Myasthenia gravis after interferon-alpha treatment.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
J Faust
Publications and source records attributed to J Faust.
Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice.
Megakaryocyte growth and development factor (MGDF) is a potent inducer of megakaryopoiesis in vitro and thrombopoiesis in vivo. The effects of MGDF appear to be lineage-selective, making this cytokine an ideal candidate for use in alleviating clinically relevant thrombocytopenias. This report describes a murine model of life-threatening thrombocytopenia that results from the combination treatment of carboplatin and sublethal irradiation. Mortality of this regimen is 94% and is associated with widespread internal bleeding. The daily administration of pegylated recombinant human MGDF (PEG-rMGDF) significantly reduced mortality (to < 15%) and ameliorated the depth and duration of thrombocytopenia. The severity of leucopenia and anemia was also reduced, although it was not clear whether these effects were direct. Platelets generated in response to PEG-rMGDF were morphologically indistinguishable from normal platelets. PEG-rMGDF administered in combination with murine granulocyte colony-stimulating factor completely prevented mortality and further reduced leukopenia and thrombocytopenia. These data support the concept that PEG-rMGDF may be useful to treat iatrogenic thrombocytopenias.
Animals↗
Inhibition of dipeptidyl peptidase IV (DP IV) by anti-DP IV antibodies and non-substrate X-X-Pro- oligopeptides ascertained by capillary electrophoresis.
Dipeptidyl peptidase IV (DP IV)-catalyzed hydrolysis of the NH2-X-Pro-containing N-terminal dodecapeptide of IL-2 was studied using free zone capillary electrophoresis as an alternative peptidase assay. In contrast to the conventional DP IV substrate glycyl-prolyl-p-nitroanilide (Gly-Pro-pNA), the hydrolysis of this peptide by DP IV was found to be significantly inhibited by anti-DP IV antibodies. Inhibition of DP IV was also observed with a number of non-substrate oligopeptides containing an N-terminal X-X-Pro- structure, including the HIV Tat protein. For Met-IL-2(1-6), we determined a competitive inhibition with an inhibition constant of ca. 100 microM.
Amino Acid Sequence↗
Inhibitors of dipeptidyl peptidase IV (DP IV, CD26) specifically suppress proliferation and modulate cytokine production of strongly CD26 expressing U937 cells.
Various studies from different laboratories have shown that the membrane ectoenzyme dipeptidyl peptidase IV (DP IV, CD26) expressed in T and NK cells is involved in the regulation of DNA synthesis and cytokine production. In this paper, we performed a biochemical and functional characterization of dipeptidyl peptidase IV on the human histiocytic lymphoma cell line U937. Using U937 clones expressing low to high levels of membrane localized CD26, we found that the synthetic reversible inhibitors of DP IV, Lys-[Z(NO2)]-thiazolidide and Lys-[Z(NO2)]-piperidide, have different effects on all functions. In U937-H cells that strongly express high levels of CD26, DP IV inhibitors were shown to suppress DNA synthesis and production of IL-1 beta, but stimulate the secretion of the IL-1 receptor antagonist (IL-1RA) and of TNF-alpha. In contrast, both inhibitors did not influence the cytokine production and DNA synthesis in U937-L cells exhibiting low level CD26 expression. These data support the hypothesis that CD26 plays a crucial role in proliferation and cytokine production, not only in T cells, but also in other cell systems, and that enzymatic activity is essential for its function.
Blotting, Western↗
Dipeptidyl peptidase IV (CD 26) and aminopeptidase N (CD 13) catalyzed hydrolysis of cytokines and peptides with N-terminal cytokine sequences.
A number of natural cytokines are characterized as having dipeptidyl peptidase (DP) IV susceptible N-terminal peptide sequences. Here we demonstrate that oligopeptides with sequences analogous to the N-terminal part of human IL-1 beta, IL-2, TNF-beta and murine IL-6 were hydrolyzed by purified DP IV and aminopeptidase N (AP-N). The rate of DP IV-catalyzed hydrolysis of these peptides was negatively correlated with their chain length. In contrast to these results, no degradation was found under our conditions for the intact recombinant cytokines, IL-1 alpha, IL-1 beta, IL-2, G-CSF and for natural IL-2, independent of whether DP IV and AP-N were used separately or in combination.
Amino Acid Sequence↗
Characterization of a human monocyte antigen, B148.4, regulated during cell differentiation and activation.
