Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indirect evidence links sensory nerves with mast cells (MC) in inflammatory reactions of airway, skin, and intestine. Isolated MC secrete histamine, serotonin, and other inflammatory mediators in response to neuropeptides such as substance P (SP) in vitro. To obtain direct evidence of nerve/MC interactions, we used a tissue culture model involving the co-culture of murine sympathetic neurons and rat basophilic leukemia (RBL) cells (homologous to mucosal MC). An electrophysiologic analysis of the consequences of neuron/RBL cell contacts showed that neurite contact with RBL cells reduced the control input resistance (Ro) of 61.8 +/- 3.2 (n = 110) M omega to 22.4 +/- 4.8 (n = 13) M omega (P less than 0.01) without change in the membrane potential. Time course studies showed that Ro of RBL cells with neurite contact was always lower by 30 to 54% than adjacent RBL cells lacking such contact. This effect was not seen in RBL cells cultured on rat fibroblasts. Direct application of SP, bradykinin, and somatostatin, but not acetylcholine, noradrenaline, or the putative neurotransmitter ATP, could partly mimic the effect of neurite contact. Therefore, neurotransmitter release from sympathetic neurons in contact with RBL cells may decrease RBL cell membrane resistance, possibly leading to activation.
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PMID:Sympathetic nerve contact alters membrane resistance of cells of the RBL-2H3 mucosal mast cell line. 137 18

Receptors for somatostatin were identified on mitogen-activated human peripheral blood lymphocytes (PBL) and human leukaemic cells in 87.5% of lymphoblastic leukaemia and in 12.5% of non-lymphocytic leukaemia, using a somatostatin radiobinding assay. The specific binding of 125I-somatostatin of these cells increased linearly with the cell numbers and was suppressed by non-iodinated somatostatin. We investigated the distribution of fluorescent somatostatin to mitogen-activated PBL by using a fluorescence-activated cell sorter (FACS). Over 95% of the cell populations bound fluorescent somatostatin and no distinct predilection was found among certain lymphocyte subpopulations and somatostatin receptor-positive cells. Scatchard analysis showed a single class (low affinity) of binding site on mitogen-activated PBL and two classes (high and low affinity) of specific binding sites on lymphoblastic leukaemia cells.
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PMID:Somatostatin receptors on human lymphocytes and leukaemia cells. 217 23

The tetradecapeptide somatostatin (SOM 14) and a 28-amino acid biosynthetic precursor (SOM 28) are constituents of diverse neuroendocrine tissues that are released by noxious stimuli from a subset of sensory nerve endings, and substantially modify the functions of basophils and mast cells. SOM-like factors were detected initially in the fluid phase of suspensions of immunologically challenged rat basophilic leukemia cells (RBL), and were purified from ethanol/0.2 M acetic acid (3/1, v/v) extracts of replicate portions of 3 X 10(9) RBL. Sephadex G-25 columns resolved factors of over 10,000, 2000 to 4000, and 300 to 1200 daltons that are antigenically related to SOM 14, as assessed by a radioimmunoassay specific for SOM 14. Only the two larger factors were detected by a radioimmunoassay for SOM 28(1-14), which binds to prepro-SOM and SOM 28 but not SOM 14. Reverse-phase high performance liquid chromatography distinguished the two smaller SOM peptides of RBL from SOM 28 and SOM 14, respectively. Amino acid analyses showed major differences in composition between the 2000 to 4000 dalton SOM of RBL and SOM 28. Picomolar to nanomolar concentrations of both of the smaller SOM peptides of RBL inhibited the IgE-dependent release of histamine from basophils to the same extent as SOM 14. The finding of 3 to 5 ng of structurally unique SOM-like peptides per 10(8) RBL suggests that endogenous mechanisms analogous to those of specialized sensory neurons may regulate the expression of hypersensitivity.
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PMID:Endogenous somatostatin-like peptides of rat basophilic leukemia cells. 241 11

The effect of somatostatin 1-14 (SS) on the natural killer (NK) activity of human peripheral blood lymphocytes was investigated. The NK activity was estimated by means of radioactive chromium (51Cr) assay with the use of human leukemia cells K 562 as targets. The previous exposure of lymphocytes obtained from healthy donors to somatostatin in the concentration of 10(-8) and 10(-6) M resulted in the enhancement of NK activity. The finding provides a further evidence of the immunomodulating somatostatin action.
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PMID:Enhancement of human lymphocyte natural killer activity by somatostatin. 256 73

Spleen cells from acutely diabetic (AD) and non-diabetic but diabetes prone (DP) BB/Wor rats lysed insulinoma target cells to a significantly greater degree than did diabetes resistant (DR) cells as determined using a 51Cr release cytotoxicity assay. There were no differences between the AD and DP groups. Lysis was not target cell specific, since somatostatin secreting RIN 14B cells, Wistar Furth leukemia cells designated LW12, PC12 cells and NK sensitive YAC-1 cells were also lysed. Lysis of all target cells was significantly reduced by pretreatment of the effector lymphocytes with antiserum to NK cells (anti-asialo GM1) and complement suggesting that NK cells mediated destruction of these cells. These data demonstrate a generalized increase in non-specific NK cell activity in BB/Wor rats. Since NK cells have been shown to mediate antibody dependent cell mediated cytotoxicity (ADCC), splenic lymphoid cells from AD rats were tested for their ability to lyse insulinoma target cells in the presence of diabetic rat sera which were demonstrated to contain islet cell surface antibodies. Three different ADCC protocols were tested but in each case the addition of serum dilutions from AD rats reduced the lysis of insulinoma cells by AD spleen cells in a dose dependent manner. This inhibition was also demonstrated when sera and effector cells from control rats were used. As a positive control, DR spleen cells were incubated with 51Cr labelled target cells that were untreated or pre-treated with anti-rat class 1 antibody (OX18). Pre-treatment of the target cells resulted in a marked increase in their subsequent lysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro natural killer cell activity in the spontaneously diabetic BB/Wor rat: effects of serum on lysis of insulinoma cells. 285 69

