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T E O'Connor

Publications and source records attributed to T E O'Connor.

At least 19 recordsLinked to original sources
PubMed1990

Patterns of cytokines released by peripheral blood leukocytes of normal donors and cancer patients during interleukin-2 activation in vitro.

We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-gamma, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (less than 300 pg/ml) and minimal levels of IFN-gamma, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1990

Levamisole meets sulfhydryl requirements of CTLL-2 cells and mediates enhanced proliferative response to mitogen stimulation without increasing interleukin-2 production.

We examined the effect of levamisole (LMS) on the proliferative response and interleukin-2 (IL-2) concentration in OKT3-, phytohemagglutinin-, and concanavalin-A-stimulated lymphocyte cultures. Although proliferative response was enhanced in lymphocyte cultures stimulated in the presence of LMS, similar levels of IL-2 were observed in stimulated and unstimulated cultures. The mechanism of the enhancement effect of LMS on proliferative response was further characterized by studying its effects on the growth of IL-2-dependent CTLL-2 cells in culture. Since this cell line has been shown to require 2-mercaptoethanol (2-ME) for normal growth in recombinant IL-2, the effect of LMS on several parameters of its growth was compared with that of 2-ME. Unlike 2-ME, LMS did not enhance 35S-cystine uptake. Both compounds increased thiol concentration in the cell culture, but (oxidized) 2-ME induced a greater increase. Generally, the effects of LMS on CTLL-2 growth were quite similar to those of structurally unrelated compounds known to have antioxidant properties, and the demonstrated thiol requirement of this cell line for growth in recombinant IL-2 was met by substituting LMS for 2-ME. When the effect of LMS on IL-2 receptor (IL-2R) expression in CTLL-2 cells was examined by a receptor-ligand binding assay involving low levels (10-80 pM) of 125IL-2, a modest increase in the level of IL-2R expression was observed. The biologically active high-affinity IL-2R complex is believed to be preferentially bound at the low levels of 125IL-2 used here, suggesting a functional relevance for this effect of LMS. These observations should be useful in minimizing the cost and duration of in vitro expansion of lymphocytes for use in adoptive immunotherapy and should be applicable in improving the response of immunologically impaired patients to immunotherapy.

Adjuvants, Immunologic↗
PubMed1988

Principles of biotherapy and its application to the treatment of disseminated renal cancer.

Monoclonal antibody technology permits the preparation of tumor-specific immunoglobulin reagents that can be used directly in tumor therapy or that can be coupled to various chemotherapeutic drugs or toxins to aid in their delivery to the tumor site and thus enhance their therapeutic effectiveness. Additionally, recombinant DNA technology has facilitated the economic production of rare lymphokines (e.g., interleukin 2, interferon alpha and interferon gamma) or cytokines (tumor necrosis factor, lymphotoxin) that can either modulate the host immune response or kill tumor cells, respectively. These developments collectively have led to the development of a fourth modality for treatment of human cancers--biotherapy--as an addition to surgery, radiation, and chemotherapy modalities. This paper presents the rationale and emerging practice of the biotherapy of cancer and documents early clinical results, including the treatment of metastatic renal carcinoma at the Biological Therapy Institute.

Animals↗
PubMed1987

Detection of a tumor-associated nucleoprotein antigen in mink lung cells transformed by two different viral oncogenes.

Salt-precipitated chromatin was prepared from cultured MvlLu line mink lung cells and from these cells transformed by either of the oncogenes v-mos (MIMS-102 line) or v-fes (F3C7 line). Xenoantisera were raised to chromatin from each of the three cell types and cross-tested in microcomplement fixation assays to determine immunospecificity. Chromatin from cells transformed by either v-mos or v-fes revealed antigenic profiles statistically indistinguishable (P less than 0.2 to 0.5) from one another with their respective cross-tested antisera, but did not react significantly with antisera to chromatin from the untransformed parental cell line. Likewise, little cross-reaction was observed with chromatin from the untransformed cells and antisera raised to chromatin from either of the oncogenically transformed lines (P less than 0.001), although each chromatin demonstrated high reactivity with its homologous antiserum preparation. These immunological data are consistent with the observed normal or transformed characteristics for each cell type, including morphology, anchorage-independent growth, and growth in the absence of serum.