We analyzed the phenotypic changes associated with monocyte activation and differentiation using a newly developed monoclonal antibody (B148.4). Among peripheral blood leukocytes, the antigen recognized by this antibody is expressed on monocytes and granulocytes at high and low density, respectively. Antigen expression is lost during in vitro differentiation of monocytes and is absent on tissue macrophages, indicating that expression of this antigen is related to monocyte differentiation. Only 1 alpha,25-dihydroxyvitamin D3 and phorbol diesters, of several inducers tested, up-regulate B148.4 antigen expression on cells (monocytes and certain myeloid cell lines) that constitutively bear the antigen, without, however, allowing its maintenance during monocytic differentiation or inducing it on negative cells. By immunoprecipitation from B148.4+ U937 cells, the antigen is a complex of a major 116-kd and two minor 38- and 46-kd molecules. Analysis of eight different tissues reveals that the antigen is shared with endothelial cells. Biochemical characteristics, cellular distribution, and expression pattern on monocytes, myeloid cell lines, and AML cells upon culture with different stimuli indicate that B148.4 is a novel monocyte differentiation antigen.
Antibodies, Monoclonal↗
Same-day surgery preparation: reduction of pediatric patient arousal and distress through participant modeling.
Twenty-six children (mean age = 5.5 years) were exposed to one of three surgery preparatory conditions: participant modeling alone (n = 9), participant modeling with mother (n = 8), and standard procedure control (n = 9). Children exposed to the modeling slide-tape without their mothers had significant reductions in physiological arousal after the slide-tape presentation, unlike children viewing the tape with their mothers and children exposed to the control condition. Both participant modeling groups exhibited significantly fewer distressful behaviors during recovery (postsurgery) than did control group children. Results are discussed with respect to previous medical preparation research. Implications of these findings concerning clinical application and future research are addressed.
Ambulatory Surgical Procedures↗
Dipeptidyl peptidase IV in the immune system. Effects of specific enzyme inhibitors on activity of dipeptidyl peptidase IV and proliferation of human lymphocytes.
Dipeptidyl peptidase IV (DP IV) is a membrane peptidase playing a significant role in the process of activation and proliferation of human thymus-derived lymphocytes. This conclusion is drawn from (1) the induction of this enzyme on mitogen-activated T lymphocytes (cf. Schön, E. & Ansorge, S. (1990) Biol. Chem. Hoppe-Seyler 371, 699-705) and (2) the impairment of different functions of activated T cells in the presence of specific inhibitors and antibodies against DP IV (Schön, E. & al. (1987) Eur. J. Immunol 17, 1821-1826). This paper is aimed at testing new active site-specific peptide inhibitors for their efficiency as inhibitors of lymphocyte DP IV and DNA synthesis of mitogen-stimulated lymphocytes. These inhibitors comprise (i) diacylhydroxylamine derivatives of Xaa-Pro or Xaa-Ala peptides, (ii) different oligopeptides with N-terminal Xaa-Pro-sequences, and (iii) amino-acid amides of the pyrrolidide and the thiazolidide type. The thiazolidides of epsilon-(4-nitrobenzyloxycarbonyl)-L-lysine and of L-isoleucine as well as Ala-Pro-nitrobenzoylhydroxylamine are the most effective inhibitors in both test systems, yielding half-maximal inhibitory concentrations in the micromolar range. Cell viability was not impaired in this effective concentration range. Other inhibitors of DP IV are one to two orders of magnitude less efficient in the suppression of lymphocyte proliferation.
Binding Sites↗
Extended investigation of the substrate specificity of dipeptidyl peptidase IV from pig kidney.
The substrate specificity of dipeptidyl peptidase IV (dipeptidyl peptide hydrolase, EC 3.4.14.5) from pig kidney was investigated, using a series of substrates, in which the amino-acid residue in position P1, a structural derivative of proline, was altered with respect to ring size and substituents. It was demonstrated that dipeptidyl peptidase IV hydrolyses substrates of the type Ala-X-pNA, where X is proline (Pro), (R)-thiazolidine-4-carboxylic acid (Thz), (S)-pipecolic acid (Pip), (S)-oxazolidine-4-carboxylic acid (Oxa), or (S)-azetidine-2-carboxylic acid (Aze). The ring size and ring structure of the residue in the P1 position influence the rate of enzyme-catalysed hydrolysis of the substrate. The highest kcat value (814 s-1) was found for Ala-Aze-pNA. In contrast, the kcat value for Ala-Pro-pNA is nearly 55 s-1. With all substrates of this series, the rate-limiting step of the hydrolysis by dipeptidyl peptidase IV is the deacylation reaction. Compounds of substrate-like structure, in which the P2 residue has an R-configuration, are not hydrolysed by dipeptidyl peptidase IV.
