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Biomedical subjects

J E Elliott

Publications and source records attributed to J E Elliott.

At least 37 records · Page 2Linked to original sources
PubMed2000

Reproductive success and chlorinated hydrocarbon contamination in tree swallows (Tachycineta bicolor) nesting along rivers receiving pulp and paper mill effluent discharges.

The insectivorous tree swallow was chosen as an indicator species to investigate the uptake of pulp mill-related chlorinated hydrocarbons from emergent aquatic insects. Nest box populations were monitored for reproductive success at locations upstream and downstream of pulp mills on two river systems in British Columbia, Canada. Also, 16-day-old nestlings were collected and analysed for polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), pesticides, chlorophenols and chloroguaiacols. Most reproductive parameters were not different between populations at upstream and downstream locations, and were equivalent to or greater than those recorded for other tree swallow populations. Chlorinated hydrocarbon contamination of nestlings was low at all sites. The highest tissue concentrations were detected downstream of pulp mills on the Fraser River, where PCDD and PCDF patterns along with the presence of pentachlorophenol (PCP) suggested that the primary source of contaminants was past use of PCP for timber preservation. Although the absolute tissue concentration of contaminants was less, the toxic concentration (as estimated with I-TEQs) was greatest in nestlings downstream of a pulp mill on the Thompson River. The proportionately larger contributions from 2,3,7,8-TCDF and PCB-77 elevated these TEQs in comparison to other populations. Nest success was the one reproductive measure that showed substantial reductions in downstream populations on both rivers; however, there was little indication that nest failures were the direct result of contamination. Failures were largely due to parental abandonment, and, while poor parental attentiveness and nest abandonment have been associated with chlorinated hydrocarbon tissue concentrations in other studies, our 1-year assessment was insufficient to establish any link with pulp mill effluent exposure. Nestling growth models showed some subtle differences in growth patterns between nest box populations on the two rivers, but an association with pulp mill effects on aquatic insect prey availability was not established.

Journal Article↗
PubMed1999

Reproductive and morphological condition of wild mink (Mustela vison) and river otters (Lutra canadensis) in relation to chlorinated hydrocarbon contamination.

We assessed chlorinated hydrocarbon contamination of mink and river otters on the Columbia and Fraser River systems of northwestern North America, in relation to morphological measures of condition. We obtained carcasses of mink and river otters from commercial trappers during the winters 1994-1995 and 1995-1996. Necropsies included evaluation of the following biological parameters: sex, body mass and length, age, thymus, heart, liver, lung, spleen, pancreas, kidney, gonad, omentum, adrenal gland and baculum masses, baculum length, and stomach contents. Livers were analyzed, individually or in pools, for residues of organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), dibenzo-p-dioxins, and dibenzofurans. Contaminant levels were relatively low compared to those documented in other North American populations, although they ranged higher than those detected during an earlier survey (1990-1992) of these regional populations. Body condition varied slightly among collection regions, but showed no relationship with contaminant burden. Mink from the upper Fraser River had less fat stores and also had some of the lowest OC contamination levels observed. Similarly, a few individuals with enlarged livers and kidneys had low contaminant levels. Although a few individual animals with gross abnormalities of reproductive systems did not show high levels of contamination, there was a significant negative correlation between total PCB concentrations (as Aroclor 1260) and baculum length in juvenile mink (r = 0.707; p = 0.033; n = 8). The association of juvenile baculum length with eventual reproductive success is unknown, but further characterization of reproductive organ morphology and relationship to contaminants should be undertaken in a larger subset of these populations.

Aging↗
PubMed1998

CD95 (Fas)-based, superantigen-dependent, CD4+ T cell-mediated down-regulation of human in vitro immunoglobulin responses.

