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PubMed1996

Resistance to tick-borne spirochete challenge induced by Borrelia burgdorferi strains that differ in expression of outer surface proteins.

Hamsters were immunized with thimerosal-killed Borrelia burgdorferi 297 or a mutant of 297 (M297) that lacks the 49-kb linear plasmid and expression of outer surface proteins A and B (OspA and OspB). Ixodes scapularis nymphs infected with either the B. burgdorferi sensu stricto strain 297 or JMNT, similar in OspA and OspB but differing in OspC expression, were used to evaluate protection. In a homologous challenge, 24 hamsters were vaccinated, 8 each with 297 or M297 and 8 sham (adjuvant)-vaccinated controls. Hamsters vaccinated with either bacterin were completely protected against a natural tick bite or subcutaneous (s.c.) inoculation of 297. Borreliae were effectively eliminated from 80 to 90% of the 297-infected ticks that fed on four hamsters immunized with the 297 bacterin. Cultures of spirochetes isolated from the ticks that remained infected were infectious and induced joint inflammation in naive hamsters. There was no reduction of strain 297 spirochetes in ticks that fed on four hamsters immunized with M297, but the hamsters were protected. Results with the M297 bacterin indicate that proteins other than OspA or OspB can protect hamsters against a tick challenge without eliminating B. burgdorferi in the tick. In a heterologous challenge, 36 hamsters were vaccinated, 12 with each bacterin and 12 controls. None of the hamsters immunized with either bacterin were protected from a challenge involving JMNT-infected ticks, while two of four were protected against an s.c. challenge. Hamsters challenged s.c. with strain 297 spirochetes were protected. There was partial elimination of JMNT spirochetes in ticks that fed on the group of four hamsters immunized with the 297 bacterin, and infection rates were reduced by 50 to 60%. JMNT spirochetes reisolated from the ticks that fed on 297-vaccinated hamsters also remained infectious for hamsters. In the JMNT-infected ticks that fed on four M297-immunized hamsters, there was no decline in the proportion of infected ticks. Destruction of spirochetes in ticks that fed on the hamsters vaccinated with the 297 bacterin suggests that antibodies to OspA and OspB may have been responsible, since the mutant did not induce this activity.

Animals↗

PubMed1963

Studies on immunity in anthrax. X. Gel-adsorbed protective antigen for immunization of man.

Puziss, Milton (Fort Detrick, Frederick, Md.) and George G. Wright. Studies on immunity in anthrax. X. Gel-adsorbed protective antigen for immunization of man. J. Bacteriol. 85:230-236. 1963.-Protective antigen in filtrates of anaerobic cultures of Bacillus anthracis was not readily precipitable by alum or other aluminum salts, but was adsorbed onto a preformed aluminum hydroxide gel under specific conditions. The adsorbed product was highly effective in immunizing rabbits, guinea pigs, and mice against challenge with virulent B. anthracis spores. Gel-adsorbed anaerobic antigens preserved with 1:10,000 thimerosal were unstable on storage at 4 C; replacement of this preservative with 1:40,000 benzethonium chloride produced a more stable product. Addition of 0.0009% formalin further increased the stability during accelerated aging at 37 C. The final product had high protective activity in animals and was well tolerated in man.

Alum Compounds↗

PubMed1965

PLASMA COAGULATION BY ORGANISMS OTHER THAN STAPHYLOCOCCUS AUREUS.

Bayliss, Berenice G. (Washington State University, Pullman), and Elizabeth R. Hall. Plasma coagulation by organisms other than Staphylococcus aureus. J. Bacteriol. 89:101-105. 1965.-Approximately 200 organisms were investigated for their ability to clot human and rabbit plasma. Various anticoagulants were used in preparing the plasma: acid-citrate-dextrose, ethylenediaminetetraacetate, balanced oxalate, potassium and sodium oxalates, and heparin. Twelve organisms were found which coagulated citrated plasma in less than 8 hr: four strains of Streptococcus faecalis; two strains of S. faecalis var. zymogenes; three strains of S. faecalis var. liquefaciens; and one strain each of S. pyogenes, Escherichia coli, and Serratia marcescens. Six strains of coagulase-positive Staphylococcus were selected for use as controls. Experiments were performed to determine the mechanism by which these microorganisms coagulated citrated plasma. As this was the only plasma clotted, it was presumed that the citrate was utilized by the microorganisms, thereby releasing the calcium which was then made available so that normal physiological clotting could occur. To test this hypothesis, a chromatographic method was employed to determine the presence or absence of citrate. Coagulation tests, by use of increasing amounts of citrate, showed a linear relationship between the amount of citrate in the plasma and the coagulation time. It was demonstrated that the organisms must be actively metabolizing to clot citrated plasma. Proof for this was obtained by using a cell-free filtrate, to which thimerosal had been added to inhibit growth, instead of whole cultures for the coagulation test. Only the coagulase-positive staphylococci coagulated the citrated plasma under these conditions. From the results obtained, it was concluded that plasma coagulation by these organisms was by citrate utilization.

