Biomedical subjects

D J Hurley

Publications and source records attributed to D J Hurley.

28 records · Page 2Linked to original sources

PubMed1987

Differentiation of peanut lectin positive suppressor T-cells from peanut lectin negative precursors in bovine cells by 12-O-tetradecanoylphorbol-13-acetate.

Although 12-O-tetradecanoylphorbol-13-acetate (TPA) can synergize with lectins to enhance lymphocyte proliferation, pretreatment of lymphocytes with TPA decreases their response. Pretreatment also inhibits the response to allogeneic cells in the mixed lymphocyte culture. In this study we determined that at least part of this inhibition was due to the generation of T-lymphocytes with the ability to suppress proliferation in vitro. By using populations enriched in lymphocytes or macrophages we determined that the interaction of TPA with lymphocytes, but not macrophages, was required to mediate the suppression. The number of macrophages present in culture (range, 0.5-10%) was irrelevant to the generation of inhibitory activity. Moreover, the TPA-induced suppressor activity copurified with T-cells. Furthermore, when peanut lectin (agglutinin) (PNA) was used to separate T-cells after treatment with TPA, essentially all of the activity copurified with the PNA positive cells. When PNA separations were carried out before treatment with TPA, the suppressor activity arose from the PNA negative fraction. Therefore, TPA appeared to cause phenotypically PNA negative T-cells to gain the PNA positive marker, as well as to function as suppressor cells in vitro. Suppressor activity was also found in the culture medium. Thus the suppression observed may be mediated through a soluble factor released by the TPA-treated cells. Although the suppressor cell activity induced by TPA can only partially account for its in vitro inhibition of lymphocyte proliferation, the development of suppressor cells merits further study with respect to lymphocyte phenotypic and functional differentiation. The results also suggest the possibility that similar processes could occur in vivo, possibly during the course of tumor promotion.

Animals↗

PubMed1987

Induction of suppressor activity by tumor-promoting phorbol esters in primary cultures of lymph node cells.

We have observed the induction of suppressor activity in primary cultures of lymphocytes by the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Suppressor activity was detected as the ability of TPA-treated lymphocytes to inhibit proliferation in mixed lymphocyte cultures (MLC). Induction of this activity was dependent on the dose of TPA and was maximal after approximately 12 h of incubation. Neither the induction of the activity, nor the activity itself was inhibited by indomethacin or interleukin 2 (IL2). A comparison of addition of TPA directly to the MLC, addition of TPA pretreated cells as participants in the MLC and addition of cells treated with TPA to induce suppressor activity suggested that the suppressor activity was only one of the ways that TPA could inhibit proliferation. This suppressor activity may account for some of the reported effects of TPA in immunological systems in vitro and suggests that suppressor cells could play a role in TPA-mediated promotion in vivo.

Animals↗

PubMed1986

Mitogenic activity of snake venom lectins.

Five lactose-inhibitable lectins have been isolated from snake venoms. These five share certain biochemical properties but are not identical (Gartner, Stocker & Williams, 1980; Gartner & Ogilvie, 1984). In this study the lectins were tested for their ability to stimulate lymphocytes to undergo DNA synthesis. We found that three of the lectins were comparable in mitogenic activity to the T cell lectin, concanavalin A (Con A). The mitogenic activity was blocked by lactose, a sugar which also blocks the haemagglutination activity of these lectins. Although mitogenic response appeared to be due to T cells, it depended on the presence of accessory cells in the culture. This requirement for macrophages could be replaced by the phorbol ester tumour promoter, 12-o-tetradecanoylphorbol-13-acetate (TPA).

Animals↗

PubMed1985

Changes in a T-cell subpopulation marker induced by tumor-promoting phorbol esters.

We observed a significant reduction in one specific T-cell rosetting marker after treatment of bovine lymph node lymphocytes with 12-O-tetradecanoylphorbol-13-acetate (TPA). There was a dose-dependent reduction in the formation of neuraminidase-treated sheep erythrocyte rosettes (En), but not aminoethylisothiouronium bromide-treated sheep rosettes (Ea) after as little as 10 min of incubation with TPA. A maximum of approximately 50% reduction was reached after 1 h. When several phorbol esters and mezerien were tested, we found that the reduction in En rosetting induced by the compounds correlated with their in vivo tumor-promoting activity. The reduction in En rosetting appears to be approximately 50% reversible for up to 6 h of treatment with TPA when the cells were incubated in TPA-free medium for an additional 24 h, but it was irreversible after at least 12 h of treatment. Addition of the tumor promoters directly to the rosetting assay had no detectable effect on the sheep erythrocytes or the percentage of Ea rosettes. This specific change in En rosetting marker may represent the maturation of a T-cell subpopulation to T-suppressor cells in the presence of tumor-promoting phorbol esters.

Animals↗

PubMed1983

System for enumerating and separating bovine lymphocytes, using coordinated En and Ea markers: evaluation of lymph node lymphocytes.

