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)

The pituitary cell line, AtT-20, synthesizes adrenocorticotropic hormone (ACTH) as a glycoprotein precursor that is cleaved into mature hormones during packaging into secretory granules. The cells also produce an endogenous leukemia virus (MuLV) that is glycosylated after translation similar to the glycosylation of the ACTH precursor. Our evidence suggests that the envelope glycoprotein and some precursor ACTH get to the cell surface in a vesicle different from the mature ACTH secretory granule. Viral glycoproteins and ACTH precursor are released from the cells much sooner after synthesis than mature ACTH. Isolated secretory granules do not contain significant amounts of the envelope glycoprotein or ACTH precursor. Exposing cells to 8Br-cAMP stimulates release of mature ACTH four to five fold, but has little effect on the release of the ACTH precursor or the viral glycoproteins. We propose that the viral glycoproteins and some of the ACTH precursor are transported by a constitutive pathway, while mature ACTH is stored in secretory granules where its release is enhanced by stimulation.
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PMID:Two distinct intracellular pathways transport secretory and membrane glycoproteins to the surface of pituitary tumor cells. 627 13

A modification of the hydroxylamine cleavage of proteins is presented in which proteins were cleaved while immobilized in the matrix of a polyacrylamide gel. The reaction under these conditions retains its high specificity for Asn-Gly bonds and has the advantage that the gel matrix, acting as a carrier, facilitates simultaneous treatment of many samples, and contributes to a high recovery efficiency (60-90%) of the cleavage products. The cleavage is performed with individual protein bands excised from dried slab gels after detection by staining, autoradiography, or fluorography. The procedure can be easily combined with other techniques to further characterize the cleavage fragments. Also a two-dimensional version of the cleavage method was developed, which allows rapid recognition of interrelationships between proteins in a complicated mixture. The versatility of the procedure is demonstrated in a number of applications. Highly related strains of murine leukemia viruses were easily distinguished from one another by the unique cleavage patterns of their gag- and env-precursor polypeptides. Comparing the env-precursor gPr82env synthesized in the presence or absence of tunicamycin with its cell-free synthesized counterpart, revealed the presence of an amino-terminal signal sequence. Cleavage patterns of pro-opiomelanocortin (POMC) from three different species revealed a high degree of homology between rat and mouse POMC, whereas Xenopus POMC was very different. Regions to which carbohydrates are attached could be identified by comparing glycosylated and unglycosylated forms of POMC. Combining the hydroxylamine cleavage procedure with immunological characterization of the fragments showed a small but significant difference between the amino-terminal sequences of the recombinant transforming protein P120 of Abelson murine leukemia virus and of its parent molecule Pr65gag of Moloney murine leukemia virus.
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PMID:Hydroxylamine cleavage of proteins in polyacrylamide gels. 662 62

Leukemia Inhibitory Factor (LIF), a pituitary cytokine, and LIF receptors are expressed in human fetal and adult adenohypophyseal cells. LIF induces adrenocorticotropin hormone (ACTH) secretion in vitro and potently synergizes with both corticotropin-releasing hormone (CRH) and cAMP-induced pro-opiomelanocortin (POMC) transcription. We therefore investigated the effects of intra-carotid administration of recombinant human LIF to chronically catheterized fetal non-human primates. LIF induced fetal monkey ACTH secretion in a time- and dose dependent manner. Maximal ACTH induction (12-fold) was achieved with 100 micrograms/kg after 60 minutes (p < 0.01). CRH (10 micrograms/kg) also induced ACTH secretion 4.8-fold at 60 minutes. Co-injection of LIF (50 micrograms/kg) and CRH (10 micrograms/kg) synergistically induced ACTH levels in a time-dependent manner up to 23-fold after 60 minutes. Thus, LIF alone induces ACTH secretion and LIF acts in synergy with CRH in vivo. As LIF is expressed early in human fetal pituitary development, and potentiates corticotroph function both in vitro and in vivo, this immuno-regulatory cytokine may be useful for clinical testing of the hypothalamic-pituitary-adrenal axis.
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PMID:Leukemia inhibitory factor (LIF) induces acute adrenocorticotrophic hormone (ACTH) secretion in fetal rhesus macaque primates: a novel dynamic test of pituitary function. 892 79

To gain insight into the neurochemical pathologies contributing to AIDS dementia complex, neurotransmitter levels were measured in the brains of mice infected with the LP-BM5 leukemia retrovirus. These mice develop immunologic and cognitive deficits analogous to human HIV-1 infection. Met-enkephalin and substance-P levels declined approximately 50% in the striatum and hypothalamus beginning as early as 4 weeks after infection. Hippocampal met-enkephalin levels were reduced to 50% only at 12 weeks after inoculation. Significant decreases (60-70%) in acetylcholine concentrations were observed in the striatum, cerebral cortex and hippocampus by 12 weeks after virus inoculation, while striatal GABA concentrations decreased to 50-60% at 8-12 weeks after infection. Striatal somatostatin levels were unchanged. Administration of the NMDA receptor antagonists MK-801 or LY 274614 ameliorated the decline in striatal met-enkephalin levels observed in mice after 8 weeks of infection. This pattern of neurotransmitter depletion and the ability of NMDA receptor antagonists to attenuate the loss of striatal met-enkephalin are consistent with an excitotoxic lesion. Thus, the elevation of glutamate levels secondary to glial activation may contribute to the contemporaneous development of cognitive deficits observed in mice infected with the LP-BM5 virus.
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PMID:The pattern of neurotransmitter alterations in LP-BM5 infected mice is consistent with glutamatergic hyperactivation. 963 May 62

