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J A Thompson

Publications and source records attributed to J A Thompson.

At least 253 records · Page 14Linked to original sources
PubMed1987

Molecular cloning of a gene belonging to the carcinoembryonic antigen gene family and discussion of a domain model.

Carcinoembryonic antigen (CEA) is a glycoprotein important as a tumor marker for colonic cancer. Immunological and biochemical studies have shown it to be closely related to a number of other glycoproteins, which together make up a gene family. We have cloned a member of this gene family by using long oligonucleotide probes (42-54 nucleotides) based on our protein sequence data for CEA and NCA (nonspecific cross-reacting antigen) and on human codon usage. The clone obtained (lambda 39.2) hybridizes with six probes and has a 15-kilobase insert. The 5' end of the gene is contained within a 2700-base-pair EcoRI fragment, which hybridizes with five of the six synthetic probes. Sequencing of the 5' end region revealed the location and structure of one exon and two putative intron boundaries. The exon encodes part of the leader sequence and the NH2-terminal 107 amino acids of NCA. Southern blot analysis of human normal and tumor DNA, using as probes two lambda 39.2 fragments that contain coding sequences, suggests the existence of 9-11 genes for the CEA family. One of the restriction fragments described here has been used by Zimmermann et al. [Zimmermann, W., Ortlieb, B., Friedrich, R. & von Kleist, S. (1987) Proc. Natl. Acad. Sci. USA 84, 2960-2964] to isolate partial cDNA clones for CEA. The identity of this clone was verified with our protein sequence data [Paxton, R., Mooser, G., Pande, H., Lee, T.D. & Shively, J.E. (1987) Proc. Natl. Acad. Sci. USA 84, 920-924]. We discuss a domain structure for CEA based on the CEA sequence data and the NCA exon sequence data. It is likely that this gene family evolved from a common ancestor shared with neural cell adhesion molecule and alpha 1 B-glycoprotein and is perhaps a family within the immunoglobulin superfamily.

Amino Acid Sequence↗
PubMed1987

Magnetic resonance imaging of bone marrow in hairy cell leukemia: correlation with clinical response to alpha-interferon.

Five patients with progressive hairy cell leukemia were treated with recombinant alpha 2-interferon and examined prospectively at 3-month intervals using serial bone marrow biopsies and magnetic resonance (MR) imaging. Pretreatment iliac crest marrow biopsies demonstrated hairy cell infiltration involving 30-90% of marrow cellularity. Concurrent pretreatment coronal images of the proximal femurs and pelvis using MR revealed extensive marrow involvement that varied in distribution from patchy to diffuse. At 6 months, all patients had responded to alpha 2-interferon with improvement in peripheral blood counts and decrease in lymphoid infiltration on marrow biopsy to 15-40%. Six-month follow-up MR scans demonstrated decreasing marrow leukemia infiltration and increasing marrow fat. MR bone marrow imaging appears useful in the initial diagnosis of hairy cell leukemia, for monitoring the response to treatment, and possibly for predicting relapse.

Bone Marrow↗
PubMed1987

The treatment of hairy cell leukemia with alpha 2b-interferon: experience with 27 patients treated more than one year.

Thirty-six patients with progressive hairy cell leukemia were treated with recombinant alpha 2b-interferon injected subcutaneously 2 X 10(6) IU/m2, three times a week. Twenty-seven patients completed 12 months of therapy and were randomized either to receive 6 months of continued interferon or to go off treatment. At the time of randomization, two patients had achieved a complete response, 22 a partial response, and three a minimal response. Three patients have relapsed, one while receiving interferon during the randomization period and two who were off therapy for 6 months. The outpatient regimen of interferon administration was well tolerated, with the principal acute toxicities being fever and an influenza-like syndrome and the major long-term toxicity being mild-moderate fatigue.

Humans↗
PubMed1986

Eradication of disseminated murine leukemia by treatment with high-dose interleukin 2.

