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T M Ellis

Publications and source records attributed to T M Ellis.

At least 73 records · Page 4Linked to original sources
PubMed1995

IL-12 activates IFN-gamma production through the preferential activation of CD30+ T cells.

CD30 is normally expressed by a subset (15 to 20%) of CD45RO+ T cells after activation by a variety of T cell stimuli and defines the principal IFN-gamma-producing T cells subset. Inasmuch as the production of IFN-gamma is regulated by IL-2 and IL-12, we have examined the effects of these cytokines on the proliferation, induction, and function of CD30+ and CD30- T cell subsets. Upon isolation, CD30+CD25+ T cells exhibit high levels of baseline proliferation compared with CD30-CD25+ T cells. Neutralizing Abs specific for IL-2, IL-4, IL-6, or IL-12 had no effect on basal levels of proliferation in CD30+CD25+ T cells, whereas anti-IL-2 inhibited the basal proliferative activity of CD30-CD25+ T cells. The addition of exogenous rIL-12 to purified CD30+CD25+ and CD30-CD25+ T cells subsets induced significantly higher maximal levels of proliferation in the CD30+ subset, whereas rIL-2 supported comparable levels of maximal proliferation in each subset. The addition of rIL-2 to anti-CD3-activated PBMC increased the relative numbers of CD30+ T cells by expansion of CD30+ T cells, as opposed to recruitment of CD30+ T cells from the CD30- population. Furthermore, the development of the CD30+ T cell subset was inhibited by either anti-IL-2, anti-IL-12, or rIL-10. Inhibition by anti-IL-2 and rIL-10 was overcome by the addition of rIL-12, but not IL-2, to the cultures. Finally, rIL-12 increased IFN-gamma production by CD30+ T cells, yet had little effect on IFN-gamma production by CD30- T cells. Thus, CD30+ T cells are preferentially regulated by IL-12, and the effects of IL-12 on T cell IFN-gamma production are mediated largely through its effects on the CD30+ subset.

Humans↗
PubMed1995

An antigen detection immunoassay for big liver and spleen disease agent.

An enzyme-linked immunosorbent assay (ELISA) able to detect an antigen associated with infection with big liver and spleen (BLS) agent was developed. The assay is a capture ELISA (C-ELISA) procedure using ELISA plates coated with mouse monoclonal antibody (mAb 1H4) for antigen capture and a polyclonal chicken Ig preparation, extracted from yolk of BLS antibody positive birds, for detection of captured BLS antigen. mAb 1H4 was produced to a partially purified antigen preparation from liver suspensions of naturally BLS infected birds. The C-ELISA was evaluated for specificity and sensitivity in naturally and experimentally BLS infected and uninfected broiler and layer breeds of domestic fowl.

Animals↗
PubMed1995

Genetic analysis of dermatophilus spp. using multilocus enzyme electrophoresis.

Multilocus enzyme electrophoresis was used to examine a collection of 41 mainly Australian isolates of Dermatophilus congolensis that had been cultured from sheep, cattle, horses, a goat, a marsupial and Chelonids. Allelic variation was examined at 16 enzyme loci. The isolates were divided into eight distinct electrophoretic types (ETs) with a mean genetic diversity per locus of 0.41. The three isolates from Chelonids represented a distinct clone in ET 1 which was separated from the remaining cluster of isolates of D. congolensis by a genetic distance of 0.852. These findings supported a previous proposal that the isolates from Chelonids represent a new species of Dermatophilus. The other 38 D. congolensis isolates were separated into two divisions (I and II) by a genetic distance of 0.560. The divisions were both subdivided into groups that either only contained alpha-hemolytic or beta-hemolytic isolates, but all isolates in each ET had only one hemolytic pattern. Isolates originating from the same animal species, or from the same geographic location, were not all closely related genetically. The allocation of isolates into ETs correlated well with their distribution into DNA restriction endonuclease analysis patterns previously established for the collection. Although relatively few distinct strains of D. congolensis were identified amongst the collection, significant genetic diversity existed within this population.

Actinomycetales↗
PubMed1995

A phase IA/IB trial of anti-CD3 murine monoclonal antibody plus low-dose continuous-infusion interleukin-2 in advanced cancer patients.

