Levels of PCB methyl sulfones (MeS0,-CBs) and DDE methyl sulfones (MeS0,-DDEs) have been determined in tissues from polar bear (Ursus rnartimus), beluga whale (Delphinapterus leucus), and false killer whale (Pseudorcu crassidens) from the Canadian environment, and grey seal (Hulichoerus grypus), otter (Lutra lutra), and wild mink (Mustela vison) from the Swedish environment. Up to 30 MeS0,-CB congeners and three MeS0,-DDE isomers were shown to be present in the analyzed tissues. The concentration of total MeS0,-CBs ranged from 0.1 to 21 pg/g extracted lipids. 3-MeSO2-2,5,2',4',5'-penta-CB is the dominating MeS0,-CB congener in all the analyzed samples, but the corresponding 4-MeS0,-CB also is present in high concentrations. A smaller number of MeS0,-CBs, always dominated by the meta-substituted MeS0,-CBs, were present in livers of grey seal, otter, and mink than in adipose tissue or muscle. In all studied mammals the concentrations of MeS0,-CBs were higher in liver than in blubber or muscle. Seven PCB congeners were identified as precursors of the PCB methyl sulfones: 2,4,2',5'tetra-CB (CB-49), 2,5,3',4'-tetra-CB (CB-70), 2,4,5,2',5'-penta-CB (CB-101), 2,3,4,5,2',5'-penta-CB (CB-87), 2,3,6,2',4',5'-hexa-CB (CB-l49), 2,3,4,2',3',6'-hexa-CB (CB-132), and 2,3,4,2',5'-hexa-CB (CB-141). All species except beluga whale contained 3-MeS02-4,4'-DDE, but at a much lower concentration in mink and otter than in the other mammals. Polar bear and grey seal liver also contained 2-MeSO2-4,4'-DDE. The concentrations of 2-and 3-MeSO2-DDE ranged from 0.01 to 1.3 pg/g extracted lipids. A hitherto unknown MeS0,-DDE isomer was determined in false killer whale blubber by GC-MS, along with 2-and 3-MeS02-4,4'-DDE and several unknown MeSO,-penta-CBs and MeS0,-hexa-CBs. tris(4-chloropheny1)methanol was identified in the aryl methyl sulfone fraction of polar bear liver and grey seal blubber samples.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants routinely found in human and animal tissues. Developmental exposure to PCBs is associated with neuropsychologic deficits, which may be related to effects on thyroid hormone (TH) signaling in the developing brain. However, PCBs may interfere with TH signaling solely by reducing circulating levels of TH, or they may exert direct effects on TH receptors (TRs). Therefore, we tested whether maternal exposure to a commercial PCB mixture, Aroclor 1254 (A1254), exerts effects in the fetal brain by one or both of these mechanisms. Dams were dosed daily with 0, 1, or 4 mg/kg A1254 from gestational day 6 (GD6) until they were sacrificed on GD16. A1254 significantly reduced circulating levels of triiodothyronine (T 3 ) and thyroxine (T 4 ) in pregnant rats but increased the expression of several THresponsive genes in the fetal cortex, including neuroendocrine-specific protein A (NSP-A), RC3/neurogranin, and Oct-1. These findings are consistent with a direct action of PCBs on TRs. However, we did not identify parent PCB congeners or metabolites that bound to rat TRs isolated from hepatic nuclei. These findings indicate that PCBs can interfere with TH signaling in the fetal brain by direct actions on the fetus rather than by producing maternal hypothyroidism. producing a variety of functional TR isoforms (TRβ1, TRβ2, TRβ3, TRα1) (Flamant and Samarut 2003). TRα1 and TRβ1 are the predominant isoforms that are expressed throughout brain development (Bradley et al. 1989(Bradley et al. , 1992(Bradley et al. , 1994 and in other tissues such as liver, intestine, and heart (Brent 2000). However, only one report has addressed this proposal directly (Cheek et al. 1999), finding that two hydroxylated PCB congeners (4´-OH-PCB-14 and 4´-OH-PCB-106) exhibit a relatively low affinity for human TRβ1 (K i = 32 µM).Considering these findings, the present studies were initiated for two reasons. First, we tested the hypothesis that maternal PCB exposure could affect the fetal cerebral cortex by reducing the availability of TH to the fetus. We previously showed that low maternal TH, produced experimentally by goitrogen treatment, can alter gene expression in the fetal cortex before the onset of fetal thyroid function (Dowling et al. , 2001. Therefore, if PCBs reduce circulating levels of maternal TH, then gene expression in the fetal cortex should respond in a manner consistent with hypothyroidism. Second, we tested the hypothesis that individual PCBs or their metabolites could bind to the TR. To test this, we used rat hepatic nuclei as a source of both TRα1 and TRβ1. Materials and MethodsChemicals. Aroclor 1254 (A1254; lot no. A8110048) and individual PCB congeners (PCBs 77, 105, 118, 126, 138, and 153) were purchased from AccuStandard, Inc. (New Haven, CT). Methylsulfonyl-PCBs (MeSO 2 -PCBs) were synthesized according to Haraguchi et al. (1987). The purity of these compounds was > 99% as determined by gas chromatography. The hydroxylated PCBs were synthesized using the ...

