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The objective of this field trial was to reduce bovine leukemia virus (BLV) transmission and prevalence in commercial dairy herds using proviral load (PVL) and lymphocyte count (LC) measurements as indicators of the most infectious animals for culling or segregation. Bovine leukemia virus causes lymphoma in <5% of infected cattle, and increased lymphocyte counts (lymphocytosis) in about one-third. Recent research has shown that dairy cows infected with BLV have altered immune function associated with decreases in milk production and lifespan. Recent findings show that a minority of infected cattle have PVL concentrations in blood and other body fluids of over 1,000 times that of other infected cattle. In combination with a high LC, these animals are thought to be responsible for most transmission of BLV in a herd. Milk or blood samples from adult cows in our 3 Midwestern dairy farm field trials were tested semiannually with ELISA for BLV antibodies, and ELISA-positive cattle were then retested using a blood LC and a quantitative PCR test for PVL to identify the animals presumed to be most infectious. Herd managers were encouraged to consider PVL and LC status when making cull decisions, and to segregate cows with the highest PVL and LC from their BLV ELISA-negative herd mates where possible. After 2 to 2.5 yr of this intervention, the incidence risk of new infections decreased in all 3 herds combined, from 13.8 to 2.2, and the overall herd prevalence decreased in all 3 herds combined from 62.0 to 20.7%, suggesting that this approach can efficiently reduce BLV transmission as well as prevalence. This is encouraging, because a very low prevalence of BLV infection would make it economically feasible to cull the remaining ELISA-positive cattle, as was achieved in national eradication programs in other countries decades ago.

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Forty-eight patients received CPX-351 (liposome-encapsulated cytarabine:daunorubicin at a 5:1 molar ratio) every other day for 3 doses at 10 dose levels. Pharmacokinetic parameters were dose-independent and exhibited low inter-patient variability. CPX-351 showed a negligible distribution phase and prolonged mono-exponential first-order plasma elimination (t(1/2)∼24 h). The plasma ratio of 5:1 was maintained at all dose levels. Nearly all of the detectable cytarabine and daunorubicin in circulation following CPX-351 administration was in the form of liposome encapsulated drug. Dose-dependent hematopoietic effects had early onset with cytopenias at 12 units/m(2), and a gradual increase in frequency and severity, until single induction complete response was achieved at 43 units/m(2). Non-hematologic effects had onset by 24 units/m(2) with shallow dose-response until maximum frequency and severity were observed at the 101-134 units/m(2) dose levels. Single induction response occurred over a 2.3-fold range of doses indicating that CPX-351 may be useful at high doses for patients suitable for intensive chemotherapy and at reduced doses for patients at increased risk of treatment-related mortality. The unique pharmacologic features of CPX-351 contribute to its promising antileukemic efficacy.

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Emerging evidence suggests that cats infected with feline herpesvirus-1 (FHV-1) may experience a brief viremic phase. The objective of this study was to determine whether natural routes of FHV-1 inoculation could result in viremic transmission of infectious virus to connective tissues (cortical bone, tendon). Three specific pathogen-free cats were experimentally inoculated with FHV-1 via a combined mucosal (oronasal, ocular) route. Cats were euthanized at the peak of clinical signs to aseptically harvest tissues (cortical bone, tendon, trachea/tongue) for co-culture with a susceptible cell line to promote spread of infectious virus. Viral infection of Crandall-Rees feline kidney cells was microscopically visualized by cytopathic effect (CPE). Additionally, co-culture DNA was extracted either at the point of CPE or 16 days of culture without evidence of CPE, to amplify FHV-1 glycoprotein B gene using real-time PCR. Infectious virus was detected in distant cortical bone (two cats, moderate to severe clinical signs) and tendon (one cat, severe clinical signs). Direct infection of mucosal (trachea, tongue) tissues also was confirmed in these two cats. In contrast, all co-cultured tissues from the third cat (mild clinical signs) were negative for FHV-1 by CPE and PCR. Results of this study demonstrated that early primary FHV-1 viremia may be distributed to distant connective tissues.