Animals↗
Expression and function of gamma delta- and alpha beta-T cell receptor heterodimers on human somatic T cell hybrids.
T cell somatic hybrids were obtained by fusion of human tetanus toxoid-specific gamma + delta + T cells and a T cell lymphoma cell line that expresses beta-chain but not alpha-chain transcripts. The hybrids simultaneously and independently expressed alpha beta and gamma delta TCR heterodimers on the cell surface without any significant differences in the level of expression. No heterodimers containing alpha delta-, beta delta-, beta gamma-, and alpha gamma-chains were transported to the cell membrane, indicating a chain specificity in dimer formation. The presence of productively rearranged gamma- and delta-alleles in the hybrid cells and immunoprecipitation of an identical type of TCR-gamma delta from both hybrid and parental gamma + delta + T cells suggests that TCR-gamma delta on the hybrid cells derives from gamma + delta + T cells. Anti-TCR (TCS-delta 1 or WT31) and anti-CD3 antibodies induced a rapid increase in [Ca2+]i in the double-positive hybrids and their variants positive for either the alpha beta or gamma delta complex. Double positive hybrid cells were refractory to stimulation with anti-CD3 antibody after pretreatment with a mixture of anti-TCR-gamma delta and anti-TCR-alpha beta antibodies but not with either antibody alone indicating the functional independence of the two receptors. However, only gamma delta heterodimer receptor was able to respond to tetanus toxoid presented on autologous APC as measured by induction of the p55 chain of IL-2R on stimulated cells.
Alleles↗
Psychological consultation in a children's hospital: an evaluation of services.
Explore the source record for details and available documents.
Hospitals, Pediatric↗
Expression of specific high capacity mevalonate transport in a Chinese hamster cell variant.
A variant of a low density lipoprotein receptor-negative Chinese hamster ovary (CHO) cell mutant was isolated using a nutritional selection called MeLoCo. The variant, designated met-18b-2, internalized and metabolized mevalonate at rates 10-40 times greater than the progenitor cells from which they were derived. The extent of incorporation of radioactivity from [3H]mevalonate into steroidal and nonsteroidal mevalonate derivatives, including modified proteins, was much greater in met-18b-2 cells than in their progenitors. Much of the internalized [3H]mevalonate was converted to nonpolar lipids. Unlike wild type CHO cells or the receptor-negative progenitors, met-18b-2 cells were killed by high concentrations of mevalonate (greater than 6 mM) in the culture medium. Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity and cholesterol esterification was dramatically more sensitive to mevalonate in met-18b-2 cells than in progenitor cells. In cell extracts, both the rates of conversion of [3H]mevalonate to cholesterol and mevalonate kinase activities were similar for met-18b-2 and progenitor cells. In contrast to progenitor cells, met-18b-2 cells internalized [3H]mevalonate with high capacity (Km approximately 0.3 mM) kinetics. The increased uptake of [3H]mevalonate was temperature dependent and highly specific. These results suggest that met-18b-2 cells express a mevalonate transport activity that is not normally expressed by CHO cells. This activity may be due to a specific mevalonate transporter that is differentially expressed in specialized tissues. Because intracellular mevalonate in met-18b-2 cells can be labeled to high specific activity, these cells should prove very useful in further characterizing the structures of mevalonate derivatives and their metabolism.
Animals↗
Physical and psychological health of young adolescents: the relationship to gender and marital conflict.
Explore the source record for details and available documents.
Adolescent↗
Preferential proliferation of natural killer cells among peripheral blood mononuclear cells cocultured with B lymphoblastoid cell lines.
