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D L Nelson

Publications and source records attributed to D L Nelson.

At least 379 records · Page 21Linked to original sources
PubMed1987

Elevated serum levels of soluble interleukin-2 receptors in active pulmonary sarcoidosis: relative specificity and association with hypercalcemia.

We have previously reported serum elevations of the soluble form of the interleukin-2 receptor (IL-2R), a marker of T-cell activation, in sarcoidosis. In the present study, an enzyme-linked immunosorbent assay for soluble IL-2R was employed to compare sera from normal controls with those from patients with active sarcoidosis or idiopathic pulmonary fibrosis (IPF). Sera from patients with active sarcoidosis and parenchymal lung disease (radiographic Stages II or III) had geometric mean values for soluble IL-2R of 1975 units/ml compared to 640 units/ml for normal controls (p less than 0.001, Student's t-test). By contrast, soluble IL-2R levels were lower (989 units/ml, p less than 0.05 compared to normals) in patients with active sarcoidosis but no radiographic evidence for parenchymal disease (Stages 0 or I). Soluble IL-2R levels were not elevated in patients with inactive sarcoidosis. Three of the 4 sarcoidosis patients with the highest levels of soluble IL-2R also manifested hypercalcemia. While levels of soluble IL-2R were elevated for the group of patients with IPF (1171 units/ml, p less than 0.05 compared to normals), the striking elevations of soluble IL-2R noted in active sarcoidosis were not seen and there was greater overlap with normal values. We conclude that marked serum elevations of soluble IL-2R are more suggestive of active pulmonary sarcoidosis than IPF.

Adrenal Cortex Hormones↗
PubMed1987

Analysis of CD3 antigen expression in patients with ataxia-telangiectasia.

The expression of CD3 molecules by the lymphocytes of five patients with ataxia-telangiectasia was examined using the murine monoclonal antibody OKT3. By immunofluorescent staining, fewer of the patients' peripheral blood mononuclear cells and purified T cells expressed CD3 compared with normals. The proliferative response of the patients' cells to OKT3 was also less than normal. However, the mononuclear cells from all five patients produced IL-2 after OKT3 stimulation; in four patients IL-2 was normal, while one patient produced greater than normal levels. While the expression of cellular IL-2 receptors and the release of these receptors into culture supernatants was generally less in ataxia-telangiectasia patients, the levels of receptor expression were not significantly less than normal. As analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis, the CD3 molecules from ataxia-telangiectasia patients' lymphocytes were no different from those of normal individuals. These results suggest that patients with ataxia-telangiectasia have structurally normal CD3 molecules which may be used to activate cells normally for some but not all T cell functions.

Adolescent↗
PubMed1986

The released interleukin 2 receptor binds interleukin 2 efficiently.

The released interleukin 2 receptor (IL 2R) molecule was characterized in order to clarify its biochemical structure and to determine its functional capacity. Enzymatic digestions demonstrated that the released IL 2R, like the cell surface IL 2R, is a complex glycoprotein, modified by the addition of both N- and O-linked carbohydrates and sialic acid residues. It has a peptide backbone that is approximately 10 Kd smaller than that of its membrane-associated counterpart. Affinity chromatography demonstrated that released IL 2R from either an HTLV-I-positive T cell line (HUT-102) or PHA-activated normal peripheral lymphocytes binds efficiently to purified recombinant IL 2. Furthermore, the interaction between the growth factor and the released receptor does not appear to require any accessory molecules. These observations suggest a potentially significant role for the released IL 2R in the regulation of IL 2-dependent lymphocyte functions.

Carbohydrates↗
PubMed1986

Characterization of Ca2+- or Mg2+-ATPase of the excitable ciliary membrane from Paramecium tetraurelia: comparison with a soluble Ca2+-dependent ATPase.

We have characterized divalent-cation-stimulated nucleoside triphosphate hydrolase activity of the excitable ciliary membrane and compared it with a soluble Ca2+-ATPase released upon deciliation of Paramecium. The membrane-bound activity is strongly dependent on a divalent cation; calcium stimulates the basal activity of this enzyme at least 10-fold; magnesium and manganese stimulate less well, and strontium and barium, although less effective, also give measurable stimulation. This membrane-bound activity prefers ATP and GTP as substrates but also hydrolyzes UTP and CTP at measurable rates. The maximum velocity at saturating ATP concentrations and optimal calcium concentrations is 0.3 mumol/min per mg. The pH optimum for the membrane-bound activity is broad and centers around pH 7. From the temperature dependence of ATP hydrolysis, we calculate activation energies of 14 and 11 kcal/mol for the Ca2+- and Mg2+-stimulated activities, respectively. The Arrhenius plot is linear over the temperature range of 4 to 25 degrees C. The membrane ATPase is relatively insensitive to ouabain, oligomycin, N,N'-dicyclohexylcarbodiimide, vanadate, Ruthenium red and two calmodulin antagonists. Polyclonal antisera raised against the purified soluble ATPase from the deciliation supernatant show low reactivity with the membrane-bound ATPase. We conclude from the comparison of properties of the two activities that the ciliary membrane-bound ATPase is distinct from the soluble ATPase released by deciliation.

