Search PubMed⌕ Search

Biomedical subjects

K Connor

Publications and source records attributed to K Connor.

At least 19 recordsLinked to original sources

Duct-to-duct biliary anastomosis for patients with sclerosing cholangitis undergoing liver transplantation.

BACKGROUND: Due to the association of strictures within the biliary ductal system, Roux-en-Y choledochojejunostomy has been the preferred method of anastomosis for liver transplant recipients with primary sclerosing cholangitis (PSC). The aim of this study was to evaluate duct-to-duct anastomosis in patients with PSC who undergo liver transplantation. METHODS: Data were collected and evaluated based on demographics, type of anastomosis preformed, malignancies, outcomes comparisons, and survival. RESULTS: Of the 60 patients transplanted for PSC, 58 were diagnosed PSC prior to transplantation and 2 were diagnosed on explant. The Roux-en-Y group (n = 38) were similar in age, gender, and race when compared to the duct-to-duct (d-d) group (n = 22). There were similar rates of anastomotic revisions when comparing d-d anastomosis with Roux-en-Y (2 [9.1%] versus 2 [5.3%], P = NS) owing to bile leaks. Based on radiologic interventions of the bile ducts, seven (18.4%) in the Roux-en-Y group had interventions compared to two (9.1%) in the duct-to-duct group (P = NS). There was also no difference in recurrence of PSC: three (7.9%) in the Roux-en-Y group compared to two (5.3%) in the duct-to-duct group (P = NS). Survival at 4 years were similar between each group (76.5% [+/- 0.07] Roux-en-Y versus 84.9% [+/- 0.08] duct-to-duct, P = NS). CONCLUSION: Duct-to-duct anastomosis at the time of liver transplantation is both safe and efficacious when used in patients with PSC. Outcomes as described by surgical interventions, radiologic interventions, retransplantation, and survival were similar between groups.

Anastomosis, Roux-en-Y↗

Adult and pediatric liver transplantation for autoimmune hepatitis.

BACKGROUND: Due to the early age that pediatric patients with autoimmune hepatitis (AIH) are transplanted, it is theorized that older AIH patients may have different outcomes than pediatric patients following liver transplantation. METHODS: This is a retrospective review of both the adult and pediatric liver transplant programs consisting of 56 patients. Rejection and recurrence of AIH were determined by biopsy. RESULTS: The autoimmune patient having rejection episodes had a 1.76-fold increase in relative risk to develop autoimmune recurrence when compared to patients without rejection [RR = 1.76; 95% CIRR (1.08, 2.86)]. The pediatric group had a 6.62-fold increase in relative risk to develop colitis following liver transplantation [RR = 6.62; 95% C.I.R.R. (1.36, 32.13); P =.02]. Mean days to recurrence of AIH were similar in both groups (1364 +/- 1074 vs 936; P = NS). There were more hospitalized days in the pediatric group compared to the adults (20.5 +/- 13.3 days vs 51.7 +/- 22.2 days, P =.039). OKT-3 was rarely used (n = 5) in either group (9.3% vs 7.7%, P = NS) and was not correlated with which patients would be weaned from steroids or recurrence. CONCLUSIONS: Based on this review, pediatric patients were more likely to develop ulcerative colitis following liver transplantation and they incurred longer hospital stays than adults. The adult group was more likely to be weaned from steroids, with AIH recurrence unrelated to weaning.

Adult↗

Nonresponders of interferon/ribavirin treatment for recurrent hepatitis C following liver transplantation.

BACKGROUND: Treatment of recurrent hepatitis C (HCV) following liver transplant currently includes alpha-interferon with ribavirin. OBJECTIVE: The aim of this study is to evaluate nonresponder protocols for patients failing current treatment for recurrent hepatitis C following liver transplantation. METHODS: From February 1998 through November 2002, 67 patients, all serum RNA-positive for hepatitis C with histological evidence of recurrent hepatitis C, underwent treatment with alpha-interferon and ribavirin. For patients who failed initial treatment, patients were begun on either amantadine along with interferon/ribavirin or peginterferon with ribavirin. RESULTS: Of the initial 67 patients, there was a complete viral clearance in only 14.9% (10/67). Of the 57 remaining patients not clearing the virus, 30 (52.6%) were taken off treatment due to adverse events associated with bone marrow or hemoglobin suppression. In the amantadine group (n = 12), three (25%) had to discontinue due to CNS side effects of slurred speech, dizziness, and increased depression. In the amantadine group, no patients cleared the virus but there was a one log drop in viral load (1.6 x 10(6) vs 0.9 x 10(6); P =.4). In the peginterferon group, there were three (20%) patients with complete viral clearance during treatment with similar drops to amantadine. There was also seen a biochemical response by month 3 with peginterferon, which was not seen with amantadine. CONCLUSIONS: Peginterferon with ribavirin appears to be superior to amantadine with interferon/ribavirin when used in nonresponders for hepatitis C viral clearance.