Naturally occurring microbial superantigens (SAg) have been implicated in several human idiopathic disorders, and a compelling argument for the role of SAg in autoantibody-associated disorders, such as systemic lupus erythematosus, has been proposed. To test the effects of SAg on human in vitro Ig responses, CD4+ T cell + B cell cultures were stimulated with graded doses of staphylococcal enterotoxin B (SEB). Ig-secreting cell (IgSC) responses were very weak in CD4+ T cell + B cell cultures stimulated with SEB at the optimal mitogenic concentration (high dose SEB; 100 ng/ml) but were strong in parallel cultures stimulated with low dose SEB (0.01 ng/ml). High dose SEB actually enhanced B cell differentiation in the presence of CD4+ T cell soluble helper factors as long as the B cells were prevented from physically contacting the CD4+ T cells. However, when cell-cell contact between CD4+ T cells and B cells was permitted, high dose, but not low dose, SEB promoted increased CD4+ T cell-mediated B cell apoptosis with resulting decreases in viable CD20+ B cells and IgSC. High dose, but not low dose, SEB triggered increased levels of soluble CD95 ligand, and down-regulation of IgSC responses and incremental apoptosis of activated B cells were prevented by antagonist anti-CD95 mAb. This strongly suggests that CD4+ T cell-mediated CD95-based killing of activated B cells plays a major role in controlling SEB-driven IgSC responses. Defects in SAg-based down-regulation may contribute to autoimmune disorders such as SLE.

Antibodies, Monoclonal↗
PubMed1998

Contaminants in ospreys from the Pacific Northwest: I. Trends and patterns in polychlorinated dibenzo-p-dioxins and -dibenzofurans in eggs and plasma.

Osprey (Pandion haliaetus) eggs were collected from 1991 to 1997 at nests (n = 121) upstream and downstream of bleached kraft pulp mills and at reference sites in the Fraser and Columbia River drainage systems of British Columbia, Washington, and Oregon. Blood samples were collected from nestling ospreys during the 1992 breeding season on the Thompson River. Samples were analyzed for polychlorinated dibenzo-p-dioxins (PCDDs) and -dibenzofurans (PCDFs). Mean concentrations of 2,3,7,8-TCDD were significantly higher in eggs collected in 1991 at downstream compared to upstream nests near pulp mills at Kamloops and Castlegar, British Columbia. There were no significant temporal trends in 2,3,7,8-TCDD, -TCDF or other measured compounds at a sample of nests monitored between 1991 and 1994 downstream of the Castlegar pulp mill, despite changes in bleaching technology (CIO2 substitution). However, by 1997 concentrations of 2, 3,7,8-TCDD and -TCDF were significantly lower than previous years in nests sampled downstream at both Castlegar and Kamloops. An unusual pattern of higher chlorinated PCDDs and PCDFs was found in many of the osprey eggs collected in this study, and considerable individual variation in the pattern existed among eggs from the same site. For example, eggs from four different nests at one study area (Quesnel) on the Fraser River had concentrations of 1,2,3,4,6,7,8-HpCDD ranging from <1 to 1,100 ng/kg and OCDD from <1 to 7,000 ng/kg wet weight. Higher mean concentrations of HpCDD and OCDD were found in eggs from the Thompson River, a tributary of the Fraser, compared to the Columbia River, and concentrations were generally higher at nests upstream of pulp mills. In plasma samples, 1,2,3,4,6,7,8-HpCDD and OCDD were the main compounds detected, with no significant differences measured between samples upstream versus downstream or earlier versus later in the breeding season. Use of chlorophenolic wood preservatives by lumber processors was considered the main source of higher chlorinated PCDD/Fs throughout the systems, based on patterns of trace PCDFs in eggs and significant correlations between egg concentrations of pentachlorophenol and both HpCDD (r = 0.891, p < 0.01) and OCDD (r = 0.870, p < 0.01).

Animals↗
PubMed1997

Impaired nonrestricted cytolytic activity in systemic lupus erythematosus: involvement of a pathway independent of Fas, tumor necrosis factor, and extracellular ATP that is associated with little detectable perforin.

OBJECTIVE: To determine the cytolytic effector pathway involved in impaired generation of nonrestricted cytolytic activity in systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) from normal subjects and SLE patients were stimulated in vitro with anti-CD3 monoclonal antibody (MAb) and interleukin-2 to promote the generation of nonrestricted cytolytic activity. On day 13 of culture, the PBMC were assayed for cytolytic activity against Fas-Daudi cells and Fas+ Jurkat cells. The effects on cytotoxicity of calcium chelation, antagonist anti-Fas MAb, tumor necrosis factor (TNF) alpha and beta, and ATP were measured. Intracellular perforin expression was determined by intracellular staining, and perforin messenger RNA levels were determined by quantitative competitive reverse transcription-polymerase chain reaction. RESULTS: We demonstrated the existence of a cytolytic pathway that is independent of Fas, TNF alpha, TNF beta, and ATP, but is dependent upon extracellular calcium. Despite its calcium dependence, this pathway is associated with low-to-undetectable levels of perforin. CONCLUSION: Impaired generation of nonrestricted cytolytic activity in SLE is likely due to decreased activity of this Fas-, TNF alpha-, TNF beta-, ATP-independent pathway associated with very low levels of perforin.