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We report measurements of the de Haas-van Alphen effect in CeIn(3) in magnetic fields extending to approximately 90 T, well above the Néel critical field of mu(0)H(c) approximately 61 T. The unreconstructed Fermi surface a sheet is observed in the high magnetic field polarized paramagnetic limit, but with its effective mass and Fermi surface volume strongly reduced in size compared to that observed in the low magnetic field paramagnetic regime under pressure. The spheroidal topology of this sheet provides an ideal realization of the transformation from a "large Fermi surface" accommodating f electrons to a "small Fermi surface" when the f-electron moments become polarized.

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Yearling Targhee ewes (n = 24; not pregnant or lactating) were used in a 2 x 2 factorial arrangement of treatments to determine the effects of supplemental vitamin E (0 IU [0vitE] vs 330 IU vitamin E x ewe(-1) x d(-1) [+vitE]) and Zn (0 mg [0Zn] vs 140 mg Zn x ewe(-1) x d(-1) [+Zn]) on serum alpha-tocopherol concentrations, antibodies to parainfluenza type 3 (PI3), ewe BW, Zn liver concentrations, and serum alkaline phosphatase activity. Ewes were managed as one group, grazed native pasture, and had ad libitum access to white salt and water. Ewes that received supplemental vitamin E were orally dosed every other day with 660 IU of DL-alpha-tocopherol acetate in a gelatin capsule beginning on d 1 and continuing to d 63 of the study. Ewes that received Zn supplement were orally dosed every other day with 280 mg of Availa-Zn 100 (Zinpro Corp., Eden Prairie, MN, IFN 6-32-054) in gelatin capsules for 63 d. All ewes were vaccinated with killed PI3 on d 22 and 42. No interactions were detected (P > 0.35); however, serum alpha-tocopherol concentrations and PI3 antibody titer dilutions changed (P = 0.001) over the length of the study. Ewe BW change, serum alkaline phosphatase activity, and liver Zn concentrations did not differ (P > 0.22) between 0Zn and +Zn or 0vitE and +vitE ewes. Serum a-tocopherol tended to be higher (P = 0.08) in +vitE than 0vitE ewes and was numerically higher (P = 0.16) in +Zn than 0Zn ewes. Antibody titer dilutions were higher (P = 0.06) in 0Zn than +Zn ewes and did not differ (P = 0.83) between 0vitE and +vitE ewes. These results indicate that high levels of supplemental Zn may have a tendency to improve serum alpha-tocopherol concentrations but may have negative impacts on humoral immune function.

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The objective of this study was to evaluate the rate and extent of Cu repletion in Holstein heifers using two Cu sources (organic and inorganic) at two levels (15 and 30 mg/kg). An additional repletion treatment included a Cu oxide bolus. Heifers (n = 50) were individually fed a total mixed ration fortified with S and Mo at 0.40%, and 15 mg/kg of dry matter of the total diet, respectively. After 111 d of depletion, heifers were stratified by liver Cu concentration and randomly allotted to one of five repletion treatments. Four treatments consisted of feed sources of Cu (feed-Cu), 1) CuSO4 at 15 mg/kg; 2) CuSO4 at 30 mg/kg; 3) Availa-Cu at 15 mg/kg; and 4) Availa-Cu at 30 mg/kg. Availa-Cu is an organic Cu source that produces a Cu-amino acid complex. A fifth treatment, consisting of an intraruminal bolus (IB), provided a single dose of 25 g of CuO needles. Repletion treatments were delivered in the same total mixed ration without supplemental S and Mo. Copper status was assessed in blood and liver samples collected on 14-d intervals for 70 d. Irrespective of treatment, all heifers increased in body weight during the repletion period. Liver Cu increased in each feed-Cu treatment over time. Heifers treated with an IB reached a peak in liver Cu concentration (165.5 mg/kg) on d 28. Mean liver Cu concentrations were higher in heifers receiving 30 mg/kg of Cu compared with heifers receiving 15 mg/kg of Cu. Red blood cell superoxide dismutase (SOD) activity was higher (P < 0.001) in heifers receiving CuSO4 than Availa-Cu (0.98 vs 0.87 U). Also, SOD activity was higher when heifers were supplemented with 30 vs 15 mg/kg Cu (0.98 vs 0.87 U). Heifers receiving the Cu IB had higher SOD activity than heifers receiving feed-Cu sources (1.03 vs 0.92 U). Plasma ceruloplasmin concentration was higher (P < 0.001) in IB-treated heifers vs. other treatments. No differences in plasma ceruloplasmin were detected for feed-Cu source or level. These results indicate that all Cu sources evaluated in this study elevated Cu status of depleted heifers, particularly when provided at higher dietary levels.