Antiviral Agents↗

Do constitutional types really exist? A further study using grade of membership analysis.

'Constitutional types' are a feature of homeopathy. Constitutions are constellations of mental, physical and general features. We present results of a 152-item 'Constitutional Type Questionnaire' (CTQ), relating to 19 major constitutional remedies. Patients referred to the Royal London Homoeopathic Hospital (RLHH) were recruited from outpatient clinics. Each remedy was assigned eight associated features. Each item is rated as it applies to the subject most of the time on a five-point scale. Grade of Membership analysis (GOM) was used for evaluation of remedy profiles. Four hundred and forty-seven individuals provided usable data. Demographic data were collected. A nine pure type solution provided the best fit to the data. Few subjects had exclusive 'membership' of one pure type. There are some difficulties in interpretation; for instance some groups were characterised by the absence of 'constitutional' features. Some pure types are coherent, recognisable types. The results give some support to the homeopathic concept of constitution. CTQ results correlate quite well with the actual prescribing of homeopaths. Further validation with other cohorts is required and with refinement it might become a useful screening method. It cannot simulate complex information processing performed by homeopathic practitioners.

Female↗

Help from our animal friends.

Animal-assisted therapy has gained widespread support and application in the past few decades. Learn its present goals and applications, including those pertinent to critical care.

Adaptation, Psychological↗

Methods for xenoestrogen testing.

Research in our laboratories has focused on development of a battery of in vivo and in vitro bioassays for determining estrogenic activity and potency of different classes of natural and synthetic industrial-derived estrogenic compounds (xenoestrogens) including food/beverage extracts, phytoestrogens, phenolic compounds, organochlorine pesticides and pollutants. For many of the weak estrogenic compounds, their activity as estrogen receptor (ER) agonists or antagonists is dependent on the gene/gene promoter, cell context and expression of ER(alpha) or ER(beta) isoform. For example, extracts of red wine, bound to the ER, exhibited estrogenic activity in T47D, MCF-7 (breast) and Hep G2 (liver) human cancer cell lines, whereas reconstituted organochlorine pesticide residues found in food were active only in Hep G2 cells that transiently expressed ER(alpha) or ER(beta). The relative potencies of red wine extracts versus reconstituted organochlorine pesticides were assay-dependent; however, estrogen equivalent daily intakes from a glass of red wine (approximately 0.5-2 microg estrogen equivalents/day) were at least 10(3) higher than observed for the reconstituted organochlorine pesticide mixtures. Risk assessment of xenoestrogens and other synthetic chemicals which modulate endocrine responses must take into account high dietary levels of natural products in food, drugs and health food store extracts which also modulate endocrine responses.

Animals↗

Human exposure to endocrine-active chemicals: hazard assessment problems.

Industrial-derived endocrine disruptors or endocrine-active chemicals (EACs) have been identified and hypothesized to play a role in human disease. Most of the xeno-EACs which have been characterized bind to the estrogen receptor, aryl hydrocarbon receptor, or androgen receptor. Hazard and risk assessment of xeno-EACs is complicated by several factors which include the following: (i) humans are exposed to relatively high levels of natural EACs compared to xeno-EACs; (ii) very little information on the effects of metabolism, serum, and intracellular binding proteins on target cell uptake of EACs is known; (iii) humans are exposed to EAC mixtures and their interactive effects may be additive, antagonistic, or synergistic and also response- and tissue-specific; and (iv) individual EACs may be agonists/antagonists for more than one endocrine response pathway. Scientific-based hazard and risk assessment of both natural and xeno-EACs clearly requires more information on dietary intakes, target organ exposures, mechanisms of action, and interactive effects of mixtures.

Animals↗

Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens: structure-activity relationships.