Adenosine Triphosphate↗
PubMed1997

Comparative toxicity of polychlorinated biphenyls to Japanese quail (Coturnix c. japonica) and American kestrels (Falco sparverius).

Polychlorinated biphenyls (PCBs) and related halogenated hydrocarbons bioaccumulate to high concentrations in top predators, such as raptorial birds, yet little is known of PCB toxicity to such species. This study explored several aspects of both the acute and chronic response of American kestrels (Falco sparverius) to three purified PCB congeners and a commercial mixture, Aroclor 1254, and compared the response to that of the Japanese quail (Coturnix c. japonica), a more studied species known to be PCB sensitive. In one experiment, adult female birds were given single oral doses of either Aroclor 1254, 3,3',4,4'-TCB (PCB 77, IUPAC nomenclature), 3,3',4,4',5-PCB (PCB 126) or 2,2',4,4',5,5'-HCB (PCB 153) and sacrificed after 5 d. In kestrels, neither the pure compounds nor the mixture affected hepatic or renal porphyrin levels. There was slight but significant hepatic and renal ethoxyresorufin O-deethylase (EROD) induction in birds dosed with PCBs 77 and 126. A cytochrome P-4501A (CYP1A) cross-reactive protein was detected in liver and kidney of kestrels given PCBs 77 and 126, but not in Aroclor 1254-dosed birds. In quail, an acute dose of Aroclor 1254 caused significant liver weight increases, hepatic and renal EROD and aminopyrine n-demethylase (APND) induction, and dose-related hepatic and renal porphyria. Quail treated with PCB 126 developed hepatic and renal porphyria; EROD and APND were also induced. Administration of PCB 77 caused only slight induction of hepatic EROD activity. PCB 153 caused some hepatic and renal porphyria and induced EROD to the same degree as PCB 126. A hepatic CYP1A cross-reactive protein was induced about 200-fold in all individual quail that exhibited significant EROD induction and was also induced in kidney of 1 quail given Aroclor 1254. A second experiment examined chronic exposure to Aroclor 1254 by feeding adult females of both species a daily dose of 7 mg/kg/d for 4-, 8-, and 12-wk periods. There were no effects on hepatic porphyrins in kestrels. APND and aldrin epoxidase (AE) were induced; EROD was not induced, although a hepatic CYP1A-like protein was detected in 1 kestrel dosed for 12 wk. Chronic exposure of quail to Aroclor 1254 caused highly significant increases in mean hepatic porphyrin levels and in activity of EROD, APND, and 4-chlorobiphenyl hydroxylase; a CYP1A-like protein was also induced about 200-fold. In both studies, Aroclor 1254 residues accumulated in tissues of both species, but there was no significant relationship between residue levels and effects. In conclusion, adult American kestrels were relatively insensitive to the effects of PCBs, from both acute and chronic exposure, on hepatic and renal porphyrin levels. Although concentrations of a CYP1A-like protein were increased in some kestrels given PCBs, EROD activity was only marginally increased, suggesting that catalytic activity of this protein differed among the two species.

Aminopyrine N-Demethylase↗
PubMed1996

Impaired recovery and cytolytic function of CD56+ T and non-T cells in systemic lupus erythematosus following in vitro polyclonal T cell stimulation. Studies in unselected patients and monozygotic disease-discordant twins.

OBJECTIVE: To determine whether there is impaired generation and cytolytic function of CD56+ T cells and non-T cells in human systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 73 patients with SLE, 39 normal controls, and 9 pairs of monozygotic (MZ) twins discordant for SLE. PBMC were stimulated with anti-CD3 monoclonal antibody, maintained in interleukin-2, and assayed for percentages of total CD56+ cells and CD56+ T cells by flow cytometry, and for cytolytic activity against 51Cr-labeled Daudi target cells. RESULTS: Despite normal total cell expansion, the percentages of recovered CD56+ T cells and total CD56+ cells were 1.6-fold and 1.8-fold lower, respectively, in patients with SLE compared with normal controls (P = 0.011 and P < 0.001, respectively). Cytolytic activities of isolated total CD56+ cells and CD56+ T cells and were also reduced in patients with SLE compared with normal controls (P = 0.033). These defects associated with SLE were independent of disease activity and immunosuppressive medications, and they reflected impaired maturation of cytolytic effector cells rather than a deficiency in precursor cell number. In MZ twins discordant for SLE, recovered percentages of CD56+ cells and cytolytic responses were very low in 4 of 8 and 6 of 9 co-twins with SLE, respectively. Cellmixing experiments with the PBMC of the MZ twins demonstrated that the E+ cell fractions (containing all T cells and CD56+ non-T cells) from the co-twins with SLE had decreased ability to generate cytolytic activity compared with the corresponding E+ cell fractions from the healthy co-twins. However, recovered percentages of CD56+ cells and non-T cells and cytolytic responses were also depressed in 4 of 8 and 4 of 9 healthy co-twins, respectively. CONCLUSION: Impaired CD56+ T cell and non-T cell responses are a feature of SLE and may antedate the onset of clinical disease.