An opiate alkaloid-selective receptor, designated mu(3), mediates inhibition by morphine of activation of human peripheral blood monocytes and granulocytes. The mu(3) receptor is present on several macrophage cell types including microglia, on cultured astrocytes, and in brain and retina. Murine macrophage cell lines and human HL-60 leukemia cells contain high concentrations of these receptors. Binding of 3H-morphine to the receptor is displaced by morphine, etorphine, naloxone, diprenorphine and morphine 6-glucuronide, but not by morphine 3-glucuronide, fentanyl, benzomorphans, enkephalins, dynorphin, beta-endorphin, endomorphin-1, other opioid peptides or nociceptin (orphanin FQ). The mu(3) receptor appears to be much more sensitive to inactivation by reduced glutathione than are classical mu, delta and kappa receptors. Evidence is also presented for G protein-coupling of these receptors. These and other data raise the possibility that the mu(3) receptor is a member of a chemokine or of another related receptor family, rather than the opioid receptor family. The affinity for morphine of mu(3) receptors of granulocytic-differentiated HL-60 cells is markedly enhanced in the presence of levorphanol and certain benzomorphans. In contrast, receptors of monocytes, macrophage cell lines, microglia, macrophage-differentiated HL-60 cells and astrocytes are not affected by levorphanol or benzomorphans. It is concluded that mu(3) receptors of granulocytic and promyelocytic cells differ from those of macrophage and astrocyte cell types, possibly due to differences in receptor subtype or to the presence of an additional component in the granulocytic and promyelocytic cells.
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PMID:Properties of mu 3 opiate alkaloid receptors in macrophages, astrocytes, and HL-60 human promyelocytic leukemia cells. 966 65

Although previous studies have suggested that human peripheral blood mononuclear cells (PBMCs) may express pro-opiomelanocortin (POMC) mRNA and synthesize its related peptides, the patho-physiological role of POMC expressed in peripheral cells is not known. In this study, we investigated the POMC gene expression in various types of human leukemia cell lines by Northern blot analysis and the reverse transcribed-polymerase chain reaction (RT-PCR) method. The POMC mRNA was not detected by Northern blot analysis in all cell lines tested except the Jurkat cell line which is derived from T-lymphoblastic leukemia. The POMC mRNA expressed in the Jurkat cells was smaller than that in the human anterior pituitary gland. The RT-PCR method revealed that a truncated-POMC transcript could be detected not only in lymphoblastic leukemia cells but also in erythroid and myeloid cells. Interestingly, two cell lines of monocytic leukemia, J-111 and U937, did not express the truncated-POMC mRNA. Treatment with concanavalin-A stimulated truncated POMC mRNA expression and ACTH-like immunoreactivity in lymphoblastic leukemia cells with T-(Jurkat) and B-(BALL-1) lymphocyte phenotypes. These results confirm that human leukemia cells except for monocytic cells express a truncated-POMC mRNA as well as in the human normal PBMC.
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PMID:Expression of truncated pro-opiomelanocortin gene transcript in human leukemia cell lines. 979 Feb 76

The initiation of DNA synthesis and secretion of Interleukin 2 (IL-2) was measured in isolated rat splenic lymphocytes following activation with Concanavalin A (ConA). The extent of 3H-thymidine incorporation into activated cells was tested when cultured with various concentrations of Adrenocorticotropic hormone (ACTH). A paradoxical dose-response curve resulted when ACTH caused a biphasic response of augmenting and inhibiting 3H-thymidine uptake in lymphocytes depending on the hormone concentration. Low levels of ACTH (0.001-1-nM) augmented 3H-thymidine uptake and high levels (10-1000 nM) reversed the effect. The optimal ACTH concentration was 10 pM ACTH in the presence of 5 ug/ml ConA and there was no ACTH effect on quiescent cells (no ConA). Conditioned media from splenic lymphocytes treated with various concentrations of ConA or ACTH was tested for increased uptake of 3H-thymidine by the IL-2 growth dependent Cytotoxic T Lymphocyte Leukemia (CTLL-2) cells. ConA conditioned medium could sustain the CTLL-2 cells indicating the presence of IL-2. Conditioned medium from splenic lymphocytes treated with both ConA and 100 pM ACTH further increased CTLL-2 cell proliferation indicating an additional increase of IL-2 secretion. The identity of IL-2 was confirmed by using an anti-rat IL-2 antibody to neutralize the growth potential of the conditioned medium. ACTH alone had no effect on the CTLL-2 cell proliferation indicating the effect is due solely to induced IL-2 found in the conditioned medium. IL-2 levels in the conditioned media were quantitated by ELISA assay; splenic lymphocytes produced 4.2 ng/ml to ConA only, 19.2 ng/ml in ConA plus 10 nM ACTH, and no detectable IL-2 at ConA plus 10 uM ACTH. These results demonstrated that ACTH modulates IL-2 secretion from activated lymphocytes, which is both biphasic and concentration dependent.
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PMID:Adrenocorticotropic hormone controls Concanavalin A activation of rat lymphocytes by modulating IL-2 production. 1104 99

