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31.
MICHAEL W. STEWART PHILIP A. GORDON WAI S. ETCHES HALYNA MARUSYK SIBRAND POPPEMA COLIN BIGAMI† BRIAN SYKESI† 《British journal of haematology》1995,90(4):900-905
Summary. The association of cardiolipin with polystyrene beads was studied using 31P-NMR and electron microscopy. In the presence and absence of fetal calf serum, cardiolipin appeared to bind to the polystyrene beads in lamellar phase as assessed by 31P-NMR imaging. Electron microscopic analysis revealed an even coating of phospholipid about the beads with extensive micelle binding. Cardiolipin-coated beads challenged with ACA-positive sera followed by immunogold indicated antibody bound to micelles associated with the bead. Studies conducted with ACA IgG purified from patient sera indicated that some ACA bound to CL beads in the absence of a source of ACA cofactor (i.e. gelatin-blocked beads), some ACA required β2-GPI for binding (i.e. no binding in the presence of β2-GPI-depleted plasma), whereas other ACA which showed negliglible binding with gelatin-blocked beads, showed enhanced binding in the presence of /?2-GPI-depleted plasma. The data indicate that: (1) cardiolipin binds to polystyrene beads in lamellar phase, (2) ACA bind to phospholipid micelles bound directly to the polystyrene beads, and (3) ACA differ between individuals displaying varying phospholipid and phospholipid/cofactor substrate specificities. 相似文献
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33.
KAMINSKI NORBERT E.; JORDAN STEPHEN D.; PAGE DENNIS; SAM KIM BYUNG; HOLSAPPLE MICHAEL 《Toxicological sciences》1989,12(2):321-332
Suppression of Humoral Immune Responses by Dialkylnitrosamines:Structure-Activity Relationships. KAMINSKI, N. E., JORDAN, S.D., PAGE, D., KIM, B. S., AND HOLSAPPLE, M. P. (1989). Fundam.Appl Toxicol 12,321-332. Comparisons between chemical structureof N, N-dialkylnitrosamine congeners and their ability to alterthe Day 4 IgM antibody response to sRBC, body weights. and organweights of female B6C3F1 mice were investigated. Short-chainnitrosamine congeners were selected for these studies on thebasis of two criteria: (1) congeners wth symmetrical aliphaticchain length [N-nitrosodimethylamine (DMN), N-nitrosodiethylamine(DEN), N-nitrdipropylamine (DPN), N-nitrosodibutylamine (DBN)]and (2) congeners possessing an N-methyl group [N-nitrosomethylethylamine(MEN), N-nitrosomethylpropylamine (MPN), and N-nitrosomethylbutylamine(MBN)]. The immunotoxicity of each congener was evaluated basedon the compound's ability to suppress the in vivo sRBC antibodyresponse following 7 consecutive days of treatment. An ED50dose was calculated, using a linear regression analysis, foreach congener and represents the millimoles of congener perkilogram body weight required to cause a 50% suppression ofthe sRBC response. These studies demonstrated two general trends:(1) those dialkylnitrosamine congeners that possessed an N-methylgroup were most immunotoxic and exhibited comparable ED50 concentrations(42-183 µmol/kg); and (2) dialkylnitrosamine congenerspossessing symmetrical aliphatic chains demonstrated an inverserelationship between aliphatic chain length and immunotoxicpotencyDMN (62 µmol/kg) > DEN (276 µmol/kg)> DPN (467 µmol/kg) > DMN (1557 µmol/kg).Comparisons were also made between the immunotoxic potency ofvarious nitrosamine congeners in the whole animal and theirpotency in an in vitro hepatocyte-spleen cell coculture system. 相似文献
34.
JUAN C. DE LA TORRE MARGARET MALLORY MICHELLE BROT LISA GOLD GEORGE KOOB MICHAEL B. A. OLDSTONE ELIEZER MASLIAH 《Virology》1996,220(2):508
Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection bothin vitroandin vivoselectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury. 相似文献
35.