Adult↗
PubMed1996

Patterns, trends, and toxicological significance of chlorinated hydrocarbon and mercury contaminants in bald eagle eggs from the Pacific coast of Canada, 1990-1994.

Bald eagle (Haliaeetus leucocephalus) eggs were collected during incubation, 1990-1992, from 16 nests near three bleached-kraft pulp mills, from six nests in the Fraser River estuary and from seven nests at a reference site on the Pacific coast of Canada. Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were present in all eggs in a qualitatively similar pattern among sites. Mean concentrations of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) were significantly higher in eggs collected from near three kraft pulp mill sites in the Strait of Georgia (44, 45, 84 ng/kg) than from the reference area in Johnstone Strait (15 ng/kg). There were few differences among sites in mean organochlorine pesticide levels, indicating the diffuse distribution of those chemicals and the domination of atmospheric inputs. Mean concentrations of total polychlorinated biphenyls (PCBs) were highest in eggs from the Strait of Georgia (4.86 mg/kg) and the PCB congener pattern was significantly different between that area and both the lower Fraser valley and Johnstone Strait. Mean mercury concentrations, which were mainly methyl-mercury, were significantly higher in eggs collected from the lower Fraser Valley (0.258 mg/kg) and Johnstone Strait (0.294 mg/kg) compared to the Strait of Georgia (0.188 mg/kg). Individual and regional variation in concentrations of organochlorine pesticides, PCBs and mercury in eagle eggs were thought to be influenced mainly by dietary differences. Toxicologically, in 1990, mean TCDD-toxic equivalents (TEQs) in bald eagle eggs were about two-fold greater than a lowest-observed-effect level, suggested elsewhere for this species, of 210 ng/kg TEQs. In the Strait of Georgia, PCCDs and PCDFs made a greater contribution to TEQs than non-ortho and mono-ortho PCBs, whereas the reverse was true for eggs outside the strait. Mean eggshell thickness was less than the pre-1947 value at all sites, although there was no significant relationship between eggshell thickness and DDE concentrations. Levels of other organochlorine pesticides and mercury were below those considered to be toxic.

Analysis of Variance↗
PubMed1996

Bald eagle mortality and chlorinated hydrocarbon contaminants in livers from British Columbia, Canada, 1989-1994.

Between 1989 and 1994, we obtained 278 carcasses of bald eagles (Haliaeetus leucocephalus) found dead or dying in British Columbia, Canada. All specimens were necropsied and the cause of death determined wherever possible. Livers from a subset of 75 birds were analyzed for polychlorinated biphenyl (PCB) and organochlorine (OC) pesticide residues. A further subset of 19 eagles found dead around the Strait of Georgia, an area of known pulp mill pollution, in summer, and therefore presumably resident birds, were analyzed for polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) and non-ortho PCBs. Liver concentrations ranged from less than 1 to 190 mg/kg for DDE, and up to 72 mg/kg for total PCBs. Concentrations of other OCs were generally less than 1 mg/kg, with the exception of chlordane-related compounds which were occasionally over 2 mg/kg. All birds analyzed for PCDDs and PCDFs contained detectable concentrations of the major 2,3,7,8-substituted isomers. Some birds were very contaminated; one eagle found near a kraft pulp mill site in 1990 contained: 400 ng/kg 2,3,7,8-TCDD, 1400 ng/kg 1,2,3,7,8-PnCDD and 4400 ng/kg 1,2,3,6,7,8-HxCDD. Birds with higher PCB and dichlorodiphenyldichloroethane (DDE) concentrations appeared to weigh less, and there was a significant negative relationship between both PCBs and DDE and numeric scoring of body condition, reflecting the well known process of starvation-induced mobilization of body lipids and contaminants. Birds with higher 2,3,7,8-TCDD concentrations tended to have unusually low concentrations of 2,3,7,8-TCDF, interpreted to indicate hepatic cytochrome P4501A-type induction by TCDD and subsequent metabolism of TCDF.