Bioaccumulation of persistent organic compounds can eventually lead to concentrations in wildlife and humans that are deleterious to health. The present paper documents the identification, quantification, and synthesis of a novel compound, 2,2'-dimethoxy-3,3',5,5'-tetrabromobiphenyl (2,2'-diMeO-BB80), present in the marine mammals Striped dolphin (Stenella coeruleoalba), Bottlenose dolphin (Tursiops truncatus), Minke whale (Balaenoptera acutorostrata), and Baird's beaked whale (Berardius bairdii) caught in the Pacific Ocean. Identification was based on comparison of the relative retention times of the compound on two gas chromatographic columns of different polarities to those of an authentic standard. Furthermore, this identification was also supported by comparison of the full scan mass spectrometric data collected employing electron ionization (El), positive ion chemical ionization (PICI), and electron capture negative ionization (ECNI). The concentrations of 2,2'-diMeO-BB80 in the samples ranged from 12 to 800 ng/g lipid, making this consistently one of the most abundant compounds among those analyzed, including polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDD), and methoxylated PBDEs. The known occurrence of 3,3',5,5'-tetrabromo-2,2'-biphenyldiol (2,2'-diOH-BB80) in the marine environment as a natural product suggests that its methylated derivative, 2,2'-diMeO-BB80, is also of natural origin. To obtain the necessary authentic standards, synthesis was performed of 2,2'-diMeO-BB80 and the known natural product 2',6-dimethoxy-2,3',4,5'-tetrabromodiphenyl ether (2',6-diMeO-BDE68).

We report two cases of surface deterioration of a zirconia ceramic femoral head associated with phase transformation after total hip arthroplasty. One head was retrieved at revision due to recurrent dislocation after six years and the other because of failure of the locking mechanism of the polyethylene liner after three years. The monoclinic content of the zirconia ceramics rose from 1% to about 30% on the surface of the heads. SEM revealed numerous craters indicating extraction of the zirconia ceramics at the surface. Surface roughness increased from an initial value of 0.006 microm up to 0.12 microm. This is the first report to show that phase transformation of zirconia ceramics causes deterioration of the surface roughness of the head in vivo after total hip arthroplasty.

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We have previously demonstrated that in mice, the decrease in serum thyroxine (T(4)) level by polychlorinated biphenyls (PCBs) occurs without an increase in the UDP-glucuronosyltransferase (T(4)-UDP-GT) for T(4) glucuronidation, although the PCB-induced decrease in rats is generally thought to occur through induction of T(4)-UDP-GT, UGT1A1, and UGT1A6. In the present study, to further clarify the relationship between the decrease in serum T(4) level and the increase in UGT1A activity by PCB in rats, we examined the relationship using Wistar rats and Gunn rats, a mutant strain of Wistar rats deficient in UGT1A isoforms. The serum total T(4) level was markedly decreased not only in the Wistar rats but also in the Gunn rats 4 days after treatment with a PCB, Kanechlor-500 (KC500, 100 mg/kg) or 2,2',4,5,5'-pentachlorobiphenyl (PentaCB, 112 mg/kg), and there was no significant difference in magnitude of the decrease between the two rat strains. At the same time, the level and activity of T(4)-UDP-GT were significantly increased by treatment with either KC500 or PentaCB in Wistar rats but not in Gunn rats. In addition, no significant change in the level of serum total triiodothyronine (T(3)) and thyroid-stimulating hormone by the KC500 treatment was observed in either Wistar or Gunn rats. Furthermore, significant decrease in the activity of hepatic type-I deiodinase, which mediates the deiodization of T(4) and T(3), by treatment with KC500 or PentaCB was observed in both Wistar and Gunn rats. From the serum of KC500- or PentaCB-treated Wistar and Gunn rats, mono- and di-hydroxylated PCB metabolites, which would bind to T(4) binding serum protein (transthyretin), were detected. In conclusion, the present results suggest that the decrease in serum total T(4) level by either KC500 or PentaCB in Gunn rats was not dependent on the increase in hepatic T(4)-UDP-GT activity. The findings further suggest that the PCB-mediated decrease in serum T(4) level might occur, at least in part, through formation of the hydroxylated PCB metabolites. Furthermore, even in Wistar rats, the PCB-mediated decrease in serum T(4) level might occur not only through the increase in hepatic T(4)-UDP-GT but also via formation of hydroxylated PCB metabolites.

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Human T cell lymphotropic virus type 1 (HTLV-1)-specific CTL are thought to be immune effectors that reduce the risk of adult T cell leukemia (ATL). However, in vivo conditions of anti-HTLV-1 CTL before and after ATL development have yet to be determined. To characterize anti-HTLV-1 CTL in asymptomatic HTLV-1 carriers (AC) and ATL patients, we analyzed the frequency and diversity of HTLV-1-specific CD8+ T cells in PBMC of 35 AC and 32 ATL patients using 16 distinct epitopes of HTLV-1 Tax or Env/HLA tetramers along with intracellular cytolytic effector molecules (IFN-γ, perforin, and granzyme B). Overall frequency of subjects possessing Tax-specific CD8+ T cells was significantly lower in ATL than AC (53 vs 90%; p = 0.001), whereas the difference in Env-specific CD8+ T cells was not statistically significant. AC possessed Tax11–19/HLA-A*0201-specific tetramer+ cells by 90% and Tax301–309/HLA-A*2402-specific tetramer+ cells by 92%. Some AC recognized more than one epitope. In contrast, ATL recognized only Tax11–19 with HLA-A*0201 and Tax301–309 with HLA-A*2402 at frequencies of 30 and 55%. There were also significant differences in percentage of cells binding Tax11–19/HLA-A*0201 and Tax301–309/HLA-A*2402 tetramers between AC and ATL. Anti-HTLV-1 Tax CD8+ T cells in AC and ATL produced IFN-γ in response to Tax. In contrast, perforin and granzyme B expression in anti-HTLV-1 CD8+ T cells of ATL was significant lower than that of AC. Frequency of Tax-specific CD8+ T cells in AC was related to proviral load in HLA-A*0201. These results suggest that decreased frequency, diversity, and function of anti-HTLV-1 Tax CD8+ T cell clones may be one of the risks of ATL development.