It is well known that prophylactic cranial irradiation is highly effective in preventing central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL). Nevertheless, there have been very few reports on the late effects, especially pituitary function and growth, in long-term survivors who were treated with 18 Gy cranial irradiation in childhood. The subjects consisted of 35 children with ALL who were treated with prophylactic 18 Gy cranial irradiation at Kanagawa Children's Medical Center between October 1981 and February 1995. All patients received cranial irradiation after first attaining complete remission with induction chemotherapy, according to the treatment protocols prescribed by the Tokyo Children's Leukemia Study Group (TCLSG) and Tokyo Children's Cancer Study Group (TCCSG). Their ages at the time of cranial irradiation ranged from 2.2-15.0 years (mean 6.8). We evaluated their pituitary functions by measuring their pituitary hormone values 0.7-11.3 years (mean 6.0) after cranial irradiation and their growth by analyzing their height standard deviation score (SDS) at diagnosis of ALL and their final height SDS at the mean follow-up period of 8.2 years after cranial irradiation. Height SDS is defined as the difference between the patient's height and the mean height of their age and sex, divided by the standard deviation of their age and sex. Eight of 35 patients had ALL relapse, involving the bone marrow in seven patients and the CNS in only one. Six of the eight patients with relapse died 1.5-6.6 years after cranial irradiation and the other two patients were salvaged by further intensive therapies. The remaining 27 relapse-free patients have survived for 1.4-15.8 years (mean 10.1) after cranial irradiation. Twenty-six of the 29 survivors are long-term survivors of more than 5 years. Although there was one patient with an abnormal result in each value of growth hormone (GH), adrenocorticotropic hormone (ACTH), and prolactin (PRL), and two patients with abnormal results in thyroid-stimulating hormone (TSH) values, none of the patients had clinical symptoms of pituitary hormone abnormality and none required hormone supplements. The final height SDS decreased significantly compared with the height SDS at diagnosis of ALL in the long-term survivors (P = 0.001) and the height SDS of the patients who had received cranial irradiation at a young age tended to decrease gradually (P = 0.019). However, no patient showed severe growth failure. It is considered that prophylactic 18 Gy cranial irradiation plus chemotherapy for ALL in childhood can effectively prevent CNS relapse and is unlikely to produce clinically significant late effects, although it may cause slight pituitary hormone abnormality.
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PMID:Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: outcomes of late effects on pituitary function and growth in long-term survivors. 1199 95

Ectopic hormone production is very rare in hematological malignancy. Here, we describe an interesting case of acute lymphoblastic leukemia (ALL) with adrenocorticotropic hormone (ACTH) production. A 47-year-old man was admitted to our hospital with a 7-month history of hyperpigmentation. The plasma level of ACTH was markedly elevated without a circadian rhythm and the level of cortisol was normal. Examination of bone marrow aspiration revealed ALL, and no other disease as a cause of the elevated ACTH was detected. Sephadex G-75 chromatography of plasma ACTH extract revealed the existence of an abnormally large molecular ACTH (probably proopiomelanocortin) in addition to authentic 1-39 ACTH. Ectopic ACTH of low biological activity is considered to be the reason for a discrepancy in the plasma levels of ACTH and cortisol. Shortly after remission induction chemotherapy, blast cells in the peripheral blood disappeared, and the plasma level of ACTH became normal, leading to an improvement of skin pigmentation. These clinical findings and laboratory data suggested that leukemia cells in this case may produce the ACTH.
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PMID:Acute lymphoblastic leukemia with large molecular ACTH production. 1275 Aug 44

The average duration of survival of 15 cases of childhood leukemia treated with corticotropin and cortisone was 6.8 months. This survival was the same as observed among 59 children who received no treatment, or treatment with x-ray, or blood transfusion alone. Despite the fact that objective evidence of remission was observed in 7 of 15 children treated with corticotropin and cortisone, the remissions were not reflected by a longer duration of life. Treatment of childhood leukemia with corticotropin and cortisone appears to be a palliative measure, without significant effect on the duration of life.
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PMID:Leukemia; duration of life in children treated with corticotropin and cortisone. 1300 66


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