The effects of structure on the estrogenicity and antiestrogenicity of hydroxylated polychlorinated biphenyls were investigated using the following estrogen-sensitive assays: competitive binding to the rat and mouse cytosolic estrogen receptor (ER); immature rat and mouse uterine wet weight, peroxidase and progesterone receptor (PR) levels; induction of luciferase activity in HeLa cells stably transfected with a Gal4:human ER chimera and a 17mer-regulated luciferase reporter gene; proliferation of MCF-7 human breast cancer cells; induction of chloramphenicol acetyl transferase (CAT) activity in MCF-7 cells transiently transfected with a full-length human ER expression plasmid and a plasmid containing an estrogen-responsive vitellogenin A2 promoter linked to a CAT reporter gene. The chemicals synthesized for this study contained a 4-hydroxy group in one ring, a 2- or 3-chloro substituent meta or ortho to the hydroxyl group, and variable substitution (2',3',4',5'-, 2',3',4',6'-, 2',3',5',6'-tetrachloro and 2',4',6'-trichloro) in the chlorophenyl ring. The compounds included: 2,2',3',4',5'- (A), 2,2',3',4',6'- (B), and 2,2',3',5',6'-pentachloro- (C); 2,2',4',6'-tetrachloro-4-biphenylol (D); 2',3,3',4',5'- (E), 2',3,3',4',6'- (F), and 2',3,3',5',6'-pentachloro (G); and 2',3,4',6'-tetrachloro-4-biphenylol (H). With the exception of 2',3,4',6'-tetrachloro-4-biphenylol (H), all of the compounds competitively bound to the mouse and rat ER with relative binding affinities [compared to 17beta-estradiol (E2)] varying from 1.4 x 10(-3) to 5.3 x 10(-5). The structure-ER binding relationships for the hydroxy-PCB congeners were different in the rat and mouse, and no dose-dependent estrogenic activities were observed in the mouse or rat uterus. Several hydroxy-PCB congeners exhibited antiestrogenic activity (primarily in the mouse uterus) and two compounds, 2,2',3',5',6- and 2,2',3',4',6'-pentachloro-4-biphenylol, inhibited E2-induced uterine wet weight, PR binding, and peroxidase activity in the mouse uterus. 2,2',3',4',5'- and 2,2',3',4',6'-Pentachloro-4-biphenylol induced CAT activity in MCF-7 cells transiently transfected with the Vit-CAT plasmid; the remaining congeners did not induce CAT activity but exhibited antiestrogenic activity in MCF-7 cells cotreated with 10(-9) E2 plus 10(-5) M hydroxy-PCBs. Complementary structure-estrogenicity relationships were observed utilizing the HeLa cell luciferase induction and MCF-7 cell proliferation assays. The placement of the 2- or 3-chloro groups in the phenolic ring had minimal effects on estrogenic activity, whereas 2,4,6-trichloro- and 2,3,4,6-tetrachloro substitution in the chlorophenyl ring (B, D, F, and H) were required for this response. Substitution in the phenolic ring was also not important for structure-antiestrogenicity relationships, and the most active compounds (A, C, E, and G) contained 2',3',4',5'- and 2',3',5',6'-tetrachlorophenyl groups. Thus, structure-estrogenicity/antiestrogenicity relationships for this series of hydroxy-PCBs were complex and response-specific.

Animals↗

Differentiation between human and ovine isolates of Bordetella parapertussis using pulsed-field gel electrophoresis.

The genetic relatedness of 18 human and 29 ovine isolates of Bordetella parapertussis was examined by macrorestriction digestion of DNA with the rarely cutting enzyme XbaI and resolution by pulsed-field gel electrophoresis. There was clear separation of human and ovine isolates and variation within host types. The human isolates were separated into three types as were the 24 Scottish ovine isolates. Species-specific bands were observed with the human isolates at 114, 134, 166, 213, 346 and 372 kb. No species-specific bands were found in the B. parapertussis ovine isolates. Isolates of B. parapertussis recovered from sheep in New Zealand gave a further two DNA banding patterns which were clearly different from the Scottish ovine and the human isolates. These results indicate that human and ovine isolates of B. parapertussis are genetically distinct and that variation exists within isolates from the same host species. Pulsed-field gel electrophoresis therefore appears to be a powerful discriminatory tool for the classification of B. parapertussis.

Animals↗

Failure of chloro-S-triazine-derived compounds to induce estrogen receptor-mediated responses in vivo and in vitro.