Animals↗

PubMed1994

Occupational hand dermatoses of hairdressers in Tainan City.

OBJECTIVES: To determine the prevalence, clinical features, and patterns of hand dermatosis in hairdressers in Tainan, Taiwan, and to examine the associations between patterns of dermatosis and risk factors such as job description, work exposure, and sensitisation to common allergens. METHODS: Interviews, examinations, and patch tests of the hairdressers from nine hairdressing stores randomly selected from Tainan City. Patch test agents included 41 substances with common allergens, shampoo preservatives, hair dyes, permanent waving and bleaching agents. RESULTS: 98 hairdressers finished the examination, 83% of them had occupational dermatosis and 32% had scissor induced scars or wounds. Most of the dermatoses belonged to either dry metacarpophalangeal dermatitis or eczema of the fingers. 44% of the hairdressers showed positive skin reaction to one or more patch test agents. The patch test results were different from previous reports in that the most common allergens were nickel, thimerosal, Captan, Kathon CG, and fragrance mix, and that the sensitivity to hair dye and permanent wave ingredients were low. The dry metacarpophalangeal dermatitis was associated with exposure to shampoo, and the eczema of the fingers with skin sensitivity to patch test agents. CONCLUSION: Hairdressers in Tainan City had a high prevalence of dermatoses including traumatic wounds, and allergic and irritant contact dermatitis. The rates of sensitivity to some of the common sensitising agents were different from previous reports.

Adolescent↗

PubMed2006

Cell cycle-dependent calcium oscillations in mouse embryonic stem cells.

During cell cycle progression, somatic cells exhibit different patterns of intracellular Ca(2+) signals during the G(0) phase, the transition from G(1) to S, and from G(2) to M. Because pluripotent embryonic stem (ES) cells progress through cell cycle without the gap phases G(1) and G(2), we aimed to determine whether mouse ES (mES) cells still exhibit characteristic changes of intracellular Ca(2+) concentration during cell cycle progression. With confocal imaging of the Ca(2+)-sensitive dye fluo-4 AM, we identified that undifferentiated mES cells exhibit spontaneous Ca(2+) oscillations. In control cultures where 50.4% of the cells reside in the S phase of the cell cycle, oscillations appeared in 36% of the cells within a colony. Oscillations were not initiated by Ca(2+) influx but depended on inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) release and the refilling of intracellular stores by a store-operated Ca(2+) influx (SOC) mechanism. Using cell cycle synchronization, we determined that Ca(2+) oscillations were confined to the G(1)/S phase ( approximately 70% oscillating cells vs. G(2)/M with approximately 15% oscillating cells) of the cell cycle. ATP induced Ca(2+) oscillations, and activation of SOC could be induced in G(1)/S and G(2)/M synchronized cells. Intracellular Ca(2+) stores were not depleted, and all three IP(3) receptor isoforms were present throughout the cell cycle. Cell cycle analysis after EGTA, BAPTA-AM, 2-aminoethoxydiphenyl borate, thapsigargin, or U-73122 treatment emphasized that IP(3)-mediated Ca(2+) release is necessary for cell cycle progression through G(1)/S. Because the IP(3) receptor sensitizer thimerosal induced Ca(2+) oscillations only in G(1)/S, we propose that changes in IP(3) receptor sensitivity or basal levels of IP(3) could be the basis for the G(1)/S-confined Ca(2+) oscillations.