Effect of Manganese on the Hepatic Mixed Function Oxidase EnzymeSystem in the Rat , M. J., and SCHNELL, R. C. (1984). Fundam.Appl. Toxicol. 4, 10091018. Experiments were conductedto examine the effect of manganese on the hepatic mixed functionoxidase system in the rat Acute treatment with manganese chloride(110 mg Mn/kg, ip) produced a significant prolongationof hexobarbital hypnosis in male rats on Days 2 and 3 followingmetal administration. The threshold dose of manganese to producethis alteration in response was 5 mg Mn/kg and the altered responsereturned to control values by Day 5. The prolonged hexobarbitalhypnosis resulted from Mn inhibition of the hepatic microsomalmixed function oxidase system, the activity of which was assessedusing aniline (23%), ethylmorphine (26%), and hexobarbital (27%)as substrates. Manganese treatment also produced significantlyreduced levels of cytochrome P-450 (23%) and b5 (21%), but thesubstrate-induced spectral binding of all three substrates wasnot altered significantly by Mn when expressed as A per nanomoleof cytochrome P-450. The activity of NADPH cytochrome c reductasewas also significantly decreased (25%) by Mn treatment Followingthe in vitro addition of Mn in concentrations ranging from 1x 106 to 1 x 103 M Mn to microsomes derived fromnaive rats, there was no decrease in the metabolism of anilineor hexobarbital or cytochrome P-450 levels. Significant inhibitionin ethylmorphine metabolism was observed with Mn concentrationsof 1 x 104 m and greater. These experiments indicatethat acute Mn treatment can alter drug response as the resultof decreased hepatic biotransformation which occurs by an indirectmechanism. 相似文献
36.
Subchronic Toxicity of Cupric Sulfate Administered in Drinking Water and Feed to Rats and Mice 总被引:2,自引:0,他引:2
HEBERT CHARLES D.; ELWELL MICHAEL R.; TRAVLOS GREGORY S.; FITZ CHAD J.; BUCHER JOHN R. 《Toxicological sciences》1993,21(4):461-475
Subchronic Toxicity of Cupric Sulfate Administered in DrinkingWater and Feed to Rats and Mice. HÉBERT, C. D., ELWELL,M. R., TRAVLOS, G. S., FITZ, C. J., AND BUCHER, J. R. (1993).Fundam. Appl. Toxicol. 21, 461475. The effects of acute poisoning by cupric sulfate in a numberof species are well known; however, the effects of chronic low-levelingestion of cupric sulfate are less well characterized. Becauseexposure of humans to cupric sulfate may occur through drinkingwater, food, soil, or ambient air, subchronic toxicity studieswere conducted in male and female F344/N rats and B6C3F1 miceby the drinking water (2-week exposure) and dosed feed (2-and13-week exposure) routes. Animals were evaluated for histopathology,clinical pathology, reproductive toxicity, and tissue metalaccumulation, and target organs were examined by a variety ofspecial stains and by electron microscopy to characterize theobserved lesions. In drinking water, cupric sulfate concentrationsof 300 to 100 ppm produced no ill effects, whereas concentrationsof 3000 to 30,000 ppm were lethal to rats and mice within 2weeks. In feed, cupric sulfate concentrations of 4000 to 16,000ppm caused significant reductions in body weight gain in bothspecies in the 2- and 13-week studies. Hyperplasia and hyperkeratosisof the limiting ridge of the forestomach were present in bothspecies in the 2- and 13-week studies. Rats in the dosed feedstudies had a dose-related increase in inflammation in the liverand changes in clinical chemistry parameters which were indicativeof hepatocellular damage and cholestasis. Histologic changesin the kidneys of rats consisted of a dose-related increasein the number and size of eosinophilic protein droplets in theepithelial cytoplasm and the lumina of the proximal convolutedtubules. Droplets were larger and more numerous in males thanin females. Urinalysis results were suggestive of renal tubularepithelial damage. Iron staining of spleens from treated animalsindicated a marked depletion of iron stores in both male andfemale rats, but not in mice, while hematologic and clinicalchemistry alterations in rats in the 13-week study, along withhistologic changes in bone in the 2-week dosed feed study, wereindicative of a microcytic anemia. Cupric sulfate produced noadverse effects on any of the reproductive parameters measuredin rats or mice of either sex. These results indicate that cupricsulfate at high exposure levels is a hepatic and renal toxicant,as well as an inducer of anemia in rodents, with rats more sensitivethan mice following subchronic exposure. 相似文献
37.