The potential estrogenic activities of atrazine and simazine were investigated in vivo using the immature female Sprague-Dawley rat uterus and in vitro using the estrogen-responsive MCF-7 human breast cancer cell line and the estrogen-dependent recombinant yeast strain PL3. Animals that were dosed with 50, 150, or 300 mg/kg of atrazine or simazine alone for 3 consecutive days did not exhibit any significant increases in uterine wet weight while decreases in cytosolic progesterone receptor (PR) binding levels and uterine peroxidase activity were observed. 17 beta-estradiol (E2)-induced increases in uterine wet weight were not significantly affected by cotreatment with either chemical; however, some dose-independent decreases in E2-induced cytosolic PR binding and uterine peroxidase activity were observed. In vitro, atrazine and simazine did not affect basal or E2-induced MCF-7 cell proliferation or the formation of nuclear PR-DNA complexes as determined by gel electrophoretic mobility shift assays. In addition, these chloro-S-triazines did not display agonist activity or antagonize E2-induced luciferase activity in MCF-7 cells transiently transfected with a Gal4-human estrogen receptor chimera (Gal4-HEGO) and a Gal4-regulated luciferase reporter gene (17m5-G-Luc). Moreover, the estrogen-dependent PL3 yeast strain was not capable of growth on minimal media supplemented with atrazine or simazine in place of E2. Collectively, these results indicate that the reported estrogenic and antiestrogenic effects elicited by these chemicals are not mediated by the estrogen receptor.

Animals↗

Structure-dependent induction of CYP2B by polychlorinated biphenyl congeners in female Sprague-Dawley rats.

The dose-response induction of hepatic microsomal pentoxyresorufin O-dealkylase (PROD) activity by phenobarbital (PB) and several polychlorinated biphenyl (PCB) mixtures and congeners was determined in the immature female Sprague-Dawley rat. At a dose of 75 mg/kg/day of PB for 3 days, the microsomal PROD activity was 2154 pmol/min/mg protein. Aroclors 1260, 1254, 1242, and 1016 did not induce maximal PROD activity at doses up to 500 mg/kg, and only Aroclor 1016 induced > a half-maximal response at the 500 mg/kg dose. The relative potencies of eighteen different PCB congeners were also determined, and the structures of these compounds differed with respect to the degree of chlorination (tri- to octochloro) and substitution patterns. The relative potencies of these compounds were estimated by comparing their induced activities at the high dose (150 or 100 mg/kg) with that of PB. The most potent inducers were 2,3,3',4',5,6-hexaCB and 2,2',3,4',5,5',6-heptaCB; at a dose of 150 mg/kg, the PROD activity induced by 2,2'3,4',5,5',6-heptaCB was comparable to that observed for PB. 2,3,3',4',5,6-HexaCB was the most potent inducer, and hepatic PROD activity in rats treated with 150 mg/kg was 4202 pmol/min/mg; this value was higher than that observed for PB at a dose of 75 mg/kg. A second group of congeners including 2,2',3,4,4',5,5'-heptaCB, 2,2',4,4',5,5'-hexaCB, 2,2',3,3',4,4',5,5'-octaCB 2,2',4,4'-tetraCB, 2,2',4,5,5'-pentaCB, 2,2',3,4,4',5',6-heptaCB, 2,2',4,4',5-pentaCB and 2,2',3,3',4',5,5',6-octaCB induced PROD activity > or = 1090 pmol/min/mg at the 150 mg/kg dose, and this value was > 50% of the maximal response observed for PB. The remaining compounds, namely 2,4,4'-triCB, 2,2',3,4'-tetraCB, 2,2',5,5'-tetraCB, 2,3',4,4',5-pentaCB, 2,3,3',4,4'-pentaCB, 2,2',4,4',5,6'-hexaCB, 2,3,3',4,4',5,5'-heptaCB and 2,2',3,3',4,4,5-heptaCB were all relatively weak inducers of hepatic microsomal PROD activity ( < 450 pmol/min/mg). In parallel experiments, western blot analysis of immunoreactive CYP2B1 and CYP2B2 protein showed that PB, the PCB mixtures, and congeners induced both proteins. Previous studies have identified a cis-acting DNA element that plays a role in regulating CYP2B1/B2 gene expression and binds nuclear trans-acting factor(s) induced by PB. The results of gel electrophoretic mobility shift assays with nuclear extracts showed that both PB and 2,2',3,4',5,5',6-heptaCB induce formation of a common retarded band using a 32P-labeled oligonucleotide corresponding the the cis-acting DNA promoter sequence. Both PB and PCBs appear to induce CYP2B1/B2 via a common mechanism. Although the results of this study do not define structure-induction (CYP2B1/B2) relationships for PCBs, two compounds, namely 2,3,3',4',5,6-hexaCB and 2,2',3,4',5,5',6-heptaCB, were identified as highly potent inducers.