Adenosine Triphosphatases↗

PubMed2005

Effects of the prostaglandins PGF2alpha and PGE2 on calcium signaling in rat hepatocyte doublets.

Coordination of intercellular Ca2+ signals is important for certain hepatic functions including biliary flow and glucose output. Prostaglandins, such as PGF2alpha and PGE2, may modify these hepatocyte functions by inducing Ca2+ increase, but very little is known about the organization of the Ca2+ signals induced by these agonists. We studied Ca2+ signals induced by PGF2alpha and PGE2 in fura-2 AM-loaded hepatocyte doublets. Even though both prostaglandins induced Ca2+ oscillations, neither PGF2alpha nor PGE2 induced coordinated Ca2+ oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by fluorescence recovery after photobleaching, showed that this absence of coordination was not related to a defect in GJP. Inositol (1,4,5)trisphosphate [Ins(1,4,5)P3] assays and the increase in Ins(1,4,5)P3 receptor sensitivity to Ins(1,4,5)P3 observed in response to thimerosal suggested that the absence of coordination was a consequence of the very small quantity of Ins(1,4,5)P3 formed by these prostaglandins. Furthermore, when PGE2 and PGF2alpha were added just before norepinephrine, they favored the coordination of Ca2+ signals induced by norepinephrine. However, GJP between hepatocyte doublets was strongly inhibited by prolonged (>or=2 h) treatment with PGF2alpha, thereby preventing the coordination of Ca2+ oscillations induced by norepinephrine in these cells. Thus, depending on the time window, prostaglandins, specially PGF2alpha, may enhance or diminish the propagation of Ca2+ signals. They may therefore contribute to the fine tuning of Ca2+ wave-dependent functions, such as nerve stimulation, hormonal regulation of liver metabolism, or bile secretion, in both normal and pathogenic conditions.

Animals↗

PubMed2001

Regulation of slow wave frequency by IP(3)-sensitive calcium release in the murine small intestine.

Slow waves determine frequency and propagation characteristics of contractions in the small intestine, yet little is known about mechanisms of slow wave regulation. We propose a role for intracellular Ca(2+), inositol 1,4,5,-trisphosphate (IP(3))-sensitive Ca(2+) release, and sarcoplasmic reticulum (SR) Ca(2+) content in the regulation of slow wave frequency because 1) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a cytosolic Ca(2+) chelator, reduced the frequency or abolished the slow waves; 2) thapsigargin and cyclopiazonic acid (CPA), inhibitors of SR Ca(2+)-ATPase, decreased slow wave frequency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP(3)-induced Ca(2+) release, abolished slow wave activity; 4) caffeine and phospholipase C inhibitors (U-73122, neomycin, and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate) inhibited slow wave frequency; 5) in the presence of CPA or thapsigargin, stimulation of IP(3) synthesis with carbachol, norepinephrine, or phenylephrine acting on alpha(1)-adrenoceptors initially increased slow wave frequency but thereafter increased the rate of frequency decline, 6) thimerosal, a sensitizing agent of IP(3) receptors increased slow wave frequency, and 7) ryanodine, a selective modulator of Ca(2+)-induced Ca(2+) release, had no effect on slow wave frequency. In summary, these data are consistent with a role of IP(3)-sensitive Ca(2+) release and the rate of SR Ca(2+) refilling in regulation of intestinal slow wave frequency.

Adrenergic alpha-Agonists↗

PubMed2004

Cyclopiazonic acid decreases spontaneous transient depolarizations in guinea pig mesenteric lymphatic vessels in endothelium-dependent and -independent manners.