In this report, we show that in vitro stimulation of human peripheral blood mononuclear cells (PBMC) with B lymphoblastoid cell lines results in preferential proliferation of cells with the phenotypic, genotypic and functional characteristics of natural killer (NK) cells. This culture system offers a useful method for obtaining large numbers of pure NK cells on which biochemical, molecular and functional studies can be performed. Using this culture system, and average 25-fold increase in NK cell number is obtained, whereas the number of T cells is increased only 3-fold. At early times, activation of both T and NK cells occurs, as detected by the presence of activation antigens on both cell types, but actual proliferation of NK cells starts on day 6 of culture. Elimination of CD3(+)/CD5(+) T cells from the cultured cells gives homogeneous preparations of large numbers of CD16(+)/NKH-1(+) cells that have the morphology of large granular lymphocytes, are powerful effectors of both spontaneous and antibody-dependent cell-mediated cytotoxicity, and rapidly proliferate in the presence of recombinant interleukin 2 (rIL-2). As fresh NK cells, NK cell-enriched preparations from 10-day cultures of Daudi-stimulated PBMC do not show rearrangement of the gene for the beta-chain of the T cell antigen receptor; the 1.3-kb functional transcript of the beta-chain gene was not expressed in NK cells, but the 1.0-kb truncated transcript was present in all preparations. Our data indicate that proliferation of both T and NK cells is dependent upon IL-2 production in the culture, because an anti-IL-2 antiserum completely suppresses proliferation. Because T cells, and in particular CD4(+) T cells, are required for preferential proliferation of NK cells, the NK cell stimulation induced by the B cell line is probably in part indirect, and due to induction of IL-2 production by allogeneic stimulation of CD4(+) cells. However, the B cell lines also need to interact directly with NK cells because neither allogeneic PBMC nor high doses of rIL-2 are sufficient to induce preferential proliferation of NK cells.
Antibodies, Monoclonal↗
Parent perceptions and parent-child interactions in clinic-referred children: a preliminary investigation of the effects of maternal depressive moods.
Explore the source record for details and available documents.
Child↗
Effects of maternal nicotine injections on brain development in the rat: ornithine decarboxylase activity, nucleic acids and proteins in discrete brain regions.
Fetal exposure to nicotine via maternal cigarette smoking produces intrauterine growth retardation and postnatal behavioral abnormalities. In this study, biochemical characteristics of brain development were compared in normal rats and in rats whose mothers received chronic nicotine injections throughout pregnancy. Nicotine exposure produced a persistent elevation of fetal ornithine decarboxylase activity preferentially in brain; in keeping with this selectivity, there was no evidence of the sparing of brain growth which ordinarily accompanies non-specific toxic insult. After birth, DNA synthesis was suppressed throughout the brain and there was a subsequent rebound during the phase of "catch-up" growth. Evidence was also obtained for regional selectivity of the adverse effects of maternal nicotine injections: the effects on DNA synthesis and levels were most profound in cerebellum (a region which matures postnatally) and growth-impairment was least evident in midbrain & brainstem, an early-maturing region. The maternal nicotine group also displayed desynchronization of the ontogenetic patterns of DNA, RNA and proteins in every brain region. These data indicate that maternally-injected nicotine compromises early biochemical events which delineate brain cell replication and differentiation; these alterations are eventually translated into abnormalities in development of specific brain regions.
Animals↗
Ontogeny of neutrophil chemotaxis in fetal lambs.
Ontogeny of neutrophil chemotactic response using endotoxin activated adult sheep plasma as a source of complement derived chemotactic factor was examined in fetal lambs of gestational age 120-150 days. (Gestational period in sheep is approximately 150 days.) Neutrophils from fetal lambs of gestational age 120-130 days failed to respond to this chemotactic factor whereas neutrophils from fetal lambs above 131 days of gestational age responded at levels comparable to adult values. Examination of neutrophil chemotaxis in older fetuses using a different chemotactic factor derived from mitogen stimulated adult mononuclear cells revealed a selective failure of fetal neutrophils to respond to lymphocyte-derived chemotactic factor in the presence of a normal response to complement derived chemotactic factor. Among prematurely delivered twin fetuses alterations in comparison with the first twin or age-matched controls in peripheral neutrophil count (increase) and in chemotaxis (increase or decrease) were noted in second of twins delivered greater than or equal to 20 min after the first lamb, suggesting an extreme sensitivity of neutrophil functions to a variety of influences, similar to that seen in humans.
Animals↗
Differentiation and activation phenotypes of lung T lymphocytes differ from those of circulating T lymphocytes.
We used dual laser two-color flow cytometry to compare the expression of surface markers associated with activation and with differentiation in lung and peripheral blood T lymphocytes from normal subjects. T cell subsets, defined based on their reactivity with monoclonal antibodies (MAb) OKT3, OKT4, and OKT8, were analyzed for expression of activation antigens as detected by MAbs to the interleukin-2 receptor, the transferrin receptor, and HLA-DR determinants. Whereas circulating T lymphocytes expressed the three activation antigens at low levels, and the total of T4+ and T8+ cells always approximated the number of T3+ cells, lung T lymphocytes of the T3+, T4+, and T8+ populations expressed the activation antigens at variable levels in combinations not seen in circulating lymphocytes, and the sum of T4+ and T8+ cells always exceeded the T3+ total. A proportion of T4+T8+ cells was detected in lung lymphocytes.
Adult↗