of controversy for many years, was found to be much longer in the rat than that reported for other species in the bulk of the literature. The longer observed half-life supports recent findings in man and is more consistent with the monthly maintenance dosing normally used in patients with rheumatoid arthritis. Excretion studies revealed that, after administration of gold sodium thiomalate, gold was eliminated via urinary and fecal pathways by approximately a 2:1 ratio. The relative importance of these pathways was not altered after multiple dosing. Biliary and intestinal excretion studies were performed to identify the means by which gold is eliminated via the feces. Only a small percentage of the dose was recovered from the bile after 2 hr, and biliary excretion was shown to be dose dependent. Results suggest that passive diffusion may be responsible for plasma-to-bile transfer and stand in contrast to the results of similar studies on other metals. Administration of gold as gold chloride [Au(III)] instead of gold sodium thiomalate [Au(I)] did not alter the excretion into bile, nor did stimulation of metallothionein, a metal-binding protein in the liver and kidney, by Cd pretreatment. Intestinal excretion was shown to be an insignificant pathway of gold elimination. The results of these studies suggest that, at high doses, gold-binding sites on plasma proteins may be saturated, resulting in an increase in excretion into the urine and bile, as well as an increase in distribution to peripheral tissues where tissue binding results in an overall increase in half-life.

Animals↗
PubMedDate not supplied

Pharmacokinetics of gold following administration of auranofin (SK+FD-39162) and myochrysine to rats.

Auranofin orally administered to rats resulted in delayed and protracted peak blood and serum gold levels occurring 24 to 48 h post administration. During this period, the gold concentration in blood was higher than in serum indicating that a major portion of gold was associated with the cellular components. During 1st order elimination (greater than 48 h), the blood/serum gold ratio decreased which suggested dissociation of cellular gold. Biliary cannulation experiments demonstrated that the protracted gold levels (24 to 48 h) could not be due to hepatic recirculation. In contrast to auranofin, gold sodium thiomalate produced blood gold levels which peaked within 3 h, rapidly declined and were consistently lower than serum gold levels.

Animals↗