A procedure was developed for enumeration and separation of bovine lymph node T-lymphocyte subpopulations. An evaluation was made of T-lymphocyte rosetting with sheep erythrocytes treated with aminoethylisothiouronium bromide and neuraminidase (Ea and En) in RPMI and L-15 media. The effect of holding the lymphocytes in culture over a period of 7 days on the En and Ea markers was established. The optimal period of incubation at 0 C for isolation of the rosetting populations with respect to initial rosette formation, enrichment of the rosetting population in the recovered cells, viability after incubation, and recovery of the cells after the separation was determined. An estimate of the overlap of the Ea and En populations also was made from the separation data. We found that approximately 32% of the lymph node lymphocytes marked with En and Ea rosettes, 11% with only En, and 27% with only Ea.

Animals↗

PubMed1980

Morphological expressions of antibiotic synergism against Pseudomonas aeruginosa as observed by scanning electron microscopy.

Antibiotic-induced changes in Pseudomonas aeruginosa were observed by means of a scanning electron microscope. Seven frequent and five less frequent morphological changes were noted. The frequent changes were: (i) elongation; (ii) chain formation; (iii) nub formation; (iv) spheroplasts; (v) surface holes or pits; (vi) super-elongation; and (vii) increased filamentation. The less frequent changes were: (i) rounded ends; (ii) streptococcal forms; (ii) stalked nubs; (iv) surface bulges; and (v) convoluted surfaces. A morphological equivalent of antibiotic synergism was found in which changes were noted due to synergistic combinations of antibiotics that were not observed when the antibiotics were used alone or when a nonsynergistic combination of antibiotics was used.

Anti-Bacterial Agents↗

PubMed1979

Human lymphocyte-tumor cell interaction. A scanning electron microscopy study.

Cells from the metastatic chest wall lesions of a patient with adenocarcinoma of the breast were incubated with autologous lymphocytes. Their interactions were observed in the scanning electron microscope. The lymphocytes first surrounded the cancer cells; cancer cells then were destroyed while the lymphocytes in contact with them lost their microvilli. The heterologous human lymphocytes being used as controls surrounded the tumor cells but did not destroy them. Lymphocytes in the presence of tumor cells showed interconnections through cytoplasmic bridging.

Adenocarcinoma↗

PubMed1979

Morphologic expression of the interactions of human lymphocytes and Pseudomonas aeruginosa as observed by scanning electron microscopy.

When human lymphocytes and Pseudomonas aeruginosa were incubated together and then observed under the scanning electron microscope, four distinct morphologic observations were made: (1) filopods extending between lymphocytes and bacteria; (2) globular structures bulging out in many of the filopods; (3) filopods connecting lymphocytes to each other in the presence of bacteria; and (4) bacteria adhering to the lymphocytes in areas where decreased numbers of microvilli were present.

Adult↗

PubMedDate not supplied

Short-term exposure to subacute doses of aflatoxin-induced depressed mitogen responses in young mallard ducks.

Mallard ducklings were fed diets containing corn naturally contaminated with mixed aflatoxins, purified T-2 toxin, or no detectable mycotoxin in two trials. The aflatoxin level used was 12 ppb in the first trial and 33 ppb in the second. T-2 was added at 2 ppm in both trials. No pathology was associated with the aflatoxin used in this study, and T-2--induced lesions were described in a previous publication. The weights of primary (thymus and bursa of Fabricius) and secondary (spleen) lymphoid organs were significantly reduced in the T-2--treated birds. The total number of viable cells recovered from the thymus was significantly reduced in aflatoxin-treated birds. The numbers of viable cells recovered from thymus, bursa of Fabricius, and spleen were all significantly reduced after treatment with T-2. In each trial, significantly lower mitogenic responses were seen to pokeweed mitogen and concanavalin A in birds fed aflatoxin or T-2, representing reduction in both B-cell and T-cell mitogenesis. Birds fed aflatoxin also had significantly reduced Escherichia coli O55 lipopolysaccharide-induced mitogenic responses. These studies indicate that subacute oral exposure to aflatoxin caused a loss of normal lymphocyte reactivity in mallard ducklings. This finding supports the hypothesis that waterfowl that ingest even small quantities of mycotoxin-contaminated waste grain are likely to be more susceptible to bacterial or viral infections.

Aflatoxins↗

PubMedDate not supplied

The short-term effect of low concentrations of dietary aflatoxin and T-2 toxin on mallard ducklings.

Two 9-day trials to study effects of dietary mycotoxins were conducted using 6-week-old mallards. Each trial involved three groups of six ducks each, three males and three females per group. One group was fed no myocotoxin (control), one was fed aflatoxin, and the third was fed T-2 toxin. Dietary aflatoxin was 12 ppb in trial 1 and 33 ppb in trial 2; dietary T-2 toxin was 2 ppm in both trials. There were no gross or microscopic lesions in controls or in ducks fed aflatoxin, nor did these groups differ significantly in final body weight or in weights of spleen or bursa of Fabricius. Ducks exposed to T-2 toxin had erosions and/or ulcerations in the oral cavity and esophagus; further, these ducks exhibited a decrease in weights of body, thymus, spleen, and bursa of Fabricius. The only microscopic change seen in lymphoid organs of ducks exposed to T-2 toxin was a moderate decrease of thymic cortical lymphocytes.

Aflatoxins↗