Interleukin 2 (IL 2) in high concentration induces lymphocytes to become nonspecifically cytolytic to a wide variety of tumor targets. We evaluated the therapeutic potential of such lymphokine-activated killer (LAK) cells in vivo and high-dose II 2 in vivo against disseminated murine leukemia. To quantitate the potential anti-leukemia effect of LAK cells in vivo, B6 mice were injected i.p. with graded doses of FBL-3 leukemia cells followed by LAK cells. In this Winn-type assay, 1 X 10(7) LAK cells were able to prevent the outgrowth of 1 X 10(2) FBL-3 cells in only 50% of mice and did not prevent the outgrowth of 1 X 10(6) tumor cells. Thus LAK cells, highly cytolytic to FBL-3 in vitro, mediated only a limited anti-tumor effect when applied directly to leukemia cells in vivo. LAK cells used as an adjunct to chemotherapy induced a small but non-curative effect against FBL-3, however. In this circumstance, LAK cells were markedly less effective than were immune spleen cells from mice previously sensitized to FBL-3. To test the anti-leukemia effect of high-dose IL 2 in vivo, B6 mice were inoculated with 5 X 10(6) FBL-3 cells followed by repeated doses of IL 2 at dose levels shown to induce LAK in vivo. "LAK-inducing" IL 2 doses on days 5 to 9 after FBL-3 inoculation, when tumor was disseminated, cured 50% of the mice. Treatment on days 5 to 9 was far more effective than on days 0 to 4, implying that the evolution of a host-tumor interaction was essential for the therapeutic effect of IL 2. Mice cured of FBL-3 by high-dose IL 2 were found to be immune to FBL-3, suggesting that tumor eradication resulted from a collaboration between LAK activity and tumor-specific immunity.

Animals↗
PubMed1986

Cytochrome P-450-catalyzed rearrangement of a peroxyquinol derived from butylated hydroxytoluene. Involvement of radical and cationic intermediates.

The p-peroxyquinol derived from butylated hydroxytoluene, 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone, was degraded by the ferric form of rat liver cytochrome P-450, and the resulting products and their mechanisms of formation were investigated. Quinoxy radical BO. from homolysis of the O-O bond reacted by competing pathways; beta-scission yielded 2,6-di-t-butyl-p-benzoquinone, and rearrangement with ring-expansion produced an oxacycloheptadienone free radical (X(.)). This rearranged radical was stabilized by the captodative effect that facilitated competitive interactions with the P-450 iron-oxo complexes formed during O-O bond scission. Approximately 15% of X(.) was captured by oxygen rebound with a hydroxyl radical from the P-450 complex (FeOH)3+ to form a hemiketal, that led to the ring-contracted product 2,5-di-t-butyl-5-(2'-oxopropyl)-4-oxa-2-cyclopentenone by spontaneous rearrangement. The major fraction of X(.), however, underwent electron transfer oxidation to form the corresponding cation. Hydration of this cation produced the ring-contracted product, and proton elimination (or, alternatively, direct H(.) removal from X(.) led to the product 2,7-di-t-butyl-4-methylene-5-oxacyclohepta-2,6-dienone. The findings indicate that cytochrome P-450 intermediate complexes are mainly responsible for oxidation of X(.). The results complement our previous study with 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone (Thompson, J. A., and Wand, M. D. (1985) J. Biol. Chem. 260, 10637-10644), demonstrating competitive heterolytic and homolytic mechanisms of O-O bond cleavage, and competitive rebound and oxidation processes when a substrate-derived radical interacts with P-450 complexes.

Animals↗
PubMed1986

Echocardiographic left ventricular mass to differentiate chronic hypertension from preeclampsia during pregnancy.

In order to differentiate pregnancy-induced hypertension from chronic systemic hypertension, we measured left ventricular mass for comparison in each trimester of pregnancy in 11 normotensive patients and 14 patients with chronic hypertension and in the third trimester in 10 patients with pregnancy-induced hypertension. The mean left ventricular mass was comparably increased above normal in the patients with chronic hypertension in all three trimesters. In the third trimester in the normotensive women, left ventricular mass (147 +/- 12 gm) was similar to that of the group with pregnancy-induced hypertension (157 +/- 16 gm), whereas the group with chronic hypertension had an elevated left ventricular mass (238 +/- 39 gm) (p less than 0.01). However, three patients with chronic hypertension developed superimposed pregnancy-induced hypertension. We concluded that an elevated left ventricular mass during pregnancy is consistent with underlying chronic hypertension but does not rule out superimposed pregnancy-induced hypertension. A normal left ventricular mass in the third trimester of a hypertensive pregnancy is most consistent with pregnancy-induced hypertension.

Adult↗
PubMed1986

T-lymphocyte analysis in cardiac allograft recipients treated with cyclosporine.

