PubMed Health⌕ Search

Biomedical subjects

N Sidell

Publications and source records attributed to N Sidell.

70 records · Page 4Linked to original sources
PubMed1984

Immunological aspects of retinoids in humans. I. Analysis of retinoic acid enhancement of thymocyte responses to PHA.

We previously reported that retinoic acid (RA) enhances the blastogenic responses of human thymocytes. In this study, we explored the mechanism(s) of this effect by determining the phenotype of cells that show augmented responses to PHA and by analyzing RA effects on regulatory events mediated by interleukin-2 (IL-2). Our results indicate that RA is required early in the PHA activation process and that thymocytes affected by RA treatment already express the "mature" T3 antigen but lack T6 and Fc mu receptors. In the presence of saturating concentrations of exogeneous IL-2, RA caused further enhancement of both unfractionated and T3+ thymocyte proliferation, but could not induce immature T3- cells to become PHA responsive. RA treatment of thymus cells did not affect IL-2 production nor IL-2-dependent T-cell blast growth. RA-induced enhancement appears to induce increased sensitivity of T3+T6-Fc mu- thymocytes to PHA activation, but does not alter either IL-2-dependent proliferation or the accessory cells involved in IL-2 production.

Cell Differentiation↗
PubMed1984

Regulation of acetylcholinesterase activity by retinoic acid in a human neuroblastoma cell line.

The ability of retinoic acid (RA) to modulate acetylcholinesterase (AChE) activity in a human neuroblastoma cell line (LN-N-5) was examined. The specific activity of AChE was significantly increased 3 days after exposure of LA-N-5 to RA and reached its maximum values after 9 or more days of culturing. Dose-response experiments demonstrated that large increases of AChE occurred at RA concentrations between 10(-7) and 10(-6) M with maximum AChE values detected at 10(-6)-10(-5) M. Increased AChE activity paralleled neurite outgrowth in LA-N-5 cultures. These findings demonstrate that RA can regulate specific AChE activity in human neuroblastoma cells in a manner consistent with neuronal maturation.

Acetylcholinesterase↗
PubMed1983

Effects of retinoic acid (RA) on the growth and phenotypic expression of several human neuroblastoma cell lines.

It has been shown that retinoic acid (RA) can promote morphologic differentiation and inhibit the growth of a human neuroblastoma cell line, LA-N-1. The present study tests the histological generality of these phenomena by determining the effects of RA on seven other human neuroblastoma cell lines. Results show that RA strongly inhibited anchorage-dependent growth and induced morphologic alterations in six of seven of the cell lines. These alternations included morphologic differentiation as evidenced by formation of neurite extensions in four of the lines, cellular enlargement and vacuolization in one culture, and formation of large, flattened epithelial or fibroblastic-like cells in another culture. Although one cell line was relatively insensitive to the effects of RA in monolayer culture, all seven were strongly inhibited by RA in soft agar assays. Cellular RA-binding proteins were detected in 2/2 lines tested. These findings suggest that, as a histological group, human neuroblastoma cells are extremely sensitive to RA-induced growth inhibition and morphological alterations generally associated with reduced expression of the malignant phenotype of this type of cancer.

Axons↗
PubMed1983

Specific high-affinity binding and biologic action of retinoic acid in human neuroblastoma cell lines.

Neuroblastoma cells are a good model for neuronal development because of their ability to extend neurites in response to various stimuli, including retinoic acid. In the present experiments, we have examined five human neuroblastoma cell lines (LA-N-1, IMR-32, LA-N-5, SK-N-MC, and CHP-100) for the presence of cellular retinoic acid binding protein (CRABP), a receptor-like protein implicated in the molecular functioning of vitamin A. CRABP is identified and quantitated by sucrose gradient centrifugation, selective inhibition by the mercurial reagent p-chloromercuribenzene sulfonic acid (PCMBS), and saturation analysis. All five lines contain significant levels of cytosolic CRABP (2.5-7.5 pmol/mg of protein), which display typical properties of specific high affinity retinoic acid binding, a sedimentation coefficient of 2 S, and inhibition by PCMBS. Three of the lines (LA-N-1, IMR-32, and LA-N-5) are strongly growth inhibited by 1 microM retinoic acid in monolayer culture, whereas two (LA-N-1 and LA-N-5) undergo marked differentiation to a stellate, fusiform morphology with characteristic neurite outgrowths. The SK-N-MC and CHP-100 lines are relatively resistant to the antiproliferative effects of retinoic acid under these conditions. Nevertheless, all five lines are effectively inhibited by retinoic acid in their ability to form anchorage-independent colonies in soft agar. Thus, although CRABP is not necessarily correlated with growth inhibition in monolayer culture, it is associated with retinoic acid's ability to inhibit neuroblastoma colony formation in soft agar. More experiments will be required to determine if this effect on growth in soft agar reflects the putative ability of retinoic acid to convert tumorigenic neuroblastoma cell lines into the normal differentiated phenotype.