Preclinical studies have shown that anti-CD3 antibodies can enhance the in vitro activation of human T lymphocytes in combination with low-dose interleukin-2 (IL-2) and induce the in vivo rejection of murine tumors. A Phase IA/IB trial combining a murine monoclonal antibody, anti-CD3 antibody (OKT3), with low-dose continuous-infusion IL-2 was conducted in cancer patients to define the toxicity and immunologic effects of this combination. OKT3 administered weekly as a 15-min infusion at dose levels of 10, 100, 200, 400, and 600 micrograms/m2 was followed 18 h later by a 100-h infusion of IL-2 at 3 MIU/m2/day for 3 consecutive weeks. When feasible, patients also received the IL-2 course without OKT3 to assess the effects of OKT3 on the IL-2 regimen within the same patient. Thirty patients were enrolled onto the study, with 24 completing the OKT3/IL-2 course and 18 completing both OKT3/IL-2 and IL-2 alone courses. OKT3 administration was associated with acute hypotension with fevers of > 40 degrees C and in two patients cerebral vascular infarcts. At 600 micrograms/m2 OKT3, these toxicities were dose limiting. In a dose-dependent manner, OKT3 induced the transient release of tumor necrosis factor (TNF) and IL-6 into the serum and a profound lymphopenia. OKT3 did not significantly enhance the toxicity of this schedule of IL-2 administration. All solid tumor patients treated at 100-600 micrograms/m2 OKT3 showed induction of a human anti-murine antibody response prior to the third week of treatment. A patient with renal cell cancer treated at the 600-micrograms/m2 OKT3 dose level experienced a 4-month partial remission, and two mixed responses were observed in a sarcoma and a melanoma patient treated at 100- and 400-micrograms/m2 OKT3 dose levels, respectively. Most importantly, we were unable to demonstrate that the addition of OKT3 enhanced immune activation within peripheral blood based upon the magnitude of rebound lymphocytosis, increase in CD56+ or CD3+, CD25+ lymphocytes, induction of natural killer, lymphokine activated killer, or cytolytic T lymphocyte cytotoxicity, or release of serum cytokines (TNF, IL-6) or soluble CD25 (as assayed 24 h following IL-2 infusion). Therefore, this approach was ineffective at enhancing the immunologic effects of a low-dose continuous-infusion IL-2 regimen and will not be pursued further in clinical trials.

Adult↗
PubMed1995

Dermatophilus chelonae sp. nov., isolated from chelonids in Australia.

Three isolates of a previously undescribed Dermatophilus sp. obtained from chelonids (two strains obtained from turtles and one strain obtained from a tortoise) were compared with 30 Dermatophilus congolensis isolates obtained from Australian mammals. The microscopic appearance, the colony morphology, and most biochemical test results for the chelonid isolates were characteristic of the genus Dermatophilus. Our isolates differed from the mammalian D. congolensis isolates in a number of cultural characteristics, including faster growth at 27 degrees C than at 37 degrees C, formation of two hemolysis zones around colonies on blood agar at 37 degrees C in the presence of 10% CO2, poor motility, and production of a distinctive odor. The DNA restriction enzyme digestion and protein electrophoresis patterns of our strains were distinct. The electrophoretic mobilities of 11 enzymes differed from the mobilities observed with D. congolensis strains. A monoclonal antibody to a surface antigen of an ovine isolate did not react with zoospores or filaments of the chelonid isolates. Biochemical differences between our isolates and D. congolensis included the ability of the chelonid isolates to reduce nitrate to nitrate and the fact that the chelonid isolates exhibit collagenase activity in vitro. We propose that the chelonid isolates should be placed in a new species, Dermatophilus chelonae. Strain W16, which was isolated from a nose scab on a snapping turtle, is the type strain; a culture of this strain has been deposited in the American Type Culture Collection as strain ATCC 51576.

Actinomycetales↗
PubMed1995

The spread of Corynebacterium pseudotuberculosis infection to unvaccinated and vaccinated sheep.

The decrease in the prevalence of Corynebacterium pseudotuberculosis after two generations of vaccination against the disease it causes, was used to estimate the rate of control of caseous lymphadenitis (CLA). Three groups of 150 sheep, of which 50 in each group were artificially infected with C pseudotuberculosis and 100 in each group were uninfected sheep, were run separately for 40 months and shorn 5 times to promote the spread of CLA. One lot of 50 infected sheep and 2 lots of 100 uninfected sheep were vaccinated against CLA. The rate of spread of CLA was recorded. Sheep vaccinated against CLA and naturally exposed to infection had a 74% lower infection rate than unvaccinated sheep. Sheep vaccinated against CLA and exposed to only vaccinated infected sheep had a 97% lower infection rate. Unvaccinated sheep had a 76% infection rate, with 77% of the transmission occurring at the 4th and 5th shearings, without any discharging CLA abscesses being observed. This study supports the view that in Australian wool producing flocks, CLA spreads mainly from sheep with discharging lung abscesses to sheep with shearing cuts. Vaccinated sheep infected with CLA have 96% fewer lung abscesses compared with unvaccinated infected sheep and are therefore less likely to spread this disease to other sheep.