Guinea pig mesenteric lymphatic vessels exhibit vasomotion through a pacemaker mechanism that involves intracellular Ca(2+) release and resultant spontaneous transient depolarizations (STDs) of the smooth muscle membrane potential. This study presents a detailed characterization of the effects of cyclopiazonic acid (CPA) on this pacemaker activity. Microelectrode recordings from smooth muscle in vessel segments revealed that application of CPA (1-10 microM) caused a hyperpolarization accompanied by a decrease in the frequency and amplitude of STDs. The CPA-induced hyperpolarization was abolished after destruction of the endothelium and in the presence of N(G)-nitro-L-arginine (100 microM) or 1H-[1,2,4]oxadiazolol-[4,3-a]quinoxaline-1-one (10 microM), which suggests a contribution of endothelium-derived nitric oxide (EDNO) in this response. In the absence of EDNO-induced effects, CPA decreased the frequency and amplitude of STDs recorded before and in the presence of the thromboxane A(2) mimetic U-46619, norepinephrine, or thimerosal. CPA abolished U-46619-induced vasomotion as determined by measurement of constriction-associated intracellular Ca2+ concentration using the ratiometric Ca2+ indicator fura-2. The endothelial actions of CPA were compared with those of ACh, which is known to cause EDNO release in this preparation. Although CPA and ACh both increased endothelial intracellular Ca2+ concentration and depolarized the membrane potential, the kinetics of action for both parameters were markedly slower for CPA than ACh. These results suggest that CPA first hyperpolarizes the lymphatic smooth muscle and decreases STD frequency and amplitude through endothelial release of EDNO, and second, consistent with the action of CPA to inhibit sarcoplasmic reticulum Ca2+-ATPase and deplete Ca2+ stores, it further reduces STD activity. Inhibition of the lymphatic smooth muscle pacemaker mechanism is thought to abolish agonist-induced vasomotion.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1995

Calcium influx is required for tannin-mediated arachidonic acid release from alveolar macrophages.

The role of Ca2+ was investigated in the response of alveolar macrophages to cotton tannin, an agent implicated in the lung disease byssinosis in textile mill workers. A physiological concentration of extracellular Ca2+ was found to be required for tannin-mediated release of radiolabeled arachidonic acid (AA). Flow cytometry using indo 1 indicated that tannin caused a rapid and dose-dependent Ca2+ increase in macrophages that also required extracellular Ca2+. Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid virtually abolished the Ca2+ influx mediated by tannin but had little effect on intracellular Ca2+ release induced by thapsigargin, N-formylmethionyl-leucylphenylalanine, or thimerosal. A mechanism for extracellular Ca2+ influx was demonstrated by rapid Mn2+ quenching of indo 1 by tannin. Verapamil inhibited tannin-mediated Ca2+ influx and AA release, but the effective concentration was 100 microM. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid chelated all Ca2+ in the cells and effectively abolished the tannin response. Exposure to tannin was not associated with cytotoxicity, as judged by 51Cr release. The data suggest that tannin induces Ca2+ influx in alveolar macrophages, which represents an important prerequisite for a cell-signaling pathway resulting in the accumulation of free AA.

Animals↗

PubMed1996

Docosahexaenoic acid reduces GABA response in substantia nigra neuron of rat.

.1. The effects of docosahexaenoic acid (DHA) on gamma-aminobutyric acid (GABA) response (IGABA) were investigated on the neuron acutely dissociated from rat substantia nigra (SN), with the use of patch recordings in a whole cell mode. 2. DHA (5 x 10(-6) M) reduced bicuculline-sensitive GABA (10(-4) M) current by 50.3 +/- 13.1% (mean +/- SE) at a holding potential (Vh) of -40 mV under voltage clamp. 3. The GABA concentrations for the half-maximum and threshold of IGABA were not altered by the presence or absence of 5 x 10(-6) M DHA in the external solution. 4. The decrease of 10(-4) M IGABA, following the peak during GABA application, was more rapid in the presence of 5 x 10(-6) M DHA than in its absence. The time constants for IGABA decay were significantly different between the two conditions. 5. DHA reduced the IGABA and the glycine-induced response (Igly) in a concentration-dependent manner. On the contrary, DHA potentiated the aspartate-induced response (Iasp) in a concentration-dependent manner, suggesting that DHA influences the activity of chloride channels but does not exhibit a nonspecific blocking effect on any ionic channel. 6. The application of thimerosal did not affect the reduction of IGABA by DHA, suggesting it unlikely that DHA reduces the IGABA by binding to phospholipids or triglycerides and altering the lipid environment around the chloride channel. 7. Arachidonic acid (AA) also reduced the IGABA in a manner similar to DHA. Docosapentaenoic acid (DPA) reduced the IGABA less potently than DHA. Other polyunsaturated and saturated fatty acids, such as docosatrienoic acid, docosatetraenoic acid, palmitic acid, and oleic acid, had very little or no effect on the IGABA. 8. DHA, as well as AA, may play an important role in modulating neuronal excitability by reducing the IGABA and Igly, and potentiating N-methyl-D-aspartate receptor-mediated responses in the SN.