Journal Article↗
PubMed1996

Poisoning of bald eagles and red-tailed hawks by carbofuran and fensulfothion in the Fraser Delta of British Columbia, Canada.

During the winter of 1990 in the Fraser Delta of British Columbia, Canada, nine birds of prey were found with symptoms of anticholinesterase poisoning. Immediate surgical removal of crop contents of three birds decreased mortality and recovery time. Chemical analysis was conducted on crop contents, which contained mainly duck parts. A bald eagle (Haliaeetus leucocephalus) contained 200 micrograms/g and a red-tailed hawk (Buteo jamaicensis) 2.2 micrograms/g carbofuran, while the crop of another red-tailed hawk contained 30 micrograms/g fensulfothion. There was evidence that granular carbofuran and fensulfothion persisted long enough in the wet, low pH conditions of the Fraser Delta to kill waterfowl and cause secondary poisoning of raptors several months after application of the pesticides.

Acetylcholinesterase↗
PubMed1995

Differential human T cell-dependent B cell differentiation induced by staphylococcal superantigens (SAg). Regulatory role for SAg-dependent B cell cytolysis.

Microbial superantigens (SAg), by virtue of their binding to TCR V beta elements and to class II MHC molecules on accessory cells, trigger T cell proliferation in a dose-dependent fashion. In contrast, SAg-induced T cell-dependent B cell differentiation occurs only at SAg concentrations that are orders of magnitude lower that those required for optimal mitogenesis (low-dose SAg). At optimal mitogenic doses (high-dose SAg), SAg-driven B cell differentiation does not ensue. In this report, we demonstrate that this dichotomy in SAg-driven B cell differentiation is due to the active inhibition of B cell differentiation by high-dose SAg. Such inhibition is not reversed by feeding cultures with fresh medium, with conditioned media, or with IL2 +/- IL4, and impaired B cell differentiation is observed in cultures containing purified T cells or CD4+ T cells + B cells, as well as in PBMC cultures. Although preincubation of either T cells or B cells with high-dose SAg impairs subsequent SAg-induced B cell differentiation, high-dose SAg is not toxic per se, since high-dose SAg does promote vigorous B cell differentiation in cultures of mitomycin C-treated T cells + B cells and does not inhibit T cell-independent B cell differentiation. No correlation exists between SAg-induced B cell surface expression of CTLA4 ligand and generation of Ig-secreting cells, but the dose of SAg does correlate with T cell-mediated SAg-dependent cytolysis of transformed B cell targets or autologous nontransformed activated B cell targets. B cell recovery from cultures stimulated with high-dose SAg is lower than that from cultures stimulated with low-dose SAg, whereas B cell apoptosis is greater in the former cultures than that in the latter cultures. T cells stimulated with high-dose SAg do not inhibit differentiation of activated B cells in the absence of physical contact between the T cells and the target B cells, supporting the notion of direct killing of activated B cells by T cells. The ability of low doses of SAg to promote B cell differentiation without generating biologically meaningful cytolytic activity and the ability of higher doses of SAg to modulate Ig production may have important pathogenetic and therapeutic ramifications for certain autoimmune disorders, such as systemic lupus erythematosus.

B-Lymphocytes↗
PubMed1995

A gamma-tubulin that associates specifically with centrioles in HeLa cells and the basal body complex in Chlamydomonas.

gamma-Tubulin is a putative component of microtubule initiating material. To further explore its subcellular distribution in plant and animal cells, we have raised a polyclonal antibody, Rb27, directed towards a conserved region (EEFATEGTDRKDVFFY) of the gamma-tubulin molecule. Immunoblotting of cell protein extracts with Rb27 reveals a polypeptide band of M(r) 49 kD in HeLa and a 58 kD band in Chlamydomonas. Although these polypeptides are comparable in size to forms of gamma-tubulin detected previously in mammalian and plant protein extracts by other antibodies to gamma-tubulin, by immunofluorescence microscopy Rb27 gives localization patterns not previously seen. It localizes specifically with the centrioles in HeLa cells and with the basal body complex in Chlamydomonas. Other gamma-tubulin antibodies label pericentriolar material. Because of the similarities in the size of the polypeptides recognized by our and other gamma-tubulin antibodies, and a restricted co-localization with known microtubule-organizing centres in evolutionarily distant organisms, we propose that Rb27 recognizes a novel conserved gamma-tubulin isotype.

