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

We have developed a series of human intrathyroidal T-T cell hybridomas and evaluated their phenotypic characteristics and lymphokine secretions in order to further understand the role of the T cell in Graves' disease. Mitogen-stimulated T cell blasts were generated from intrathyroidal lymphocyte preparations and fused with a hypoxanthine-, aminopterin-, and thymidine-sensitive variant of the Molt 4 human leukemia T cell line. The resulting intrathyroidal T-T cell hybridomas and T-T cell hybridomas obtained from normal peripheral blood mitogen-stimulated T cell blasts were expanded and tested for their biological function. None of the generated T cell hybridomas exhibited antigen-specific IL-2 secretion when stimulated with autologous thyrocytes, although 60% of the hybridomas expressed CD3 antigen and the T cell receptor alpha/beta heterodimer. However, 9 intrathyroidal and 11 peripheral blood T cell hybridomas secreted a factor(s) that significantly enhanced immunoglobulin G secretion in vitro (P less than 0.005, by Student-Newman-Keuls test; mean +/- SEM, 338 +/- 60% increase). In summary, we have successfully used a technique that allows the construction of T-T cell hybridomas derived from intrathyroidal T cell cultures. The data demonstrated that a predominance of helper factor-secreting T cells were available for fusion within the Graves' thyroid gland. Such observations are further evidence for intact T cell help within the thyroid gland of patients with Graves' disease.
 ...
PMID:Successful production of intrathyroidal human T cell hybridomas: evidence for intact helper T cell function in Graves' disease. 253 Nov 54

The envelope glycoprotein (gp70) of a molecularly cloned, replication-defective feline leukemia virus (FeLV-FAIDS clone 61C) carries determinants for induction of fatal immunodeficiency disease, whereas the gp70 of its companion replication-competent, probably parent virus (clone 61E) does not. Immunoprecipitation analysis of the extracellular glycoproteins of 61E and EECC, a replication-competent viral construct composed of the 61C env and 3' long terminal repeat fused to the 61E gag-pol genes, demonstrated that the gp70 of EECC could be distinguished from that of 61E by both feline immune serum and a murine monoclonal antibody. Molecular weights of both the envelope precursor polyprotein (gp80) and the mature extracellular glycoprotein (gp70) of 61E were smaller than the corresponding proteins from the pathogenic EECC. Both the molecular weight disparity and monoclonal antibody discrimination of the two gp80s were abolished by inhibition of envelope protein glycosylation with tunicamycin, whereas the apparent gp70 size differences were resolved by enzymatic removal of N-linked oligosaccharides. Pulse-chase studies in EECC-infected cells demonstrated that processing of gp80 to gp70 was delayed and that this retardation of envelope glycoprotein processing could be simulated in 61E-infected cells by treatment with the glucosidase inhibitor N-methyldeoxynojirimycin, a compound that causes retention of oligosaccharides in the high-mannose form. The resultant 61E gp70 then could be recognized by sera from EECC-immunized cats. The presence of a higher content of sialic acid on the apathogenic 61E gp70 indicated that oligosaccharides of 61E and EECC gp70 were processed differently. These data suggested that the unique biochemical properties which distinguish the envelope glycoproteins of the FeLV-FAIDS variant from its companion apathogenic parent virus were responsible for T-cell cytopathicity and induction of immunodeficiency disease. Further biochemical characterization of these glycoproteins should be useful in understanding the pathogenic mechanisms of immunodeficiency disease induced by retroviruses.
 ...
PMID:Posttranslational modifications distinguish the envelope glycoprotein of the immunodeficiency disease-inducing feline leukemia virus retrovirus. 253 25

Nucleotide sequence analysis of the env gene of two different endogenous feline leukemia virus (FeLV) loci, CFE-6 and CFE-16, of domestic cats revealed the following characteristics. (i) Both proviruses contain an open reading frame in the env region; (ii) whereas the full complement of the exogenous FeLV env is generally present in CFE-6 DNA, it is truncated in CFE-16 DNA such that the 5' half of the gp70 domain and the untranslated region 3' to the p15E domain have been fused by an internal deletion, resulting in loss of the C-terminal half of the gp70- and all of the p15E-coding sequences; (iii) endogenous env is highly homologous to large sequence domains conserved in all three exogenous FeLV subgroups (A, B, and C) but is similar to FeLV-B sequence domains in the variable regions detected in these viruses; and (iv) there are four other sequence domains, one residing at the C terminus of gp70 and three scattered in p15E, which are unique for the endogenous env, thereby distinguishing it from the FeLV-B gene.
 ...
PMID:Nucleotide sequence and distinctive characteristics of the env gene of endogenous feline leukemia provirus. 253 25