Animals↗
PubMed1994

CD30 defines a subset of activated human T cells that produce IFN-gamma and IL-5 and exhibit enhanced B cell helper activity.

CD30 is a lymphoid activation Ag expressed by activated B and T lymphocytes, as well as selected lymphoid malignancies. In T cells, CD30 expression is limited to a minority (15 to 25%) of activated CD45RO+ T cells. Studies were undertaken to define unique functional properties of CD30+ T cells by identifying the profile of cytokine production by CD30+ T cells, and by assessing their ability to provide help for B cell Ig production. Assessment of cytokine mRNA transcripts by reverse transcription-PCR (RT-PCR) revealed the presence of IFN-gamma mRNA transcripts only in CD30+ T cells derived from FACS purified from activated CD45RO+ T cells. IFN-gamma mRNA was present neither in the CD30- subset of activated CD45RO+ T cells, nor in activated CD45RA+ T cells. Both CD30+ and CD30- subsets expressed IL-10 and IL-2R alpha mRNAs after 3 days of activation, but neither population expressed IL-4 or IL-6 transcripts at this time. Furthermore, production of secreted IFN-gamma was significantly greater in activated CD30+CD45RO+ cells (564 +/- 250 pg/ml) than in CD30-CD45RO+ (50 +/- 33 pg/ml) or CD45RA+ (0 +/- 0) T cells. CD30+ T cells also expressed IL-5 mRNA and secreted significantly higher levels of IL-5 (320 +/- 73) than activated CD30-CD45RO+ (17 +/- 5) T cells. In contrast, CD30- T cells produced significantly higher levels of IL-2 than CD30+ T cells (1270 +/- 380 vs 450 +/- 128). Induction of IFN-gamma in CD30+ T cells was not a result of CD30 engagement by Abs used during the isolation process, although an anti-CD30 Ab (M44) known to exert agonist activity was capable of inducing IFN-gamma production by T cells when immobilized to plastic. Finally, CD30+CD4+ T cells exhibit significantly greater helper activity for B cell Ig production than CD30-CD4+ T cells. These results demonstrate that CD30 identifies a unique subset of T cells that comprise the major IFN-gamma- and IL-5-producing cells in the T cell compartment, and exhibit potent helper activity for B cell Ig production.

Antibody Formation↗
PubMed1994

A phase I trial of continuous infusion interleukin-4 (IL-4) alone and following interleukin-2 (IL-2) in cancer patients.

BACKGROUND: Interleukin-4 (IL-4) can enhance immune function within various leukocyte populations and mediate antitumor effects in mice. In vitro, IL-4 activation of human lymphocytes is enhanced by prior exposure to interleukin-2 (IL-2). This phase I trial of continuous intravenous infusion (CI i.v.) IL-4 was performed to determine its toxicity and biologic activity. IL-2 was administered prior to a second course of IL-4 in the same patients to determine whether IL-2 exposure can enhance IL-4 effects in vivo. PATIENTS AND METHODS: Seventeen patients with non-hematologic malignancies were entered on this trial. Treatment consisted of 7 days of CI i.v. IL-4 followed by a 2 week period off therapy, then a 4 day course of CI i.v. IL-2 at 11.2 MIU/m2/day followed by 3 days rest, and then a second 7 day course of CI i.v. IL-4. IL-4 dose escalation included 40 micrograms/m2/day (6 pts.), 120 micrograms/m2/day (3 pts.), 360 micrograms/m2/day (5 pts.), and 600 micrograms/m2/day (3 pts.). RESULTS: Dose limiting toxicity occurred at 600 micrograms/m2/day of IL-4; a dose at which 2 of 3 patients exhibited a vascular leak syndrome characterized by weight gain, peripheral edema, effusions, oliguria, and diffuse rash. Pretreatment with IL-2 did not significantly enhance IL-4 toxicity in the 40-360 micrograms dose range. IL-4 treatment was associated with a modest, but significant increase in peripheral eosinophil counts (p = 0.004), but no consistent change in lymphocyte phenotype or function. Patients treated at the higher dose of IL-4 (360 micrograms) administered following IL-2, exhibited a marked increase in peripheral eosinophils after IL-4 therapy (p = 0.007). Following the second course of IL-4, we observed increases in the percent CD56+ (NK/LAK marker) lymphocytes (mean increase = 6.8%), above levels induced by the preceding IL-2 treatment (p = 0.055). A single minor durable tumor response was seen in a patient with metastatic renal cancer. CONCLUSIONS: IL-4 administered at 360 micrograms/m2/day CI i.v. over seven days is the maximum tolerated dose and is tolerable following a 4 day course of IL-2. IL-4 therapy alone is associated with a modest eosinophilia. In patients receiving IL-2 prior to IL-4, both circulating eosinophils and CD56+ cells increased above levels observed early after IL-2 treatment. Based upon these results, phase II trials of IL-4 in combination with IL-2 could be planned in 'IL-2 sensitive' malignancies.