The MT-2, derived from an adult T-cell leukaemia (ATL) cell, the Molt-4F, a human T-cell line, and the Isk, an EB virus-transformed B-cell line, were found to have high-affinity receptors for somatostatin, a cyclic tetradecapeptide that inhibits the release of substances such as growth hormone, TSH, glucagon, insulin, secretin, gastrin and cholecystokinin. The quantity of radioactivity bound varied linearly with the number of cells, and was displaced by non-radioactive somatostatin in a concentration-dependent manner. Specific binding of 125I-somatostatin was time- and temperature-dependent and at 22 degrees reached equilibrium within 120 min. Scatchard analysis demonstrated one class of specific-binding sites on MT-2 cells, Isk cells and Molt-4F cells that had respective densities and dissociation constants of 109 pM and 0.64 nM, 102 pM and 1.1 nM, and 5.8 pM and 0.22 nM.
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PMID:Identification of lymphoid cell lines bearing receptors for somatostatin. 289 85

Daily injections of somatostatin into mice with myeloid leukemia retarded the tumor growth. This myeloid leukemia is an insulin-dependent tumor (in that it grows more slowly in hypoinsulinemic diabetic mice than in nondiabetic animals). Since somatostatin decreased the level of immunoreactive insulin in mice with myeloid leukemia, and since the treatment with insulin abrogated the antileukemic effect of somatostatin, we attribute retarded growth of this leukemia to decreased secretion of insulin, caused by somatostatin.
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PMID:Somatostatin suppresses growth of murine myeloid leukemia in vivo. 611 Apr 47

The various pharmacological effects of somatostatin may be explained by the hypothesis that the paracrine peptide, by "stabilizing" cell membranes, inhibits the secretion of hormones as well as protects other cells (vascular endothelium, parenchyma) from different lesions (vasculo-, organo-, cytoprotection). This hypothesis was tested in vitro, using bischloroethyl-nitrosourea (BCNU)-intoxicated stem cells of normal mouse granulopoiesis and of the L 1210 leukemia. Clonogenic mouse bone marrow and L 1210 cells were grown in agar-containing glass capillaries. Using these colony assays and a ID90 of BCNU, cyclic somatostatin influenced the BCNU-cytotoxicity neither at simultaneous nor at subsequent application. However, when given 2 h prior to BCNU, the inhibition of colony growth was almost totally abolished. This cytoprotective effect was seen with normal granulopoietic as well as with leukemic cells. The effect did not show up, if the inactive linear somatostatin was used. N-acetyl-cysteine, a SH-compound applied as a chemoprotective adjunct, did not reveal a cytoprotective effect under identical experimental conditions, either. The results were discussed in view of common efforts to reduce the toxicity of cancer chemotherapy.
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PMID:Cytoprotection by somatostatin of normal and malignant clonogenic cells against the in vitro cytotoxicity of bischloroethylnitrosourea (BCNU). 615 Jul 18

The release of mediators from unpurified human basophils challenged with anti-human myeloma IgE serum was suppressed significantly by somatostatin at respective concentrations of 3 x 10(-13) M to 10(-9) M for histamine and 10(-13) M to 10(-11) M for leukotriene D4, which had no effect on release elicited by ionophore A23187. A direct effect of picomole-nanomole concentrations of somatostatin on basophils predominated, as shown by the significant inhibition of immunologically stimulated mediator release from monocyte-free human basophils of 15 to 32% purity and from rat basophil leukemia cells. The dependence of basophil inhibition on the conformation of somatostatin was suggested by the lower potency of reduced and alkylated somatostatin and the lack of inhibitory activity of [D-Trp8] somatostatin. Somatostatin thus may mediate suppressive effects of sensory nerves in some basophil-dependent hypersensitivity reactions.
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PMID:Inhibition by somatostatin of the release of mediators from human basophils and rat leukemic basophils. 620 74

Somatostatin (SS) is a 14 amino acid peptide which is secreted by the hypothalamus and the pancreatic islets. It expresses antiproliferative activity in various organ systems, experiments have suggested effects of SS on hematopoietic cells. Here we present investigations regarding the effect of SS and its analog SMS 201-995 (SMS) on the in vitro proliferation of acute lymphoblastic leukemia (ALL; n = 7 cases), acute myeloid leukemia (AML; n = 21 cases) and chronic lymphocytic leukemia (CLL; n = 2 cases). Both SS and SMS inhibited spontaneous leukemic cell growth in approximately 1/3 of cases (i.e. 7/19). G-CSF stimulated AML cells were inhibited by SMS in 11/21 cases. AML cell proliferation induced by IL-3 or GM-CSF was suppressed in only 3/21 and 6/21 cases, respectively. In ALL cells, IL-7-induced proliferation was suppressed by SMS in 3/7 cases. The effect of SMS seemed to depend on the type of the hematopoietic growth factor, and on their concentrations. In fact, high concentrations of G-CSF could override SMS blocking completely. Colony formation by normal marrow progenitors and DNA synthesis by HL-60 and T11/65 leukemic cell lines were not affected by SMS. In conclusion, somatostatin may act as a negative regulator of the proliferative activity of human leukemia.
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PMID:Somatostatin and its cyclic octapeptide analog SMS 201-995 as inhibitors of proliferation of human acute lymphoblastic and acute myeloid leukemia. 750 Jun 46


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