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The antibody response patterns of cattle after subcutaneous and intranasal immunizations with adhesin Tf190 of Tritrichomonas foetus were investigated. Reactions of antibody from cattle parenterally immunized with Tf190 revealed antigen specificity and Tf190 sensitization in the majority of the animals, as determined by Western blotting. The results also demonstrated strong preimmune immunoglobulin G2 (IgG2) binding to T. foetus antigens not seen in IgG1 profiles. Subcutaneous injections of Tf190 resulted in significant (P < 0.05) increases in serum IgG1 and IgG2 titers over time, as determined by parasite specific enzyme-linked immunosorbent assay. Immune sera also significantly inhibited parasite adhesion to mammalian cell lines compared to the level of inhibition obtained with preimmune sera (P < 0.05). Intranasal immunization with Tf190 failed to produce measurable parasite-specific antibody in serum; however, this immunization route did result in significant (P < 0.05) increases in parasite-specific IgA titers in cervical mucus secretions from immunized animals that were more resistant to intravaginal challenge with T. foetus than controls. These results suggest that systemic immunization with Tf190 results in serum antibody production and antiparasitic adhesin antibodies. Additionally, the results of challenge experiments with intranasally immunized animals suggests that Tf190 primes protective immune responses that lead to lower rates of infection among these animals.

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Inpatient treatment of individuals with borderline personality disorder (BPD) is typically fraught with difficulty and failure. Patients and staff often become entangled in intense negative therapeutic spirals that obliterate the potential for focused, realistic, and effective treatment interventions. We describe an inpatient treatment approach to BPD patients which is an application of Dialectical Behavior Therapy (DBT), a cognitive-behavioral therapy for patients with BPD which has been shown to be effective in reducing suicidal behavior, hospitalization, and treatment dropout and improving interpersonal functioning and anger management. The inpatient DBT staff creates a validating treatment milieu and focuses on orienting and educating new patients and identifying and prioritizing their treatment targets. Inpatient DBT treatment techniques include contingency management procedures, skills training and coaching, behavioral analysis, structured response protocols to suicidal and egregious behaviors on the unit, and consultation team meetings for DBT staff.

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Thirty 6-yr-old Targhee ewes were randomly allotted to one of five supplemental treatments to evaluate supplementation effects on liver and fecal Zn and Cu concentrations and serum alkaline phosphatase activity: 1) control, 2) Zn complex, 3) Zn and Cu (ZnCu) complex, 4) Zn sulfate, and 5) ZnCu sulfates. Supplements were administered daily in gelatin capsules for 56 d. Liver biopsies and serum samples were collected every 14 d starting on d 0. Supplemental Zn and Cu levels were formulated to provide 90 mg/kg Zn and 10 mg/kg Cu, respectively, on a daily dry matter intake basis. Form (complex vs sulfate) x type (Zn vs ZnCu) interactions were not detected (P > 0.35). Therefore, contrast statements were used to make the following treatment comparisons: 1) control vs supplement, 2) Zn vs ZnCu, and 3) complex vs sulfate. Ewe BW at the end of the study (P = 0.09) and ewe BW change from beginning to end of the study (P = 0.07) were greater for supplemented than control ewes. Body weight and BW change did not differ between sulfate and complex (P > 0.39) or Zn- and ZnCu- (P > 0.40) supplemented ewes. Liver Cu concentrations did not differ (P = 0.41) between control and supplemented ewes. Liver Cu concentrations were higher (P < 0.10) for ewes supplemented with ZnCu than Zn and complex than sulfate forms of supplement. Liver Zn concentration tended (P = 0.13) to be higher in ZnCu than Zn-supplemented ewes. Liver and fecal Zn concentration were higher (P < 0.06) in ewes fed complex than sulfate supplements. However, serum alkaline phosphatase activity tended (P = 0.12) to be greater in ewes fed sulfate than complex supplements. Supplementing mature ewes with complexed minerals resulted in higher concentrations of Zn and Cu in the liver. In addition, supplemental Cu tended to increase concentrations of Zn in the livers of ewes; however, high levels of supplemental Zn did not negatively impact liver Cu concentrations.