Several fused tri- and tetracyclic quinolines (I and II) with [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino or [3-(N,N-dimethylamino)propyl]amino side chains were prepared, and their DNA intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. Some compounds having both intercalative ability and KB cytotoxicity were found to be inactive in vivo. However, a positive correlation was seen between the ability to induce topoisomerase II dependent DNA cleavage and antitumor activity in vivo. The indeno- (13a), benzofuro- (21a), and benzothieno- (22a) quinoline derivatives exhibited potent antitumor activities in vitro and in vivo, comparable to those of m-AMSA. They also intercalate DNA and induce topoisomerase II dependent DNA cleavage. Extended screening of 13a showed it to be active against solid tumors such as M5076 sarcoma, B16 melanoma, and colon 38 carcinoma.
 ...
PMID:Synthesis and antitumor activity of fused tetracyclic quinoline derivatives. 1. 254 58

Murine immunocytoma cell line, NS-1, was fused with spleen cells of Balb/C mice which had been stimulated by tolerogenic disaggregated human gamma globulin and immunized by purified serum IgM from the patient with chronic B cell leukemia (B-CLL). 10 hybridoma cell lines secreting monoclonal anti-idiotype (anti-Id) antibodies to human CLL were obtained. The McAbs were subclasses belonging to IgM and of IgG mouse. Specificity and biologic characters of the monoclonal anti-Id antibodies from culture fluid or ascites were assayed by ELISA, indirect mixed ELISA sandwich, ELISA inhibition, immunofluorescence (IF) and IF inhibition. The study also proved that monoclonal anti-Id antibodies could react with homologous IgM, but not with Ig from normal donors or a panel of patients with myeloma. The results of IF and IF inhibition assay showed that monoclonal anti-Id antibodies were bound to lymphocytes of patient with B-CLL. Their reactivity was inhibited by homologous IgM, but not by lymphocytes of patients with ALL or lymphoma. Monoclonal anti-Id antibodies were heterogenous reactive patterns with cell lines in vitro.
 ...
PMID:Studies on monoclonal anti-idiotypic antibodies to human B cell leukemia. 263 Jun 54

Results of our study on the activation of N-ras oncogene by point mutation in human leukemia and myelodysplastic syndrome have been described in this article. Point mutation was observed mainly on the 12th, 13th and 61st amino acid codon of ras genes. Therefore, oligomers containing mutations at these codons were used as probes for dot blot analysis of DNA derived from patient's bone marrow cells or leukemia cells. Polymerase chain reaction technique was used to amplify the DNA of ras genes containing 12th, 13th and 61st codons. By this technique, sensitivity of the method to detect the point mutations in ras oncogene was remarkably increased. Detection of the mutation in ras gene is considered to be very useful for the diagnosis, determination of remission and finding of relapse at an early stage. Study on the fused gene of bcr-abl, its mRNA and protein in chronic myelogenous leukemia is a good and reliable method to prove the existence of Ph1 positive chromosome by gene technology. Identification of the Ph1 acute lymphoblastic leukemia (ALL) has become possible by studying abl oncogene in Ph1 positive ALL. This method can be used also for the diagnosis of Ph1 ALL.
 ...
PMID:[Oncogenes in human leukemia]. 265 Jun 33

The interactions of glucocorticoids with their receptors somehow determine the cellular responses seen. The high potency glucocorticoid cortivazol differs from the usual glucocorticoids in two ways, structurally and in binding to receptors. Cortivazol contains a phenylpyrazol fused at carbon atoms 2 and 3 to the A ring of the cyclophenathrene, replacing the supposedly essential 3-keto,4,5-double bond pattern of glucocorticoids. Cortivazol binds to the glucocorticoid receptor in the cytosol from CEM C7 cells (a human acute lymphoblastic leukemia line) in a fashion consistent with interaction with at least two sites. Standard glucocorticoids show only one-site binding. In mutant leukemia cells derived from CEM C7, resistant to kill by 10(-6) M dexamethasone and deficient in standard glucocorticoid binding sites, cortivazol still finds a binding site and kills the cells. In wild-type leukemia cells, the binding sites of cortivazol, those with both higher (Kd approximately 5 x 10(-10) M) and lower (Kd approximately 1 x 10(-8] affinity appear to be on forms of the glucocorticoid receptor itself, and not on two different classes of molecules.
 ...
PMID:Interactions of the phenylpyrazolo steroid cortivazol with glucocorticoid receptors in steroid-sensitive and -resistant human leukemic cells. 270 65