Animals↗
PubMed1986

Antigen-specific murine T cell clones produce soluble interleukin 2 receptor on stimulation with specific antigens.

In this study, we used monoclonal antibodies to the murine IL 2 receptor (IL 2R) termed 3C7 and 7D4, which bind to different epitopes on the murine IL 2R, to develop an ELISA to measure soluble murine IL 2R. Surprisingly, stimulated murine spleen cells not only expressed cell-associated IL 2R, but also produced a considerable level of cell free IL 2R in the culture supernatant fluid. To assess the fine specificity of this response, myoglobin-immune murine T cell clones were stimulated with appropriate or inappropriate antigen and syngeneic or allogeneic presenting cells. Proliferation, measured by [3H] thymidine incorporation, and levels of soluble IL 2R were determined at day 4. The production of soluble IL 2R displayed the same epitope fine specificity, genetic restriction, and antigen dose-response as the proliferative response. Indeed, in some cases there was sharper discrimination of epitope specificity and genetic restriction with the soluble IL 2R levels. There was also reproducible clone-to-clone variation in the amount of soluble receptor produced in response to antigen among 12 T cell clones and lines tested. In time course experiments, proliferation was greatest at day 3, whereas soluble IL 2R levels continued to rise in subsequent days. To our knowledge, this is the first demonstration of release or secretion of soluble IL 2R by murine T cells, and the first demonstration of the fine specificity and genetic restriction of the induction of soluble IL 2R by specific antigen.

Animals↗
PubMed1986

A secreted form of the human interleukin 2 receptor encoded by an "anchor minus" cDNA.

The DNA sequence encoding all of the putative intracytoplasmic domain and most of the trans-membrane domain of the human IL 2 receptor was deleted from a full length receptor cDNA. After expression in mouse L cells, the resultant "anchor minus" cDNA was found to direct the synthesis of a secreted rather than membrane-associated form of the IL 2 receptor. The secreted receptor protein (44,000 to 46,000 Mr) retained the capacity to bind both IL 2 and the monoclonal anti-Tac antibody, as evidenced by retention on IL 2 and anti-Tac affinity columns, inhibition of [3H]-anti-Tac binding to HUT 102B2 cells, and partial inhibition of IL 2-induced CTLL proliferation. Removal of these domains from the IL 2 receptor did not alter the posttranslational processing or rate of export of the truncated receptor protein. These data confirm the proposed membrane orientation of the IL 2 receptor (NH2 terminus out, COOH terminus in) and underscore the anchoring function of this carboxy terminal receptor segment. The availability of such anchor minus receptor cDNA constructs may facilitate purification of large quantities of receptor protein for further analysis of receptor structure, valency, and localization of the IL 2 binding site(s).

Amino Acid Sequence↗
PubMed1986

Regulation of ciliary motility by membrane potential in Paramecium: a role for cyclic AMP.

The membrane potential of Paramecium controls the frequency and direction of the ciliary beat, thus determining the cell's swimming behavior. Stimuli that hyperpolarize the membrane potential increase the ciliary beat frequency and therefore increase forward swimming speed. We have observed that 1) drugs that elevate intracellular cyclic AMP increased swimming speed 2-3-fold, 2) hyperpolarizing the membrane potential by manipulation of extracellular cations (e.g., K+) induced both a transient increase in, and a higher sustained level of cyclic AMP compared to the control, and 3) the swimming speed of detergent-permeabilized cells in MgATP was stimulated 2-fold by the addition of cyclic AMP. Our results suggest that the membrane potential can regulate intracellular cAMP in Paramecium and that control of swimming speed by membrane potential may in part be mediated by cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1986

An analysis of the cellular requirements for the production of soluble interleukin-2 receptors in vitro.