Amino Acid Sequence↗
PubMed1994

Human T cell-dependent B cell differentiation induced by staphylococcal superantigens.

Microbial superantigens (SAgs), by virtue of their binding to TCR V beta elements on T cells and to class II MHC molecules on accessory cells (AC), trigger T cell activation. Although anti-CD3 mAb (which also trigger T cell activation via surface CD3/TCR) can readily induce T cell-dependent B cell differentiation in unmanipulated PBMC cultures, induction of Ig production in SAg-stimulated cultures has usually required special manipulation of the T cells, such as irradiating them or treating them with mitomycin C. We now demonstrate that eight different staphylococcal SAgs, typically at concentrations 10- to 100-fold lower than those required for proliferation, can each trigger unmanipulated peripheral blood and tonsil T cells to drive polyclonal B cell differentiation. Such SAg-induced T cell-dependent generation of Ig-secreting cells (IgSC) requires T cells and B cells only and occurs in the absence of monocytes as long as there are adequate numbers of B cells to serve as (DR+) AC. Physical contact among T cells, responder B cells, and AC (when different from the responder B cells) is required. The fusion protein CTLA4Ig inhibits SAg-induced IgSC generation in a dose-dependent fashion, whereas a control fusion protein has no such effect. In contrast, CTLA4Ig has, at best, only modest effects on SAg-induced T cell proliferation, indicating that CD28 (CTLA4)/B7 (B7-like) interactions play a more prominent role in SAg-induced IgSC generation than in SAg-induced T cell proliferation. These results establish SAg-induced T cell-dependent B cell differentiation as a useful model for T cell/B cell interactions, inasmuch as no other cell types are necessary for successful B cell differentiation; these results also demonstrate the importance of CD28 (CTLA4)/B7 (B7-like)-dependent mechanisms in this process.

Abatacept↗
PubMed1994

Enhancing effects of interleukin 2-treated peripheral blood mononuclear cells on subsequent B cell differentiation.

Despite an extensive literature dealing with IL2-induced cytolytic activity, noncytotoxicity-related effects of IL2 on peripheral blood mononuclear cells (PBMC) or T cell function have received less attention. We have focused on the effects of irradiated, IL2-activated PBMC (PBMC*rIL2) on anti-CD3- and formalin-fixed heat-killed Staphylococcus aureus-induced polyclonal B cell differentiation in secondary cultures. PBMC*rIL2 act directly on B cells and cross major histocompatibility complex barriers to augment polyclonal B cell differentiation as measured by plaque-forming cell (PFC) generation. These effects are preferentially mediated by T (both CD4+ and CD8+) cells, and physical contact between effector PBMC*rIL2 and target B cells is not absolutely required for enhanced PFC generation. PBMC*rIL2 must be present for the initial 24 hr of the secondary cultures, indicating that some soluble B cell differentiation factor rapidly released by PBMC*rIL2 mediates the PFC-enhancing effect. Of IL2, IL4, IL5, IL6, IL10, IFN-gamma, and TNF-alpha, only IFN-gamma mRNA is appreciably and reproducibly increased in irradiated, IL2-activated T cells (T cells*rIL2). Nevertheless, exogenous rIFN-gamma cannot mimic and anti-IFN antibodies cannot block the PFC-enhancing effects of T cells*rIL2, indicating that some unidentified soluble factor(s) apart from or in addition to IFN-gamma is involved. IL2-induced effects on T cell noncytolytic function may help explain certain observed immune anomalies in IL2-treated patients, and a better understanding of the IL2-induced effects on T cell noncytolytic function may have ramifications for autoimmune diseases such as SLE.

Antibody-Producing Cells↗
PubMed1994

Polyclonal in vitro T cell proliferation and T cell-dependent B cell differentiation supported by activated autologous B cells.