Adult↗
PubMed1994

New infection with Corynebacterium pseudotuberculosis reduces wool production.

The effect of natural Corynebacterium pseudotuberculosis infection on wool production and quality in sheep was examined in light of evidence that artificial C pseudotuberculosis infection causes wool production loss. A toxin ELISA was used to identify sheep that had been infected with C pseudotuberculosis. Greasy and clean fleece weights and fibre diameter were compared in infected and uninfected sheep. C pseudotuberculosis infection caused a 3.8 to 4.8% decrease in greasy wool production and a 4.1 to 6.6% decrease in clean wool production. C pseudotuberculosis infection did not affect fibre diameter. The effects of caseous lymphadenitis (the disease caused by C pseudotuberculosis infection) cause an annual loss of about $17 million in wool production to the Australian wool industry.

Abattoirs↗
PubMed1994

Regulation of lung liquid secretion in immature fetal sheep: hormonal interaction.

The present studies were designed to test the hypothesis that arginine vasopressin (AVP) can interact with hydrocortisone and 3,5,3'-triiodothyronine (T3) to induce maturation of lung liquid reabsorptive processes in fetal sheep < 130 days gestation. Lung liquid production rates were measured in chronically catheterized thyroidectomized fetal sheep during eight different experimental treatments. Each experiment consisted of a 2-h control period followed by a 5-h treatment period. Net secretion or reabsorption of lung liquid was measured by using impermeant marker dilution techniques. AVP alone (50 mU/kg bolus plus 5.0 mU.kg-1.min-1 i.v. infusion) does not alter lung liquid secretion in fetal sheep 125 +/- 0.72 (SE) days gestation. In contrast, AVP (same dose as above) with T3 (30 micrograms) and hydrocortisone (6.94 mg/min) depressed lung liquid secretion and caused reabsorption of fluid. T3 alone, T3 and hydrocortisone, T3 and AVP, hydrocortisone alone, hydrocortisone and AVP, and saline did not result in net lung liquid reabsorption over a 5-h treatment period. These investigations demonstrate that AVP, T3, and hydrocortisone interact to cause lung liquid reabsorption in immature fetal lungs.

Absorption↗
PubMed1993

CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells.

CD30 has been extensively studied as a cell surface marker expressed by Reed-Sternberg cells of Hodgkin's disease and other hematologic malignancies, although little is known about its expression by normal lymphoid cells. We therefore characterized the requirements for the induction of CD30 expression and identified the subsets of T cells that express CD30. CD30 is inducible on approximately 15% of normal PBMC stimulated with any of a variety of nonspecific T cell activators, including PHA, Con A, anti-T11(2) + T11(3), and anti-CD3; ionomycin alone induced lower percentages of CD30+ T cells (3 +/- 2%) compared to other stimuli. Maximal numbers of CD30+ cells were observed at 48 to 72 h of activation and the addition of rIL-2 did not affect these kinetics. However, CD30 expression was enhanced by the addition of exogenous rIL-2 to any of the stimuli tested, although rIL-2 alone did not lead to CD30 expression. The induction of CD30 during anti-CD3 mitogenesis was completely inhibitable by anti-IL-2 antibodies and partially inhibitable by rIL-4, indicating a requirement for both TCR triggering and IL-2 for its expression. Dual immunofluorescence analysis revealed that CD30+ cells were confined to CD3+ T cells that coexpressed higher levels of the p55 IL-2 receptor (CD25) than the CD30- population. Furthermore, CD30 expression was restricted to a subset of cells derived from CD45RO+ T cell precursors. Cell cycle analysis showed that CD30+ expression was not cell cycle dependent. Cross-linking of membrane CD30 induced Ca2+ in TCR+, but not TCR- Jurkat T cells. These results demonstrate that CD30 can serve as a T cell signal-transducing molecule and expressed by a unique subset of activated CD45RO+ T cells.