Following activation in vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL-2R) and also release soluble IL-2R into culture supernatants. The present studies were undertaken to define which normal cells were responsible for the release of soluble IL-2R in vitro. Both cell-associated and soluble IL-2R were quantitatively measured with a "sandwich" enzyme-linked immunoassay employing two monoclonal antibodies. PBMC were separated into populations of surface immunoglobulin-negative cells (T cells and monocytes) and surface immunoglobulin-positive cells (B cells and monocytes), and the T-cell population was further separated into OKT4-positive (OKT4+) cells and OKT4-negative (OKT4-) cells. Following activation with phytohemagglutinin, pokeweed mitogen, and the monoclonal antibody OKT3, large amounts of soluble IL-2R were released by PBMC, unseparated T cells, OKT4+ T cells, and OKT4- T cells. The population containing B cells and monocytes made small but readily detectable amounts of soluble IL-2R when stimulated with these T-cell mitogens; likely the result of contaminating T cells in the population. However, when highly purified B cells were stimulated with Staphylococcus aureus Cowan and recombinant IL-2, they also released small amounts of soluble IL-2R. The release of soluble IL-2R by T cells appeared monocyte dependent when OKT3, but not phytohemagglutinin, was employed for activation, and monocytes themselves released no detectable IL-2R under the conditions employed. These studies define the cellular requirements for the release of soluble IL-2R in vitro and demonstrate that such receptors are released by B cells, T cells, and both OKT4+ and OKT4- T-cell subsets.

B-Lymphocytes↗
PubMed1986

Gene replacement therapy for inborn errors of purine metabolism.

Effective retroviral vectors carrying the human HPRT and ADA genes have been described. Initial characterization of the retroviral gene transfer system using the HPRT vector allowed the delineation of several parameters important in viral titer, expression, and stability. Using the HPRT and ADA vectors, we have initiated experiments designed to insert these human genes into various tissues of the mouse and have demonstrated expression of both transduced genes in mouse bone marrow cells. Further work with these and other vector constructions is underway in the hope that this technique may allow safe and effective treatment of ADA and HPRT deficiencies, paving the way for treatments of other inborn errors of metabolism through somatic gene replacement therapy.

Adenosine Deaminase↗
PubMed1986

Serum immunoglobulin G antibody subclass responses to respiratory syncytial virus F and G glycoproteins after primary infection.

Because the immunoglobulin G (IgG) response to carbohydrate antigens is typically from the IgG2 subclass and the IgG response to protein antigens is typically from the IgG1 and sometimes the IgG3 subclass, two respiratory syncytial virus glycoproteins, F and G, which differ substantially in the amount of glycosylation, were used as antigens in an enzyme-linked immunosorbent assay to determine IgG subclass responses in 20 infants and young children with naturally acquired respiratory syncytial virus infection. Both glycoproteins elicited primarily IgG1 and IgG3 responses, indicating that the protein moieties of the glycoproteins may be immunodominant in this age group.

Antigens, Viral↗
PubMed1986

Eucaryotic chromosome transfer: production of a murine-specific cosmid library from a neor-linked fragment of murine chromosome 17.

We recently developed a procedure for the molecular analysis of specific mammalian chromosomal fragments. This procedure allows for the transfer of contiguous chromosomal fragments, varying in size from a fraction to several centimorgans in length, from the donor cell of one species into a recipient cell of a different species. Specifically, we inserted a neor gene, encoded by a recombinant retrovirus, into the murine major histocompatibility complex (MHC). Metaphase chromosome transfers with this neor-tagged chromosome into recipient hamster, primate, and canine fibroblasts produced a panel of primary neor transferents, each containing a portion of, or all of, the murine MHC. A cosmid library was made from one such transferent, CHMD(D)B1. Cosmid clones were divided, using species-specific repeat probes, into those containing murine (donor) DNA sequences and those containing sequences derived from the recipient cell. The murine-specific cosmids were clustered into overlapping DNA segments by restriction enzyme digest analysis of the cosmid DNAs coupled with Southern blot analysis with, as probes, murine-specific repeat sequences and nick-translated murine genomic DNA. These cosmid clusters were analyzed for their position within or outside of the MHC, using recombinant mouse strains, and for the presence within them of known murine MHC genes.

Animals↗
PubMed1986

The production of soluble and cellular interleukin-2 receptors by cord blood mononuclear cells following in vitro activation.

Cord blood mononuclear cells (CBMC) were investigated for their capacity to generate both cellular and soluble, supernatant interleukin-2 receptors (IL-2R) following cellular activation in vitro. Soluble IL-2R were measured in cell-free supernatants and in detergent-solubilized cell extracts with a "sandwich" enzyme-linked immunosorbent assay. CBMC and adult peripheral blood mononuclear cells were activated with phytohemagglutinin or the murine monoclonal antibody OKT3. CBMC and adult peripheral blood mononuclear cells generated cellular and soluble IL-2R in response to both activators. Peak values for supernatant IL-2R were observed on day 7, while peak values of cell-associated IL-2R occurred on day 5, followed by a decline on day 7. With the exception of supernatant IL-2R production induced by OKT3 stimulation, CBMC produced IL-2R in amounts comparable to adult mononuclear cells. Cord blood plasma also contained amounts of IL-2R comparable to that found in adult sera/plasma. Thus, CBMC appear largely immunocompetent with regard to the expression of IL-2R.