Although anti-CD3-induced T cell proliferation and T cell-dependent B cell differentiation are not supported well by resting (nonactivated) B cells as AC, human peripheral blood B cells activated in vitro with SAC, rIL2, or anti-IgM effectively subserve AC function in a manner qualitatively similar to that of blood monocytes and support polyclonal anti-CD3-driven T cell-dependent B cell differentiation. Physical contact among T cells, responder B cells, and (irradiated) activated B cells is required, and the ability of activated B cells to support anti-CD3-driven generation of IgSC parallels surface B7 expression by the activated B cells. The fusion protein CTLA4Ig, which binds to B7 and B7-like molecules with high avidity and disrupts the interaction of T cell surface CD28 with B7, inhibits B cell differentiation in a dose-dependent fashion, whereas a control fusion protein has no such effect. Thus, activated B cells support polyclonal T cell-dependent B cell differentiation via a CD28 (CTLA4)/B7 (B7-like)-dependent mechanism.

Abatacept↗
PubMed1994

Chlorinated hydrocarbons and shell thinning in eggs of (Accipiter) hawks in Ontario, 1986-1989.

Eggs of sharp-shinned hawks (Accipiter striatus), Cooper's hawks (A. cooperii), and northern goshawks (A. gentilis) were collected from nests in south-central Ontario from 1986 to 1989. Detectable levels of the chlorinated hydrocarbons DDE, DDT, DDD, mirex, photomirex, cis-nonachlor, trans-nonachlor, oxychlordane, dieldrin, heptachlor expoxide, HCB and PCB were present in all the eggs analyzed. Mean contaminant levels were highest in sharp-shinned hawks, slightly lower in Cooper's hawks, and significantly lower in goshawks; for example, mean DDE values were 7.23, 4.48 and 0.90 mg kg(-1) (wet weight), respectively. Total PCB levels were generally less than 1.5 mg kg(-1), lower than those associated with reproductive effects in field and laboratory studies with other species. Mean shell thicknesses of sharp-shinned and Cooper's hawk eggs were significantly less than mean pre-DDT era thicknesses (-10 and -8%, respectively), reductions that were probably not relevant to reproductive success. Goshawk eggs exhibited no significant reduction in shell thickness. Contaminant levels among the three species probably reflect differing food habits and migratory patterns.

Journal Article↗
PubMed1994

Biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in double-crested cormorant chicks (Phalacrocorax auritus).

The present project assessed the effect of environmental contamination with polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) on hepatic microsomal ethoxyresorufin O-deethylase (EROD) activities and morphological parameters in matched double-crested cormorant (Phalacrocorax auritus) hatchlings from egg clutches chosen for chemical analysis. Double-crested cormorant eggs were collected from five colonies across Canada, with differing levels of contamination. Levels of contamination expressed in sum of 2,3,7,8-tetrachlorodibenzo-p-dioxin-toxic equivalents (TCDD-toxic equivalents or TEQ, ng/kg egg; mean +/- SEM) were: Saskatchewan, 250 +/- 50; Chain Islands, 672 +/- 73; Christy Islet, 276 +/- 14; Crofton, 131, n = 1; and Lake Ontario, 1606 +/- 118. In the hatchlings, hepatic EROD activities (pmol/min/mg protein; mean +/- SEM) were: Saskatchewan, 283 +/- 42; Chain Islands, 516 +/- 98; Christy Islet, 564 +/- 91; Crofton, 391 +/- 52; and Lake Ontario, 2250 +/- 156. Hepatic microsomal EROD activity (pmol/min/mg protein) regressed positively on TEQ (r2 = .69; p < .00005; n = 25). Yolk weight (g) regressed negatively on TEQ (r2 = .44; p = .00005). Wing length (mm) regressed negatively on PCB-169 (r2 = .28; p = .007). Monospecific antibodies raised against rat cytochrome P-450 1A1 recognized a protein in the hepatic microsomes of the double-crested cormorant, and also in those of the great blue heron (Ardea herodias), using immunoblotting. The intensity of the stained band increased with increased EROD activity, supporting the assumption that ethoxyresorufin is a suitable substrate for avian cytochrome P-450 1A1. These results validate the use of avian hepatic microsomal EROD activity as an index of cytochrome P-450 1A1 induction by environmental levels of polychlorinated aromatic hydrocarbons and as a useful screening tool to determine the extent of exposure to such chemicals. Furthermore, the induction of cytochrome P-450 1A1 observed in the cormorant indicates that the Ah receptor-mediated process, by which TCDD and related chemicals exert many of their toxicities, has been activated.

Abnormalities, Drug-Induced↗