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Whereas retinoic acids control nuclear events, a second class of retinol metabolites, that is, the hydroxylated forms exemplified by 14-hydroxy-retro-retinol (HRR), operate primarily in the cytoplasm. They function as regulatory cofactors for cell survival/cell death decisions. In accordance with these biological aspects, we demonstrate that these retinoids bound protein kinase C (PKC) alpha with nanomolar affinity and markedly enhance the activation of PKC alpha and the entire downstream MAP kinase pathway by reactive oxygen species. HRR was 10 times more efficient than retinol, and the optimum doses are 10-7 and 10-6 M, respectively. PKC alpha activation was reversed rapidly by imposition of reducing conditions. The retinoid binding site was mapped to the first cysteine-rich region in the regulatory domain, C1A, yet was distinct from the binding sites of diacylglycerol and phorbol esters. The C1B domain bound retinoids poorly. The emerging theme is that retinoids serve as redox regulators of protein kinase C.

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Concentrations of arsenic, cadmium, chromium, copper, lead, mercury, selenium, and zinc were measured in coral, crab, eel, fish, lobster, and sediment samples collected from French Frigate Shoals, North Pacific Ocean. The sediments contained relatively high concentrations of selenium; moderate concentrations of arsenic, cadmium, copper and lead; and low concentrations of chromium and zinc. Metal concentrations were also determined in coral and crabs collected from the island of Oahu. Notably, a crab (Grapsus tenuicrustatus) and the undulated moray eel (Gymnothorax undulatus) exhibited high levels of copper and arsenic, respectively, relative to the other species studied. The concentrations of arsenic in the eel averaged 225 microg g(-1) dry wt, which was 3-12 times higher than that in all of the other species tested. The average concentration of copper in the crab was 343 microg g(-1) dry wt, 3-86 times greater than that in the other species studied. These data indicate background and comparative levels of the metals among the studied species. Lead levels in the coral (9-10 microg g(-1) dry wt) and crab (42-57 microg g(-1) dry wt) from Tern and Disappearing Islands were 23-283-fold greater than those from Oahu (0.4 and 0.2 microg g(-1) dry wt, respectively).

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Performance, immune response, and liver trace mineral status were measured in growing heifers supplemented with different copper (Cu) concentrations and sources when diets contained the Cu antagonists Mo, S, and Fe. Sixty Angus x Hereford heifers were managed in two groups for 112 d and were either individually fed diets and mineral treatments using individual feeding stalls (Stall) or pen-fed grass hay and individually supplemented mineral treatments (Pen). The basal diet of grass hay, rolled barley, and soybean meal was analyzed to contain 6 mg Cu/kg DM. The treatments consisted of 1) no supplemental Cu (Control); 2) 49 mg Cu/kg DM from Cu sulfate (i.e. approximately five times NRC recommendation for Cu from CuSO4) (5X-SO4); 3). 22 mg Cu/kg DM from CuSO4 (2X-SO4); 4). 22 mg Cu/kg DM from a combination of 50% CuSO4 and 50% Cu-amino acid complex (50-50); and 5). 22 mg Cu/kg DM from a combination of 25% CuSO4, 50% Cu-amino acid complex, and 25% Cu oxide (CuG) (25-50-25). All heifers were supplemented with the Cu antagonists Mo (10 mg/kg DM), S (2,900 mg/kg DM), and Fe (500 mg/kg DM). These diets resulted in dietary Cu:Mo ratios that averaged 0.5:1 for Control, 4.5:1 for the 5X-SO4, and 2.4:1 for 2X-SO4, 50-50, and 25-50-25. Rate and efficiencies of gain and cell-mediated immune function were not different (P > 0.10) among treatments. Data suggest supplements containing combinations of inorganic and complexed Cu interacted differently in the presence of Mo, S, and Fe. Heifers consuming the 25-50-25 supplement in the Stall group initially lost hepatic Cu rapidly but this loss slowed from d 50 to d 100 compared to the Control (P = 0.07), 50-50 (P < 0.05), and 2X-SO4 (P < 0.05) heifers and was similar (P > 0.10) to that in the 5X-SO4 heifers. In the Pen group, total hepatic Cu loss tended to be greater for 25-50-25 and 2X-SO4 compared to 5X-SO4 heifers (P = 0.09 and P = 0.06, respectively); Cu loss in the 50-50 heifers was similar (P > 0.10) to that in the 5X-SO4 heifers. This suggests that supplementing combinations of inorganic and amino acid-complexed Cu was as effective in limiting hepatic Cu loss during antagonism as was increasing dietary Cu levels to five times the NRC recommendation. A combination of 25% CuSO4 , 50% Cu-amino acid complex, and 25% CuO limited liver accumulation of Mo compared to supplements without CuO and could provide a strategic supplementation tool in limiting the systemic effects of Cu antagonism in beef cattle.