Carrier Proteins↗
PubMed1983

Human monoclonal antibody to a neuroectodermal tumor antigen (OFA-I-2).

Human IgM kappa monoclonal antibody to human tumors of neuroectodermal origin was produced in the spent medium of an Epstein-Barr virus-transformed B-lymphoblastoid cell line, L72. Chemically, the antigen was identified as ganglioside GD2 [Gal NAc beta 1----4 (Neu Ac alpha 2----8 Neu Ac alpha 2---3) Gal beta 1----4 Glc----ceramide]. Twenty-seven mg of pure human IgM were obtained from 10 liters of L72 spent medium using salt and hypotonic precipitation, ultracentrifugation, and Sephacryl-S 300 superfine gel filtration. The monoclonal origin of the antibody was determined by agarose isoelectrofocusing. This human monoclonal antibody may be a particularly useful reagent for immunotherapy trials in cancer patients.

Antibodies, Monoclonal↗
PubMed1982

Interleukin 2 and stimulator lymphoblastoid cells will induce human thymocytes to bind and kill K562 targets.

Human thymocytes cultured in the presence of IL-2 and an irradiated B cell line became cytotoxic to K562 target cells. Thymocytes cultured alone or with only IL-2 exhibited almost no killing, but thymocytes cultured in the presence of stimulator cells alone exhibited low levels of cytotoxic activity. Removal of Fc gamma receptor-bearing cells from the activated thymocyte population almost completely abolished the binding and lytic activity. Separation of thymocytes into Fc microns+ and Fc microns-cells before culturing with IL-2 and stimulator cells revealed that only the Fc microns+ subpopulation developed into K562 killer cells. These findings indicate that modulation of Fc microns to Fc gamma receptors on the thymocyte cell surface is part of the maturation process of this particular subset of cytotoxic cells. Morphologically, most of the activated Fc gamma+ K562-binding cells were large, granulated lymphocytes. Only very few of the round, nongranulated small thymocytes were bound to K562 target cells.

Cell Differentiation↗
PubMed1982

Failure to detect killer cell activity in rabbits.

Rabbit lymphoid cells from spleen, peripheral blood, and peritoneal cavity lacked killer (K)-cell activity against cell lines of rabbit and human origin, including virus-infected human tumor cells. This lack of activity was not affected by antibody concentration, source of antibodies, effector/target cell ratio, or length of assay. Rabbit leukocytes, however, were capable of lysing antibody-coated chicken erythrocytes. Hamster leukocytes, serving as a known source of K cells, mediated antibody-dependent cellular cytotoxicity against all targets. EA-rosette assays and mixed effector cell competition tests suggested a deficiency in rabbit K-cell activity which is not a result of an inherent lack of Fc receptor-positive cells or of some suppressor mechanism operating in the rabbit cell populations. Our data support the concept that antibody-dependent cellular cytotoxicity may not be a significant in vivo immune mechanism in certain species.

Animals↗
PubMed1982

Neuroblastoma: clinical perspectives, monoclonal antibodies, and retinoic acid.

Neuroblastoma, the second commonest solid tumor in children, is a neoplasm of the peripheral autonomic nervous system that usually occurs before children are 6 years old. Therapy of localized tumor (clinical stage I and II) and of a special form of metastatic tumor (clinical stage IV-S) is usually successful, but treatment of widespread regional (clinical stage III) or metastatic (clinical stage IV) neuroblastoma is almost uniformly unsuccessful. Unfortunately, two thirds of children have stage III or IV disease at diagnosis. Several clinical trials are in progress. Preclinical investigations with monoclonal antibodies and retinoic acid may lead to new therapies. Monoclonal antibodies that react relatively selectively with neuroblastoma cells may be useful for diagnosis and therapy. Neuroblastoma cells have cytoplasmic retinoic-acid-binding proteins; treatment of cultured cells with retinoic acid induces morphologic maturation and markedly inhibits proliferation.