Animals↗

PubMed1981

Calcitonin fragmentation by procine tissue in vitro characterized by gel filtration chromatography.

The cytosolic fraction of porcine thyroid, liver, kidney and brain tissue contains proteolytic activity capable of calcitonin degradation into peptide fragments. The degree and pattern of calcitonin fragmentation produced by the tissue examined in this study were determined by subjecting aliquots of incubation media to gel filtration chromatography immediately after incubation. Thyroid cytosol produced calcitonin fragmentation in a time-dependent manner. Fragmentation produced by liver, kidney and brain appeared to be quantitatively and qualitatively different from that produced by the thyroid. Hormone degradation produced by thyroid cytosol was substantially inhibited by p-hydroxymercuribenzoate, thimerosal and iodoacetamide but not by pepstatin. The thyroid cytosolic peptidase may be involved in calcitonin turnover and presecretory regulation within the "C' cell. Further, fragmentation within the thyroid may be responsible for the multiple immunoreactive forms of calcitonin which have been detected in the circulation.

Animals↗

PubMed1997

Contact allergy in patients with periorbital eczema: an analysis of allergens. Data recorded by the Information Network of the Departments of Dermatology.

BACKGROUND: Periorbital eczema may be an expression of a constitutional disease or an irritant or allergic dermatitis. An allergic contract dermatitis is believed to be the most common cause. OBJECTIVE: We tried to determine which allergens may cause an allergic contact dermatitis and if there exists a leading allergen. METHODS: 609 patients with periorbital eczema were assessed with patch testing in 22 hospitals to evaluate the relevance of an allergic contact dermatitis in the pathogenesis of periorbital eczema. Additionally, 116 patients were tested with their own products. RESULTS: 81% of the cases involving the eyelids were women. A relevant allergic contact dermatitis was found in 52% of the patients with periorbital eczema. Furthermore, a positive patch test was present in every third patient with the clinical diagnosis of an atopic dermatitis. Antibiotics, phenylephrine and thimerosal could be determined to be the leading allergens responsible for allergic periorbital eczema. Positive reactions for potassium dichromate and fragrance mix occurred less frequently in patients with periorbital eczema. 132 positive reactions were found in patients tested with their own products, including 33% with a positive reaction to eye ointments, 15% to face creams, 10% to eye shadows, 10% to makeup, 10% to shampoos and 4% to nail varnish. Only 6% reacted to perfume. CONCLUSION: The data underline the importance of performing patch tests in the case of periorbital eczema, especially in atopic patients.

Adult↗

PubMed1995

Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine.

The goal of this study was to determine whether nitric oxide (NO) and the NO donor, S-nitrosocysteine (cysNO), modulate the activity of carotid sinus baroreceptors. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in anesthetized rabbits. Baroreceptor activity decreased in a dose-dependent manner after injection of either NO or cysNO as constant pressure was maintained, and activity recovered spontaneously over time, within seconds to minutes. The baroreceptor pressure-activity relation was shifted significantly to the right by cysNO, with a profound suppression of activity at high pressure. Baroreceptor activity at 160 mm Hg averaged 76 +/- 8%, 60 +/- 6%, and 36 +/- 5% of the control maximum during exposure to 10(-4), 2 to 3 x 10(-4), and 10(-3) mol/L cysNO, respectively. The inhibition of activity by the L and D isomers of cysNO was equivalent and was blocked by reduced hemoglobin, suggesting that the effect was mediated by NO. The suppression of baroreceptor activity by cysNO was not related to vascular relaxation as measured by videomicrometer. Inhibition of soluble guanylate cyclase with methylene blue or 6-anilinoquinoline-5,8-quinone (LY83583, 10(-5) mol/L) did not attenuate and dibutyryl cGMP (10(-3) mol/L) did not mimic the suppression of baroreceptor activity by cysNO, suggesting a cGMP-independent mechanism. Activation of endogenous NO formation with thimerosal (10(-5) to 10(-4) mol/L) reduced maximum baroreceptor activity in five of eight experiments to 59 +/- 7% of the control maximum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Oxygen-derived free radical stress activates nonselective cation current in guinea pig ventricular myocytes. Role of sulfhydryl groups.