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Literature on depression in rural and Hispanic elderly adults is sparse. This report describes the prevalence of depressive symptoms in 1,151 community-dwelling, Hispanic and non-Hispanic White participants in the San Luis Valley Health and Aging Study, conducted in rural Colorado during 1993-1995. The prevalence and odds ratios of high depressive symptoms, defined as a Center for Epidemiologic Studies Depression Scale score of > or = 16, were calculated. The crude prevalence of high depressive symptoms was 11.4% (95% confidence interval: 9.6, 13.6). Female gender, chronic diseases, dissatisfaction with social support, living alone, and lower income and education were associated with depressive symptoms. There were no ethnic differences in the men. The age-adjusted odds ratio of depressive symptoms in Hispanic women compared with that of non-Hispanic White women was 2.11 (95% confidence interval: 1.32, 3.38). After adjustment for multiple sociodemographic and health risk factors, the odds ratio in Hispanic women was 2.12 (95% confidence interval: 1.19, 3.80). Higher depressive symptoms in Hispanic women varied by acculturation level. The odds ratio in the high acculturation stratum was 1.56 (95% confidence interval: 0.75, 3.27) and in the low acculturation stratum was 2.51 (95% confidence interval: 1.11, 5.70). A lower acculturation level may increase the risk for depression in older Hispanic women.

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The gammaherpesvirus bovine herpesvirus-4 (BHV-4) has been isolated from a wide variety of animals, including lions and domestic cats. Although BHV-4 antibodies have been detected in normal cats and cats with urinary disorders, the epidemiology and pathogenic role of BHV-4 in cats is unknown. The purpose of this study was to determine the prevalence of BHV-4 antibodies and viral nucleic acid in a population of free-roaming cats. Plasma and peripheral blood leukocyte samples were collected from 52 male and 52 female free-roaming cats impounded at a regional animal control facility in Central Michigan. Plasma concentrations of BHV-4 antibodies were measured with an indirect fluorescent antibody test. Peripheral blood leukocyte DNA was isolated, and a 2-stage polymerase chain reaction with heminested primers delineating a conserved portion of the BHV-4 glycoprotein B gene homologue was used to amplify BHV-4-specific DNA sequences. BHV-4 antibodies were detected in 38 (73%) male and 23 (44%) female cats. Seropositive cats were significantly more likely to be male than female (odds ratio = 3.22; P = .007). Cell-associated viremia was detected in 17 (33%) male and 11 (21%) female cats. Of the 61 seropositive cats, 23 (38%) had a detectable viremia; only 5 (12%) seronegative cats had detectable viremia. Seropositive cats were significantly more likely to be viremic than seronegative cats (OR = 4.30: P = .009). Our results suggest that BHV-4 infection may be more widespread in certain cat populations than previously reported. Furthermore, many cats seropositive for BHV-4 antibodies have a concurrent cell-associated viremia.