Animals↗

Naringenin: a weakly estrogenic bioflavonoid that exhibits antiestrogenic activity.

Treatment of immature 21-day-old female Sprague-Dawley rats with 17 beta-estradiol (E2) (0.5 microgram/rat) caused a significant increase in uterine wet weight, DNA synthesis, progesterone receptor (PR) binding, and peroxidase activity. At doses as high as 40 mg/rat, the bioflavonoid naringenin did not cause a significant increase in any of these E2-induced responses. However, in rats cotreated with E2 (0.5 microgram/rat) plus naringenin (30 mg/rat); there was a significant decrease in E2-induced uterine wet weight, DNA synthesis, PR binding, and peroxidase activity, indicating that naringenin exhibits antiestrogenic activity in the immature rodent uterus. The binding of uterine nuclear extracts to a 32P-labeled estrogen responsive element (ERE) or progesterone responsive element (PRE) was determined using gel electrophoretic band shift assays. Incubation of [32P]ERE with uterine nuclear extracts from rats treated with naringenin or E2 resulted in the formation of estrogen receptor (ER):ERE complexes; a higher mobility complex was prominent in the extracts from E2-treated rats, whereas a lower mobility complex was observed using nuclear extracts from naringenin-treated animals. There was a significant decrease in the intensity of the E2-induced complex using nuclear extracts from rats treated with E2 plus naringenin. In contrast, transformed cytosol from control rats gave an intense ER:ERE complex, whereas the intensity of the band was decreased markedly using transformed uterine cytosol from treated rats. Formation of a PR:PRE complex was also determined using transformed uterine cytosol. Cytosol from E2-treated rats gave an intense retarded band, whereas only weak bands were observed using cytosols from DMSO- (solvent), naringenin-, or naringenin plus E2-treated cells. The results of in vitro studies showed that 1 nM E2 increased (3- to 4-fold) the growth of MCF-7 human breast cancer cells, whereas 1-1000 nM naringenin had no effect on cell proliferation. In cells cotreated with 1 nM E2 plus 1000 nM naringenin, there was a significant decrease in E2-induced cell growth. In MCF-7 cells transiently transfected with a pS2 promoter-regulated luciferase reporter gene, naringenin exhibited weak estrogenic activity. In cells cotreated with 0.1 or 1.0 microM naringenin plus 1 nM E2, naringenin inhibited E2-induced luciferase activity. The results of these studies confirmed that naringenin is a weak estrogen that also exhibits partial antiestrogenic activity in the female rat uterus and MCF-7 human breast cancer cells.

Animals↗

Characterisation of ovine Bordetella parapertussis isolates by analysis of specific endotoxin (lipopolysaccharide) epitopes, filamentous haemagglutinin production, cellular fatty acid composition and antibiotic sensitivity.

Isolates of Bordetella parapertussis, recovered from sheep or man, were characterised by reaction with specific anti-Bordetella lipopolysaccharide monoclonal antibodies, production of filamentous haemagglutinin, fatty acid patterns, and antibiotic sensitivity. Generally, the isolates lay within one of four groups, with separation of the ovine isolates into two groups. Reactions with specific monoclonal antibodies against lipopolysaccharide separated the ovine isolates into these two groupings. Analysis of the cellular fatty acid compositions by cluster analysis differentiated between the human and the ovine strains and also showed variation within the ovine isolates. When the production of filamentous haemagglutinin was analysed in an ELISA system, a similar pattern emerged. Varying concentrations of filamentous haemagglutinin (11-429 ng (mg total protein)-1) were extracted from the human isolates and the one group of ovine isolates with no significant protein detected in the other ovine group. These studies demonstrate variation between and within B. parapertussis isolates recovered from two mammalian sources.

Adhesins, Bacterial↗

Phorbol ester and diacylglycerol activation of native protein kinase C species from various tissues.