Oxygen-derived free radicals (O-Rs) cause alterations in cardiac electrical activity, including sustained depolarization, which may contribute to arrhythmic activity in reperfusion after ischemia. The ionic current(s) and cellular mechanism(s) underlying the sustained depolarization are not well defined. We used the whole-cell variant of the patch-clamp technique to study sustained depolarization in guinea pig ventricular myocytes during the extracellular application of O-Rs (generating system: dihydroxyfumaric acid, 3 to 6 mmol/L; FeCl3/ADP, 0.05:0.5 mmol/L). Myocytes superfused with O-Rs (pipette EGTA, 0.1 mmol/L) showed (1) sustained depolarization to between -40 and -10 mV, (2) oscillations in membrane potential, and (3) triggered activity. The depolarization resulted from an increase in quasi-steady state difference current reversing at approximately -18 mV, and the oscillations were due to transient inward current. The latter were inhibited with ryanodine (10 mumol/L) or high pipette EGTA (5 mmol/L), but the steady state current was unaffected. Nonselective cation current (INSC) (recorded with Cs+, Li+, and Mg2+ replacing K+, Na+, and Ca2+, respectively; 20 mmol/L tetraethylammonium chloride [TEA] and 5 mmol/L BAPTA in the pipette solution and 10 mmol/L TEA, 10 mumol/L tetrodotoxin, and 10 mumol/L nicardipine in the bath solution) was activated by O-Rs; the increase in current was unaffected by preventing changes in [Ca2+]i but was inhibited with dithiothreitol. Oxidizing agents (diamide and thimerosal) or caffeine (pipette EGTA, 0.1 mmol/L) produced a similar increase in membrane conductance. INSC activated with O-Rs, oxidizing agents, or caffeine was sensitive to SK&F 96365. O-R treatment was without effect when INSC was already activated with caffeine. The data suggest that (1) extracellular O-Rs activate a Ca(2+)-sensitive INSC in the absence of changes in [Ca2+]i, (2) oxidative modification of extracellular sulfhydryl groups may be involved, and (3) this mechanism is different from the Ca(2+)-dependent activation of INSC by intracellular O-Rs, indicating that O-Rs may alter ion channel activity by differential mechanisms, depending on the compartment, extracellular or intracellular, in which they are present.

Animals↗

PubMed1992

Hydrogen peroxide increases the availability of arachidonic acid for oxidative metabolism by inhibiting acylation into phospholipids in the alveolar macrophage.

Reactive oxygen species stimulate metabolism of arachidonic acid (AA) to eicosanoids in a variety of cells and tissues, yet the pathway(s) by which oxidants increase the availability of AA for oxidative metabolism are not known. Thus, we explored the effects of hydrogen peroxide (H2O2) on deacylation and reacylation of AA to determine the enzymatic mechanism(s) by which this oxidant increases levels of free, unesterified AA, and thereby its oxidative metabolism to eicosanoids, in the rat alveolar macrophage (AM). Over the range from 0.1 to 0.5 mM, H2O2 caused marked time- and dose-dependent inhibition of incorporation of [3H]AA into macrophage phospholipids, whereas calcium ionophore A23187 and zymosan particles did not cause such inhibition. Within this concentration range, there was an almost exact reciprocal correlation between inhibition of [3H]AA acylation and H2O2-stimulated accumulation of free [3H]AA in prelabeled AM cultures. Thimerosal, which blocks AA reacylation but spares deacylation via phospholipase A2 (PLA2), did not affect accumulation of free [3H]AA in prelabeled cells stimulated with H2O2, while markedly augmenting [3H]AA release in response to A23187 and to zymosan. Despite its ability to block AA acylation almost completely, H2O2 did not directly inhibit arachidonoyl CoA synthetase or arachidonoyl CoA:lysophosphatide acyltransferase, which catalyze AA incorporation into phospholipids. However, H2O2 (0.1 to 0.5 mM) markedly depleted AMs of ATP, required for synthesis of the acylation intermediate arachidonoyl CoA, suggesting that this was the means by which H2O2 inhibited acylation. Notably, H2O2 (0.03 to 3 mM) failed to stimulate macrophage PLA2 activity. We conclude that H2O2, in contrast to A23187 and zymosan, inhibits incorporation of AA into phospholipids, and that this represents the major mechanism by which the oxidant increases the availability of free AA for oxidative metabolism in the AM. This may be an important basis for release of eicosanoids in oxidant-induced inflammation and injury of the lung.