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To test the hypothesis that rhinovirus (RV)-induced immune responses influence the outcome of RV infections, we inoculated 22 subjects with allergic rhinitis or asthma with RV16. Nasal secretions and induced sputum were repeatedly sampled over the next 14 d. RV16 infection increased nasal granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-8, which was accompanied by neutrophilia in blood and nasal secretions. Nasal G-CSF correlated closely with increased blood neutrophils (r(s) = 0.69, p < 0.005), whereas nasal neutrophils correlated with both G-CSF (r(s) = 0.87, p < 0.001) and IL-8 (r(s) = 0.75, p < 0.001). Although similar relationships were present in sputum, changes in sputum neutrophils and G-CSF with RV16 infection were relatively modest. In addition, virus-induced changes in the sputum interferon-gamma-to-IL-5 messenger RNA ratio were inversely related to both peak cold symptoms (r(s) = -0.60, p < 0.005) and the time to viral clearance (undetectable picornavirus RNA). These results indicate that airway IL-8 and G-CSF are closely associated with virus-induced neutrophilic inflammation during an experimental RV infection in atopic volunteers. In addition, the balance of airway T-helper cell type 1 (Th1)- and Th2-like cytokines induced by RV infection may help determine the clinical outcome of common cold infections, raising the possibility that the individual subject's immune response, rather than atopic status per se, is important in this regard.

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This study describes a pharmacokinetic evaluation of amphotericin B (AMB) lipid complex injection (ABLC or Abelcet) in 17 patients with systemic fungal infection administered 5 mg/kg of body weight/day by infusion for 10 to 17 days. The results showed that AMB exhibited multiexponential disposition with high clearance, large volume of distribution at steady state, and long apparent elimination half-life but no evidence of accumulation in the blood after multiple daily doses. The results confirm previous observations and further reinforce the suggestion that ABLC may exist as a depot in the tissues from which free AMB is slowly released to limit exposure.

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Vitamin A and its biologically active derivatives, the retinoids, are recognized as key regulators of vertebrate development, cell growth, and differentiation. Although nuclear receptors have held the attention since their discovery a decade ago, we report here on serine/threonine kinases as a new class of retinoid receptors. The conserved cysteine-rich domain of the NH(2)-terminal regulatory domains of cRaf-1, as well as several select domains of the mammalian protein kinase C (PKC) isoforms alpha, delta, zeta, and mu, the Drosophila and yeast PKCs, were found to bind retinol with nanomolar affinity. The biological significance was revealed in the alternate redox activation pathway of these kinases. Retinol served as a cofactor to augment the activation of both cRaf and PKC alpha by reactive oxygen, whereas the classical receptor-mediated pathway was unaffected by the presence or absence of retinol. We propose that bound retinol, owing to its electron transfer capacity, functions as a tag to enable the efficient and directed redox activation of the cRaf and PKC families of kinases.

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Polychlorinated biphenyls (PCBs) were analyzed in: sediment; coral (Porites evermanni); fish (Stegastes fasciolatus, Neoniphon sammara, Acanthurus triostegus and Mulloidichthys vanicolensis); crab (Grapsus tenuicrustatus); lobster (Panulirus marginatus); and eel (Conger cinereus, Gymnothoraxflavimarginatus, G. undulatus and G. meleagris) samples collected from Tern Island and the corresponding reference samples from Disappearing Island. The two islands are part of French Frigate Shoals, a national wildlife refuge in the North Pacific Ocean. The dominant congeners 118, 138 and 153 represent 22-25, 32-34, 12-39, 37-46 and 30-55% of the sum of PCBs in the coral, sediment, fish, crab and eel, respectively. In general, high trophic species such as eels were found to highly bioaccumulate PCBs. The total average PCB concentrations were as high as 96 and 29 microg/g dry wt. in eels and damselfish, respectively, from Tern Island. The localized behavior and high bioaccumulation potential for PCBs suggest that damselfish are an excellent species for monitoring PCBs in small areas in the ocean. The high average concentrations of the sum of PCBs in different food chain levels suggest that pollution source(s) are around Tern Island and possibly around Disappearing Island. Aroclor 1254 and its analogs are suspected sources responsible for PCBs in the samples.

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