Transient expression assays were used to investigate the restriction of Moloney murine leukemia virus (MoMuLV) expression in undifferentiated mouse F9 embryonal carcinoma (EC) cells. We previously reported that the MoMuLV long terminal repeat (LTR) is inactive in undifferentiated F9EC cells due to inactivity of the tandemly repeated MoMuLV transcriptional enhancers. Others suggested that the inactivity was due to the presence of negative regulatory elements that interact with the MoMuLV tandem repeats. Two heterologous enhancer sequences that are active in undifferentiated F9 EC cells were inserted into the MoMuLV LTR: the B enhancers from the F101 variant of polyomavirus and a cellular enhancer sequence isolated from EC cells that we previously identified. The chimeric LTRs were then fused to the bacterial chloramphenicol acetyltransferase gene and tested for expression by transfection into F9 EC or NIH 3T3 cells. Insertion of these enhancers either upstream or downstream of the MoMuLV tandem repeats resulted in transcriptionally active LTRs in undifferentiated EC cells, which did not support the existence of negative regulatory elements interacting with the tandem repeats. In our previous MoMuLV enhancer deletion constructs, the GC-rich sequences downstream from the tandem repeats were also deleted, which might have contributed to the inactivity in EC cells. However, restoration of the GC-rich sequences did not yield an active LTR. The experiments also suggested that the EC cellular enhancer was preferentially active in undifferentiated EC cells and inactive in NIH 3T3 cells. The possibility of negative regulatory sequences in the vicinity of the MoMuLV primer-binding site was tested by inserting MoMuLV sequences from +30 to +419 base pairs into the LTR-chloramphenicol acetyltransferase gene constructs downstream of the transcriptional start site. Transient expression assays confirmed that these sequences reduced expression from functional LTRs in undifferentiated F9 EC cells but reduced expression significantly less in NIH 3T3 cells. Moreover, equivalent sequences from myeloproliferative sarcoma virus did not exhibit this effect. These results supported restriction of MoMuLV expression in undifferentiated F9 EC cells at two levels, inactivity of the MoMuLV enhancers and interaction of negative regulatory factors in the vicinity of the primer-binding site.
 ...
PMID:Two blocks in Moloney murine leukemia virus expression in undifferentiated F9 embryonal carcinoma cells as determined by transient expression assays. 270 78

Regulation of albumin gene expression is believed to be mediated by multiple nuclear factors that interact with cis-acting DNA sequences within the first 160 base pairs (bp) of the promoter. The minimal promoter sequence required to generate tissue-specific expression has not been clearly defined. We have constructed a series of transient expression vectors containing progressive deletions of the mouse albumin gene 5'-flanking sequence fused to the bacterial chloramphenicol acetyltransferase (CAT) gene and include the Moloney murine leukemia viral (Mo-MuLV) enhancer. Promoter activity was determined in mouse hepatoma and fibroblast cell lines by chloramphenicol acetyltransferase and S1 nuclease analyses. All constructions were compared with -623 Albcat-Mo-MuLV which contains all the sequence homology between the rat and mouse promoters. Low levels of expression were observed with -60 Albcat-Mo-MuLV (10%) in hepatoma but not fibroblast cells. Addition of promoter sequence to -208 bp progressively increased activity to 190% in the hepatoma cells, while -308 and -1612 Albcat-Mo-MuLV had activity similar to the -623 Albcat-Mo-MuLV level, and -3000 Albcat-Mo-MuLV showed a 2-fold reduction in transcriptional activity. The inclusion of promoter sequences upstream of -60 generated low levels of expression in the fibroblasts. We also show that factors from mouse liver nuclear extracts protect at least five regions of the albumin promoter upstream of -160. Our results indicate that tissue specificity is established within the proximal promoter region and that additional cis-acting elements that may have a functional role in the efficiency of albumin gene expression are located upstream of -160 bp.
 ...
PMID:Cell-specific expression of mouse albumin promoter. Evidence for cell-specific DNA elements within the proximal promoter region and cis-acting DNA elements upstream of -160. 272 22

The leukaemic cells of more than 90% of chronic myelogenous leukaemia (CML) patients and of 10% of acute lymphocytic leukaemia (ALL) patients carry the t(9:22) (q34:q11) translocation which generates the Philadelphia chromosome (Ph1). In CML the abl gene is translocated from chromosome 9 to the centre of the bcr gene on chromosome 22 and this results in production of chimaeric bcr-abl RNA translated into a protein of relative molecular mass (Mr) 210,000 (210K). Our data indicate that in ALL abl is translocated into the 5' region of the bcr gene. The consequence of this is the expression of a fused transcript in which the first exon of bcr is linked to the second abl exon. This transcript encodes a 190K protein kinase.
 ...
PMID:A new fused transcript in Philadelphia chromosome positive acute lymphocytic leukaemia. 282 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>