Acylation↗

PubMed1989

A simple time-resolved fluoroimmunoassay of total thyroxine in serum.

We describe a non-isotopic heterogeneous competitive immunoassay of total thyroxine in serum. Thyroxine, released from its binding proteins by merthiolate (thimerosal), competes with immobilised thyroxine (thyroxine-bovine globulin conjugate) for binding to a monoclonal biotinylated antibody. The amount of biotinylated antibody bound, which is inversely related to the amount of thyroxine in the sample, is then quantified by adding streptavidin labelled with the europium chelator 4,7-bis(chlorosulphophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA) in the presence of excess Eu3+. The complex formed (bovine globulin-thyroxine-antibody-biotin-streptavidin-BCPDA-Eu3+) is measured on the solid-phase by time-resolved fluorescence. The assay is simple to perform and its characteristics are similar to those of other currently used immunoassay techniques.

Bacterial Proteins↗

PubMed2003

Tissue-mimicking oil-in-gelatin dispersions for use in heterogeneous elastography phantoms.

A ten-month study is presented of materials for use in heterogeneous elastography phantoms. The materials consist of gelatin with or without a suspension of microscopic safflower oil droplets. The highest volume percent of oil in the materials is 50%. Thimerosal acts as a preservative. The greater the safflower oil concentration, the lower the Young's modulus. Elastographic data for heterogeneous phantoms, in which the only variable is safflower oil concentration, demonstrate stability of inclusion geometry and elastic strain contrast. Young's modulus ratios (elastic contrasts) producible in a heterogeneous phantom are as high as 2.7. The phantoms are particularly useful for ultrasound elastography. They can also be employed in MR elastography, although the highest achievable ratio of longitudinal to transverse relaxation times is considerably less than is the case for soft tissues.

Elasticity↗

PubMedDate not supplied

Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism.

Similar to many complex autoimmune diseases, genetic and environmental factors including diet, infection and xenobiotics play a critical role in the development of autism. In this study, we postulated that infectious agent antigens such as streptokinase, dietary peptides (gliadin and casein) and ethyl mercury (xenobiotic) bind to different lymphocyte receptors and tissue enzyme (DPP IV or CD26). We assessed this hypothesis first by measuring IgG, IgM and IgA antibodies against CD26, CD69, streptokinase (SK), gliadin and casein peptides and against ethyl mercury bound to human serum albumin in patients with autism. A significant percentage of children with autism developed anti-SK, anti-gliadin and casein peptides and anti-ethyl mercury antibodies, concomitant with the appearance of anti-CD26 and anti-CD69 autoantibodies. These antibodies are synthesized as a result of SK, gliadin, casein and ethyl mercury binding to CD26 and CD69, indicating that they are specific. Immune absorption demonstrated that only specific antigens, like CD26, were capable of significantly reducing serum anti-CD26 levels. However, for direct demonstration of SK, gliadin, casein and ethyl mercury to CD26 or CD69, microtiter wells were coated with CD26 or CD69 alone or in combination with SK, gliadin, casein or ethyl mercury and then reacted with enzyme labeled rabbit anti-CD26 or anti-CD69. Adding these molecules to CD26 or CD69 resulted in 28-86% inhibition of CD26 or CD69 binding to anti-CD26 or anti-CD69 antibodies. The highest % binding of these antigens or peptides to CD26 or CD69 was attributed to SK and the lowest to casein peptides. We, therefore, propose that bacterial antigens (SK), dietary peptides (gliadin, casein) and Thimerosal (ethyl mercury) in individuals with pre-disposing HLA molecules, bind to CD26 or CD69 and induce antibodies against these molecules. In conclusion, this study is apparently the first to demonstrate that dietary peptides, bacterial toxins and xenobiotics bind to lymphocyte receptors and/or tissue enzymes, resulting in autoimmune reaction in children with autism.

Adolescent↗