In Vivo and in Vitro Percutaneous Absorption and Skin Decontamination of Arsenic from Water and Soil 总被引:1,自引:1,他引:0
WESTER RONALD C.; MAIBACH HOWARD I.; SEDIK LENA; MELENDRES JOSEPH; WADE MICHAEL 《Toxicological sciences》1993,20(3):336-340
The objective was to determine the percutaneous absorption ofarsenic-73 as H3AsO4 from water and soil. Soil (Yolo County65-California-57-8) was passed through 10-, 20-, and 48-meshsieves. Soil retained by 80 mesh was mixed with radioactivearsenic-73 at a low (trace) level of 0.0004 µg/cm2 (microgramsarsenic per square centimeter skin surface area) and a higherdose of 0.6 µg/cm2. Water solutions of arsenic-73 at alow (trace) level of 0.000024 µg/cm2 and a higher doseof 2.1 µg/cm2 were prepared for comparative analysis.In vivo in Rhesus monkey a total of 80.1 ± 6.7% (SD)intravenous arsenic-73 dose was recovered in urine over 7 days;the majority of the dose was excreted in the first day. Withtopical administration for 24 hr, absorption of the low dosefrom water was 6.4 ± 3.9% and 2.0 ± 1.2% fromthe high dose. In vitro percutaneous absorption of the low dosefrom water with human skin resulted in 24-hr receptor fluid(phosphate-buffered saline) accumulation of 0.93 ± 1.1%dose and skin concentration (after washing) of 0.98 ±0.96%. Combining receptor fluid accumulation and skin concentrationgave a combined amount of 1.9%, a value less than that in vivo(6.4%) in the Rhesus monkey. From soil, receptor fluid accumulationwas 0.43 ± 0.54% and skin concentration was 0.33 ±0.25%. Combining receptor fluid plus skin concentrations gavean absorption value of 0.8%, an amount less than that with invivo absorption (4.5%) in the Rhesus. These absorption valuesdid not match current EPA default assumptions. Washing withsoap and water readily removed residual skin surface arsenic,both in vitro and in vivo. The partition coefficient of arsenicin water to powdered human stratum corneum was 1.1 x 104andfrom water to soil it was 2.5 x 104. This relative similarityin arsenic binding to powdered human stratum corneum and soilmay indicate why arsenic absorption was similar from water andsoil. This powdered human stratum corneum partition coefficientmodel may provide a facile method for such predictions. 相似文献
38.
39.
KELICH STEPHANIE L.; MERCIECA MICHAEL D.; POHLAND RAYMOND C. 《Toxicological sciences》1995,27(2):239-246
N-Methylformamide (NMF) is a metabolite of dimethylformamide(DMF), a solvent with wide applications in the chemical industry.The potential developmental toxicity of NMF was evaluated inCD rats and New Zealand white rabbits. Pregnant rats and rabbitswere dosed once daily by gavage on Gestation Days 615and 618, respectively. Doses for rats were 0, 1, 5, 10,or 75 mg/kg; doses for rabbits were 0, 5, 10, or 50 mg/kg. Cesareansections were performed on rats and rabbits on Gestation Days20 and 29, respectively. No treatment-related maternal deathsor clinical signs occurred in either species. Body weight gainand food consumption were depressed in rats given 75 mg/kg andrabbits given 50 mg/kg. Fetal viability was reduced at 75 mg/kgin rats and at 50 mg/kg in rabbits. In rats, a significant increasein the incidence of malformations including cephalocele andstern-oschisis was observed in fetuses from the 75 mg/kg group.In addition, a developmental delay was indicated by reductionof fetal weight and by a significant increase in the occurrenceof incomplete ossification of various skeletal structures. Inthe rabbit, fetal body weight was reduced at 50 mg/kg. Malformationsobserved at 50 mg/kg included gastroschisis, cephalocele, domedhead, flexed paw, and skull and sternum anomalies. The lowest-observed-adverse-effectlevels for maternal and developmental toxicity in the rat andrabbit were 75 and 50 mg/kg, respectively. The no-observed-adverse-effectlevel for maternal and developmental toxicity in the rat andrabbit was 10 mg/kg. 相似文献
40.
DE JONGH JOOST; DE VITO MICHAEL; NIEBOER RUUD; BIRNBAUM LINDA; VAN DEN BERG MARTIN 《Toxicological sciences》1995,25(2):264-270
One group of male C57BL/6J mice received a single oral doseof 1 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg. Sixother groups received single oral doses of 100, 300, or 1000µmol2,2',4,4',5,5'-hexachlorobiphenyl (HxCB)/kg, alone or in combinationwith 1 nmol/kg TCDD. Liver deposition of both compounds wasstudied at Day 3 after dosage. Hepatic CYP1A1 and CYP1A2 proteinlevels and related 7-ethoxyres-orufin-O-deethylation (EROD)and acetanilide 4-hydroxylation (ACOH) activities were alsostudied. A significant increase in the hepatic deposition ofTCDD was observed in all three mixed dose groups but TCDD didnot influence hepatic HxCB deposition. TCDD did increase bothCYP1A1 and CYP1A2 protein levels. In the HxCB-treated groups,CYP1A2 levels were also increased in a dose-dependent way butCYP1A1 levels were not increased. CYP1A2 activities (ACOH),but not protein levels, in the TCDD groups cotreated with HxCBwere higher than those in the group treated with TCDD alone.CYP1A1-dependent EROD activity and CYPlA2-dependent ACOH activitywere induced in all treated dose groups. It is concluded thatthe present results do not confirm a direct role of CYP1A2 inductionin the increase of hepatic TCDD levels by HxCB cotreatment inthe mixed HxCB/TCDD dose groups. However, in this aspect, thediscrepancy between CYP1A2 activities and protein levels remainsto be explained. 相似文献