The characteristics of PKC activation induced by a number of compounds were investigated using PKCs, partially-purified from sources with a naturally high abundance of certain Ca2+ dependent PKC isoforms. Native isoforms were used rather than PKC isoforms expressed from a baculovirus system to assess the effect of tissue specific factors on activity. However, some data using recombinant PKC alpha were included for comparison. The presence of specific PKC isoforms in different tissues was determined using Western blot analysis. Protein kinase C alpha, beta 1, delta, epsilon, and zeta/iota were all present in rat midbrain cytosolic extract, PKC alpha, beta 1, delta, and zeta/iota were present in spleen cytosol, and PKC alpha and zeta/iota were present in COS 7 cell cytosol. The predominance of alpha and beta activities in COS 7 and spleen extracts respectively was confirmed by enzymic assay. The PKC activity assay was configured such that the Ca2+ dependence of the PKC activity induced by different PKC activators could be determined. Phorbol 12,13-dibutyrate (PDBu) was virtually equipotent on the Ca(2+)-dependent PKC activity from midbrain and spleen and slightly less potent on that from COS 7 cells. In the absence of Ca2+, PDBu was considerably less potent overall (as, indeed, were the other PKC activators) and was less potent on COS 7 cell PKC than on those from midbrain or spleen. Mezerein was more potent than PDBu at inducing PKC activity in COS 7 cell extracts in either the absence or presence of Ca2+ whereas in the presence of Ca2+, mezerein was slightly less potent on midbrain and spleen than PDBu and equipotent in the absence of Ca2+. Maximum values for Ca(2+)-independent activation by mezerein indicated that this activator was particularly effective in recruiting Ca(2+)-dependent PKC isoform activity in a Ca2+ free environment. The greater potency of mezerein on PKC alpha was confirmed using PKC alpha and beta further purified from rat spleen by hydroxylapatite (HAP) chromatography. The effects of both PDBu and mezerein were investigated using anterior pituitary tissue where a particularly high potency of mezerein in the absence of Ca2+ was noted. The diacylglycerol, 1,2-dioctanoyl-sn-glycerol (DOG), appeared to cause little or no activation of native Ca(2+)-dependent isoforms in Ca2+ free conditions unlike another longer chain diacylglycerol, 1,2-dioleoyl-sn-glycerol. Also DOG activated midbrain PKCs more potently than PKCs from spleen or COS 7 cells (or lung and pituitary tissue) in the presence of Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: nonadditive (antagonistic) interactions.

The dose-response inhibition of the splenic plaque-forming cell (PFC) response and serum IgM units to the antigen, trinitrophenyl-lipopolysaccharide, was determined for several polychlorinated biphenyl (PCB) mixtures and congeners in female B3C3F1 mice. The ED50 values for Aroclor 1260-, 1254-, 1248-, and 1242-induced immunotoxicity varied by less than twofold from 355 to 699 mg/kg. The range of ED50 values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4'-tetrachlorobiphenyl, 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'-hexaCB, 2,3,3',4,4'-pentaCB, 2,3',4,4',5-pentaCB, 2,3,3',4,4',5-hexaCB, 2,3,3',4,4',5,5'-heptaCB, 2,2',3,3',4,4',5-heptaCB, and 2,2',3,4,4',5,5'-heptaCB were 4.6 to 4.9, 134 to 245, 4.7 to 7.0, 6.9 to 11.1, 88,000 to 121,000, 122,000 to 132,000, 99,000 to 157,000, 89,000 to 129,000, 117,000 to 240,000, and 132,000 to 238,000 micrograms/kg, respectively. The immunotoxicity-derived toxic equivalency factors (TEFs) for these congeners could be calculated from the ED50 (TCDD)/ED50 (congener) ratios and the TEF values were within the range of those previously determined for other aryl hydrocarbon receptor-mediated responses. Based on the known concentrations of these congeners in the PCB mixtures, TCDD or toxic equivalents (TEQs) in the mixture were calculated [i.e., TEQ = sigma (PCBcongener x TEF)] using the immunotoxicity-derived TEFs (plaque-forming cells/10(6) viable cells). TEQ values for Aroclors 1260, 1254, 1248, and 1242 were 16.0, 54.4, 260.4, and 197 ppm, respectively. Based on the ED50 value for the immunosuppressive activity of TCDD (4.8 micrograms/kg), the calculated ED50 values for immune suppression by Aroclors 1260, 1254, 1248, and 1242 were 300, 88, 18, and 24 mg/kg, respectively. The ED50 (observed)/ED50 (calculated) ratios were 1.2, 5.9, 21, and 22.0 for Aroclors 1260, 1254, 1248 and 1242, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