Antibodies, Monoclonal↗
PubMed1982

Retinoic acid-induced growth inhibition and morphologic differentiation of human neuroblastoma cells in vitro.

Retinoic acid (RA) induced concentration-dependent morphologic differentiation and growth inhibition in the LA-N-1 human neuroblastoma cell line. Time course studies demonstrated a significant increase in the formation of long neurites in LA-N-1 cultures within 48 hours of RA addition; maximum expression of differentiation occurred at approximately 4 days. This differentiation profile corresponded to a detectable decrease in [3H]thymidine incorporation at 48 hours and complete inhibition of cell growth after 3-4 days. The RA-induced morphologic differentiation and growth inhibition persisted despite removal of the drug. A soft agar assay system showed that RA also inhibited the ability of LA-N-1 cells to form anchorage-independent colonies and induced morphologic differentiation in colonies that did develop. These findings suggest that RA promoted the differentiation of LA-N-1 neuroblastoma cells, resulting in an altered expression of the malignant phenotype.

Cell Differentiation↗
PubMed1981

Augmentation of human thymocyte proliferative responses by retinoic acid.

When 10(-5) to 10(-7) M all-trans retinoic acid (RA) was added to human thymocyte or tonsil lymphocyte cultures in the presence of mitogens or allogeneic stimulator cells, blastogenesis was increased up to 2.5-fold. No augmentation in proliferative responses of peripheral blood or spleen lymphocytes was observed. In the thymus, lymphocytes in the subclass of cells that did not bind peanut agglutinin (PNA) were responsible for the RA-induced enhancement. RA also increased the number of mitogen-stimulated thymocyte colonies developing in soft agar. These results indicate that the targets of RA activity must be lymphoid cells at a later stage of maturation than those identified by binding to PNA, and that one mechanism of RA enhancement is an increase in the number of lymphocytes that undergo blast transformation.

Humans↗
PubMed1980

Lymphocyte surface markers and cytotoxicity following cryopreservation.

The effects of cryopreservation (CP) on lymphocyte subpopulation distribution and functional activity in blastogenic and cytotoxicity assays were tested. Peripheral blood lymphocytes (PBL) from 12 healthy human donors were obtained by Ficoll-Hypaque separation. Half of each sample was tested fresh, while the other half was cryopreserved and then thawed and tested the same day. Each sample of CP-PBL was compared to fresh PBL from the same donor in simultaneous assays. Following CP there was a significant reduction in the percentage of E, EA gamma, and EA mu rosette-forming cells with a reciprocal increase in EAC rosette-forming cells. The blastogenic response to alloantigens was stable following CP while blastogenesis in unstimulated control cultures was significantly reduced. Mixed lymphocyte culture (MLC)-induced cell-mediated lympholysis (CML) was consistently and significantly diminished by CP. Cytotoxicity in 4 h chromium release NK (K562), ADCC, and LDCC assays was also significantly diminished by CP. In contrast, cytotoxicity was unaffected in an 18 h cytotoxicity assay against adherent cultured melanoma target cells.

Cell Survival↗
PubMed1977

Dual action of pancuronium on succinylcholine block.

The effects of pretreatment with both sub-paralyzing and paralyzing doses of pancuronium and d-tubocurarine, on the onset and duration of succinylcholine-induced neuromuscular blockade were evaluated and compared in 225 patients. D-tubocurarine antagonized both onset and duration of succinylcholine block, while pancuronium produced a dual effect, antagonizing the onset and potentiating the duration of succinylcholine block. Pretreatment with d-tubocurarine (0.07 mg/kg, 0.3 mg/kg and 0.6 mg/kg) increased the time to onset of succinylcholine paralysis from 28 to 118%, and decreased the duration from 16 to 37%. Pancuronium (0.02 mg/kg, 0.04 mg/kg and 0.08 mg/kg) also antagonized the onset of succinylcholine paralysis with increases of 32 to 114%, but potentiated its duration from 30 to 103% compared with succinylcholine alone in the same patients. Although pancuronium markedly inhibited serum cholinesterase in vitro (I50=5 X 10(-7) mol) there was only a 10% inhibition of cholinesterase in vivo after pancuronium 0.08 mg/kg.

Adult↗