Antigens, CD↗
PubMed1993

Detection of Haemonchus contortus surface antigen in faeces from infected sheep.

An antigen capture enzyme-linked immunosorbent assay (ELISA) has been developed that could identify Haemonchus contortus antigens in dilute suspensions of worm homogenates and in faeces from sheep naturally infected with moderate burdens of the parasite. The ELISA is based on a polyclonal (rabbit or sheep) antibody coated solid-phase that captures parasite antigen from a suspension of worms or faeces. The captured antigen is detected by a mouse monoclonal antibody (MAb E2) that is reactive with a cuticle surface antigen of H. contortus. Binding of MAb E2 was shown to be specific for H. contortus and the ELISA was able to detect this antigen in faeces of some infected sheep. Characterisation of the antigen reacting with MAb E2 indicates it to be a collagenase and protease resistant surface protein of H. contortus that under reducing conditions in SDS-polyacrylamide gel electrophoresis exists as polypeptides of molecular weight 122, 56 and 49 kDa.

Animals↗
PubMed1993

Blood T6-lymphocyte antigen levels as a poor resistance marker in ovine dermatophilosis.

Merino ewes lambs from a flock expected to have a high prevalence of dermatophilosis were examined for lesions at marking, weaning and prior to first shearing. Blood was collected at marking and prior to shearing to enable quantification of T6-lymphocyte antigen levels in peripheral blood mononuclear cells (PBM) using monoclonal antibody SBU-T6 20-27. A group of the lambs that had persistent and/or severe dermatophilosis had significantly lower (P < 0.05) mean levels of T6-lymphocyte staining in PBM than those with minimal or no dermatophilosis in blood samples collected prior to shearing. However, the wide variability of this parameter in resistant and susceptible lambs indicated that this would not be a satisfactory procedure to rank sheep for resistance to dermatophilosis.

Actinomycosis↗
PubMed1993

Variation in cultural, morphological, biochemical properties and infectivity of Australian isolates of Dermatophilus congolensis.

Recent vaccination studies with Dermatophilus congolensis showed that variation of challenge strains had a considerable influence on protection afforded by the vaccines. In this study cultural, morphological and biochemical properties of 30 D. congolensis isolates from throughout Australian were investigated. The infective dose required to produce lesions of equivalent severity by these isolates for sheep, rabbits and guinea pigs was also examined and the isolates were grouped into four clusters of similar infectivity ranking. Analysis of the relationship between cultural, morphological and biochemical characteristics and infectivity rankings of clusters was undertaken to determine if certain properties were linked to infectivity. Considerable variability was found in haemolytic activity on blood agar, mucoid nature of colonies, motility, flagella density and polarity, capsule width, restriction enzyme profiles of bacterial DNA, protein electropherotype, carbohydrate content, and enzymic activity against proteins, maltose, chondroitin-4-sulphate, phospholipids and lipids. Of these properties haemolytic activity and enzyme activity against casein, chondroitin-4-sulphate and lipids showed some link with infectivity ranking for these isolates.

Actinomycetales↗
PubMed1993

Use of a repetitive element isolated from Mycobacterium tuberculosis in hybridization studies with Mycobacterium bovis: a new tool for epidemiological studies of bovine tuberculosis.

Typing of M. bovis isolates for epidemiological purposes is possible using restriction endonuclease analysis (REA). However, the DNA fragment patterns obtained are complex and difficult to analyse due to the large number of bands produced. In an attempt to develop a less complicated typing scheme two DNA probes were used in hybridization studies to detect restriction fragment length polymorphisms (RFLP) in M. bovis. An oligonucleotide probe which matches part of the insertion sequence IS6110 produced few bands and failed to discriminate between bovine isolates of M. bovis. A probe prepared from a highly repeated DNA sequence, cloned from M. tuberculosis when used on southern blots of AluI digested M. bovis DNA, resulted in a discriminating typing scheme which was easier to perform and analyse than the REA. The RFLP typing scheme identified 27 different strains from a total of 36 isolates of M. bovis and 7 reference strains from the M. tuberculosis complex. Using REA, 24 types were identified using BclI and PvuII digests and 23 different types using BstEII digests. When results of all 3 enzyme digests were combined, the REA identified 27 types from the same strains. Ten isolates of M. bovis from 5 properties involved in an outbreak of bovine tuberculosis were all identified as the same type with both techniques.

Animals↗