Animals↗
PubMed1985

Oncogenes: targets for immunodiagnosis and chemotherapy?

A hypothesis is presented that cellular proto-oncogenes encode proteins that play a regulatory role in embryonic development and in the terminal differentiations of cells in various tissues and that alterations in these genes yield oncogenes whose expression results in neoplasia. The hypothesis suggests that study of the disturbance in cell regulation introduced by oncogenes could permit the rational design of inhibitors capable of restoring neoplastic cells to normal differentiation lineages. Proteins encoded by oncogenes may be immunogenic and thus provide diagnostic markers in the tumor-bearing host.

Animals↗
PubMed1983

Effects of divalent metal cations on composition and neoplasia-specific antigenicity of chromatins.

The antigenicity and composition of chromatins differ markedly in chromatin preparations obtained by different procedures. Rat Novikoff hepatoma chromatin (NC) obtained by the "salt precipitation" and the micrococcal nuclease digestion procedures using significant levels of EDTA and NaCl each shows a common complement fixation (CF) capacity, exceeding chromatin preparations obtained from normal rat liver when tested with rabbit antisera raised to dehistonized NC. In contrast, "structured" NC preparations, which have been postulated to retain a native physical conformation, show minimal CF capacity when tested with the same antiserum but show high CF following elution of histones. While further progressive elution of non-histone proteins (NHPs) did not alter the CF capacity per unit DNA, the completely separated DNA and NHP fractions each showed minimal CF. The data suggest that the antigens detected in the CF assay predominantly represent an artifactual but specific complex of DNA and NHP arising from a denaturation of the native chromatin following elution of metal ions or histones. A qualitatively similar profile of NHPs in salt-precipitated NCs shows a range of total protein/DNA ratios, suggesting that the NHPs found in chromatin preparations may not be intrinsic to the native chromatin structure.

Animals↗
PubMed1980

Effects of polyethylene glycol on reverse transcriptase and other polymerase activities.

Polyethylene glycol enhances reverse transcription, augmenting both the rate and duration of polymerization. The effective mean molecular weight of polyethylene glycol is 6000 and the optimal concentration is 12% (w/w). Polyethylene glycol is effective on the reverse transcriptase reaction of all ten type B, C, and D viruses tested under a variety of exogenous, endogenous, and reconstitution assay systems, including the highly efficient conditions involving calf thymus DNA oligonucleotide primers. By three methods of synthesis, polyethylene glycol increased the yields of complementary [3H]DNA by a factor of 1.8--6.5. Polyethylene glycol does not alter the divalent cation requirements of the specificities of the enzyme. Complementary [3H]DNAs made in the presence of polyethylene glycol are indistinguishable in terms of size and sequence complementarity from those made in the absence of the polymer. The stimulatory effect was partly due to the ability of polyethylene glycol to stabilize reverse transcriptase. Preliminary tests indicate that polyethylene glycol also stimulates other nucleotide polymerases, such as the DNA-dependent DNA and RNA polymerases of Escherichia coli and the terminal transferase of calf thymus.

Escherichia coli↗
PubMed1977

Interruption of oncornavirus replication by modified rifamycin antibiotics.

Thirteen rifamycin SV derivatives containing 3'-alkylaminomethyl substituents fail to inhibit the activities of the simian sarcoma virus Type 1 DNA polymerase, and of cellular DNA, RNA, and poly(A) polymerases prepared from NIH Swiss mouse embryos. These compounds show a range in their toxicities for NIH Swiss mouse 3T3 cells and in their capacities to inhibit production of foci of morphologically altered cells by murine sarcoma virus (MSV). Three compounds--the N-methyl-N-hydroxyethylaminomethyl, the N,N-dimethyl-aminomethyl, and the N4-methylpiperazinomethyl rifamycin derivatives--are comparable to adenine arabinoside and ribavirin in their toxicity for 3T3 cells, but these compounds show superior focus inhibition. These compounds inhibit oncornavirus production apparently by exacerbation of a delay in growth that results from infection of 3T3 cells with MSV.

Cell Survival↗