Adult↗
PubMed1986

Affective meanings of life review through activities and discussion.

Life review is often incorporated into therapy with the elderly in the form of verbal or activity groups. This study compares the affective meanings of life review through activities with life review through discussion. Twenty-two women between 60 and 85 years of age participated in one of two activity groups or in one of two discussion groups. Individuals in the activity groups expressed a positive event or accomplishment of their past by drawing and making collages. Then they discussed their finished products. In the discussion groups, subjects took turns describing a positive life event to other group members. Afterward, all subjects rated how they felt about themselves during the group using Osgood's semantic differential scale. Analyses of variance for nested designs were completed on the scale's evaluation, power, and action factors of affective meaning. They revealed significant differences between the groups within the activity and discussion conditions. However, differences between the activity and discussion conditions were not significant. In terms of clinical practice, life review was perceived as good, powerful, and active by this sample, and practitioners are urged to consider the importance of group-to-group differences in responses to activities.

Aged↗
PubMed1986

The human interleukin-2 receptor: normal and abnormal expression in T cells and in leukemias induced by the human T-lymphotropic retroviruses.

The human receptor for interleukin-2 (T-cell growth factor) plays a critical role in the growth of T cells and is required for full expression of the normal immune response. Through hybridoma and recombinant DNA techniques, the interleukin-2 receptor protein has been biochemically characterized and purified; full-length copies of its complementary DNA have been molecularly cloned, sequenced, and expressed in eukaryotic cells; and the receptor gene has been characterized. Transient expression of the interleukin-2 receptor gene occurs during normal T-cell activation, and high- and low-affinity forms of the membrane receptor exist. A naturally occurring, soluble receptor has also been isolated, and its levels in serum correlate with the activity of various diseases. Deregulation of interleukin-2 receptor expression occurs in T-cell leukemias produced by the human T-lymphotropic retroviruses types I and II (HTLV-I and -II) and has been causally linked to the action of the trans-activator (taf) gene of these viruses. Monoclonal antibodies specific for the interleukin-2 receptor are being evaluated in the treatment of HTLV-I-induced leukemias and other conditions involving the inappropriate function of activated T cells.

Amino Acid Sequence↗
PubMed1986

Dissociation constants of serotonin agonists in the canine basilar artery correlate to Ki values at the 5-HT1A binding site.

Attempts to correlate 5-hydroxytryptamine (5-HT) binding sites and the receptor mediating 5-HT-induced contractions in the canine basilar artery (CBA) have led to discrepant claims, particularly regarding the potencies of antagonists (which appear to act noncompetitively) in the CBA. In the classical theoretical model for noncompetitive antagonism, the antagonist does not inhibit agonist binding. Thus attempts to correlate noncompetitive antagonist pD2' values with binding measurements are inconsistent with this model and are of questionable significance. Only agonist dissociation constants (KA values) were measured in the CBA (by the irreversible antagonist method) and correlated to binding data. Logs of these KA values did not correlate with log Ki values for the inhibition of binding of the 5-HT2 ligand [3H] ketanserin (r = 0.2253, P greater than .05) or log IC50 values for inhibition of [3H]5-HT binding (r = 0.5732, P greater than 0.05), which labels both 5-HT1A and 5-HT1B sites. A correlation was observed between the CBA values and log Ki values for the 5-HT1A binding site subtype (r = 0.9456, P less than .01). The agonist ED50 and KA values were in most cases essentially identical, which suggests that in this tissue there are no spare receptors for 5-HT. Also, identical values were obtained when apparent noncompetitive antagonists were used in a manner analogous to the irreversible antagonist method to determine KA. These findings suggest the hypothesis that the apparent noncompetitive antagonism may be produced by slow dissociation of the antagonist-receptor complex, producing a pseudoirreversible action which is unmasked due to the lack of spare receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Composition and dietary effects of the fish oil from "mandi" (Pinelodus clarias).

A study was carried out to determine the chemical composition and dietary effects of the oil from "mandi" (Pimelodus clarias). Findings revealed that it had a low proportion of essential C18:2 fatty acids and a high percentage of oleic acid (20.93%), as well as polyunsaturated fatty acids with more than 18 carbon atoms. Of the long-chain fatty acids, C22:6 was present in the highest percentage (1.94%). When rats were fed a diet the lipid source of which was the oil of mandi, they showed a reduced growth rate as compared to animals receiving the control diet (corn oil). The fatty acid composition of the liver and heart of rats from the experimental group was modified. The greatest variation occurred in the percentage of C22:6 in the heart muscle, wherein a five-fold increase was observed. Reduction of growth and alteration in the polyunsaturated fatty acids levels may be due to a deficiency in C18:2-w6, or to a possible imbalance between C18:2-w6 and C18:3-w3.

Animals↗