To assess the usefulness of circulating T-lymphocyte analysis in cardiac transplantation, T helper (Th) and T suppressor-cytotoxic (Ts-c) subsets were serially monitored in 33 cardiac allograft recipients treated with cyclosporine. The short-term prognosis of their 47 treated rejection episodes were retrospectively correlated with the changes in T-cell subpopulations. The data indicate three main findings. Reversed Th to Ts-c ratio (less than 1) was associated with a reduced incidence of rejection onset and a benign clinical course after treatment for rejection. Reversed Th:Ts-c ratio caused by antirejection therapy was associated with less chance of recurrence during the rest of hospitalization, regardless of the mode of therapy and irrespective of whether the rejection was primary or recurrent. These changes were mainly mediated by a reduction in T helper cells rather than changes in the T suppressor-cytotoxic subset or total T cells. Titration of antirejection therapy based on these T-cell dynamics may reduce either overtreatment or undertreatment. A prospective randomized study seems warranted to evaluate this approach as an alternative to a predetermined antirejection protocol.

Cyclosporins↗
PubMed1986

Potential uses of interleukin 2 in cancer therapy.

Interleukin 2 (IL 2) has several potential uses in cancer therapy including: the augmentation of specific T cell mediated anti-tumor immunity and the activation of non-specific cytolytic effector cells, termed lymphokine-activated killer (LAK) cells. The current review will present data from our laboratory demonstrating in animal models the feasibility of both potential approaches. Studies to be reviewed show that: IL 2 can induce the proliferation and expansion in number of tumor-reactive T cells in vitro; T cells grown in culture in IL 2 can be effective reagents in vivo for specific tumor therapy; the administration of exogenous IL 2 can induce the growth and augment the function of cultured T cells in vivo; however, as a corollary, T cells cultured long-term in vivo with IL 2 are functionally limited in vivo without the administration of exogenous IL 2 in vivo; by contrast, T cells grown in vitro with specific antigen, as opposed to IL 2, as the major stimulus for proliferation are able to proliferate rapidly in vivo, distribute widely in host lymphoid organs, and mediate therapy of disseminated murine leukemia; importantly, such antigen-driven long-term cultured T cells can survive long-term in vivo and provide specific immunologic memory, and, the administration of low-dose IL 2 in vivo can induce the growth of antigen-driven long-term cultured T cells in vivo and thereby increase the number of functional memory T cells; the culture of lymphoid cells in high concentrations of IL 2 can induce LAK cells in vitro capable of lysing leukemia in vitro; LAK cells generated in vitro can mediate a small but detectable anti-tumor effect in vivo against disseminated leukemia as an adjunct to chemotherapy; and, high-dose IL 2 administered in vivo can activate LAK cells in vivo and cure disseminated murine leukemia. Therefore, it is highly likely that IL 2 can become an effective reagent for the therapy of human cancer.

Animals↗
PubMed1986

Role of sympathetic nerves in the metabolism of exogenous noradrenaline in rabbit gingival tissue and ear artery.

Uptake and metabolism of 3H-noradrenaline 0.18 mumol/l was examined in rabbit gingival slices and ear artery segments. The tissues were incubated with the 3H-amine for 30 min. The artery accumulated approximately ten times more of the 3H-amine and generated four times more 3H-metabolites than the gingiva. In both tissues, chronic sympathetic denervation resulted in marked decreases in 3H-noradrenaline accumulation and deamination. An inhibitor of sympathetic neuronal uptake, cocaine 30 mumol/l, strongly inhibited the firmly-bound component of 3H-noradrenaline accumulation by the tissues and strongly decreased the accumulation of deaminated metabolites in the incubating medium. It is concluded that the sympathetic nerve terminals play an important role in the accumulation and deamination of noradrenaline in the gingiva and in the artery. Chronic sympathetic denervation resulted in increased 3H-normetanephrine (NMN) formation by the gingiva and the artery, indicating that in both tissues the noradrenaline was O-methylated at sites extraneuronal to the sympathetic nerves. Differences between the effects of cocaine in the gingiva and artery, with respect to 3H-NMN accumulation in the incubating medium, are interpreted as evidence that in the gingiva, but not in the artery, cocaine inhibits extraneuronal O-methylation, as well as neuronal uptake, of noradrenaline.

Animals↗